FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Larsen, LH Meiselman, S Iyengar, G Klipfel, N Chantra, PK Palmer, S AF Larsen, Hovanessian L. Meiselman, S. Iyengar, G. Klipfel, N. Chantra, P. K. Palmer, S. TI Granulomatous Mastitis: An Update of Clinical, Imaging, and Pathological Features Reported in a Large Series of 35 Cases SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Larsen, Hovanessian L.; Meiselman, S.; Iyengar, G.; Klipfel, N.; Palmer, S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Chantra, P. K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM lhovanes@usc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900288 ER PT J AU Lee, EW Masih, S Alex, FD Modarresi, S AF Lee, E. W. Masih, S. Alex, F. D. Modarresi, S. TI MRI and CT Diagnosis of Previously Missed Occult Fractures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Lee, E. W.] Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. [Masih, S.; Alex, F. D.; Modarresi, S.] Vet Adm Greater Los Angeles, Dept Radiol, Los Angeles, CA USA. EM EdwardLee@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900628 ER PT J AU Lee, EW Modarresi, S Masih, S Freitas, AD AF Lee, E. W. Modarresi, S. Masih, S. Freitas, A. D. TI MRI and CT Evaluation of Shoulder Pain and Weakness Caused by Nerve Compression SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Lee, E. W.] Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. [Modarresi, S.; Masih, S.; Freitas, A. D.] Vet Adm Greater Los Angeles, Dept Radiol, Los Angeles, CA USA. EM EdwardLee@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900589 ER PT J AU Li, J Udayasankar, UK Kalra, MK Small, WC AF Li, J. Udayasankar, U. K. Kalra, M. K. Small, W. C. TI Automatic Kilovoltage Selection Technique in Abdomen MDCT: Radiation Dose and Image Quality SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Li, J.; Udayasankar, U. K.; Small, W. C.] Emory Univ, Sch Med, Atlanta, GA USA. [Kalra, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jhli98@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900430 ER PT J AU Li, J Udayasankar, UK Kalra, MK Small, WC AF Li, J. Udayasankar, U. K. Kalra, M. K. Small, W. C. TI Adrenal Mass: Differentiation by Attenuation Characteristics Using Dual-energy MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Li, J.; Udayasankar, U. K.; Small, W. C.] Emory Univ, Sch Med, Atlanta, GA USA. [Kalra, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jhli98@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900194 ER PT J AU Matin, A Masih, S Freitas, AD Modarresi, S Learch, TJ AF Matin, A. Masih, S. Freitas, A. D. Modarresi, S. Learch, T. J. TI MRI Pictorial Review of Bursal Anatomy and Pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Matin, A.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Learch, T. J.] Univ So Calif, Univ Hosp, Los Angeles, CA USA. [Masih, S.; Freitas, A. D.; Modarresi, S.] Vet Adm Greater Los Angeles, Los Angeles, CA USA. EM amatin@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900541 ER PT J AU Namasivayam, S Kalra, MK Kalva, S Sahani, DV AF Namasivayam, S. Kalra, M. K. Kalva, S. Sahani, D., V TI Role of Curved Multiplanar Reformation for Multidetector Row CT in Body and Vascular Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Namasivayam, S.; Kalra, M. K.; Kalva, S.; Sahani, D., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM namasivayam2005@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900433 ER PT J AU Namasivayam, S Kalra, MK Waldstein, P Heagy, TA Knipfer, JE Sahani, DV AF Namasivayam, S. Kalra, M. K. Waldstein, P. Heagy, T. A. Knipfer, J. E. Sahani, D., V TI CT Power Injectors: A Primer for Radiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Waldstein, P.] EZEM Inc, Lake Success, NY USA. [Namasivayam, S.; Kalra, M. K.; Sahani, D., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Heagy, T. A.] Medrad Inc, Indianola, PA USA. Tyco Healthcare Mallinckrodt, St Louis, MO USA. EM namasivayam2005@yahoo.com NR 0 TC 0 Z9 0 U1 3 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900425 ER PT J AU Namasivayam, S Kalra, MK Mittal, PK Sahani, DV Small, WC AF Namasivayam, S. Kalra, M. K. Mittal, P. K. Sahani, D. V. Small, W. C. TI Multi-bolus Contrast Injection Protocol for Multidetector Row CT Angiography of Renal Donors: Evaluation with Surgical Correlation (Work-in-progress) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Mittal, P. K.; Small, W. C.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Namasivayam, S.; Kalra, M. K.; Sahani, D. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM namasivayam2005@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900252 ER PT J AU Namasivayam, S Kalra, MK Udayasankar, UK Sahani, DV Small, WC AF Namasivayam, S. Kalra, M. K. Udayasankar, U. K. Sahani, D., V Small, W. C. TI Can Body Water Content Measured with Bio-electric Impedance Method Allow Contrast Material Dose Optimization for MDCT of Abdomen? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Udayasankar, U. K.; Small, W. C.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Namasivayam, S.; Kalra, M. K.; Sahani, D., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM namasivayam2005@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900032 ER PT J AU Prasitvoranan, W Srisuwan, T Kaewlai, R Muennuch, W Yenarkarn, P Chuapetcharasopon, C AF Prasitvoranan, W. Srisuwan, T. Kaewlai, R. Muennuch, W. Yenarkarn, P. Chuapetcharasopon, C. TI Spectrum of Radiographic Abnormalities in 2004 Tsunami Victims: a Pictorial Essay SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Prasitvoranan, W.; Srisuwan, T.; Muennuch, W.; Yenarkarn, P.; Chuapetcharasopon, C.] Bumrungrad Int Hosp, Bangkok, Thailand. [Kaewlai, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM wit3070@csloxinfo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900410 ER PT J AU Sachdev, K Hoffmann, U AF Sachdev, K. Hoffmann, U. TI Differences in Clinical Information Gained From Imaging Modalities Including MR, CT, and Nuclear Studies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Hoffmann, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sachdev, K.] St Francis Hosp, Evanston, IL USA. EM karinasachdev@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900344 ER PT J AU Sahani, DV Shah, ZK Fernandez-Del Castillo, C Hahn, PF AF Sahani, D., V Shah, Z. K. Fernandez-Del Castillo, C. Hahn, P. F. TI Can MDCT Accurately Characterize Serous Cystadenomas of the Pancreas? Imaging-Pathologic Correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sahani, D., V; Shah, Z. K.; Fernandez-Del Castillo, C.; Hahn, P. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dsahani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900066 ER PT J AU Sahani, DV Lepanto, L Nelson, R Heiken, JP AF Sahani, D., V Lepanto, L. Nelson, R. Heiken, J. P. TI Does Contrast Concentration Matter? A Double-blind Comparison of Contrast Enhancement after Iopamidol or Iodixanol in Patients Undergoing Contrast Enhanced Multidetector CT of the Liver SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Lepanto, L.] CHUM Hosp St Luc, Montreal, PQ, Canada. [Nelson, R.] Duke Univ, Durham, NC USA. [Sahani, D., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Heiken, J. P.] Washington Univ, St Louis, MO USA. EM dsahani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900029 ER PT J AU Sainani, NI Prabhakar, HB Uppot, RN Blake, MA Mino-Kenudson, M Sahani, DV AF Sainani, N., I Prabhakar, H. B. Uppot, R. N. Blake, M. A. Mino-Kenudson, M. Sahani, D., V TI MDCT and PET/CT of Gastrointestinal Tract Tumors: Discussion on the Technique with Radiopathological Correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sainani, N., I; Prabhakar, H. B.; Uppot, R. N.; Blake, M. A.; Mino-Kenudson, M.; Sahani, D., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nsainani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900487 ER PT J AU Sainani, NI Catalano, OA Fernandez-Del Castillo, C Hahn, PF Sahani, DV AF Sainani, N., I Catalano, O. A. Fernandez-Del Castillo, C. Hahn, P. F. Sahani, D., V TI Characterization of Small Pancreatic Cyst (3 cm or smaller): A Comparison Between MDCT and MRI/MRCP for Assessing Cyst Morphology and Predicting Malignancy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sainani, N., I; Catalano, O. A.; Fernandez-Del Castillo, C.; Hahn, P. F.; Sahani, D., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nsainani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900065 ER PT J AU Saksena, M Braschi, M Katkar, AS Ventura, E Hahn, P Harisinghani, MG AF Saksena, M. Braschi, M. Katkar, A. S. Ventura, E. Hahn, P. Harisinghani, M. G. TI Lymphotrophic Nanoparticle-enhanced MRI (LNMRI) in Prostate Cancer: Incidence of Metastatic Perirectal Lymphadenopathy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Saksena, M.; Braschi, M.; Katkar, A. S.; Ventura, E.; Hahn, P.; Harisinghani, M. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mansisaksena@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900155 ER PT J AU Saksena, M Gervais, DA Dawson, S Hahn, P Katkar, AS Harisinghani, MG AF Saksena, M. Gervais, D. A. Dawson, S. Hahn, P. Katkar, A. S. Harisinghani, M. G. TI Impact of Lymphotrophic Nanoparticle-enhanced MRI (LNMRI) on CT-guided Percutaneous Lymph Node Biopsy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Saksena, M.; Gervais, D. A.; Dawson, S.; Hahn, P.; Katkar, A. S.; Harisinghani, M. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mansisaksena@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900154 ER PT J AU Sebastian, S Kalra, M Fox, T Small, W AF Sebastian, S. Kalra, M. Fox, T. Small, W. TI Can Multienergy MDCT Help to Differentiate Between Polyps and Fecal Matter in an Unprepped Colon? A Phantom Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sebastian, S.; Fox, T.; Small, W.] Emory Univ, Sch Med, Atlanta, GA USA. [Kalra, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Sunit.Sebastian@emoryhealthcare.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900083 ER PT J AU Setty, BN Ratai, E Sagar, P Krishnamoorthy, KS Grant, EP AF Setty, B. N. Ratai, E. Sagar, P. Krishnamoorthy, K. S. Grant, E. P. TI Significance of Lactate on 1H-MRS in Patients with a Central Pattern of Hypoxic Ischemic Injury on DWI within the First 3 Days of Life SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Setty, B. N.; Ratai, E.; Sagar, P.; Krishnamoorthy, K. S.; Grant, E. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM bsetty@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900167 ER PT J AU Sheehy, NP Johnston, C Israel, D Ramaiya, N Van den Abbeele, AD AF Sheehy, N. P. Johnston, C. Israel, D. Ramaiya, N. Van den Abbeele, A. D. TI 18FDG-PET/CT in Soft Tissue Sarcoma: Looking Beyond GIST SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sheehy, N. P.; Johnston, C.; Israel, D.; Ramaiya, N.; Van den Abbeele, A. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM nsheehy@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900706 ER PT J AU Simoneaux, S Karsli, T Udayasankar, U Lorenzo, R Small, WC Hahn, P Kalra, MK AF Simoneaux, S. Karsli, T. Udayasankar, U. Lorenzo, R. Small, W. C. Hahn, P. Kalra, M. K. TI Can Focused Follow-up CT of Abdomen and Pelvis Provide Required Information and Allow Reduction of Radiation Dose? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Simoneaux, S.; Karsli, T.; Udayasankar, U.; Lorenzo, R.; Small, W. C.] Emory Univ, Sch Med, Atlanta, GA USA. [Hahn, P.; Kalra, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM stephen.simoneaux@choa.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900169 ER PT J AU Sindhwani, V Sainani, N Catalano, O Fernandez, C Hahn, P Sahani, D AF Sindhwani, V Sainani, N. Catalano, O. Fernandez, C. Hahn, P. Sahani, D. TI Secretin-enhanced MRCP: A Step Ahead in Evaluation of Pancreatic Duct Anatomy and Related Abnormalities SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sindhwani, V; Sainani, N.; Catalano, O.; Fernandez, C.; Hahn, P.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM vsindhwani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900474 ER PT J AU Sindhwani, V Rabinowitz, C Gervais, D Prabhakar, H Sahani, D AF Sindhwani, V Rabinowitz, C. Gervais, D. Prabhakar, H. Sahani, D. TI Interventional Radiology: A Powerful Imaging and Therapeutic Strategy Awaiting to Reveal Its Full Potential in Management of Complications of Crohn's Disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sindhwani, V; Rabinowitz, C.; Gervais, D.; Prabhakar, H.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM vsindhwani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900413 ER PT J AU Sindhwani, V Singh, A Mino-Kenudson, M Thiim, M Sahani, D AF Sindhwani, V Singh, A. Mino-Kenudson, M. Thiim, M. Sahani, D. TI Diagnosing Type of NonViral Hepatitis Based on Imaging: Pathologic Correlation and Impact on Management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sindhwani, V; Singh, A.; Mino-Kenudson, M.; Thiim, M.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM vsindhwani@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900412 ER PT J AU Sindhwani, V Singh, A Hertel, M Samir, A Sahani, D AF Sindhwani, V Singh, A. Hertel, M. Samir, A. Sahani, D. TI Mapping Living Liver Donor Vascular Anatomy: Comparative Performance of Gd-BOPTA and 16 MDCT Angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Sindhwani, V; Singh, A.; Hertel, M.; Samir, A.; Sahani, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM VSINDHWANI@PARTNERS.ORG NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900216 ER PT J AU Singh, AK Sahani, DV Harris, G Joshi, M Uppot, R AF Singh, A. K. Sahani, D., V Harris, G. Joshi, M. Uppot, R. TI Great 3DCT Images! But Do We Need Them All?-Abdominal Organ Specific Views and Newer MDCT Scanner Console-A Harmonious Collage SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Joshi, M.] GE Healthcare, Belmont, MA USA. [Singh, A. K.; Sahani, D., V; Harris, G.; Uppot, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dranandsingh@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900492 ER PT J AU Singh, AK Sahani, DV Joshi, M Ouellette-Depiazzo, K Thrall, JH AF Singh, A. K. Sahani, D., V Joshi, M. Ouellette-Depiazzo, K. Thrall, J. H. TI Overcoming Hurdles to Improve CT Workflow-A Reimagination SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Joshi, M.] GE Healthcare, Belmont, MA USA. [Singh, A. K.; Sahani, D., V; Ouellette-Depiazzo, K.; Thrall, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dranandsingh@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900383 ER PT J AU Singh, AK Sahani, DV Ouellette-Piazzo, K Novelline, RA AF Singh, A. K. Sahani, D. V. Ouellette-Piazzo, K. Novelline, R. A. TI Comparison of Automated CT Reconstructions from 64-MDCT with Manual Reformats from 16-MDCT in Emergency Radiology Setting: An Image Quality Analysis Based on Patient Body Weight and Workflow Considerations SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Singh, A. K.; Sahani, D. V.; Ouellette-Piazzo, K.; Novelline, R. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dranandsingh@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900092 ER PT J AU Udayasankar, UK Namasivayam, S Baumgarten, D Kalra, M Small, WC AF Udayasankar, U. K. Namasivayam, S. Baumgarten, D. Kalra, M. Small, W. C. TI Multidetector Row CT of the Urinary Tract: Newer Techniques and Strategies to Reduce Radiation Dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Udayasankar, U. K.; Baumgarten, D.; Small, W. C.] Emory Univ, Sch Med, Atlanta, GA USA. [Namasivayam, S.; Kalra, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM uudayas@emory.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900522 ER PT J AU Udayasankar, UK Kalra, MK Small, WC AF Udayasankar, U. K. Kalra, M. K. Small, W. C. TI Applying the Concepts of Evidence-Based Medicine in Radiology: Principles and Practice SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Udayasankar, U. K.; Small, W. C.] Emory Univ, Sch Med, Atlanta, GA USA. [Kalra, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM uudayas@emory.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900375 ER PT J AU Udayasankar, UK Li, J Kalra, MK Baumgarten, D Small, WC AF Udayasankar, U. K. Li, J. Kalra, M. K. Baumgarten, D. Small, W. C. TI Ultra-Low-Dose MDCT of Abdomen and Pelvis in Patients with Acute Nonspecific Abdominal Pain: Impact on Patient Care and Management SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Udayasankar, U. K.; Li, J.; Baumgarten, D.; Small, W. C.] Emory Univ, Sch Med, Atlanta, GA USA. [Kalra, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM uudayas@emory.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900091 ER PT J AU Uppot, RN Gervais, DA Arellano, RS Hahn, PF Mueller, PR AF Uppot, R. N. Gervais, D. A. Arellano, R. S. Hahn, P. F. Mueller, P. R. TI Image-guided Percutaneous Urological Interventions-From Diagnosis to Treatment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Uppot, R. N.; Gervais, D. A.; Arellano, R. S.; Hahn, P. F.; Mueller, P. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ruppot@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900539 ER PT J AU Uppot, RN Hahn, PF Sahani, DV Blake, MA Gervais, DA Mueller, PR AF Uppot, R. N. Hahn, P. F. Sahani, D., V Blake, M. A. Gervais, D. A. Mueller, P. R. TI Fat - From Head to Toe - Imaging Significance of Fat Visualized in Various Lesions throughout the Body SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Uppot, R. N.; Hahn, P. F.; Sahani, D., V; Blake, M. A.; Gervais, D. A.; Mueller, P. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ruppot@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900423 ER PT J AU Uppot, RN Sahani, DV Blake, MA Hahn, PF Gervais, DA Mueller, PR AF Uppot, R. N. Sahani, D., V Blake, M. A. Hahn, P. F. Gervais, D. A. Mueller, P. R. TI Scar-From Head to Toe-Imaging Significance of Scars/Central Scars Visualized in Various Lesions throughout the Body SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Uppot, R. N.; Sahani, D., V; Blake, M. A.; Hahn, P. F.; Gervais, D. A.; Mueller, P. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ruppot@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900422 ER PT J AU Zarzhevsky, N Shah, Z Fernandez-del Castillo, C Sahani, DV AF Zarzhevsky, N. Shah, Z. Fernandez-del Castillo, C. Sahani, D., V TI Pancreatic Cystic Lesions: Multidetector CT (MDCT) Based Diagnosis and Classification SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Shah, Z.; Fernandez-del Castillo, C.; Sahani, D., V] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zarzhevsky, N.] Univ Michigan, Ann Arbor, MI 48109 USA. EM nzarzhev@med.umich.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900475 ER PT J AU Butt, AA Tsevat, J Ahmad, J Shakil, AO Mrus, JM AF Butt, Adeel A. Tsevat, Joel Ahmad, Jawad Shakil, A. Obaid Mrus, Joseph M. TI Biochemical and virologic parameters in patients co-infected with hepatitis C and HIV versus patients with hepatitis C mono-infection SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ALPHA-2A PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; LIVER-DISEASE; VIREMIA; COINFECTION; DIAGNOSIS; MORTALITY; GENOTYPE; IMPACT AB Background. Previous studies of patients with hepatitis C virus (HCV) infection looking at the effect of human immunodeficiency virus (HIV) co-infection on biochemical parameters and HCV RNA level have shown conflicting results. Accurate characterization of the effect of HIV is important for evaluation and treatment of HCV in co-infected persons. Methods: We studied 315 HCV mono-infected and 75 HCV-HIV coinfected subjects to determine the effect of HIV on biochemical parameters and HCV RNA and to determine the predictors of elevated serum alanine aminotransferase (ALT) levels and HCV RNA levels. Results: The co-infected subjects were more likely to be African-American (55% vs 26%, P < 0.0005), have used injection drugs (68% vs 60%, P = 0.02), have detectable HCV RNA (84% vs 70.5%, P = 0.018), have HCV RNA levels > 6 log(10) IU/mL (60% vs 38%, P = 0.001), and have lower mean serum ALT levels (50.4 IU/mL vs 73.7 IU/mL, P = 0.006). In multivariable analyses, the following factors predicted an ALT level > 50 IU/mL: log,0 HCV RNA (OR, 1.15; 95% CI, 1.00 to 1.32); HIV co-infection (OR, 0.48; 95% CI, 0.25 to 0.89); and having ever been treated for HCV (OR, 1.92; 95% CI, 1.16 to 3.18). The only significant predictor of HCV RNA level > 6 log,0 IU/mL was HIV co-infection (OR, 2.75; 95% CI, 1.46 to 5.15). Significant predictors of having a detectable HCV RNA level were female sex (OR, 3.81; 95% CI, 1.18 to 12.25); HIV co-infection (2.45; 95% CI, 1.14 to 5.26); and ever being treated for HCV (OR, 1.96; 95% CI, 1.10 to 3.48). Conclusions: HCV-HIV co-infected persons have higher HCV RNA levels but lower serum ALT levels than HCV mono-infected patients. Criteria for performing liver biopsy and treating HCV infection in co-infected patients may need to be revisited. C1 Univ Pittsburgh, Med Ctr, Div Infect Dis, VA Pittsburgh Healthcare Syst,Ctr Hlth Equ Res &, Pittsburgh, PA 15213 USA. Vet Healthcare Syst Ohio, Cincinnati, OH USA. Univ Cincinnati, Med Ctr, Dept Internal Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Inst Study Hlth, Cincinnati, OH 45267 USA. Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Div Infect Dis, VA Pittsburgh Healthcare Syst,Ctr Hlth Equ Res &, 3601 5th Ave,Suite 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. EM butta@dom.pitt.edu FU AHRQ HHS [1-R03-HS13220-01]; NCCIH NIH HHS [1-R01-AT01147, K24 AT001676]; NIAID NIH HHS [U01-AI-25897]; NIDA NIH HHS [1-K23-DA016175-01A1] NR 18 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAY PY 2007 VL 333 IS 5 BP 271 EP 275 DI 10.1097/MAJ.0b013e31805341f0 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 173VS UT WOS:000246901200003 PM 17505167 ER PT J AU Kawai, T Sachs, DH Spitzer, T Tolkoff-Rubin, N Saidman, S Williams, W Dey, B Goes, N Ko, D Wong, WC Colvin, RB Sykes, M Cosimi, AB AF Kawai, Tatsuo Sachs, David H. Spitzer, Thomas Tolkoff-Rubin, Nina Saidman, Susan Williams, Winfred Dey, Bimalangshu Goes, Nelson Ko, Dicken Wong, Waichi Colvin, Robert B. Sykes, Megan Cosimi, A. Benedict TI The long-term evaluation of HLA-mismatched combined kidney and bone marrow transplant recipients after complete withdrawal of immunosuppression. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Biol Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 2 BP 147 EP 147 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370200003 ER PT J AU Dormond, O Pal, S Madsen, JC Briscoe, DM AF Dormond, Olivier Pal, Soumitro Madsen, Joren C. Briscoe, David M. TI Critical role for rictor in CD40-mediated activation of endothelial cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 28 BP 154 EP 154 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370200029 ER PT J AU Akoad, M Francis, F Wagener, M Cacciarelli, TV AF Akoad, Mohamed Francis, Fadi Wagener, Marilyn Cacciarelli, Thomas V. TI The impact of recipient disease severity on outcome with the use of extended criteria donors in liver transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 84 BP 168 EP 168 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370200085 ER PT J AU Fiorina, P Jurewicz, M Tanaka, K Augello, A Vergani, A Smith, NR Sayegh, MH Abdi, R AF Fiorina, Paolo Jurewicz, Mollie Tanaka, Katsunori Augello, Andrea Vergani, Andrea Smith, Neat R. Sayegh, Mohamed H. Abdi, Reza TI Characterization of donor dendritic cells and enhancement of DC efflux with CC-chemokine ligand 21: A novel strategy to prolong islet allograft survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Harvard Univ, Sch Med, Childrens Hosp, Brigham & Womens Hosp,Transplantat Res Ctr, Boston, MA USA. Ist Sci San Raffaele, I-20132 Milan, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Augello, Andrea/C-7321-2013 OI Augello, Andrea/0000-0001-5959-7989 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 112 BP 175 EP 175 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370200113 ER PT J AU Jackson, AM Zachary, AA Breimer, ME Rydberg, L Klimmalm, GB Smith, DM Pelletier, RM von Visger, J Williams, WW Saidman, SL Holgersson, J Tyden, G Holgersson, S Grufman, P AF Jackson, Annette M. Zachary, Andrea A. Breimer, Michael E. Rydberg, Lennart Klimmalm, Goran B. Smith, Douglas M. Pelletier, Ron M. von Visger, Jon Williams, Winfred W., Jr. Saidman, Susan L. Holgersson, Jan Tyden, Gunnar Holgersson, Suchitra Grufman, Per TI Clinical trial data evaluating the XM-One endothelial cell crossmatch test in predicting early rejection episodes in renal transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. Sahlgrens Univ Hosp, Dept Transplantat & Liver Surg, S-41345 Gothenburg, Sweden. Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX USA. Ohio State Univ, Med Ctr, Dept Gen Surg, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Karolinska Univ Hosp, Karolinska Inst, Dept Clin Immunol, Stockholm, Sweden. AbSorber, Stockholm, Sweden. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 211 BP 201 EP 202 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370200212 ER PT J AU Fan, ZG Spencer, J Lu, Y Gao, WD Strom, TB Lin, CP Koulmanda, M AF Fan, Zhigang Spencer, Joel Lu, Yan Gao, Wenda Strom, Terry B. Lin, Charles P. Koulmanda, Maria TI In vivo time-lapse imaging of naive T cells conversion to regulatory T cells in allograft islet transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA 02215 USA. Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02114 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 283 BP 220 EP 220 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370200284 ER PT J AU Weiss, MJ Sahara, H Wikiel, KJ Cochrane, ME Sayre, JK Ng, CY Cho, PL Homer, BM Houser, SL Wain, JC Sachs, DH Madsen, JC Huang, CA Allan, JS AF Weiss, Matthew J. Sahara, Hisashi Wikiel, Krzysztof J. Cochrane, Meghan E. Sayre, Jessica K. Ng, Choo Y. Cho, Patricia L. Homer, Bell M. Houser, Stuart L. Wain, John C. Sachs, David H. Madsen, Joren C. Huang, Christene A. Allan, James S. TI Mixed hematopoietic chimerism prevents lung allograft rejection in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Harvard Med Sch, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 591 BP 301 EP 301 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201027 ER PT J AU Saidi, RF Hartono, C Elias, N Kawai, T Hertl, M Farrel, M Goes, N Tolkoff-Rubin, N Delmonico, F Cosimi, AB Ko, D AF Saidi, Reza F. Hartono, C. Elias, N. Kawai, T. Hertl, M. Farrel, M. Goes, N. Tolkoff-Rubin, N. Delmonico, F. Cosimi, A. B. Ko, D. TI Outcome of kidney transplantation using expanded criteria donors and donation after cardiac death kidneys: Reality and cost. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 617 BP 308 EP 309 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201053 ER PT J AU Streblow, D Kreklywich, C Moses, A Andoh, T Nelson, J Orloff, SL AF Streblow, Daniel Kreklywich, Crai Moses, Ashlee Andoh, Takeshi Nelson, Jay Orloff, Susan L. TI Activation of tissue repair/angiogenesis genes during CMV-accelerated transplant vascular sclerosis in rat cardiac allografts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 642 BP 315 EP 315 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201078 ER PT J AU Ollinger, R Kogler, P Bosch, F Sucher, R Thomas, M Mark, W Troppmair, J Bach, FH Margreiter, R AF Oellinger, Robert Kogler, Pamela Boesch, Florian Sucher, Robert Thomas, Michael Mark, Walter Troppmair, Jakob Bach, Fritz H. Margreiter, Raimund TI Bilirubin rinse suppresses early MAPK activation in cardiac ischemia-reperfusion injury. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Med Univ Innsbruck, Innsbruck, Austria. Harvard Univ, Sch Med, Immunol Res Ctr, BIDMC, Boston, MA USA. RI Ollinger, Robert/D-1538-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 660 BP 319 EP 320 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201096 ER PT J AU Ueno, T Jurewiez, M Tanaka, K Shea, S Fiorina, P Smith, RN Sayegh, MH Abdi, R AF Ueno, Takuya Jurewiez, Mollie Tanaka, Katsunori Shea, Susan Fiorina, Paolo Smith, Rex N. Sayegh, Mohamed H. Abdi, Reza TI Divergent role of Tissue/Donor dendritic cells in rejection versus tolerance of cardiac allografts: Studies with CX3CR1 deficient mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 695 BP 328 EP 328 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201131 ER PT J AU Porcheray, F Marina, O Wong, W Wu, CJ Saidman, SI Tolkoff-Rubin, N Dey, BR Spitzer, TR Kawai, T Cosimi, BA Colvin, RB Sachs, DH Sykes, M Zom, E AF Porcheray, Fabrice Marina, Ovidiu Wong, Waichi Wu, Catherine J. Saidman, Susan I. Tolkoff-Rubin, Nina Dey, Bimal R. Spitzer, Thomas R. Kawai, Tatsuo Cosimi, Benedict A. Colvin, Robert B. Sachs, David H. Sykes, Megan Zom, Emmanuel TI B cell responses after combined kidney and bone marrow transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 723 BP 337 EP 337 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201169 ER PT J AU Dormond, O Madsen, JC Briscoe, DM AF Dormond, Olivier Madsen, Joren C. Briscoe, David M. TI Rapamycin blocks prosurvival signaling pathways in mature endothelial cells (EC) by inhibiting the activation of akt. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 933 BP 387 EP 388 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201369 ER PT J AU Delmonico, FL McBride, MA Edwards, E Edwards, L AF Delmonico, Francis L. McBride, Maureen A. Edwards, Erick Edwards, Leah TI An analysis of patient deaths on the wait list undermines the argument for a regulated market of organ sales. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. United Network Organ Sharing, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 950 BP 392 EP 392 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201386 ER PT J AU Smith, RN Ueno, T Ito, T Tanaka, K Izawa, A Shea, S Jurewicz, M Sayegh, MH Abdi, R AF Smith, R. Neal Ueno, Takuya Ito, Toshiro Tanaka, Katsunori Izawa, Atsushi Shea, Susan Jurewicz, Mollie Sayegh, Mohamed H. Abdi, Reza TI Chemokines and chronic heart allograft rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Harvard Med Sch, Transplantat Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1048 BP 417 EP 417 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201484 ER PT J AU Yoon, MH Konduru, B Gallo, DJ Otterbein, LE Hanto, DW AF Yoon, Myunghee Konduru, Bhaskar Gallo, David J. Otterbein, Leo E. Hanto, Doug W. TI Carbon monoxide prevents rejection and delayed graft function following kidney transplantation in rats and pigs. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1049 BP 417 EP 417 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370201485 ER PT J AU Freeman, RB Ruthazer, R Schore, A Mithofer, AM Ngyuen, K Agarwal, P Harper, A Edwards, EB AF Freeman, Richard B. Ruthazer, Robin Schore, Anthony Mithofer, Abigail M. Ngyuen, Khanh Agarwal, Prakhar Harper, Ann Edwards, Erick B. TI Pre-operative ablation is beneficial for HCC candidates waiting for liver transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. United Network Organ Sharing, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1243 BP 467 EP 467 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370202108 ER PT J AU Griesemer, A Hirakata, A Shimizu, A Okumi, M Moran, S Etter, J Caputo, L Sachs, DH Yamada, K AF Griesemer, Adam Hirakata, Atsushi Shimizu, Akira Okumi, Masayoshi Moran, Shannon Etter, Justin Caputo, Louis Sachs, David H. Yamada, Kazuhiko TI Linked suppression of the immune response to renal transplants across a fully MHC-Mismatched barrier in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1309 BP 483 EP 483 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370202174 ER PT J AU Benatuil, L Ghosh, S Cretin, N Kaye, J Cariappa, A Pillai, S Iacomini, J AF Benatuil, Lorenzo Ghosh, Shamik Cretin, Nathalie Kaye, Joel Cariappa, Annaiah Pillai, Shiv Iacomini, John TI The development of immunoglobulin knock-in mice producing? Gal specific anti-carbohydrate antibodies. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Brigham & Womens Hosp, Childrens Hosp, Harvard Med Sch, Transplantat Res Ctr, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. Teva Pharmaceut, Dept Pharmacol, Netanya, Israel. Massachusetts Gen Hosp, Harvard Med Sch, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1366 BP 498 EP 498 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370202231 ER PT J AU Kotton, CN Gribbons, M Halpern, EF Pavlakis, M AF Kotton, Camille N. Gribbons, Megan Halpern, Elkan F. Pavlakis, Martha TI Immune response to influenza vaccination in renal transplant recipients taking sirolimus. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1382 BP 502 EP 502 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370202247 ER PT J AU Akoad, M Francis, F Wagener, MM Cacciarelli, TV AF Akoad, Mohamed Francis, Fadi Wagener, Marilyn M. Cacciarelli, Thomas V. TI The adverse impact of orthotopic liver retransplantation (re-OLT) and hepatitis C virus infection on graft survival: A single center experience. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1575 BP 552 EP 552 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370202440 ER PT J AU Ghazi, A Griesemer, A Hirakata, A Hirsh, E Lo, D Okumi, M Sykes, M Sachs, DH Yamada, K Huang, CA AF Ghazi, Ahmed Griesemer, Adam Hirakata, Atsushi Hirsh, Erica Lo, Diana Okumi, Masayoshi Sykes, Megan Sachs, David H. Yamada, Kazuhiko Huang, Christene A. TI Specific non-responsiveness to pig in baboons receiving BMT from GaIT-KO pigs. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Annual American Transplant Congress CY MAY 05-09, 2007 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 SU 2 MA 1695 BP 583 EP 583 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 166HQ UT WOS:000246370202559 ER PT J AU Dew, MA Jacobs, CL Jowsey, SG Hanto, R Miller, C Delmonico, FL AF Dew, M. A. Jacobs, C. L. Jowsey, S. G. Hanto, R. Miller, C. Delmonico, F. L. TI Guidelines for the psychosocial evaluation of living unrelated kidney donors in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE living kidney donor; kidney transplantation; psychosocial evaluation; psychosocial outcomes ID LIVE ORGAN DONOR; QUALITY-OF-LIFE; TERM-FOLLOW-UP; ALTRUISTIC STRANGERS; VANCOUVER FORUM; DONATION; ETHICS; TRANSPLANTATION; SOLICITATION; PANCREAS AB Under the auspices of the United Network for Organ Sharing, the American Society of Transplant Surgeons and the American Society of Transplantation, a meeting was convened on May 25, 2006, in Washington, DC, to develop guidelines for the psychosocial evaluation of prospective living kidney donors who have neither a biologic nor longstanding emotional relationship with the transplant candidate. These 'unrelated' donors are increasingly often identified by transplant candidates via the Internet, print media and other public appeals. The expansion of living donor kidney transplantation to include significant numbers of donors with little to no preexisting relationship to the candidate has caused concern in the medical community regarding such psychosocial factors as donor psychological status, motivation, knowledge about donation and the potential for undue pressure to donate under some circumstances. Therefore, experts in mental health; psychosocial, behavioral and transplant medicine; and medical ethics met to specify (a) characteristics of unrelated donors that increase their risk for, or serve as protective factors against, poor donor psychosocial outcomes, (b) basic principles underlying informed consent and evaluation processes pertinent to these donors and (c) the process and content of the donor psychosocial evaluation. The meeting deliberations resulted in the recommendations made in this report. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Epidemiol, Pittsburgh, PA USA. Med Ctr, Pittsburgh, PA USA. Univ Minnesota, Med Ctr, Dept Social Work, Minneapolis, MN 55455 USA. Mayo Clin, Dept Psychiat, Rochester, MN USA. Mayo Clin, Dept Psychol, Rochester, MN USA. New England Organ Bank Inc, Newton, MA USA. New England Program Kidney Exchange, Newton, MA USA. Cleveland Clin Fdn, Liver Transplant Program, Cleveland, OH 44195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. United Network Organ Sharing, Richmond, VA USA. RP Dew, MA (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. EM dewma@upmc.edu NR 35 TC 83 Z9 86 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 IS 5 BP 1047 EP 1054 DI 10.1111/j.1600-6143.2007.01751.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 160JU UT WOS:000245937500004 PM 17359510 ER PT J AU Koyama, I Nadazdin, O Boskovic, S Ochiai, T Smith, RN Sykes, M Sogawa, H Murakami, T Strom, TB Colvin, RB Sachc, DH Benichou, G Cosimi, AB Kawai, T AF Koyama, I. Nadazdin, O. Boskovic, S. Ochiai, T. Smith, R. N. Sykes, M. Sogawa, H. Murakami, T. Strom, T. B. Colvin, R. B. Sachc, D. H. Benichou, G. Cosimi, A. B. Kawai, T. TI Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE kidney transplantation; memory T cell; mixed chimerism; tolerance ID DONOR-SPECIFIC TRANSFUSION; MONOCLONAL-ANTIBODY; NONHUMAN-PRIMATES; HETEROLOGOUS IMMUNITY; CYNOMOLGUS MONKEYS; REGULATORY CELLS; MIXED CHIMERISM; BARRIER; LYMPHOCYTES; HOMEOSTASIS AB Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti-CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naive T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide 'proof of principle' that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp E, Sch Med,Dept Surg, Transplantat Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Res Ctr,Dept Med, Boston, MA 02215 USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. EM tkawai@partners.org FU NCRR NIH HHS [R24 RR016001, RR016001]; NHLBI NIH HHS [P01 HL018646, P01-HL18646]; NIAID NIH HHS [5R01 AI50987-03, AI040101, R01 AI037692, R01 AI037692-09, R01 AI037692-10, R01 AI050987, R21 AI037692, R21 AI037692-06]; PHS HHS [R01 A137692] NR 30 TC 70 Z9 72 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 IS 5 BP 1055 EP 1061 DI 10.1111/j.1600-6143.2006.01703.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 160JU UT WOS:000245937500005 PM 17286617 ER PT J AU Lacy-Hulbert, A Ueno, T Ito, T Jurewicz, M Izawa, A Smith, RN Chase, CM Tanaka, K Fiorina, P Russell, PS Auchincloss, H Sayegh, MH Hynes, RO Abdi, R AF Lacy-Hulbert, A. Ueno, T. Ito, T. Jurewicz, M. Izawa, A. Smith, R. N. Chase, C. M. Tanaka, K. Fiorina, P. Russell, P. S. Auchincloss, H., Jr. Sayegh, M. H. Hynes, R. O. Abdi, R. TI beta 3 integrins regulate lymphocyte migration and cytokine responses in heart transplant rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE acute rejection; chronic rejection; extracellular matrix; integrin; migration ID METALLOPROTEINASE INDUCTION SYSTEM; CELL-ADHESION MOLECULE-1; CD8(+) T-CELLS; VITRONECTIN RECEPTOR; ALLOGRAFT-REJECTION; COSTIMULATORY PATHWAY; DENDRITIC CELLS; UP-REGULATION; SKIN-GRAFTS; IN-VIVO AB Integrin alpha v beta 3 is important for cell survival, signaling and migration, particularly during angiogenesis and tumorigenesis, where it has been proposed as a therapeutic target. alpha v beta 3 is up-regulated following transplantation and beta 3 polymorphisms are associated with increased acute kidney rejection, suggesting that alpha v beta 3 may also play a role in transplant rejection. Here, using a model of allogeneic heart transplantation, we show that allograft survival is prolonged in beta 3 integrin-deficient (beta 3(-/-)) mice. This is associated with Th2-type immune responses and reduced T-cell infiltration into grafts and T cells from beta 3(-/-) mice show impaired adhesion and migration, consistent with a role for alpha v beta 3 in transmigration. These studies provide evidence that targeting beta 3 integrins impairs recruitment of effector cells and alters cytokine production, so prolonging graft survival. We also show that low doses of blocking antibodies against leukocyte function associated antigen-1 (LFA-1)/alpha L beta 2 and very late antigen-4 (VLA-4)/alpha 4 beta 1, when combined with deletion of beta 3, lead to long-term survival of allografts with no evidence of chronic rejection. Hence we provide strong mechanistic evidence supporting previous genetic studies, demonstrate the involvement of beta 3 integrins in both acute and chronic rejection and identify beta 3 as a new target for immunosuppressive therapy. C1 MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Univ Edinburgh, MRC, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh, Midlothian, Scotland. Brigham & Womens Hosp, Transplantat Res Ctr, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg & Pathol, Boston, MA 02114 USA. Shinshu Univ, Grad Sch Med, Dept Organ Regenerat, Div Cardiovasc Sci, Matsumoto, Nagano 390, Japan. RP Abdi, R (reprint author), MIT, Ctr Canc Res, Howard Hughes Med Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rabdi@rics.bwh.harvard.edu OI Lacy-Hulbert, Adam/0000-0003-2162-0156 FU NHLBI NIH HHS [P01HL66105]; NIAID NIH HHS [P01 AI50157]; Wellcome Trust [064487] NR 39 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2007 VL 7 IS 5 BP 1080 EP 1090 DI 10.1111/j.1600-6143.2007.01757.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 160JU UT WOS:000245937500008 PM 17359504 ER PT J AU Kim, MS Cote, CJ Cristoloveanu, C Roth, AG Vornov, P Jennings, MA Maddalozzo, JP Sullivan, C AF Kim, Michelle S. Cote, Charles J. Cristoloveanu, Carmen Roth, Andrew G. Vornov, Polina Jennings, Melissa A. Maddalozzo, John P. Sullivan, Cristine TI There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSTOPERATIVE NAUSEA; PREOPERATIVE DEXAMETHASONE; INTRAVENOUS DEXAMETHASONE; STRABISMUS SURGERY; CHILDREN; METAANALYSIS; ONDANSETRON; MORBIDITY; STEROIDS AB BACKGROUND: Tonsillectomy is associated with postoperative nausea and vomiting (PONV) if no prophylaxis is administered. Previous studies have shown that a single dose of dexamethasone decreases the incidence of PONV. The most effective dose of dexamethasone to affect clinical outcome is yet to be defined. METHODS: One-hundred-twenty-five children were enrolled in a double-blind, prospective, randomized, dose-escalating study of dexamethasone: 0.0625, 0.125, 0.25, 0.5, or 1 mg/kg, maximum dose 24 mg. Nonparametric ANOVA was used to analyze the incidence of vomiting by treatment group for 0 to <= 5 h, > 5 to 24 h. The Cox Proportional Likelihood Ratio Test was used to compare the time of first vomit and time to first pain medication across treatment groups. RESULTS: There was no difference in the incidence of vomiting for the five escalating doses of dexamethasone in the time period. There were no differences in secondary outcomes (analgesic requirements, time to first liquid, and change in voice) across treatment groups. CONCLUSION: We conclude that the lowest dose of dexamethasone (0.0625 mg/kg) was as effective as the highest dose of dexamethasone (1.0 mg/kg) for preventing PONV or reducing the incidence of other secondary outcomes following tonsillectomy or adenotonsillectomy. There is no justification for the use of high-dose dexamethasone for the prevention of PONV in this cohort of children. C1 Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60611 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Div Pediat Anesthesia, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Dept Pediat Anesthesia, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Childrens Mem Hosp, Div Clin Otolaryngol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Childrens Mem Hosp, Mary Ann & J Milburn Smith Child Hlth Res Program, Feinberg Sch Med, Chicago, IL 60611 USA. RP Kim, MS (reprint author), Valley Anesthesiol Consultants, LTD 2901 N,Cent Ave Suite 500, Phoenix, AZ 85012 USA. EM mkimdoc@yahoo.com NR 32 TC 41 Z9 42 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2007 VL 104 IS 5 BP 1052 EP 1058 DI 10.1213/01.ane.0000263276.52287.3b PG 7 WC Anesthesiology SC Anesthesiology GA 161FB UT WOS:000245998800011 PM 17456652 ER PT J AU Desai, SP Desai, MS Maddi, R Battit, GE AF Desai, Sukumar P. Desai, Manisha S. Maddi, Rosemarie Battit, George E. TI A tale of two paintings - Depictions of the first public demonstration of ether anesthesia SO ANESTHESIOLOGY LA English DT Article C1 Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Massachusetts, Memorial Healthcare, Dept Anesthesiol, Sch Med, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02115 USA. RP Desai, SP (reprint author), Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM sdesai@partners.org NR 14 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2007 VL 106 IS 5 BP 1046 EP 1050 DI 10.1097/01.anes.0000265166.14383.0d PG 5 WC Anesthesiology SC Anesthesiology GA 161RF UT WOS:000246032500023 PM 17457138 ER PT J AU Minehart, RD Podraza, MA Raemer, DB Simon, R Walzer, TB Pian-Sinith, MC AF Minehart, R. D. Podraza, M. A. Raemer, D. B. Simon, R. Walzer, T. B. Pian-Sinith, M. C. TI Teaching residents to question and challenge their teachers: A simulator-based approach to improve education and promote patient safety SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAY 16-19, 2007 CL Banff, CANADA C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2007 VL 106 IS 5 BP B33 EP B33 PG 1 WC Anesthesiology SC Anesthesiology GA 161RF UT WOS:000246032500088 ER PT J AU Minehart, RD Podraza, MA Raemer, DB Gardner, R Walzer, TB Simon, R Pian-Smith, MC AF Minehart, R. D. Podraza, M. A. Raemer, D. B. Gardner, R. Walzer, T. B. Simon, R. Pian-Smith, M. C. TI Explicit communication during obstetric emergencies: Room for improvement? SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAY 16-19, 2007 CL Banff, CANADA C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2007 VL 106 IS 5 BP B17 EP B17 PG 1 WC Anesthesiology SC Anesthesiology GA 161RF UT WOS:000246032500057 ER PT J AU Randhawa, IS Junaid, I Klaustermeyer, WB AF Randhawa, Inderpal Singh Junaid, Imran Klaustermeyer, William B. TI Allergen immunotherapy in a patient with human immunodeficiency virus: effect on T-cell activation and viral replication SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ANTIRETROVIRAL THERAPY; INFLUENZA IMMUNIZATION; CHILDREN; HIV AB Background: Allergen immunotherapy is a major therapeutic modality in the treatment of allergic rhinitis. However, with T-cell activation potential, its role in patients with human immunodeficiency virus (HIV) was theoretically limited. Objective: To report the results of allergen immunotherapy in a patient with HIV treated with highly active antiretroviral therapy (HAART). Methods: A 44-year-old man with a history of HIV did not respond to medical therapy for allergic rhinitis. His HIV status was well controlled with HAART. Owing to the severity of his allergic rhinitis symptoms, he accepted the risk of allergy immunotherapy despite the unknown effect of immunotherapy in patients with HIV. Results: After 6 weeks of weekly immunotherapy injections, his viral load remained undetectable and his CD4 cell count changed from 540 to 570 cells/mu L. After 16 weeks of weekly immunotherapy, his viral load increased to 10,900 copies/mL, and his CD4 cell count increased to 665 cells/mu L. After 24 weeks of weekly immunotherapy, his viral load returned to an undetectable level, and his CD4 cell count stabilized at 356 cells/mu L. Despite his notable change in HIV status, he continues to receive the same HAART. He currently continues en route to maintenance immunotherapy. Conclusions: The effect of allergen immunotherapy on HIV infection has not been previously reported. A concern remains that any form of immunotherapy may negatively affect HIV disease progression. This case illustrates that weekly allergen immunotherapy may have induced limited T-cell proliferation and a modest increase in RNA viral load, which resolved with continuation of HAART. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Randhawa, IS (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Suite 111R, Los Angeles, CA 90073 USA. EM docrandhawa@yahoo.com NR 11 TC 9 Z9 10 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAY PY 2007 VL 98 IS 5 BP 495 EP 497 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 170GQ UT WOS:000246651200014 PM 17521037 ER PT J AU Parchman, ML Pugh, JA Romero, RL Bowers, KW AF Parchman, Michael L. Pugh, Jacqueline A. Romero, Raquel L. Bowers, Krista W. TI Competing demands or clinical inertia: The case of elevated glycosylated hemoglobin SO ANNALS OF FAMILY MEDICINE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the North-American-Primary-Care-Research-Group CY OCT 15-18, 2005 CL Quebec City, CANADA SP N Amer Primary Care Res Grp DE diabetes mellitus, type 2; hemoglobin A, glycosylated; ambulatory care; primary care; health care delivery; health services research; quality of care; practice-based research networks; office visits ID PRIMARY-CARE PHYSICIANS; DIABETES-MELLITUS; GLYCEMIC CONTROL; MANAGEMENT; RISK; AMERICANS; DISEASES; THERAPY; ADULTS AB PURPOSE This study aimed to examine the contribution of competing demands to changes in hypoglycemic medications and to return appointment intervals for patients with type 2 diabetes and an elevated glycosylated hemoglobin (A(1c)) level. METHODS We observed 211 primary care encounters by adult patients with type 2 diabetes in 20 primary care clinics and documented changes in hypoglycemic medications. Competing demands were assessed from length of encounter, number of concerns patients raised, and number of topics brought up by the clinician. Days to the next scheduled appointment were obtained at patient checkout. Recent A,, values and dates were determined from the chart. RESULTS Among patients with an A,, level greater than 7%, each additional patient concern was associated with a 49% (95% confidence interval, 35%-60%) reduction in the likelihood of a change in medication, independent of length of the encounter and most recent level of A,,. Among patients with an A,, level greater than 7% and no change in medication, for every additional minute of encounter length, the time to the next scheduled appointment decreased by 2.8 days (P = .001). Similarly, for each additional 1% increase in A,, level, the time to the next scheduled appointment decreased by 8.6 days (P = .001). CONCLUSIONS The concept of clinical inertia is limited and does not fully characterize the complexity of primary care encounters. Competing demands is a principle for constructing models of primary care encounters that are more congruent with reality and should be considered in the design of interventions to improve chronic disease outcomes in primary care settings. C1 S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care Syst, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU AHRQ HHS [K08 HS013008-02] NR 29 TC 117 Z9 118 U1 0 U2 4 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAY-JUN PY 2007 VL 5 IS 3 BP 196 EP 201 DI 10.1370/afm.679 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 183FK UT WOS:000247557900002 PM 17548846 ER PT J AU Lynn, J Baily, MA Bottrell, M Jennings, B Levine, RJ Davidoff, F Casarett, D Corrigan, J Fox, E Wynia, MK Agich, GJ O'Kane, M Speroff, T Schyve, P Batalden, P Tunis, S Berlinger, N Cronenwett, L Fitzmaurice, JM Dubler, NN James, B AF Lynn, Joanne Baily, Mary Ann Bottrell, Melissa Jennings, Bruce Levine, Robert J. Davidoff, Frank Casarett, David Corrigan, Janet Fox, Ellen Wynia, Matthew K. Agich, George J. O'Kane, Margaret Speroff, Theodore Schyve, Paul Batalden, Paul Tunis, Sean Berlinger, Nancy Cronenwett, Linda Fitzmaurice, J. Michael Dubler, Nancy Neveloff James, Brent TI The ethics of using quality improvement methods in health care SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CLINICAL-RESEARCH; SERVICES RESEARCH; UNITED-STATES; DELIVERY; IMPACT AB Quality improvement (QI) activities can improve health care but must be conducted ethically. The Hastings Center convened leaders and scholars to address ethical requirements for QI and their relationship to regulations protecting human subjects of research. The group defined QI as systematic, data-guided activities designed to bring about immediate improvements in health care delivery in particular settings and concluded that Ql is an intrinsic part of normal health care operations. Both clinicians and patients have an ethical responsibility to participate in QI, provided that it complies with specified ethical requirements. Most QI activities are not human subjects research and should not undergo review by an institutional review board; rather, appropriately calibrated supervision of QI activities should be part of professional supervision of clinical practice. The group formulated a framework that would use key characteristics of a project and its context to categorize it as QI, human subjects research, or both, with the potential of a customized institutional review board process for the overlap category. The group recommended a period of innovation and evaluation to refine the framework for ethical conduct of QI and to integrate that framework into clinical practice. C1 Hastings Ctr, Garrison, NY 10524 USA. RAND Corp, Washington, DC USA. Vet Hlth Adm, Natl Qual Forum, Washington, DC USA. Natl Comm Qual Assurance, Washington, DC USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Vet Hlth Adm, Seattle, WA USA. Yale Univ, New Haven, CT USA. Inst Healthcare Improvement, Cambridge, MA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Amer Med Assoc, Chicago, IL 60610 USA. Joint Commiss Accreditat Healthcare Org, Oak Brook Terrace, IL USA. Bowling Green State Univ, Bowling Green, OH 43403 USA. Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. Dartmouth Coll Sch Med, Hanover, NH USA. Hlth Tech, San Francisco, CA USA. Univ N Carolina, Chapel Hill, NC USA. Agcy Hlth Care Policy & Res, Rockville, MD USA. Intermt Inst Hlth Care Delivery Res, Salt Lake City, UT USA. RP Baily, MA (reprint author), Hastings Ctr, 21 Malcolm Gordan Rd, Garrison, NY 10524 USA. EM bailym@thehastingscenter.org FU AHRQ HHS [1R13HS13369] NR 32 TC 124 Z9 125 U1 3 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 2007 VL 146 IS 9 BP 666 EP 673 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 162EV UT WOS:000246070500006 PM 17438310 ER PT J AU Blijlevens, N Sonis, S AF Blijlevens, N. Sonis, S. TI Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis SO ANNALS OF ONCOLOGY LA English DT Review DE anti-neoplastic agents; adverse effects; growth factors; haematopoietic stem-cell transplantation; keratinocyte growth factor; mucositis; palifermin ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TOTAL PARENTERAL-NUTRITION; MOUSE INTESTINAL EPITHELIUM; MUCOSAL BARRIER INJURY; HIGH-DOSE CHEMOTHERAPY; NECROSIS-FACTOR-ALPHA; ORAL MUCOSITIS; CELL-PROLIFERATION; CANCER-THERAPY AB Oral and intestinal mucositis are among the most significant dose-limiting toxic effects of intensive cancer treatment and are associated with adverse clinical and economic outcomes. Palifermin (Kepivance (TM)), an N-truncated recombinant human keratinocyte growth factor-1, is the first agent to be approved for prevention of oral mucositis. Keratinocyte growth factor, a potent epithelial mitogen, appears to play a major role in the healing process. Palifermin has multiple biological activities that appear to protect the mucosal epithelium and promote its early regeneration after irradiation- and chemotherapy-induced injury. These include inhibition of epithelial cell apoptosis and DNA damage, up-regulation of detoxifying enzymes and down-regulation of pro-inflammatory cytokines, as well as enhanced migration, proliferation and differentiation of epithelial cells. Palifermin reduces the incidence, severity and duration of oral mucositis in patients with haematological malignancies undergoing myelotoxic conditioning therapy and haematopoietic stem-cell transplantation. Clinical sequelae, including febrile neutropenia and resource use (opioid analgesia and parenteral feeding), are concomitantly reduced. Other potential applications being explored include use in the solid tumour setting, reduction of intestinal mucositis and reduction of GVHD in allogenic transplantation. Thus, the development of palifermin and other potential new agents for preventing chemotherapy- and radiotherapy-induced mucositis represents an important breakthrough in oncological supportive care. C1 Univ Med Ctr St Radboud, Dept Haematol, NL-6500 HB Nijmegen, Netherlands. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Blijlevens, N (reprint author), Univ Med Ctr St Radboud, Dept Haematol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM Blijlevens@HEMAT.umcn.nl RI Blijlevens, N.M.A./H-8012-2014 NR 104 TC 63 Z9 72 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2007 VL 18 IS 5 BP 817 EP 826 DI 10.1093/annonc/mdl332 PG 10 WC Oncology SC Oncology GA 178SU UT WOS:000247241200002 PM 17030544 ER PT J AU Mauriac, L Keshaviah, A Debled, M Mouridsen, H Forbes, JF Thurlimann, B Paridaens, R Monnier, A Lang, I Wardley, A Nogaret, JM Gelber, RD Castiglione-Gertsch, M Price, KN Coates, AS Smith, I Viale, G Rabaglio, M Zabaznyi, N Goldhirsch, A AF Mauriac, L. Keshaviah, A. Debled, M. Mouridsen, H. Forbes, J. F. Thuerlimann, B. Paridaens, R. Monnier, A. Lang, I. Wardley, A. Nogaret, J.-M. Gelber, R. D. Castiglione-Gertsch, M. Price, K. N. Coates, A. S. Smith, I. Viale, G. Rabaglio, M. Zabaznyi, N. Goldhirsch, A. TI Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant endocrine therapy; aromatase inhibitor; breast cancer; early relapse; letrozole; prognostic factors ID ADJUVANT ENDOCRINE THERAPY; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; TAMOXIFEN THERAPY; ASSOCIATION; ANASTROZOLE; EXPRESSION; CARCINOMA AB Background: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. Patients and methods: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. Results: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. Conclusion: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors. C1 Inst Bergonie, French Breast Canc Grp, F-33076 Bordeaux, France. Dana Farber Canc Inst, Ctr Stat, Int Breast Canc Study Grp, Boston, MA 02115 USA. Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen, Denmark. Univ Newcastle, Newcastle Mater Hosp, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. Kantonsspital, Senol Ctr Eastern Switzerland, Swiss Grp Clin Canc Res, St Gallen, Switzerland. Catholic Univ Louvain, Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Ctr Hosp Belfort, Montbeliard, France. Natl Inst Oncol, Budapest, Hungary. S Manchester Univ Hosp Trust, Christie Hosp NHS Trust, Manchester, Lancs, England. Inst Jules Bordet, B-1000 Brussels, Belgium. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Int Breast Canc Study Grp,Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Univ Bern, Inselspital, CH-3010 Bern, Switzerland. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Univ Sydney, Sydney, NSW 2006, Australia. Royal Marsden Hosp, London SW3 6JJ, England. European Inst Oncol, Milan, Italy. Moscow Municipal Oncol Hosp 62, Stepanovskoe, Russia. Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Mauriac, L (reprint author), Inst Bergonie, French Breast Canc Grp, 229 Cours Argonne, F-33076 Bordeaux, France. EM mauriac@bergonie.org RI Wardley, ANdrew/N-8135-2015 OI Wardley, ANdrew/0000-0002-9639-0888 FU NCI NIH HHS [CA-75362] NR 21 TC 95 Z9 98 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2007 VL 18 IS 5 BP 859 EP 867 DI 10.1093/annonc/mdm001 PG 9 WC Oncology SC Oncology GA 178SU UT WOS:000247241200007 PM 17301074 ER PT J AU Wall, C Kos, MI Guyot, JP AF Wall, Conrad, III Kos, Maria Izabel Guyot, Jean-Philippe TI Eye movements in response to electric stimulation of the human posterior ampullary nerve SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE implant; prosthesis; vestibular system ID SEMICIRCULAR CANAL PROSTHESIS AB Objectives: The concept of a vestibular implant to restore balance, similar to that of a cochlear implant to restore hearing in deaf patients, has been investigated in animal models. It remains to be shown, however, that electric stimulation of the human end organ or its vestibular nerve branches is capable of eliciting a nystagmic eye movement response. Methods: Three subjects were given electric stimulation of their posterior ampullary nerve, which was surgically exposed under local anesthesia, by a procedure developed by Gacek. The stimulus was a multiphasic, charge-balanced train of electric pulses. Results: In all subjects, a pulse repetition rate of 200 pulses per second produced a robust vertical nystagmus without any apparent change in the slow component velocity of the preexisting horizontal nystagmus. Conclusions: We have been able to replicate in humans a finding somewhat similar to that of Suzuki and Cohen in monkeys for electric stimulation of the posterior semicircular canal. The similarity is an eye movement with a large, predominant vertical component. The difference is that we saw no horizontal response component, and were not able to measure a torsional response, because we used 2-dimensional video methods. In addition, we found a robust nystagmus with slow component velocities that are large enough to compensate for vertical head movements. This is an essential step in demonstrating the feasibility of a vestibular prosthesis using electric stimulation. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Hosp Geneva, Dept Otorhinolaryngol Head & Neck Surg, Geneva, Switzerland. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 38 Z9 38 U1 1 U2 7 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2007 VL 116 IS 5 BP 369 EP 374 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 168QM UT WOS:000246539100009 PM 17561766 ER PT J AU Shrank, W Avorn, J Rolon, C Shekelle, P AF Shrank, William Avorn, Jerry Rolon, Cony Shekelle, Paul TI Effect of content and format of prescription drug labels on readability, understanding, and medication use: A systematic review SO ANNALS OF PHARMACOTHERAPY LA English DT Review DE patient information; prescription drug label ID PHYSICIAN-PATIENT COMMUNICATION; THE-COUNTER MEDICATIONS; INFORMATION LEAFLETS; DECISION-MAKING; ANTIRETROVIRAL THERAPY; PHARMACOLOGICAL CARE; ELDERLY PATIENTS; GENERAL-PRACTICE; AMBULATORY-CARE; HEALTH LITERACY AB OBJECTIVE: To evaluate the evidence regarding the optimal content and format of prescription labels that might improve readability, understanding, and medication use. DATA SOURCES: We performed a systematic review of randomized controlled trials, observational studies, and systematic reviews from MEDLINE and the Cochrane Database (1990-June 2005), supplemented by reference mining and reference lists from a technical expert panel. STUDY SELECTION: We selected studies that focused on the content of physician-patient communication about medications and the content and format of prescription drug labels. DATA EXTRACTION: Two reviewers extracted and synthesized information about study design, populations, and outcomes. DATA SYNTHESIS: Of 2009 articles screened, 36 that addressed the content of physician-patient communication about medications and 69 that were related to the content or format of medication labels met review criteria. Findings showed that patients request information about a drug's indication, expected benefits, duration of therapy, and a thorough list of potential adverse effects. The evidence about label format supports the use of larger fonts, lists, headers, and white space, using simple language and logical organization to improve readability and comprehension. Evidence was not sufficient to support the use of pictographic icons, Little evidence linked label design or content to measurable health outcomes, adherence, or safety. CONCLUSIONS: Evidence suggests that specific content and format of prescription drug labels facilitate communication with and comprehension by patients. Efforts to improve the labels should be guided by such evidence, although additional study assessing the influence of label design on medication-taking behavior and health outcomes is needed. Several policy options exist to require minimal standards to optimize medical therapy, particularly in light of the new Medicare prescription drug benefit. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. So Calif EPC RAND, Santa Monica, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Div Gen Internal Med, Santa Monica, CA USA. RP Shrank, W (reprint author), 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM wshrank@partners.org NR 136 TC 57 Z9 59 U1 3 U2 17 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 2007 VL 41 IS 5 BP 783 EP 801 DI 10.1345/aph.1H582 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 165CG UT WOS:000246280800008 PM 17426075 ER PT J AU El-Tamer, MB Ward, BM Schifftner, T Neumayer, L Khuri, S Henderson, W AF El-Tamer, Mahmoud B. Ward, B. Marie Schifftner, Tracy Neumayer, Leigh Khuri, Shukri Henderson, William TI Morbidity and mortality following breast cancer surgery in women - National benchmarks for standards of care SO ANNALS OF SURGERY LA English DT Article ID SURGICAL RISK; INFECTIONS; OPERATIONS; MASTECTOMY; MODELS AB Background: Most reports on postoperative (OP) morbidity and mortality following breast cancer surgery (BCS) are limited by relatively small sample size resulting in a lack of national benchmarks for quality of care. This paper reports the 30-day morbidity and mortality following BCS in women using a large prospective multi-institutional database. Methods: The National Surgical Quality Improvement Program Patient Safety in Surgery, prospectively collected inpatient and outpatient 30 day postoperative morbidity and mortality data on patients undergoing surgery at 14 university and 4 community centers. Using the procedure CPT code, the database was queried for all women undergoing mastectomy (MT) or lumpectomy with an axillary procedure (L-ANP). Morbidity and mortality were categorized as mortality, wound, cardiac, renal, pulmonary, and central nervous system. Logistic regression models for the prediction of wound complications were developed. Preoperative variables having bivariate relationships with postoperative wound complications with P <= 0.20 were submitted for consideration. Results: We identified 1660 and 1447 women who underwent MT and L-ANP, respectively. The mean age was 55.9 years. The majority of procedures were under general anesthesia. The 30-day postoperative mortality for MT and L-ALNP were 0.24% and 0%, respectively. The most frequent morbid complication was wound infection. more commonly occurring in the mastectomy (4.34%) group versus the lumpectomy group (1.97%). Cardiac and pulmonary complications occurred infrequently in the mastectomy group (cardiac: MT, 0.12%. and pulmonary: NIT, 0.66%). There were no cardiac or pulmonary complications in the lumpectomy group. CNS morbidities were rare in both surgical groups (MT, 0.12%; and L-ALNP, 0.07%). Development of a UTI was more common in women who underwent a mastectomy (0.66%) when compared with women that had a lumpectomy (0.14%). The only significant predictors of a wound complication were morbid obesity (BMI > 30), having had a MT, low preoperative albumin and hematocrit greater than 45%. Conclusion: Morbidity and mortality rates following BCS in women are low, limiting their value in assessing quality of care. Mastectomy carries higher complication rate than L-ANP with wound infection being the most common. C1 Columbia Univ, New York Presbyterian Hosp, Dept Surg, New York, NY USA. N Shore Univ Hosp, Long Isl Jewish Med Ctr, Long Isl City, NY USA. Univ Colorado, NSQIP, Hlth Outcomes Program, Aurora, CO USA. George E Whalen Salt Lake City Vet Affairs Hlth C, Salt Lake City, UT USA. Univ Utah, Dept Surg, Salt Lake City, UT USA. VA Boston Healthcare Syst, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP El-Tamer, MB (reprint author), Atchley Pavil,10th Floor,161 Ft Washington Ave, New York, NY 10032 USA. EM me180@columbia.edu FU AHRQ HHS [1U18 HS 11913-03, U18 HS011913] NR 16 TC 88 Z9 91 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2007 VL 245 IS 5 BP 665 EP 671 DI 10.1097/01.sla.0000245833.48399.9a PG 7 WC Surgery SC Surgery GA 161SS UT WOS:000246036700004 PM 17457156 ER PT J AU Yeo, Y Ito, T Bellas, E Highley, CB Marini, R Kohane, DS AF Yeo, Yoon Ito, Taichi Bellas, Evangelia Highley, Christopher B. Marini, Robert Kohane, Daniel S. TI In situ cross-linkable hyaluronan hydrogels containing polymeric nanoparticles for preventing postsurgical adhesions SO ANNALS OF SURGERY LA English DT Article ID ACID AB Objective: To develop a combined barrier method and drug delivery system ("hybrid system") for preventing postoperative peritoneal adhesions, which could combine the biocompatibility and ease of application of in situ cross-linkable hydrogels with the controlled release features of polymeric nanoparticles. Methods: Poly(lactic-co-glycolic acid) nanoparticles were dispersed in aldehyde- and hydrazide-modified hyaluronic acids (HA), then combined via a double-barreled syringe. The material was subjected to mechanical testing and was assayed for in vitro cytotoxicity to murine mesothelial cells. Subsequently, it was tested for biocompatibility by intraperitoneal injection in mice. The hybrid's effectiveness in preventing postsurgical adhesions was assessed using a rabbit sidewall defect-cecum abrasion model, where it was applied to both injured surfaces. Results: The in situ hybrid gel system formed a flexible and durable hydrogel in less than 10 seconds. It had low in vitro cytotoxicity. In the mouse. the cross-linked HA maintained the polymeric nanoparticles in the peritoneum for I week, which we had previously shown would have cleared in less than 2 days, and no animals developed adhesions. Notably, the hybrid gel, even in the absence of encapsulated drug, was highly effective in preventing peritoneal adhesions in the rabbit model employed. Animals treated with the hybrid (n = 8) had no adhesions in 62.5% of cases, and none had adhesions that could only be separated by sharp dissection. In contrast, only 4.2% of untreated animals (n = 24) had no adhesions, and 58.3% developed adhesions requiring sharp dissection. Conclusions: The hybrid cross-linked HA-nanoparticle system described here appears to be a biocompatible and highly effective adhesion barrier, which could also deliver antiadhesion drugs. C1 Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Pediat Intens Care Unit, Ellison 317,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [R01 GM073626] NR 7 TC 58 Z9 59 U1 0 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2007 VL 245 IS 5 BP 819 EP 824 DI 10.1097/01.sla.0000251519.49405.55 PG 6 WC Surgery SC Surgery GA 161SS UT WOS:000246036700025 PM 17457177 ER PT J AU Grillo, HC Benfield, JR AF Grillo, Hermes C. Benfield, John R. TI Richard M. Peters, MD (1922-2006) SO ANNALS OF THORACIC SURGERY LA English DT Biographical-Item C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90049 USA. Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. Univ Calif Los Angeles, Hlth Sci Ctr, Dept Thorac Surg, Los Angeles, CA 90049 USA. RP Benfield, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 11611 Terryhill Pl, Los Angeles, CA 90049 USA. EM j.benfield@verizon.net NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2007 VL 83 IS 5 BP 1916 EP 1917 DI 10.1016/j.athoracsur.2006.12.048 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 160XD UT WOS:000245975700069 ER PT J AU Nieder, C Astner, ST Grosu, AL Molls, M AF Nieder, Carsten Astner, Sabrina T. Grosu, Anca-Ligia Molls, Michael TI Evaluation of late neurologic adverse events in patients with brain metastases from non-small cell lung cancer SO ANTICANCER RESEARCH LA English DT Article DE radiotherapy; chemotherapy; brain metastases; non-small cell lung cancer; neurotoxicity; NSCLC ID RANDOMIZED PHASE-III; RADIOTHERAPY; RADIATION; CHEMOTHERAPY; IRRADIATION; TRIAL; TEMOZOLOMIDE; CARCINOMA; CISPLATIN; TOXICITY AB Aim: The purpose of this prospective evaluation was to assess the late neurologic adverse events and Karnofsky performance status (K-PS) in patients with at least two brain metastases from non-small cell lung cancer treated with whole-brain radiotherapy (WBRT) with or without sequential systemic chemotherapy. Patients and Methods: All patients were required to have an initial KPS of at least 70%. During the first six months, the patients were re-examined every four weeks, later every 3 months or whenever the clinical condition worsened. Due to slow accrual, the protocol was closed prematurely in 2005. Sixteen adult patients (median age 56 years) treated with 10x3 Gy were studied. Results: Late adverse events : grade 2 (CTC AE v3.0) in imaging-confirmed absence of progressive brain metastases developed in 3 patients after a median of 5 months. With a median overall survival of 7 months., the actuarial risk of late adverse events at that time was 0% after WBRT alone and 37% after WBRT and chemotherapy. Thus, larger studies assessing the impact of multimodal treatment are recommended. C1 Nordlandssykehuset HF, Dept Internal Med, Radiat Oncol Unit, N-8092 Bodo, Norway. Tech Univ Munich, Klinikum Rechts Isar, Dept Radiat Oncol, D-8000 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Francis H Burr Proton Therapy Ctr, Boston, MA 02115 USA. RP Nieder, C (reprint author), Nordlandssykehuset HF, Dept Internal Med, Radiat Oncol Unit, N-8092 Bodo, Norway. EM carsten.nieder@nlsh.no NR 24 TC 4 Z9 4 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2007 VL 27 IS 3B BP 1701 EP 1704 PG 4 WC Oncology SC Oncology GA 170GL UT WOS:000246650700049 PM 17595800 ER PT J AU Hu, G Taylor, AB McAlister-Henn, L Hart, PJ AF Hu, Gang Taylor, Alexander B. McAlister-Henn, Lee Hart, P. John TI Crystal structure of the yeast nicotinamidase Pnc1p SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Nicotinamidase; Sir2p; X-ray crystallography; kinetic analyses; NAD(+); multiple isomorphous replacement; multiwavelength anomalous diffraction ID LIFE-SPAN EXTENSION; N-CARBAMOYLSARCOSINE AMIDOHYDROLASE; DEPENDENT ISOCITRATE DEHYDROGENASE; NAD(+) SALVAGE PATHWAY; SACCHAROMYCES-CEREVISIAE; CALORIE RESTRICTION; MYCOBACTERIUM-TUBERCULOSIS; GENE; SIR2; PYRAZINAMIDE AB The yeast nicotinamidase Pnc1p acts in transcriptional silencing by reducing levels of nicotinamide, an inhibitor of the historic deacetylase Sir2p. The Pnc1p structure was determined at 2.9 A resolution using MAD and MIRAS phasing methods after inadvertent crystallization during the pursuit of the structure of histidine-tagged yeast isocitrate dehydrogenase (IDH). Pnc1p displays a cluster of surface histidine residues likely responsible for its co-fractionation with IDH from Ni2+-coupled chromatography resins. Researchers expressing histidine-tagged proteins in yeast should be aware of the propensity of Pnc1p to crystallize, even when overwhelmed in concentration by the protein of interest. The protein assembles into extended helical arrays interwoven to form an unusually robust, yet porous superstructure. Comparison of the Pnc1p structure with those of three homologous bacterial proteins reveals a common core fold punctuated by amino acid insertions unique to each protein. These insertions mediate the self-interactions that define the distinct higher order oligomeric states attained by these molecules. Pnc1p also acts on pyrazinamide, a substrate analog converted by the nicotinamidase from Mycobacterium tuberculosis into a product toxic to that organism. However, we find no evidence for detrimental effects of the drug on yeast cell growth. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Xray Crystallog Core Lab, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Geriatr Res Educ & Clin Ctr, Dept Vet Affairs,S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. RP McAlister-Henn, L (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM henn@uthscsa.edu; pjhart@biochem.uthsesa.edu FU NIGMS NIH HHS [R01 GM051265-12, GM051265, R01 GM051265] NR 45 TC 19 Z9 22 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 2007 VL 461 IS 1 BP 66 EP 75 DI 10.1016/j.abb.2007.01.037 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 165RS UT WOS:000246323800009 PM 17382284 ER PT J AU Belogrudov, GI AF Belogrudov, Grigory I. TI A 24-residue presequence localizes human factor B to mitochondria SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE factor B; presequence; precursor; mitochondria; confocal microscopy; HEK293 cells ID COUPLING FACTOR-B; BOVINE FACTOR-B; OXIDATIVE-PHOSPHORYLATION; ATP SYNTHESIS; PURIFICATION; TRANSLATION; SEQUENCES; SIGNAL; EXPORT AB We reported previously that the human factor B precursor is a 215-amino acid polypeptide, the first 40 amino acid residues of which function as a mitochondrial targeting presequence [G.I. Belogrudov, Y. Hatefi, J. Biol. Chem. 277 (2002) 6097-6103]. Confocal microscopy of live HEK293 cells, transiently transfected with factor B constructs tagged at the C-terminus with green fluorescent protein (GFP) revealed that either a 40- or 25-residue presequence localized factor B to mitochondria. Indirect immunofluorescent labeling of fixed, permeabilized HEK293 cells that were transiently transfected with a construct lacking a presequence, showed diffuse, intracellular staining that was consistent with targeting of ectopically expressed factor B to cellular compartments distinct from the mitochondria. Mutants in which either Met(-25) or both Met(-25)/Met(-24) residues of the presequence were deleted exhibited decreased or undetectable levels, respectively, of the GFP-tagged factor B. The factor B presequence alone was shown to target a reporter polypeptide GFP to mitochondria. Our studies, therefore, demonstrate that a 24-residue presequence is sufficient to localize factor B to mitochondria, and suggest that the human factor B precursor is a 199-amino acid polypeptide. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Belogrudov, GI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM gbelo@ucla.edu FU NIGMS NIH HHS [R01 GM066085] NR 21 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 2007 VL 461 IS 1 BP 95 EP 103 DI 10.1016/j.abb.2007.01.032 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 165RS UT WOS:000246323800012 PM 17359931 ER PT J AU Marra, DE Pourrabbani, S Fincher, EF Moy, RL AF Marra, Diego E. Pourrabbani, Shahram Fincher, Edgar F. Moy, Ronald L. TI Fractional photothermolysis for the treatment of adult colloid milium SO ARCHIVES OF DERMATOLOGY LA English DT Article C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Internal Med, Los Angeles, CA USA. RP Moy, RL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM rmoy@ucla.edu NR 11 TC 21 Z9 23 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2007 VL 143 IS 5 BP 572 EP 574 DI 10.1001/archderm.143.5.572 PG 3 WC Dermatology SC Dermatology GA 167UF UT WOS:000246477300002 PM 17515508 ER PT J AU Eichler, F Mahmood, A Loes, D Bezman, L Lin, D Moser, HW Raymond, GV AF Eichler, Florian Mahmood, Asif Loes, Daniel Bezman, Lena Lin, Doris Moser, Hugo W. Raymond, Gerald V. TI Magnetic resonance imaging detection of lesion progression in adult patients with X-linked adrenoleukodystrophy SO ARCHIVES OF NEUROLOGY LA English DT Article ID LONG-CHAIN; MEMBRANE MICROVISCOSITY; FATTY-ACIDS; ADRENOMYELONEUROPATHY; PATHOGENESIS; ABNORMALITY; PHENOTYPES; CELLS; MRI AB Background: An inherited disorder, X-linked adrenoleukodystrophy (X-ALD) is known to cause progressive inflammatory demyelination. Objective: To analyze the adult pattern of disease progression in X-ALD. Design, Setting, and Patients: We retrospectively assessed magnetic resonance (MR) images obtained in adult patients who had developed cerebral disease between January 1, 1985, and December 31, 2005. We identified 103 adult patients with X-ALD with lesions on their MR images. Of these, 56 had serial MR examinations at least 1 year apart and were included in this study. Main Outcome Measure: Progression of X-ALD lesions on MR images. Results: On initial presentation, 17 patients with X-ALD had corticospinal tract lesions without splenium or genu involvement, 24 had symmetric corticospinal tract lesions with additional involvement of the splenium or genu, and 15 did not have corticospinal tract involvement but had other white matter lesions. In 18 of 21 patients with progressive lesions, corticospinal tract involvement preceded or occurred concurrently with progressive inflammatory demyelination. Conclusions: Brain MR imaging abnormalities in adults with X-ALD progress slower than those reported in childhood. The involvement of the corticospinal tracts is prominent and may at times represent a variant course of progressive inflammatory demyelination. C1 Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD USA. Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD USA. Suburban Radiol Consultants Ltd, Minneapolis, MN USA. Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Raymond, GV (reprint author), Johns Hopkins Univ, Kennedy Krieger Inst, 707 N Broadway,Room 500L, Baltimore, MD 21218 USA. EM raymond@kennedykrieger.org FU NCRR NIH HHS [M01-RR00052, M0RR11]; NICHD NIH HHS [HD10981]; NLM NIH HHS [LM9-3537]; PHS HHS [L08MS52550-01A1] NR 23 TC 24 Z9 24 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2007 VL 64 IS 5 BP 659 EP 664 DI 10.1001/archneur.64.5.659 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 166RV UT WOS:000246398600007 PM 17502464 ER PT J AU Resto, VA McKenna, MJ Deschler, DG AF Resto, Vicente A. McKenna, Michael J. Deschler, Daniel G. TI Pectoralis major flap in composite lateral skull base defect reconstruction SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Head-and-Neck-Society/Research Workshop on the Biology, Prevention and Treatment of Head and Neck Cancer CY AUG 17-20, 2006 CL Chicago, IL SP Amer Head & Neck Soc ID MYOCUTANEOUS ISLAND FLAP; FREE TISSUE TRANSFER; TEMPORAL BONE; NECK AB Objective: To report our experience with the pectoralis major myocutaneous flap (PMF) for the reconstruction of composite lateral temporal bone defects extending beyond the temporal line. Design: Retrospective review and illustration of specific technical modifications. Setting: Academic tertiary care center. Patients: Eight patients with composite lateral skull base defects that were reconstructed with the PMF between February 2001 and February 2006. Intervention: Reconstruction with the modified pedicled PMF. Main Outcome Measures: Reconstruction outcomes and complications. Results: Eight patients (median age, 80 years) underwent total or near-total auriculectomy, wide skin excision, and lateral temporal bone resection as part of the surgical ablation, thus requiring obliteration of the middle ear cavity as well as extensive replacement of skin cover. All patients received radiation therapy. The median post-surgical follow-up was 9 months. Complete healing of the reconstructed surgical defect with no flap loss was achieved in all cases. Conclusion: With specific technical modifications, the PMF can be reliably used for the reconstruction of composite lateral skull base defects extending up to and beyond the temporal line, making this flap an important alternative to free flap reconstruction in selected cases. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Otolaryngol Head & Neck Surg, Galveston, TX 77550 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu RI Resto, Vicente/D-9891-2014 NR 20 TC 13 Z9 14 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAY PY 2007 VL 133 IS 5 BP 490 EP 494 DI 10.1001/archotol.133.5.490 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 168KC UT WOS:000246522500010 PM 17520764 ER PT J AU Primack, BA Switzer, GE Dalton, MA AF Primack, Brian A. Switzer, Galen E. Dalton, Madeline A. TI Improving measurement of normative beliefs involving smoking among adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CIGARETTE-SMOKING; PSYCHOSOCIAL PREDICTORS; POPULAR FILMS; HIGH-SCHOOL; TOBACCO USE; PREVALENCE; INTENTIONS; INITIATION; BEHAVIORS; PROMOTION AB Objectives: To identify different components of smoking normative beliefs and determine if each component is independently associated with 2 clinically relevant measures of smoking in adolescents. Design: Cross-sectional survey. Setting: One large suburban high school. Participants: A total of 1211 high school students aged 14 to 18 years. Outcome Measures: Current smoking and susceptibility to smoking. Results: Of the 1138 students with data on current smoking, 216 (19.0%) reported current smoking, and 342 (38.3%) of the 893 nonsmoking students with susceptibility data were susceptible to future smoking. Factor analysis identified 3 normative belief constructs, labeled "perceived prevalence of smoking," "perceived popularity of smoking among elite/successful elements of society," and "disapproval of smoking by parents/peers." On average, students believed that 56% of people in the United States smoke cigarettes; 27.7% believed that wealthy people smoke more than poor people. Multiple logistic regression showed that each of the 3 constructs was independently associated with current smoking (adjusted odds ratios, 1.05 [95% confidence interval {CI}, 1.02-1.08], 1.12 [95% Cl, 1.02-1.23], and 0.66 [95% CI, 0.59-0.75], respectively), even after controlling for covariates. Students' perceptions of smoking among the successful/elite and disapproval by parents/peers were independently associated with susceptibility to future smoking (adjusted odds ratios, 1.20 [95% Cl, 1.11-1.29] and 0.87 [95% Cl, 0.79-0.96], respectively). Conclusions: Adolescents' normative beliefs about smoking are multidimensional and include at least 3 distinct components, each of which was independently related to smoking outcomes. These distinct components should be considered in the design and evaluation of programs related to prevention and cessation of adolescent smoking. C1 Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Div Adolescent Med, Dept Pediat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ & Promot, Pittsburgh, PA USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pediat, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Community Hlth Res Program,Hood Ctr Children & Fa, Hanover, NH 03756 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, 230 Kee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, K07 CA114315-01A1, K07-CA114315] NR 35 TC 28 Z9 28 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 2007 VL 161 IS 5 BP 434 EP 439 DI 10.1001/archpedi.161.5.434 PG 6 WC Pediatrics SC Pediatrics GA 164VP UT WOS:000246263200001 PM 17485617 ER PT J AU Wayne, PM Kiel, DP Krebs, DE Davis, RB Savetsky-German, J Connelly, M Buring, JE AF Wayne, Peter M. Kiel, Douglas P. Krebs, David E. Davis, Roger B. Savetsky-German, Jacqueline Connelly, Maureen Buring, Julie E. TI The effects of Tai Chi on bone mineral density in postmenopausal women: A systematic review SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE bone mineral density; exercise; osteopenia; osteoporosis; rehabilitation; Tai Chi ID QUALITY-OF-LIFE; OSTEOPOROTIC FRACTURES; OLDER-ADULTS; CARDIORESPIRATORY FUNCTION; RHEUMATOID-ARTHRITIS; CHUAN PRACTITIONERS; POSTURAL STABILITY; AEROBIC EXERCISE; CONTROLLED-TRIAL; BALANCE AB Objective: To evaluate the evidence for Tai Chi as an intervention to reduce rate of bone loss in postmenopausal women. Data Sources: Literature search using Medline, Science Citation Index, Cochrane databases, China Biological Medicine Database, and additional manual reference searches of retrieved articles and personal libraries. Study Selection: Randomized controlled trials (RCTs), prospective cohort studies, and cross-sectional studies that included Tai Chi as an intervention, and had at least 1 outcome related to measurement of bone mineral density (BMD). Data Extraction: Authors critically reviewed studies, evaluated methodologic quality, and synthesized study results in a summary table. Data Synthesis: Six controlled studies were identified by our search. There were 2 RCTs, 2 nonrandomized prospective parallel cohort studies, and 2 cross-sectional studies. The 2 RCTs and 1 of the prospective cohort studies suggested that Tai Chi-naive women who participated in Tai Chi training exhibited reduced rates of postmenopausal declines in BMD. Crosssectional studies suggested that long-term Tai Chi practitioners had higher BMD than age-matched sedentary controls, and had slower rates of postmenopausal BMD decline. No adverse effects related to Tai Chi were reported in any trial. Conclusions: Conclusions on the impact of Tai Chi on BMD are limited by the quantity and quality of research to date. This limited evidence suggests Tai Chi may be an effective, safe, and practical intervention for maintaining BMD in postmenopausal women. In combination with research that indicates Tai Chi can positively impact other risk factors associated with low BMD (eg, reduced fall frequency, increased musculoskeletal strength), further methodologically sound research is warranted to better evaluate the impact of Tai Chi practice on BNID and fracture risk in postmenopausal women. C1 Harvard Univ, Sch Med, Osher Inst, Boston, MA 02215 USA. New England Sch Acupuncture, Watertown, MA USA. Inst Aging Res, Hebrew SeniorLife, Boston, MA USA. Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02114 USA. RP Wayne, PM (reprint author), Harvard Univ, Sch Med, Osher Inst, 401 Pk Dr,Ste 22A, Boston, MA 02215 USA. EM peter_wayne@hms.harvard.edu OI Kiel, Douglas/0000-0001-8474-0310 FU NCCIH NIH HHS [R21 AT003503-02, U19 AT002022-02] NR 88 TC 55 Z9 59 U1 1 U2 21 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2007 VL 88 IS 5 BP 673 EP 680 DI 10.1016/j.apmr.2007.02.012 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 164MN UT WOS:000246238200020 PM 17466739 ER PT J AU Villa-Bellosta, R Bogaert, YE Levi, M Sorribas, V AF Villa-Bellosta, Ricardo Bogaert, Yolanda E. Levi, Moshe Sorribas, Victor TI Characterization of phosphate transport in rat vascular smooth muscle cells - Implications for vascular calcification SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE vascular calcification; phosphate transport; VSMC; Pit1; Pit2 ID CHRONIC KIDNEY-DISEASE; APE LEUKEMIA-VIRUS; IN-VITRO; COTRANSPORTER; EXPRESSION; PIT-1; DETERMINANTS; MECHANISMS; RECEPTORS; PROTEINS AB Objective - Hyperphosphatemia and inorganic phosphate (Pi) transport by vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of vascular calcification. The aim of this work has been to characterize Pi transport in VSMCs. Methods and Results - Primary cultures of VSMCs express both high affinity Na-dependent and Na-independent components of Pi transport. Under physiological conditions both transport systems are saturated, show similar activity, and are inhibited by increasing pH. The Na-dependent transport is also weakly inhibited by phosphonoformic acid (PFA) (3.9 mmol/L IC50 at 0.05 mmol/L Pi). Real-time polymerase chain reaction shows that Pit1 and Pit2 are expressed to the same degree, and no other Pi transporters are significantly expressed. When expressed in Xenopus oocytes they are strictly Na-dependent, with high affinities for Pi, and are inhibited by increasing pH, but only weakly inhibited by PFA. We have used RNA interference to demonstrate that Pit1 and Pit2 are the transporters responsible for Na-dependent Pi transport in VSMCs. Conclusions - Taken together these novel findings suggest new roles of Pi transport in the pathogenesis of VC and have implications as potential future clinical targets. C1 Univ Zaragoza, Mol Toxicol Lab, Fac Vet, E-50013 Zaragoza, Spain. Denver VAMC, Dept Med, Div Renal Dis & Hypertens, Denver, CO USA. Denver VAMC, Dept Physiol & Biophys, Div Renal Dis & Hypertens, Denver, CO USA. Univ Colorado, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Sorribas, V (reprint author), Univ Zaragoza, Mol Toxicol Lab, Fac Vet, Calle Miguel Servet 177, E-50013 Zaragoza, Spain. EM sorribas@unizar.es OI Levi, Moshe/0000-0002-6225-946X; Sorribas, Victor/0000-0003-3457-323X FU NIDDK NIH HHS [1 R01 DK066029-01] NR 30 TC 60 Z9 64 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2007 VL 27 IS 5 BP 1030 EP 1036 DI 10.1161/ATVBAHA.106.132266 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 158RE UT WOS:000245810400010 PM 17322102 ER PT J AU Kiss, RS Kavaslar, N Okuhira, KI Freeman, MW Walter, S Milne, RW McPherson, R Marcel, YL AF Kiss, Robert S. Kavaslar, Nihan Okuhira, Kei-ichiro Freeman, Mason W. Walter, Stephanie Milne, Ross W. McPherson, Ruth Marcel, Yves L. TI Genetic etiology of isolated low HDL syndrome - Incidence and heterogeneity of efflux defects SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE lipoproteins; cholesterol; genes; HDL; monocyte; macrophage ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; LECITHIN-CHOLESTEROL ACYLTRANSFERASE; PHOSPHOLIPID TRANSFER PROTEIN; CORONARY-ARTERY DISEASE; CASSETTE TRANSPORTER 1; FISH-EYE DISEASE; TANGIER-DISEASE; APOA-I; BINDING AB Objective - We have used a multitiered approach to identify genetic and cellular contributors to high-density lipoprotein (HDL) deficiency in 124 human subjects. Methods and Results - We resequenced 4 candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 2 in apolipoprotein A-I (APOA1), 4 in lecithin: cholesterol acyltransferase (LCAT), 1 in phospholipid transfer protein (PLTP), and 7 in the ATP-binding cassette transporter ABCA1, leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. Cholesterol efflux assays performed using cholesterol-loaded monocyte-derived macrophages from the 124 low HDL subjects and 48 control subjects revealed that 33% (41/124) of low HDL subjects had low efflux, despite the fact that the majority of these subjects (34/41) were not carriers of dysfunctional ABCA1 alleles. In contrast, only 2% of control subjects presented with low efflux (1/48). In 3 families without ABCA1 mutations, efflux defects were found to cosegregate with low HDL. Conclusions - Efflux defects are frequent in low HDL syndromes, but the majority of HDL deficient subjects with cellular cholesterol efflux defects do not harbor ABCA1 mutations, suggesting that novel pathways contribute to this phenotype. C1 Univ Ottawa, Inst Heart, Lipoprot & Atherosclerosis Res Grp, Ottawa, ON K1Y 4W7, Canada. Univ Ottawa, Dept Med, Div Cardiol, Ottawa, ON K1Y 4W7, Canada. Univ Ottawa, Dept Pathol & Lab Med, Ottawa, ON K1Y 4W7, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Marcel, YL (reprint author), Univ Ottawa, Inst Heart, Lipoprot & Atherosclerosis Res Grp, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM rmcpherson@ottawaheart.org; ylmarcel@ottawaheart.ca NR 43 TC 31 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2007 VL 27 IS 5 BP 1139 EP 1145 DI 10.1161/ATVBAHA.106.137646 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 158RE UT WOS:000245810400025 PM 17303779 ER PT J AU Game, BA He, L Jarido, V Nareika, A Jaffa, AA Lopes-Virella, MF Huang, Y AF Game, Bryan A. He, Lin Jarido, Veronica Nareika, Alena Jaffa, Ayad A. Lopes-Virella, Maria F. Huang, Yan TI Pioglitazone inhibits connective tissue growth factor expression in advanced atherosclerotic plaques in low-density lipoprotein receptor-deficient mice SO ATHEROSCLEROSIS LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Diabetes-Association CY JUN 10-14, 2005 CL San Diego, CA SP Amer Diabet Assoc DE diabetes mellitus; peroxisome proliferator-activated receptor; thiazolidinediones; connective tissue growth factor; arteriosclerosis ID SMOOTH-MUSCLE-CELLS; ANTIDIABETIC DRUGS; GAMMA; TROGLITAZONE; MECHANISMS; APOPTOSIS; DISEASE; LESIONS; BETA AB Connective tissue growth factor (CTGF) is expressed in atherosclerotic plaques. It is generally recognized that CTGF contributes to atherosclerosis by stimulating vascular smooth muscle cell (VSMC) proliferation and extracellular matrix production during the development of atherosclerosis. Recent studies indicate that CTGF may also contribute to plaque destabilization as it induces apoptosis and stimulates MMP-2 expression in VSMCs. Thiazolidinediones (TZDs), a new class of insulin sensitizing drugs for type 2 diabetes, inhibit atherosclerosis. However, their effect on CTGF expression in atherosclerotic plaques remains unknown. In this study, male LDL receptor-deficient mice were fed high-fat diet for 4 months to induce the formation of atherosclerotic plaques and then given the high-fat diet with or without pioglitazone for the next 3 months. At the end of the 7-month study, CTGF expression in aortic atherosclerotic lesions was examined. Results showed that CTGF expression was increased in mice fed the high-fat diet by seven-fold as compared to that in mice fed normal chow, but the treatment with pioglitazone significantly inhibited the high-fat diet-induced CTGF expression. To verify these in vivo observations, in vitro studies using human aortic SMC were conducted. Quantitative real-time PCR and Western blot showed that pioglitazone inhibited TGF-beta-stimulated CTGF expression. In conclusion, the present study has demonstrated that pioglitazone inhibits CTGF expression in mouse advanced atherosclerotic plaques and in cultured human SMCs, and hence unveiled a possible mechanism potentially involved in the inhibition of atherosclerosis by TZD. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St,Room 531, Charleston, SC 29403 USA. EM huangyan@musc.edu NR 27 TC 22 Z9 29 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2007 VL 192 IS 1 BP 85 EP 91 DI 10.1016/j.atherosclerosis.2006.06.025 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 170IB UT WOS:000246655400011 PM 16901490 ER PT J AU Berka, C Levendowski, DJ Lumicao, MN Yau, A Davis, G Zivkovic, VT Olmstead, RE Tremoulet, PD Craven, PL AF Berka, Chris Levendowski, Daniel J. Lumicao, Michelle N. Yau, Alan Davis, Gene Zivkovic, Vladimir T. Olmstead, Richard E. Tremoulet, Patrice D. Craven, Patrick L. TI EEG correlates of task engagement and mental workload in vigilance, learning, and memory tasks SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article DE cognition; neuroergonomics; military operations; brain monitoring; human-computer interface; neurophysiology; psychophysiology ID SLEEP-APNEA PATIENTS; ADAPTIVE AUTOMATION; WORKING-MEMORY; SYSTEM; PERFORMANCE; ALERTNESS; COMPONENT; SPECTRUM; INDEXES AB Introduction: The ability to continuously and unobtrusively monitor levels of task engagement and mental workload in an operational environment could be useful in identifying more accurate and efficient methods for humans to interact with technology. This information could also be used to optimize the design of safer, more efficient work environments that increase motivation and productivity. Methods: The present study explored the feasibility of monitoring electroencephalographic (EEG) indices of engagement and workload acquired unobtrusively and quantified during performance of cognitive tests. EEG was acquired from 80 healthy participants with a wireless sensor headset (F3-F4,C3-C4,Cz-POz,F3-Cz,Fz-C3,Fz-POz) during tasks including: multi-level forward/backward-digit-span, grid-recall, trails, mental-addition, 20-min 3-Choice Vigilance, and image-learning and memory tests. EEG metrics for engagement and workload were calculated for each 1-s of EEG. Results: Across participants, engagement but not workload decreased over the 20-min vigilance test. Engagement and workload were significantly increased during the encoding period of verbal and image-learning and memory tests when compared with the recognition/recall period. Workload but not engagement increased linearly as level of difficulty increased in forward and backward-digit-span, grid-recall, and mental-addition tests. EEG measures correlated with both subjective and objective performance metrics. Discussion: These data in combination with previous studies suggest that EEG engagement reflects information-gathering, visual processing, and allocation of attention. EEG workload increases with increasing working memory load and during problem solving, integration of information, analytical reasoning, and may be more reflective of executive functions. Inspection of EEG on a second-by-second timescale revealed associations between workload and engagement levels when aligned with specific task events providing preliminary evidence that second-by-second classifications reflect parameters of task performance. C1 Adv Brain Monitoring Inc, Carlsbad, CA 92008 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Lockheed Martin Adv Technol Labs, Cherry Hill, NJ USA. RP Berka, C (reprint author), Adv Brain Monitoring Inc, 2850 Pio Pico Dr,Suite A, Carlsbad, CA 92008 USA. EM chris@b-alert.com FU NHLBI NIH HHS [HL070484]; NIDA NIH HHS [DA019357] NR 56 TC 133 Z9 135 U1 5 U2 47 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD MAY PY 2007 VL 78 IS 5 SU S BP B231 EP B244 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 167OK UT WOS:000246460800032 PM 17547324 ER PT J AU Koh, HJ Hirshman, MF He, HM Ll, YF Manabe, Y Balschi, JA Goodyear, LJ AF Koh, Ho-Jin Hirshman, Michael F. He, Huamei Ll, Yangfeng Manabe, Yasuko Balschi, James A. Goodyear, Laurie J. TI Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes SO BIOCHEMICAL JOURNAL LA English DT Article DE adrenaline; AMP-activated protein kinase (AMPK); cAMP-dependent protein kinase (PKA); exercise; fatty acid synthesis; lipolysis ID HORMONE-SENSITIVE LIPASE; INTRAABDOMINAL ADIPOSE-TISSUE; SKELETAL-MUSCLE; UPSTREAM KINASE; GLUCOSE-UPTAKE; RAT MUSCLE; FAT-CELLS; BETA; PHOSPHORYLATION; METABOLISM AB Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPK alpha 1 and alpha 2 activities and ACC (acetyl-CoA carboxylase) Ser(79) phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the beta-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPK alpha 1 and alpha 2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPK alpha 1 and alpha 2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, NMR Lab Physiol Chem, Div Cardiovasc Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM Laurie.Goodyear@joslin.harvard.edu FU NHLBI NIH HHS [R01 HL046033, R29 HL046033, HL 46033]; NIAMS NIH HHS [R01 AR045670, AR45670]; NIDDK NIH HHS [P30 DK036836, R01 DK068626, DK36836, DK068626] NR 49 TC 63 Z9 67 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2007 VL 403 BP 473 EP 481 DI 10.1042/BJ20061479 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 162ZF UT WOS:000246127300011 PM 17253964 ER PT J AU Bogdanov, AA Querol, M Chen, JW AF Bogdanov, A. A., Jr. Querol, M. Chen, J. W. TI Visualization of the enzymatic activity in living systems using activated NMR contrast agents SO BIOFIZIKA LA Russian DT Article DE magnetic resonance imaging; contrast agent; enzymatic activity; gadolinium; paramagnetic effect; relaxivity ID MRI CONTRAST; GADOLINIUM-DTPA; GD-DTPA; IN-VIVO; ANGIOGRAPHY; COMPLEXES; POLYLYSINE; RELAXIVITY; EXCHANGE; LIGANDS AB New approaches to the development and some applications of novel paramagnetic "sensing" contrast agents designed for specific visualization of the enzymatic activity in living systems are reviewed. The activation of the above sensing agents includes either the cleavage or the synthesis of reactive precursor compounds that recombine with macromolecules with the formation of immobilized or rotationally inhibited paramagnetic cations. This effect results in strong-changes of water proton relaxivity. The need in such agents is justified by efforts to utilize magnetic resonance imaging (MRI) for the visualization of fine structures in the living tissue as well as for increasing the molecular specificity of MRI. The review also contains information regarding recent efforts of increasing the sensitivity of MRI to the presence of paramagnetic cations in living systems. C1 Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. NR 39 TC 1 Z9 1 U1 1 U2 1 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0006-3029 J9 BIOFIZIKA+ JI Biofizika PD MAY-JUN PY 2007 VL 52 IS 3 BP 389 EP 400 PG 12 WC Biophysics SC Biophysics GA 180BV UT WOS:000247335800001 PM 17633527 ER PT J AU Armand, P Antin, JH AF Armand, Philippe Antin, Joseph H. TI Allogeneic stem cell transplantation for aplastic anemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE aplastic anemia; allogeneic stem cell transplantation; immunosuppressive therapy ID BONE-MARROW-TRANSPLANTATION; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; VERSUS-HOST-DISEASE; HIGH-DOSE CYCLOPHOSPHAMIDE; CORD BLOOD TRANSPLANTATION; IDENTICAL SIBLING DONORS; ANTI-THYMOCYTE GLOBULIN; TERM-FOLLOW-UP; ANTITHYMOCYTE GLOBULIN; FANCONI-ANEMIA AB Aplastic anemia encompasses a heterogeneous group of diseases with distinct pathophysiologies and a common clinical endpoint of marrow failure. Patients with severe aplastic anemia can be treated with immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Over the last 30 years, advances in both treatment modalities have significantly improved the prognosis for this disease; yet this evolution complicates the central therapeutic question in aplastic anemia: which patients should receive IST and which ones should receive HSCT as front-line therapy? In this review, we describe the major improvements that have occurred in transplantation for aplastic anemia in the last 3 decades. We then outline a framework for deciding which patients should be considered for upfront transplantation. (c) 2007 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org FU NCI NIH HHS [T32 CA009172] NR 104 TC 23 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2007 VL 13 IS 5 BP 505 EP 516 DI 10.1016/j.bbmt.2007.02.005 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 164RV UT WOS:000246252600001 PM 17448909 ER PT J AU O'Shaughnessy, MJ Chen, ZM Gramaglia, I Taylor, PA Panoskaltsis-Mortari, A Vogtenhuber, C Palmer, E Grader-Beck, T Bozssiotis, VA Blazar, BR AF O'Shaughnessy, Matthew J. Chen, Zong-Ming Gramaglia, Irene Taylor, Patricia A. Panoskaltsis-Mortari, Angela Vogtenhuber, Christine Palmer, Ed Grader-Beck, Thomas Bozssiotis, Vassiliki A. Blazar, Bruce R. TI Elevation of intracellular cyclic AMP in alloreactive CD4(+) T cells induces alloantigen-specific tolerance that can prevent GVHD lethality in vivo SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE GVHD; tolerance; T cells; mice; transgenic; immune response ID VERSUS-HOST-DISEASE; MEDIATED GROWTH-INHIBITION; CAMP-PROTEIN-KINASE; INTERLEUKIN-2 TRANSCRIPTION; CLONAL EXPANSION; DOWN-REGULATION; EX-VIVO; ANERGY; ACTIVATION; LYMPHOCYTES AB Cyclic AMP (cAMP) is an important negative regulator of T cell activation, and an increased level of cAMP is associated with T cell hyporesponsiveness in vitro. We sought to determine whether elevating intracellular cAMP levels ex vivo in alloreactive T cells during primary mixed lymphocyte reactions (MLR) is sufficient to induce alloantigen-specific tolerance and prevent graft-versus-host disease (GVHD). Primary MLRs were treated with exogenous Br-8-cAMP and IBMX, a compound that increases intracellular cAMP levels by inhibition of phosphodiesterases. T cell proliferation and IL-2 responsiveness in the treated primary MLR cultures were greatly reduced, and viable T cells recovered on day 8 also had impaired responses to restimulation with alloantigen compared to control-treated cells, but without an impairment to nonspecific mitogens. Labeling experiments showed that cAMP/IBMX inhibited alloreactive T cell proliferation by limiting the number of cell divisions, increasing susceptibility to apoptosis, and rendering nondeleted alloreactive T cells hyporesponsive to alloantigen restimulation. cAMP/IBMX-treated CD4(+) T cells had a markedly reduced capacity for GVHD lethality in major histocompatibility complex class II disparate recipients, but maintained the capacity to mediate other CD4(+) T cell responses in vivo. Thus, our results provide the first preclinical evidence of using cAMP-elevating pharmaceutical reagents to achieve long-term alloantigen-specific T cell tolerance that is sufficient to prevent GVHD. (c) 2007 American Society for Blood and Marrow Transplantation. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. Univ Basel Hosp, Lab Transplantat Immunol & Nephrol, Dept Res, CH-4031 Basel, Switzerland. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Blazar, BR (reprint author), Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. EM blaza001@umn.edu FU NCI NIH HHS [CA104596]; NHLBI NIH HHS [HL56067]; NIAID NIH HHS [AI34495]; PHS HHS [AOA43552] NR 39 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2007 VL 13 IS 5 BP 530 EP 542 DI 10.1016/j.bbmt.2007.01.071 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 164RV UT WOS:000246252600004 PM 17448912 ER PT J AU Banta, S Vemula, M Yokoyama, T Jayaraman, A Berthiaume, F Yarmush, ML AF Banta, Scott Vemula, Murali Yokoyama, Tadaaki Jayaraman, Arul Berthiaume, Francois Yarmush, Martin L. TI Contribution of gene expression to metabolic fluxes in hypermetabolic livers induced through burn injury and cecal ligation and puncture in rats SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE hypermetabolism; liver perfusion; metabolic flux analysis; DNA microarray analysis ID NECROSIS-FACTOR-ALPHA; AMINO-ACID; THERMAL-INJURY; ESCHERICHIA-COLI; FAILURE MODEL; IN-VIVO; SEPSIS; GLUCOSE; ENDOTOXEMIA; GLUTAMATE AB Severe injury activates many stress-related and inflammatory pathways that can lead to a systemic hypermetabolic state. Prior studies using perfused hypermeatbolic rat livers have identified intrinsic metabolic flux changes that were not dependent upon the continual presence of elevated stress hormones and substrate loads. We investigated the hypothesis that such changes may be due to persistent alterations in gene expression. A systemic hypermetabolic response was induced in rats by applying a moderate burn injury followed 2 days later by cenum ligation and puncture (CLP) to produce sepsis. Control animals recieved a sham- burn followed by CLP, or a sham-burn followed by a sham-CLP. Two days after CLP, or a sham-burn followed by sham-CLP. Two days after CLP, livers were analyzed for gene expression changes using DNA microarrays and for metaboloism alterations by ex vivo perfusion coupled with Metabolic Flux Analysis. Burn injury prior to CLP increased fluxes while decreases in gene expression levels were observed. Conversely, CLP alone significantly increased metabolic gene expression, but decreased many decreased many of the corresponding metabolic fluxes. Burn injury combined with CLP led to the most dramatic changes, where concurrent changes in fluxes and gene expression, while CLP treatment up-regulated the metabolic machinery by transcriptional mechanisms. Overall, these data show that mRNA changes measured at a single time point by DNA microarray analysis do not reliably metabolic flux changes in perfused livers. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [R01 DK 59766, R01 DK059766, P30 DK040561-12, P30 DK040561] NR 58 TC 22 Z9 23 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD MAY 1 PY 2007 VL 97 IS 1 BP 118 EP 137 DI 10.1002/bit.21200 PG 20 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 156KL UT WOS:000245646700010 PM 17009336 ER PT J AU Cho, CH Park, J Nagrath, D Tilles, AW Berthiaume, F Toner, M Yarmush, ML AF Cho, Cheul H. Park, Jaesung Nagrath, Deepak Tilles, Arno W. Berthiaume, Francois Toner, Mehmet Yarmush, Martin L. TI Oxygen uptake rates and liver-specific functions of hepatocyte and 3T3 fibroblast co-cultures SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE oxygen uptake rate; hepatocyte; co-culture; seeding density; mathematical modeling ID FIBER BIOARTIFICIAL LIVER; CELL-CELL INTERACTIONS; SANDWICH CONFIGURATION; CONTROLLED-TRIAL; GROWTH-FACTOR; PORCINE HEPATOCYTES; COLLAGEN SANDWICH; GENE-EXPRESSION; PRIMARY CULTURE; GEL-ENTRAPMENT AB Bioartificial liver (BAL) devices have been developed to treat patients undergoing acute liver failure. One of the most important parameters to consider in designing these devices is the oxygen consumption rate of the seeded hepatocytes which are known to have oxygen consumption rates 10 times higher than most other cell types. Hepatocytes in various culture configurations have been tested in BAL devices including those formats that involve co-culture of hepatocytes with other cell types. In this study, we investigated, for the first time, oxygen uptake rates (OUR)s of hepatocytes co-cultured with 3T3-J2 fibroblasts at various hepatocyte to fibroblast seeding ratios. OURs were determined by measuring the rate of oxygen disappearance using a ruthenium-coated optical probe after closing and sealing the culture dish. Albumin and urea production rates were measured to assess hepatocyte function. Lower hepatocyte density co-cultures demonstrated significantly higher OURs (2 to 3.5-fold) and liver-specific functions (1.6-fold for albumin and 4.5-fold for urea production) on a per cell basis than those seeded at higher densities. Increases in OUR correlated well with increased liver-specific functions. OURs (V-m) were modeled by fitting Michaelis-Menten kinetics and the model predictions closely correlated with the experimental data. This study provides useful information for predicting BAL design parameters that will avoid oxygen limitations, as well as maximize metabolic functions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. EM ireis@sbi.org RI Yu, weiting/I-7417-2013; OI Nagrath, Deepak/0000-0002-8999-2282 FU NIBIB NIH HHS [EB002503]; NIDDK NIH HHS [DK43371, DK59766, DK66040] NR 49 TC 50 Z9 52 U1 1 U2 19 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD MAY 1 PY 2007 VL 97 IS 1 BP 188 EP 199 DI 10.1002/bit.21225 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 156KL UT WOS:000245646700016 PM 17054120 ER PT J AU Brambilla, P MacDonald, AW Sassi, RB Johnson, MK Mallinger, AG Carter, CS Soares, JC AF Brambilla, Paolo MacDonald, Angus W., III Sassi, Roberto B. Johnson, Melissa K. Mallinger, Alan G. Carter, Cameron S. Soares, Jair C. TI Context processing performance in bipolar disorder patients SO BIPOLAR DISORDERS LA English DT Article DE attention; cognition; continuous performance test (CPT); executive functions; mood disorders; neuropsychology; working memory ID DORSOLATERAL PREFRONTAL CORTEX; COGNITIVE IMPAIRMENT; WORKING-MEMORY; I DISORDER; SCHIZOPHRENIC DEFICITS; DYSFUNCTION; MANIA; PSYCHOSIS; DISTURBANCES; SPECIFICITY AB Objectives: Context processing is the adaptive control of current behavior through the use of prior context information. It has been found to be impaired in schizophrenia. Some studies have indicated that, compared with patients with schizophrenia, those with bipolar disorder (BPD) display a similar but less severe neuropsychological pattern of impairment. However, this cognitive dimension has not yet been examined in BPD patients in the existing literature. Methods: An expectancy version of the AX continuous performance test (AX-CPT) was administered to 15 bipolar outpatients and 26 healthy controls. Patients with schizophrenia, in which context processing deficits are known to occur, were used as a reference group. Results: Bipolar patients showed a context processing deficit relative to healthy controls, although this was less severe and generalized than in schizophrenia patients. Conclusions: These findings suggest there are milder impairments in context processing in BPD compared with schizophrenia. However, the severity of possible context processing deficits in BPD may have been underestimated in our sample of mostly euthymic outpatients. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX 78229 USA. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Sci Inst IRCCS E Medea, Udine, Italy. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Calif Davis, Dept Psychiat, Sacramento, CA 95817 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol,Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Program, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010; MacDonald, Angus/M-9855-2016 OI brambilla, paolo/0000-0002-4021-8456; MacDonald, Angus/0000-0003-4588-931X FU NCRR NIH HHS [RR 020571]; NIMH NIH HHS [MH 01736, MH 068662, MH 068766, MH 30915] NR 54 TC 21 Z9 21 U1 4 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2007 VL 9 IS 3 BP 230 EP 237 DI 10.1111/j.1399-5618.2007.00398.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 152WM UT WOS:000245392900005 PM 17430297 ER PT J AU Perlick, DA Rosenheck, RA Miklowitz, DJ Chessick, C Wolff, N Kaczynski, R Ostacher, M Patel, J Desai, R AF Perlick, Deborah A. Rosenheck, Robert A. Miklowitz, David J. Chessick, Cheryl Wolff, Nancy Kaczynski, Richard Ostacher, Michael Patel, Jayendra Desai, Rani CA STEP-BD Family Experience Collabor TI Prevalence and correlates of burden among caregivers of patients with bipolar disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; caregiver burden; correlates; prevalence ID MENTAL-HEALTH; ALZHEIMERS-DISEASE; SPOUSAL CAREGIVERS; CARE RECIPIENTS; SOCIAL SUPPORT; FAMILY; SCHIZOPHRENIA; ILLNESS; IMPACT; DEMENTIA AB Objectives: Caring for a relative with schizophrenia or dementia is associated with reports of high caregiver burden, symptoms of depression, poor physical health, negligence of the caregiver's own health needs, elevated health service use, low use of social supports, and financial strain. This study presents the design and preliminary data on the costs and consequences of caring for a relative or friend with bipolar disorder from the Family Experience Study, a longitudinal study of the primary caregivers to 500 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder. Methods: Subjects were primary caregivers of 500 patients with bipolar disorder diagnosed by the Mini International Neuropsychiatric Interview and the Affective Disorder Evaluation. Caregivers were evaluated within 1 month after patients entered Systematic Treatment Enhancement Program using measures of burden, coping, health/mental health, and use of resources and costs. Results: Eighty-nine percent, 52%, and 61% of caregivers, respectively, experienced moderate or higher burden in relation to patient problem behaviors, role dysfunction, or disruption of household routine. High burden caregivers reported more physical health problems, depressive symptoms, health risk behavior and health service use, and less social support than less burden caregivers. They also provided more financial support to their bipolar relative. Conclusions: Burdens experienced by family caregivers of people with bipolar disorder are associated with problems in health, mental health, and cost. Psychosocial interventions targeting the strains of caregiving for a patient with bipolar disorder are needed. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, W HAven VAMC, NE Program Evaluat Ctr, New Haven, CT 06520 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Rutgers State Univ, Sch Planning & Publ Policy, New Brunswick, NJ 08903 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. RP Perlick, DA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230,1 Gustav L Levy Pl, New York, NY 10029 USA. EM deborah.perlick@mssm.edu OI Ostacher, Michael/0000-0003-0353-7535 FU NIMH NIH HHS [MH-65015, MH-8001] NR 53 TC 68 Z9 69 U1 4 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2007 VL 9 IS 3 BP 262 EP 273 DI 10.1111/j.1399-5618.2007.00365.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 152WM UT WOS:000245392900009 PM 17430301 ER PT J AU Hernandez-Diaz, S Smith, CR Wyszynski, DF Holmes, LB AF Hernandez-Diaz, S. Smith, C. R. Wyszynski, D. F. Holmes, L. B. TI Risk of major malformations among infants exposed to carbamazepine during pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 MassGen Hosp Children, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2007 VL 79 IS 5 MA 12 BP 357 EP 357 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 167BO UT WOS:000246425800013 ER PT J AU Yang, W Shaw, GM Carmichael, SL Rasmussen, SA Waller, DK Pober, BR Anderka, M AF Yang, W. Shaw, G. M. Carmichael, S. L. Rasmussen, S. A. Waller, D. K. Pober, B. R. Anderka, M. TI Nutrient intakes in women and corozenital diaphragmatic hemia in their offspring SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Calif Birth Defect Monitoring Program, Berkeley, CA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. MassGen Hosp Children, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, Bur Family & Commun Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2007 VL 79 IS 5 MA 16 BP 359 EP 359 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 167BO UT WOS:000246425800017 ER PT J AU McDougal, WS AF McDougal, W. Scott TI Radiofrequency ablation of renal cell carcinoma SO BJU INTERNATIONAL LA English DT Article DE radiofrequency ablation; renal cell carcinoma ID RADIO-FREQUENCY ABLATION; 100 TUMORS; FOLLOW-UP; EXPERIENCE; KIDNEY C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 17 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2007 VL 99 IS 5 BP 1271 EP 1272 DI 10.1111/j.1464-410X.2007.06827.x PN B PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 157AZ UT WOS:000245692300013 PM 17441922 ER PT J AU Luscinskas, FW Mayadas, T AF Luscinskas, Francis W. Mayadas, Tanya TI Fc gamma Rs join in the cascade SO BLOOD LA English DT Editorial Material ID NEUTROPHIL RECRUITMENT; IMMUNE-COMPLEXES; LEUKOCYTE; SELECTINS; ROLES C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Luscinskas, FW (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2007 VL 109 IS 9 BP 3615 EP 3616 DI 10.1182/blood-2007-02-072728 PG 2 WC Hematology SC Hematology GA 162MJ UT WOS:000246091400003 ER PT J AU Chauhan, D Anderson, KC AF Chauhan, Dharminder Anderson, Kenneth C. TI Bcl-B and Nur77/TR3: a deadly combination SO BLOOD LA English DT Editorial Material ID CELL-DEATH C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chauhan, D (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2007 VL 109 IS 9 BP 3622 EP 3622 DI 10.1182/blood-2007-02-072694 PG 1 WC Hematology SC Hematology GA 162MJ UT WOS:000246091400010 ER PT J AU Luciano, F Krajewska, M Ortiz-Rubio, P Krajewski, S Zhai, DY Faustin, B Bruey, JM Bailly-Maitre, B Lichtenstein, A Kolluri, SK Satterthwait, AC Zhang, XK Reed, JC AF Luciano, Frederic Krajewska, Maryla Ortiz-Rubio, Paulina Krajewski, Stan Zhai, Dayong Faustin, Benjamin Bruey, Jean-Marie Bailly-Maitre, Beatrice Lichtenstein, Alan Kolluri, Siva Kumar Satterthwait, Arnold C. Zhang, Xiao-Kun Reed, John C. TI Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma SO BLOOD LA English DT Article ID PRO-APOPTOTIC ACTIVITY; NEGATIVE REGULATOR; FAMILY PROTEIN; DEATH; BAX; ACTIVATION; BINDS; BFL-1/A1; APAF-1; MEMBER AB Defects in apoptosis mechanisms play important roles in malignancy and autoimmunity. Orphan nuclear receptor Nur77/ TR3 has been demonstrated to bind antiapoptotic protein Bcl-2 and convert it from a cytoprotective to a cytodestructive protein, representing a phenotypic conversion mechanism. Of the 6 antiapoptotic human Bcl-2 family members, we found that Nur77/TR3 binds strongest to Bcl-B, showing selective reactivity with Bcl-B, Bcl-2, and Bfl-1 but not Bcl-X-L, Mcl-1, or Bcl-W. Nur77 converts the phenotype of Bcl-B from antiapoptotic to proapoptotic. Bcl-B is prominently expressed in plasma cells and multiple myeloma. Endogenous Bcl-B associates with endogenous Nur77 in RPMI 8226 myeloma cells, where RNA interference experiments demonstrated dependence on Bcl-B for Nur77-induced apoptosis. Furthermore, a Nur77-mimicking peptide killed RPMI 8226 myeloma cells through a Bcl-B-dependent mechanism. Because Bcl-B is abundantly expressed in plasma cells and some myelomas, these findings raise the possibility of exploiting the Nur77/Bcl-B mechanism for apoptosis for eradication of autoimmune plasma cells or myeloma. C1 Burnham Inst Med Res, La Jolla, CA 92037 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Reed, JC (reprint author), Burnham Inst Med Res, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM reedoffice@burnham.org FU NIGMS NIH HHS [GM 60554, R01 GM060554] NR 34 TC 50 Z9 51 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2007 VL 109 IS 9 BP 3849 EP 3855 DI 10.1182/blood-2006-11-056879 PG 7 WC Hematology SC Hematology GA 162MJ UT WOS:000246091400040 PM 17227826 ER PT J AU Tissing, WJE den Boer, ML Meijerink, JPP Menezes, RX Swagemakers, S van der Spek, PJ Sallan, SE Armstrong, SA Pieters, R AF Tissing, Wirn J. E. den Boer, Monique L. Meijerink, Jules P. P. Menezes, Renee X. Swagemakers, Sigrid van der Spek, Peter J. Sallan, Stephen E. Armstrong, Scott A. Pieters, Rob TI Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells SO BLOOD LA English DT Article ID GLUCOCORTICOID-INDUCED APOPTOSIS; FACTOR-KAPPA-B; PROTEIN-KINASE; MOLECULAR-MECHANISMS; THIOREDOXIN FUNCTION; EXPRESSION PATTERNS; SIGNALING PATHWAYS; OXIDATIVE STRESS; EPITHELIAL-CELLS; EVOKED APOPTOSIS AB Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours of prednisolone exposure in leukemic cells of 13 children as compared with nonexposed cells. Following 3 hours of exposure no significant changes in gene expression could be identified. Following 8 hours of exposure, 51 genes were differentially expressed (P < .001 and false discovery rate < 10%) with 39 genes being up-regulated (median, 2.4-fold) and 12 genes were downregulated (median, 1.7-fold). Twenty-one of those genes have not been identified before to be transcriptionally regulated by prednisolone. Two of the 3 most highly up-regulated genes were tumor suppressor genes, that is, thioredoxin-interacting protein (TXNIP; 3.7-fold) and zinc finger and BTB domain containing 16 (ZBTB16; 8.8-fold). About 50% of the differentially expressed genes were functionally categorized in 3 major routes, namely MAPK pathways (9 genes), NF-KB signaling (11 genes), and carbohydrate metabolism (5 genes). Biologic characterization of these genes and pathways might elucidate the action of glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid resistance and new potential targets for therapy. C1 Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, NL-3015 GJ Rotterdam, Netherlands. Univ Groningen, Dept Pediat Oncol Hematol, Beatrix Childrens Hosp, Groningen, Netherlands. Univ Groningen, Med Ctr, Groningen, Netherlands. Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. Erasmus MC, Dept Bioinformat, Rotterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP den Boer, ML (reprint author), Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. EM m.l.denboer@erasmusmc.nl RI Meijerink, Jules/D-4393-2017 OI Meijerink, Jules/0000-0002-6860-798X NR 53 TC 61 Z9 62 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2007 VL 109 IS 9 BP 3929 EP 3935 DI 10.1182/blood-2006-11-056366 PG 7 WC Hematology SC Hematology GA 162MJ UT WOS:000246091400050 PM 17218380 ER PT J AU Vallat, LD Park, Y Li, C Gribben, JG AF Vallat, Laurent D. Park, Yuhyun Li, Cheng Gribben, John G. TI Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ZAP-70 EXPRESSION; MUTATION STATUS; GENOMIC ABERRATIONS; ANTIGEN RECEPTORS; CD38 EXPRESSION; SURFACE IGM; APOPTOSIS; PATTERNS; SETS AB Gene expression in cells is a dynamic process but is usually examined at a single time point. We used gene expression profiling over time to build temporal models of gene transcription after B-cell receptor (BCR) signaling in healthy and malignant B cells and chose this as a model since BCR cross-linking induces both cell proliferation and apoptosis, with increased apoptosis in chronic lymphocytic leukemia (CLL) compared to healthy B cells. To determine the basis for this, we examined the global temporal gene expression profile for BCR stimulation and developed a linear combination method to summarize the effect of BCR simulation over all the time points for all patients. Functional learning identified common early events in healthy B cells and CLL cells. Although healthy and malignant B cells share a common genetic pattern early after BCR signaling, a specific genetic program is engaged by the malignant cells at later time points after BCR stimulation. These findings identify the molecular basis for the different functional consequences of BCR cross-linking in healthy and malignant B cells. Analysis of gene expression profiling over time may be used to identify genes that might be rational targets to perturb these pathways. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Barts & London Sch Med, Charterhouse Sq, London EC1M 6BQ, England. EM john.gribben@cancer.org.uk FU NCI NIH HHS [P01 CA081534, P01 CA 81538] NR 37 TC 30 Z9 30 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2007 VL 109 IS 9 BP 3989 EP 3997 DI 10.1182/blood-2006-09-045377 PG 9 WC Hematology SC Hematology GA 162MJ UT WOS:000246091400057 PM 17234734 ER PT J AU Lindahl, H Oden, A Garellick, G Malchau, H AF Lindahl, H. Oden, A. Garellick, G. Malchau, H. TI The excess mortality due to periprosthetic femur fracture. A study from the Swedish national hip arthroplasty register SO BONE LA English DT Article DE periprosthetic fracture; osteoarthritis; mortality; arthroplasty ID BONE-MINERAL DENSITY; LIFE EXPECTANCY; OSTEOPOROTIC FRACTURES; FOLLOW-UP; REPLACEMENT; WOMEN; AGE; OSTEOARTHRITIS; SURVIVAL; RISK AB A rare but serious adverse event of total hip replacement (THR) is periprosthetic femoral fracture. The aim of the present study was to assess whether there was an excess mortality due to such a fracture and to estimate the probability of death caused by the fracture. We studied primary total hip replacement in 27,652 men and 35,930 women with osteoarthritis from The Swedish National Hip Arthroplasty Register operated from 1979 to 2000. From the same register we also studied 392 men and 344 women with periprosthetic fracture from 1979 to 2000, all with osteoarthritis as the primary diagnosis. By the special method applied, it was possible to perform the estimation of death due to the fracture event though we could not determine in the individual case whether the fracture caused the death. Compared to the total population of patients operated with a primary THR there was a higher mortality rate immediately after the surgery for patients with periprosthetic fracture and in the longer run for patients below the age of 70 years. At the age of 70 years the estimated probability of death due to the fracture was 2.1% for men and 1.2% for women. At the age of 80 years at fracture the corresponding probabilities were 3.9% and 2.2% for men and women, respectively. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Gothenburg, Sahlgrens Univ Hosp, Inst Surg Sci, Dept Orthoped, SE-41345 Gothenburg, Sweden. Chalmers, Dept Math Sci, SE-41296 Gothenburg, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lindahl, H (reprint author), Univ Gothenburg, Sahlgrens Univ Hosp, Inst Surg Sci, Dept Orthoped, SE-41345 Gothenburg, Sweden. EM hans.lindahl@vgregion.se NR 22 TC 48 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2007 VL 40 IS 5 BP 1294 EP 1298 DI 10.1016/j.bone.2007.01.003 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 162ZS UT WOS:000246128700016 PM 17314077 ER PT J AU Leverenz, JB Yu, CE Montine, TJ Steinbart, E Bekris, LM Zabetian, C Kwong, LK Lee, VMY Schellenberg, GD Bird, TD AF Leverenz, J. B. Yu, C. E. Montine, T. J. Steinbart, E. Bekris, L. M. Zabetian, C. Kwong, L. K. Lee, V. M-Y. Schellenberg, G. D. Bird, T. D. TI A novel progranulin mutation associated with variable clinical presentation and tau, TDP43 and alpha-synuclein pathology SO BRAIN LA English DT Article DE frontotemporal dementia; progranulin; tau; alpha synuclein; neurogenetics ID FRONTOTEMPORAL LOBAR DEGENERATION; DEMENTIA; GENE; CHROMOSOME-17; INCLUSIONS; ANTIBODIES; FAMILIES; MISSENSE; DISEASE; CELLS AB Mutations in the progranulin (GRN) gene have recently been reported as a cause of the frontotemporal dementia (FTD) syndrome. We performed a clinical, neuropathological and molecular genetic study of two families with FTD and the same novel mutation in GRN. Age of onset ranged from 35 to 75 years and all individuals progressed to a severe dementia syndrome with a mean disease duration of similar to 6-10 years. Variable clinical presentations included language impairment, behaviour change or parkinsonism. Seven total autopsies in the families (five in Family 1, two in Family 2) showed gross and microscopic evidence of neuronal loss in the neocortex, striatum, hippocampus and substantia nigra. All cases with material available for immunohistochemistry had cytoplasmic and intranuclear ubiquitin positive, tau negative inclusions that stained best with an antibody to the TDP43 protein. In addition, all but one had evidence of distinctive tau pathology. Two cases in Family I also had alpha-synuclein (SNCA) pathology, one with diffuse neocortical inclusions and neurites and unusual striatal cytoplasmic inclusions. Affected persons in both families had the same mutation in GRN (c.709-2A > G). A minigene construct showed that this mutation alters splicing of exon 7 and results in reduced mRNA message in brain. A single GRN mutation in these two families was associated with variable clinical presentations consistent with the FTD syndrome. All cases had ubiquitin/TDP43 immuno-positive inclusions and most had additional tau pathology. Two cases had SNCA pathology. These findings suggest a link between mutations in GRN and aggregation of tau, TDP43 and SNCA. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. RP Bird, TD (reprint author), 1660S Columbian Way S-182-GRECC, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu OI Zabetian, Cyrus/0000-0002-7739-4306 FU NIA NIH HHS [P50 AG 005 136-22, AG17586] NR 31 TC 80 Z9 83 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2007 VL 130 BP 1360 EP 1374 DI 10.1093/brain/awm069 PN 5 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 165GW UT WOS:000246293400019 PM 17439980 ER PT J AU Caplan, D Waters, G Dede, G Michaud, J Reddy, A AF Caplan, David Waters, Gloria DeDe, Gayle Michaud, Jennifer Reddy, Amanda TI A study of syntactic processing in aphasia I: Behavioral (psycholinguistic) aspects SO BRAIN AND LANGUAGE LA English DT Review ID SHORT-TERM-MEMORY; SPOKEN-LANGUAGE COMPREHENSION; MOVING-WINDOW TECHNIQUE; VERBAL WORKING-MEMORY; SENTENCE COMPREHENSION; BROCAS APHASIA; AGRAMMATIC APHASIA; INDIVIDUAL-DIFFERENCES; GRAMMATICAL STRUCTURE; COGNITIVE-PROCESSES AB This paper presents the results of a study of syntactically based comprehension in aphasic patients. We studied 42 patients with aphasia secondary to left hemisphere strokes and 25 control participants. We measured off-line, end-of-sentence, performance (accuracy and reaction time) in two tasks that require comprehension-enactment and sentence-picture matching-and in grammaticality judgment, with whole sentence auditory presentation. We also used sentence-picture matching and grammaticality judgment as tasks in two self-paced listening studies with the same patients to measure on-line performance. In each task and presentation format, we presented sentences that tested the ability to assign and interpret three structural contrasts chosen to examine different basic syntactic operations: actives and passives, subject and object extracted relative clauses, and reflexive pronouns and matched sentences without these elements. We examined these behavioral data to determine patterns of impairment in individual patients and in groups of patients, using correlational analyses, factor analyses, and analyses of variance. The results showed that almost no individual patients had stable deficits referable to the ability to interpret individual syntactic structures, that a variety of structural features contributed to sentence processing complexity both on-line and off-line, that correct responses were associated with normal on-line and errors with abnormal performance, and that the major determinant of performance is a factor that affected performance on all sentence types. The results indicate that the major cause of aphasic impairments of syntactically based comprehension are intermittent reductions in the processing capacity available for syntactic, interpretive.. and task-related operations. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Sargent Coll, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD NIH HHS [DC 00942] NR 113 TC 71 Z9 73 U1 5 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 2007 VL 101 IS 2 BP 103 EP 150 DI 10.1016/j.bandl.2006.06.225 PG 48 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 175LO UT WOS:000247015300002 PM 16999989 ER PT J AU Caplan, D Waters, G Kennedy, D Alpert, N Makris, N Dede, G Michaud, J Reddy, A AF Caplan, David Waters, Gloria Kennedy, David Alpert, Nathanial Makris, Nikos DeDe, Gayle Michaud, Jennifer Reddy, Amanda TI A study of syntactic processing in aphasia II: Neurological aspects SO BRAIN AND LANGUAGE LA English DT Article DE syntactic comprehension disorder; localization of syntactic comprehension disorder ID CRANIAL COMPUTED TOMOGRAPHY; SENTENCE COMPREHENSION; HUMAN BRAIN; LANGUAGE COMPREHENSION; LESION LOCALIZATION; DEFICITS; MEMORY; HEMIDECORTICATION; MORPHOMETRY; METABOLISM AB This paper presents the results of a study of the effects of left hemisphere strokes on syntactically-based comprehension in aphasic patients. We studied 42 patients with aphasia secondary to left hemisphere strokes and 25 control subjects for the ability to assign and interpret three syntactic structures (passives, object extracted relative clauses, and reflexive pronouns) in enactment, sentence-picture matching and grammaticality judgment tasks. We measured accuracy, RT and self-paced listening times in SPM and G.J. We obtained magnetic resonance (MR) and 5-deoxyglucose positron emission tomography (FDG PET) data on 31 patients and 12 controls. The percent of selected regions of interest (ROIs) that was lesioned on MR and the mean normalized PET counts per voxel in ROIs were calculated. In regression analyses, lesion measures in both perisylvian and non-perisylvian ROIs predicted performance. Patients who performed at similar levels behaviorally had lesions of very different sizes, and patients with equivalent lesion sizes varied greatly in their level of performance. The data are consistent with a model in which the neural tissue that is responsible for the operations underlying sentence comprehension and syntactic processing is localized in different neural regions in different individuals. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Sargent Coll, Dept Speech & Communicat Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. EM dcaplan@partners.org RI Kennedy, David/H-3627-2012 FU NIDCD NIH HHS [DC 00942] NR 65 TC 31 Z9 31 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 2007 VL 101 IS 2 BP 151 EP 177 DI 10.1016/j.bandl.2006.06.226 PG 27 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 175LO UT WOS:000247015300003 PM 16997366 ER PT J AU Tancredi, M De, NA Sensi, E Cipollini, G Lombardi, G Aretini, P Barbuti, S Sobhian, B Bevilacqua, G Drapkin, R Caligo, MA AF Tancredi, M. De, Nicolo A. Sensi, E. Cipollini, G. Lombardi, G. Aretini, P. Barbuti, S. Sobhian, B. Bevilacqua, G. Drapkin, R. Caligo, M. A. TI Identification of a novel BRIP1 germline mutation in a woman with early onset breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Pisa, I-56100 Pisa, Italy. Univ Hosp Pisa, Pisa, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Padua, I-35100 Padua, Italy. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2007 VL 103 IS 1 BP 120 EP 121 PG 2 WC Oncology SC Oncology GA 160TX UT WOS:000245966300025 ER PT J AU Koo, SW Hirakawa, S Fujii, S Kawasumi, M Nghiem, P AF Koo, S-W. Hirakawa, S. Fujii, S. Kawasumi, M. Nghiem, P. TI Protection from photodamage by topical application of caffeine after ultraviolet irradiation SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE apoptosis; caffeine; hairless mouse; photodamage; photoprotection; ultraviolet ID HUMAN-SKIN; CONNECTIVE-TISSUE; DAMAGE; MICE; SUN; UVB; CHECKPOINTS; ANTAGONISM; APOPTOSIS; TRETINOIN AB Background Characterization of mechanisms that can reverse residual damage from prior skin exposure to ultraviolet (UV) would be of considerable biological and therapeutic interest. Topical caffeine application to mouse skin that had previously been treated with UV has been shown to inhibit the subsequent development of squamous cell carcinomas. Objectives We used an established mouse photodamage model to investigate other possible effects of topical caffeine application after UV. Methods SKH-1 hairless mice were treated with ultraviolet B (UVB) followed immediately by topical application of caffeine or vehicle three times weekly for 11 weeks. Results Caffeine applied topically after UV treatment resulted in a significant decrease in UV-induced skin roughness/transverse rhytides as assessed by treatment-blinded examiners. Histologically, topical caffeine application after a single dose of UVB more than doubled the number of apoptotic keratinocytes as evaluated by sunburn cell formation, caspase 3 cleavage and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) staining. A trend towards decreased solar elastosis was noted in the caffeine-treated group although this was not statistically significant. Other histological parameters including epidermal hyperplasia, solar elastosis and angiogenesis were increased in mice treated with UV but topical application of caffeine did not alter these particular UV effects. Conclusions These findings support the concept that topical application of caffeine to mouse skin after UV irradiation promotes the deletion of DNA-damaged keratinocytes and may partially diminish photodamage as well as photocarcinogenesis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Nghiem, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM pnghiem@u.washington.edu RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X NR 28 TC 17 Z9 18 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2007 VL 156 IS 5 BP 957 EP 964 DI 10.1111/j.1365-2133.2007.07812.x PG 8 WC Dermatology SC Dermatology GA 160KG UT WOS:000245938700022 PM 17388926 ER PT J AU Alcantara, O Boldt, DH AF Alcantara, Orlando Boldt, David H. TI Iron deprivation blocks multilineage haematopoietic differentiation by inhibiting induction of p21(WAF1/CIP1) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE iron; haematopoiesis; p21(WAF1/CIP1); CD34(+) cells ID CELL-CYCLE; LEUKEMIC-CELLS; EXPRESSION; INVITRO; GROWTH; DESFERRIOXAMINE; INVIVO; APOPTOSIS AB Iron is required for the differentiation of HL-60 cells along the monocyte lineage in vitro, reflecting a requirement for iron in the transcriptional induction of the p21(WAF1/CIP1) gene. To determine if the same requirement holds true for differentiation in other cell lineages and for primary human CD34(+) bone marrow precursor cells, we induced granulocyte differentiation by treating HL-60 cells with dimethyl sulphoxide, and erythroid or megakaryocytic differentiation by treating K562 cells with butyrate or phorbol myristate acetate, respectively. Nitro blue tetrazolium reduction, expression of haem, or expression of CD41 was used to assess granulocytic, erythroid, or megakaryocytic differentiation respectively. Purified CD34(+) cells were cultured with granulocyte/macrophage-colony stimulating factor and stem cell factor to induce myelomonocytic differentiation. Iron deprivation was induced by desferrioxamine. p21(WAF1/CIP1) antisense oligonucleotides were used to inhibit p21 expression. Iron deprivation blocked p21 induction as judged by real-time polymerase chain reaction assays. In addition, both iron deprivation and p21 antisense blocked CD34(+) cell differentiation. These observations were not explained by induction of widespread apoptosis under conditions of iron deprivation. We concluded that both iron and functional p21(WAF1/CIP1) are required for in vitro differentiation of human haematopoietic precursors along multiple cell lineages. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Boldt, DH (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr,Mail Code 7880, San Antonio, TX 78229 USA. EM boldt@uthscsa.edu FU NCI NIH HHS [P30 CA54174.]; NIDDK NIH HHS [R01 DK5042] NR 21 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2007 VL 137 IS 3 BP 252 EP 261 DI 10.1111/j.1365-2141.2007.06549.x PG 10 WC Hematology SC Hematology GA 152WR UT WOS:000245393400011 PM 17408467 ER PT J AU Kahana, A Marcet, MM Albert, DM Thliveris, AT AF Kahana, Alon Marcet, Marcus M. Albert, Daniel M. Thliveris, Andrew T. TI Drug-induced cicatrising granulomatous conjunctivitis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53792 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, William S Middleton Mem Vet Hosp, Madison, WI 53792 USA. RP Kahana, A (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 600 Highland Ave, Madison, WI 53792 USA. EM kahana@wisc.edu RI Marcet, Marcus/E-9876-2010; OI MARCET, Marcus/0000-0003-0433-4684; Kahana, Alon/0000-0002-5667-2274 NR 6 TC 1 Z9 2 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 2007 VL 91 IS 5 BP 691 EP 692 DI 10.1136/bjo.2006.099085 PG 6 WC Ophthalmology SC Ophthalmology GA 158XW UT WOS:000245829900034 PM 17446509 ER PT J AU Wolpin, BM Meyerhardt, JA Mamon, HJ Mayer, RJ AF Wolpin, Brian M. Meyerhardt, Jeffrey A. Mamon, Harvey J. Mayer, Robert J. TI Adjuvant treatment of colorectal cancer SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review ID GROWTH-FACTOR RECEPTOR; III COLON-CANCER; FLUOROURACIL PLUS LEUCOVORIN; RANDOMIZED CONTROLLED-TRIAL; HOSPITAL PROCEDURE VOLUME; TOTAL MESORECTAL EXCISION; AMERICAN JOINT COMMITTEE; BLACK-WHITE DIFFERENCES; LOW-DOSE LEUCOVORIN; LARGE BOWEL-CANCER AB Colorectal cancer is the fourth most common noncutaneous malignancy in the United States and the second most frequent cause of cancer-related death. Approximately three quarters of patients are diagnosed with disease limited to the bowel wall or surrounding lymph nodes. Over the past decade, significant progress has been made in the treatment of localized colorectal cancer due to advances in surgery, radiotherapy, and chemotherapy. For patients with Stage III colon cancer, an overall survival benefit for fluorouracil-based chemotherapy has been firmly established, and recent data have shown further efficacy through the inclusion of oxaliplatin into adjuvant treatment programs. For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at high risk for disease recurrence. In the treatment of patients with rectal cancer, improved outcomes have been noted with the use of total mesorectal excision and preoperative concurrent chemoradiotherapy. Current randomized clinical trials in the adjuvant therapy of colorectal cancer are examining the value of adding agents known to be active in metastatic disease, including those that modify specific molecular targets. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Gastrointestinal Oncol,Dept Med Oncol, Boston, MA 02115 USA. RP Wolpin, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 168 TC 154 Z9 160 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2007 VL 57 IS 3 BP 168 EP 185 PG 18 WC Oncology SC Oncology GA 170EX UT WOS:000246646300005 PM 17507442 ER PT J AU Knight, SJ Latini, DM Hart, SL Sadetsky, N Kane, CJ DuChane, J Carroll, PR AF Knight, Sara J. Latini, David M. Hart, Stacey L. Sadetsky, Natalia Kane, Christopher J. DuChane, Janeen Carroll, Peter R. CA CaPSURE Investigators TI Education predicts quality of life among men with prostate cancer cared for in the department of veterans affairs - A longitudinal quality of life analysis from CaPSURE SO CANCER LA English DT Article DE prostate cancer; education; health related quality of life; socioeconomic status; disparities; VA health care system ID LOW-INCOME PATIENTS; SYSTEM; LITERACY; DATABASE AB BACKGROUND. Previous findings have suggested that patient educational attainment is related to cancer stage at presentation and treatment for localized prostate cancer, but there is little information on education and quality of life outcomes. Patient education level and quality of life were examined among men diagnosed with prostate cancer and cared for within an equal-access health care system, the Department of Veterans Affairs Veterans Health Administration (VA). METHODS. Participants were 248 men with prostate cancer cared for in the VA and enrolled in CaPSURE. Repeated-measures analysis of variance was used to examine quality of life over time according to education level, controlling for age, ethnicity, income, site of clinical care, and year of diagnosis. RESULTS. Patients with lower levels of education tended to be younger, nonwhite, and have lower incomes. Controlling for age, ethnicity, income, year of diagnosis, and site, men with less formal education, compared with those with more, had worse functioning in the physical (P = .0248), role physical (P = .0048), role emotional (P = .0089), vitality (P = .0034), mental health (P = .0054), social function (P = .0056), and general health (P = .0002) domains and worse urinary (P = .003) and sexual (P = .0467) side effects. CONCLUSIONS. Men with less education experienced worse health-related quality of life across a wide range of domains and greater urinary and sexual symptoms than their peers who had more education. Clinicians should be aware that, even within an equal access to health care system, men with less education are vulnerable, having greater difficulty functioning in their daily lives after their prostate cancer treatment. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Knight, SJ (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM sara.knight@ucsf.edu RI Hart, Stacey/E-4819-2011; OI Latini, David/0000-0002-6161-4861 FU PHS HHS [P50 C89520] NR 25 TC 38 Z9 38 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2007 VL 109 IS 9 BP 1769 EP 1776 DI 10.1002/cncr.22597 PG 8 WC Oncology SC Oncology GA 160JP UT WOS:000245937000011 PM 17380491 ER PT J AU Dileo, P Morgan, JA Zahrieh, D Desai, J Salesi, JM Harrnon, DC Quigley, MT Polson, K Demetri, GD George, S AF Dileo, Palma Morgan, Jeffrey A. Zahrieh, David Desai, Jayesh Salesi, Jeanine M. Harrnon, David C. Quigley, M. Travis Polson, Kathleen Demetri, George D. George, Suzanne TI Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas - Results of a phase II trial SO CANCER LA English DT Article DE soft-tissue sarcoma; gemcitabine; vinorelbine; dose rate infusion ID COOPERATIVE-ONCOLOGY-GROUP; ADVANCED BREAST-CANCER; CLINICAL-TRIALS; DOSE-RATE; DOXORUBICIN; IFOSFAMIDE; DOCETAXEL AB BACKGROUND. Single-agent gemcitabine and vinorelbine have activity in treatment of patients with soft-tissue sarcomas. The combination of gemcitabine plus vinorelbine has activity against several forms of metastatic carcinoma with acceptable toxicity. This study evaluated the efficacy and tolerability of gemcitabine plus vinorelbine in advanced soft-tissue sarcoma. METHODS. A single academic center performed this phase II trial. Eligible patients had unresectable or metastatic soft-tissue sarcomas, Eastern Cooperative Group performance status of 0-2, adequate organ function, and <= 1 prior regimen. Gemcitabine 800 rug/rui was given over 90 minutes on Days 1 and 8 of a 21-day cycle after administration of vinorelbine 25 mg/m(2). Dosing schedule was modified for toxicity (doses constant but administered on Days 1 and 15 of a 28-day cycle). Dose reductions were allowed if unacceptable toxicities recurred. RESULTS. The study accrued 40 patients, and 248 dosing cycles were administered (range, 1-32). No treatment-related deaths occurred. Of 9 episodes of grade 4 toxicities, 8 were hematologic. Of 38 episodes of grade 3 toxicity, 24 were hematologic. Clinical benefit was seen in 25% of patients and was defined as complete response (CR), partial response (PR), or stable disease (SD) at >4 months. There has been 1 CR lasting >1 year in a patient with high-grade pleomorphic spindle-cell sarcoma. CONCLUSIONS. Gemcitabine given by a fixed-dose rate of infusion combined with vinorelbine was associated with clinically meaningful rates of disease control in patients with advanced soft-tissue sarcoma. Toxicity was acceptable. This study contributed to data that have supported the administration of fixed-dose rate gemcitabine-based drug regimens in soft-tissue sarcomas. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ludwig Ctr Canc Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Sgeorge2@partners.org NR 27 TC 33 Z9 36 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2007 VL 109 IS 9 BP 1863 EP 1869 DI 10.1002/cncr.22609 PG 7 WC Oncology SC Oncology GA 160JP UT WOS:000245937000024 PM 17385194 ER PT J AU Yuza, Y Glatt, KA Jiang, JR Greulich, H Minami, Y Woo, MS Shimamura, T Shapiro, G Lee, JC Ji, HB Feng, W Chen, TH Yanagisawa, H Wong, KK Meyerson, M AF Yuza, Yuki Glatt, Karen A. Jiang, Jingrui Greulich, Heidi Minami, Yuko Woo, Michele S. Shimamura, Takeshi Shapiro, Geoffrey Lee, Jeffrey C. Ji, Hongbin Feng, Whei Chen, Tzu-Hsiu Yanagisawa, Haruhiko Wong, Kwok-Kin Meyerson, Matthew TI Allele-dependent variation in the relative cellular potency of distinct EGFR inhibitors SO CANCER BIOLOGY & THERAPY LA English DT Article DE lung cancer; EGFR mutation; EGFR inhibitors; pharmacogenomics; Ba/F3 cells ID GROWTH-FACTOR-RECEPTOR; LUNG-CANCER PATIENTS; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; BCR-ABL; ACQUIRED-RESISTANCE; CYTOGENETIC RESPONSES; ACTIVATING MUTATIONS; PROLONGED SURVIVAL AB Targeted cancer therapies impede cancer cell growth by inhibiting the function of activated oncogene products. Patients with non-small cell lung cancer and somatic mutations of EGFR can have a dramatic response to treatment with erlotinib and gefitinib; different somatic mutations are associated with different times to progression and survival. In this study, the relative and absolute potencies of two distinct EGFR tyrosine kinase inhibitors, erlotinib and an investigational irreversible inhibitor, HKI-272, were found to vary significantly in a panel of Ba/F3 cells transformed by representative EGFR somatic mutations. HKI-272 more potently inhibited the primary exon 20 insertion mutants, the secondary erlotinib-resistance mutants including T790M and many erlotinib-sensitive mutants including L858R. In contrast, erlotinib is a more potent inhibitor of the major exon 19 deletion mutants than is HKI-272. Analyses of EGFR autophosphorylation patterns confirmed the mutation-specific variation in relative potency of these tyrosine kinase inhibitors. Our finding that distinct EGFR inhibitors are more effective in vitro for different mutant forms of the protein suggests that tyrosine kinase inhibitor treatment could be tailored to specific EGFR mutations. More broadly, these results imply that the development and deployment of targeted therapies should focus on inhibition of specific cancer-causing mutations, not only on the mutated target. C1 Dana Farber Canc Inst, Dept Med Oncol, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Broad Inst Harvard, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Ctr Canc Genome Discovery, 44 Binney St D, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU NCI NIH HHS [R01 CA116010] NR 48 TC 46 Z9 46 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2007 VL 6 IS 5 BP 661 EP 667 PG 7 WC Oncology SC Oncology GA 193FN UT WOS:000248259900017 PM 17495523 ER PT J AU de Moor, JS Puleo, E Butterfield, RM Li, FP Emmons, KM AF de Moor, Janet S. Puleo, Elaine Butterfield, Rita M. Li, Frederick P. Emmons, Karen M. TI Availability of smoking prevention and cessation services for childhood cancer survivors SO CANCER CAUSES & CONTROL LA English DT Article DE smoking cessation services; childhood cancer survival; cancer prevention ID YOUNG-ADULT SURVIVORS; PRIMARY-CARE PRACTICE; ORGANIZATIONAL CHARACTERISTICS; WORKSITE CHARACTERISTICS; CLINICAL-PRACTICE; HEALTH-CARE; INTERVENTIONS; INITIATIVES; QUALITY; COMMIT AB Objective To characterize the smoking-related services available to childhood cancer survivors and describe organizational characteristics that were related to institutions' capacity to provide smoking services. Methods Institutions affiliated with the Children's Oncology Group were surveyed from 2003 to 2004. Results Of the 132 responding institutions, 85% assessed the smoking status of their cancer survivors intermittingly, but only 3% assessed smoking status at every visit, as recommended by the PHS guidelines. A minority of sites offered either smoking prevention (39%) or cessation (25%) services; 58% of sites had a mechanism in place to refer survivors for cessation services. In multivariate analyses, the most parsimonious model predicting capacity for smoking service delivery included barriers, respondents' attitudes, complexity, and institutional stability. Conclusions These data highlight an important need to improve the availability of smoking services for childhood cancer survivors. Additionally, these findings will inform the development of future interventions that are sensitive to barriers and facilitators to providing prevention services. C1 Harvard Sch Publ Hlth, Ctr Community Based Res, Dana Farber Canc Inst, Dept Soc Human Dev & Hlth, Boston, MA USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Ctr Community Based Res, Dept Epidemiol, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP de Moor, JS (reprint author), Ohio State Univ, Sch Publ Hlth, Div Hlth Behav & Hlth Promot, 454 Cunz Hall,1841 Millikin Rd, Columbus, OH 43210 USA. EM jdemoor@sph.osu.edu FU NCI NIH HHS [2R25CA057711-11A2, R01CA77780, 5R01CA106914-03]; PHS HHS [45CFR46.110] NR 26 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2007 VL 18 IS 4 BP 423 EP 430 DI 10.1007/s10552-006-0110-y PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 147HL UT WOS:000244993900009 PM 17297556 ER PT J AU Girnun, GD Naseri, E Vafai, SB Qu, L Szwaya, JD Bronson, R Alberta, JA Spiegelman, BM AF Girnun, Geoffrey D. Naseri, Elnaz Vafai, Scott B. Qu, Lishu Szwaya, Jeffrey D. Bronson, Roderick Alberta, John A. Spiegelman, Bruce M. TI Synergy between PPAR gamma ligands and platinum-based drugs in cancer SO CANCER CELL LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; CELL LUNG-CANCER; OVARIAN-CARCINOMA CELLS; CISPLATIN RESISTANCE; COLORECTAL-CANCER; COLON-CANCER; PHASE-II; METALLOTHIONEIN; DIFFERENTIATION; EXPRESSION AB PPAR gamma is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPAR gamma ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPAR gamma activation with chemotherapeutic agents in current use for specific cancers. We observed a striking synergy between rosiglitazone and platinum-based drugs in several different cancers both in vitro and using transplantable and chemically induced "spontaneous" tumor models. The effect appears to be due in part to PPAR gamma-mediated downregulation of metallothioneins, proteins that have been shown to be involved in resistance to platinum-based therapy. These data strongly suggest combining PPAR gamma agonists and platinum-based drugs for the treatment of certain human cancers. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK 57670, DK 064685, K01 DK064685, K01 DK064685-04, R01 DK057670, R01 DK057670-05, R37 DK 31405, R37 DK031405, R37 DK031405-25] NR 58 TC 86 Z9 86 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2007 VL 11 IS 5 BP 395 EP 406 DI 10.1016/j.ccr.2007.02.025 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 167GI UT WOS:000246439100003 PM 17482130 ER PT J AU Niederdeppe, J Levy, AG AF Niederdeppe, Jeff Levy, Andrea Gurmankin TI Fatalistic beliefs about cancer prevention and three prevention behaviors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICANS; HEALTH BEHAVIOR; BREAST-CANCER; LIFE-STYLE; WOMEN; PREDICTORS; KNOWLEDGE; NUTRITION; ADULTS AB Background: A substantial proportion of US adults hold fatalistic beliefs about cancer prevention. Although evidence suggests that fatalistic beliefs discourage people from engaging in screening behaviors that can reduce their cancer risk, far less is known about associations between cancer fatalism and other prevention behaviors. We examined sociodemographic correlates of these beliefs and their associations with regular exercise, smoking, and fruit and vegetable consumption with a national sample of American adults. Methods: Data were analyzed from the first wave of the Health Information National Trends Survey (HINTS 2003). HINTS used random-digit dialing to complete phone interviews with adult Americans (N = 6,369). Results: Nearly half of respondents (47.1%) agreed that "It seems like almost everything causes cancer," 27.0% agreed that "There's not much people can do to lower their chances of getting cancer," and 71.5% agreed that "There are so many recommendations about preventing cancer, it's hard to know which ones to follow." These beliefs were stronger in subjects who were less educated but generally weaker among both African Americans and Hispanics relative to Whites. Fatalistic beliefs about cancer prevention were negatively associated with exercising weekly, not smoking, and eating five or more fruits and vegetables daily in multivariate analysis controlling for sociodemographic characteristics. Conclusions: Americans who hold fatalistic beliefs about cancer prevention may be at greater risk of cancer because they are less likely to engage in various prevention behaviors. Results have notable implications for future cancer communication and education efforts. C1 Univ Wisconsin, Dept Populatr Hlth, Madison, WI 53726 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Niederdeppe, J (reprint author), Univ Wisconsin, Dept Populatr Hlth, Rm 707,WHARF Bldg,610 Walnut St, Madison, WI 53726 USA. EM niederdeppe@wisc.edu FU NCI NIH HHS [P50 CA101404] NR 41 TC 126 Z9 127 U1 3 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2007 VL 16 IS 5 BP 998 EP 1003 DI 10.1158/1055-9965.EPI-06-0608 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 170FX UT WOS:000246649200025 PM 17507628 ER PT J AU Prabhakar, S Messerli, SM Stemmer-Rachamimov, AO Liu, TC Rabkin, S Martuza, R Breakefield, XO AF Prabhakar, S. Messerli, S. M. Stemmer-Rachamimov, A. O. Liu, T-C Rabkin, S. Martuza, R. Breakefield, X. O. TI Treatment of implantable NF2 schwannoma tumor models with oncolytic herpes simplex virus G47 Delta SO CANCER GENE THERAPY LA English DT Article DE neurofibromatosis type 2; oncolytic virus; HSV; mouse schwannoma; schwannoma cell line; human schwannoma ID NEUROFIBROMATOSIS TYPE-2; TRANSGENIC MICE; MOUSE MODELS; GENE; SUPPRESSOR; COMPLEX; PROTEIN; VECTOR; ORIGIN; MUTANT AB Schwannomas are benign tumors composed of dedifferentiated Schwann cells that form along peripheral nerves causing nerve compression often associated with pain and loss of function. Current surgical therapy involves total or subtotal surgical removal of the tumor, which may cause permanent nerve damage. In the present study, we explore an alternate means of therapy in which schwannomas are injected with a replication-conditional herpes simplex virus (HSV) vector to shrink the tumor through cell lysis during virus propagation. The oncolytic vector used, G47 Delta, has deletions in HSV genes, which allow it to replicate selectively in dividing cells, sparing neurons. Two schwannoma cell lines were used to generate subcutaneous tumors in nude mice: HEI193, an immortalized human line previously established from an NF2 patient and NF2S-1, a newly generated spontaneous mouse line. Subcutaneous HEI193 tumors grew about ten times as fast as NF2S-1 tumors, and both regressed substantially following injection of G47D. Complete regression of HEI193 tumors was achieved in most animals, whereas all NF2S-1 tumors resumed growth within 2 weeks after vector injection. These studies provide a new schwannoma model for testing therapeutic strategies and demonstrate that oncolytic HSV vectors can be successfully used to shrink growing schwannomas. C1 Massachusetts Gen Hosp, Mol Neurogenet Univ, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Univ, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 29 TC 21 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAY PY 2007 VL 14 IS 5 BP 460 EP 467 DI 10.1038/sj.cgt.7701037 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 156LV UT WOS:000245650900003 PM 17304235 ER PT J AU Cigler, T Goss, PE AF Cigler, Tessa Goss, Paul E. TI Breast cancer adjuvant endocrine therapy SO CANCER JOURNAL LA English DT Article DE breast cancer; adjuvant; hormonal; tamoxifen; aromatase inhibitors; postmenopausal; premenopausal ID BONE-MINERAL DENSITY; QUALITY-OF-LIFE; NONSTEROIDAL AROMATASE INHIBITOR; PLASMA ESTROGEN-LEVELS; BOWEL PROJECT P-1; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; PREMENOPAUSAL PATIENTS; TAMOXIFEN THERAPY; ATAC TRIAL AB Adjuvant endocrine therapy with the selective estrogen receptor modulator, tamoxifen, has significantly improved mortality from early-stage breast cancer for both pre- and postmenopausal women with hormone receptor-positive breast cancer. Recent large clinical trials have demonstrated a clear and consistent benefit for the incorporation of aromatase inhibitor (AI) therapy within adjuvant endocrine regimens for postmenopausal women. The AIs, which are associated with myalgias, arthralgias, and a reduction in bone mineral density, are generally well tolerated and have lower risks of endometrial carcinoma and thromboembolic events than tamoxifen. Data are awaited from ongoing trials to better define the optimal sequencing strategy, duration, and Al agent. Attempts to further optimize adjuvant endocrine therapy by identifying predictive biomarkers of response, as well as by developing strategies to overcome endocrine resistance are underway. In premenopausal women AI monotherapy is currently contraindicated and tamoxifen remains the standard of care. The role of ovarian function suppression in addition to tamoxifen or combined with Al therapy is being explored. The hope is that continued advances in endocrine therapy will translate into improved survival among both pre- and postmenopausal women with receptor-positive breast cancer. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org NR 75 TC 12 Z9 12 U1 2 U2 3 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2007 VL 13 IS 3 BP 148 EP 155 DI 10.1097/PPO.0b013e318074d363 PG 8 WC Oncology SC Oncology GA 185NM UT WOS:000247717700003 PM 17620763 ER PT J AU Ng, K Meyerhardt, JA Fuchs, CS AF Ng, Kimmie Meyerhardt, Jeffrey A. Fuchs, Charles S. TI Adjuvant and neoadjuvant approaches in gastric cancer SO CANCER JOURNAL LA English DT Article DE adenocarcinoma; chemotherapy; adjuvant; combined modality therapy; neoadjuvant therapy; neoplasm recurrence; local; neoplasm staging; radiotherapy; adjuvant; stomach neoplasms/drug therapy; stomach neoplasms/mortality; stomach neoplasms/radiotherapy ID RANDOMIZED FAMTX TRIAL; DATA-BASE REPORT; CURATIVE RESECTION; FOLLOW-UP; PREOPERATIVE CHEMOTHERAPY; GASTROESOPHAGEAL CANCER; CLINICAL-TRIAL; METAANALYSIS; CARCINOMA; CISPLATIN AB Despite the recent decline in the incidence of gastric cancer in North America and Western Europe, treatment remains a challenging problem for oncologists. Surgery is the primary modality for managing early-stage disease, but most patients who undergo a curative resection develop locoregional or distant recurrence. Consequently, there has been great interest in evaluating strategies to prevent recurrences and improve overall mortality. This article is a review of data on adjuvant and neoadjuvant treatment approaches for gastric cancer, including radiotherapy, chemotherapy, and chemoradiotherapy. Compared with surgery alone, the North American Intergroup 0116 trial demonstrated a clear survival benefit with the administration of a postoperative regimen of 5-fluorouracil, leucovorin, and external beam radiation therapy, and these findings have made concurrent chemoradiation a standard of care in patients with resected gastric cancer. More recently, the British Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) study found that preoperative and postoperative administration of epirubicin, cisplatin, and 5-fluorouracil significantly improved survival beyond surgery alone. Thus, after decades of negative studies, 2 successful strategies in localized gastric cancer are now available. Ongoing and proposed trials include the current Intergroup study (Cancer and Leukemia Group B 80101), which is assessing the role of a potentially more active postoperative chemoradiation regimen. The proposed MAGIC-B study will examine the role of adding bevacizumab to perioperative chemotherapy, and the planned CRITICS study by the Dutch Gastric Cancer Group will evaluate the role of postoperative chemoradiation in combination with preoperative chemotherapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Ng, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kng4@partners.org FU NCI NIH HHS [T32 CA009172] NR 48 TC 25 Z9 27 U1 0 U2 3 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2007 VL 13 IS 3 BP 168 EP 174 DI 10.1097/PPO.0b013e318074e351 PG 7 WC Oncology SC Oncology GA 185NM UT WOS:000247717700006 PM 17620766 ER PT J AU Ogawa, K Boucher, Y Kashiwagi, S Fukumura, D Chen, D Gerweck, LE AF Ogawa, Kazuhiko Boucher, Yves Kashiwagi, Satoshi Fukumura, Dai Chen, David Gerweck, Leo E. TI Influence of tumor cell and stroma sensitivity on tumor response to radiation SO CANCER RESEARCH LA English DT Article ID RADIOSENSITIVITY; RADIOTHERAPY; IRRADIATION; XENOGRAFTS; CARCINOMA; SURVIVAL; IMPACT; MICE AB In this study, we evaluated the role of tumor cell and tumor stroma sensitivity as determinants of radiation-induced tumor growth delay. A DNA double-strand break repair-defective DNA-PKcs(-/-) tumor cell line and its radioresistant DNA-PKcs(+/+)-transfected counterpart were used to initiate tumors in nude and hypersensitive severe combined inummodeficient (SCID) mice. Insertion of the human DNA-PKcs(+/+) gene substantially increased the intrinsic radioresistance of the DNA-PKcs-/- tumor cells and substantially decreased tumor response to radiation in both nude and hypersensitive SCID mice. Tumor cell radiosensitivity was the major determinant of tumor response in nude mice. In SCID mice, both tumor cell sensitivity and radiation-induced stromal damage contributed to response. The relative contribution of host and tumor cell sensitivity on tumor response was unchanged for single doses of 1 X 15 and 6 X 3 Gy-fractionated dose irradiation. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Radiat Oncol, Div Mol Radiat Oncol, Dallas, TX 75230 USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM lgerweck@partners.org FU NCI NIH HHS [CA092366] NR 22 TC 37 Z9 39 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2007 VL 67 IS 9 BP 4016 EP 4021 DI 10.1158/0008-5472.CAN-06-4498 PG 6 WC Oncology SC Oncology GA 165UC UT WOS:000246330300006 PM 17483312 ER PT J AU Dimri, M Naramura, M Duan, L Chen, J Ortega-Cava, C Chen, GS Goswami, R Fernandes, N Gao, QS Dimri, GP Band, V Band, H AF Dimri, Manjari Naramura, Mayumi Duan, Lei Chen, Jing Ortega-Cava, Cesar Chen, Gengsheng Goswami, Rasna Fernandes, Norvin Gao, Qingshen Dimri, Goberdhan P. Band, Vimla Band, Hamid TI Modeling breast cancer-associated c-Src and EGFR overexpression in human MECs: c-Src and EGFR cooperatively promote aberrant three-dimensional acinar structure and invasive behavior SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; MAMMARY EPITHELIAL-CELLS; TYROSINE KINASE INHIBITORS; BASEMENT-MEMBRANE CULTURES; SIGNAL-TRANSDUCTION; FAMILY KINASES; MOUSE MODELS; TRANSFORMATION; ADHESION; METASTASIS AB Epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, is overexpressed in as many as 60% cases of breast and other cancers. EGFR overexpression is a characteristic of highly aggressive molecular subtypes of breast cancer with basal-like and BRCA1 mutant phenotypes distinct from ErbB2-overexpressing breast cancers. Yet, EGFR is substantially weaker compared with ErbB2 in promoting the oncogenic transformation of nontumorigenic human mammary epithelial cells (human MEC), suggesting a role for cooperating oncogenes. Here, we have modeled the co-overexpression of EGFR and a biologically and clinically relevant potential modifier c-Src in two distinct immortal but nontumorigenic human MECs. Using a combination of morphologic analysis and confocal imaging of polarity markers in three-dimensional Matrigel culture together with functional analyses of early oncogenic traits, we show for the first time that EGFR and c-Src co-overexpression but not EGFR or c-Src overexpression alone unleashes an oncogenic signaling program that leads to hyperproliferation and loss of polarity in three-dimensional acinar cultures, marked enhancement of migratory and invasive behavior, and anchorage-independent growth. Our results establish that EGFR overexpression in an appropriate context (modeled here using c-Src overexpression) can initiate oncogenic transformation of nontumorigenic human MECs and provide a suitable in vitro model to interrogate human breast cancer-relevant oncogenic signaling pathways initiated by overexpressed EGFR and to identify modifiers of EGFR-mediated breast oncogenesis. C1 Evanston NW Healthcare Res Inst, Dept Med, Feinberg Sch Med, Div Mol Oncol, Evanston, IL 60201 USA. Evanston NW Healthcare Res Inst, Dept Med, Feinberg Sch Med, Div Canc Biol, Evanston, IL 60201 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Band, H (reprint author), Evanston NW Healthcare Res Inst, Dept Med, Feinberg Sch Med, Div Mol Oncol, 1001 Univ Pl, Evanston, IL 60201 USA. EM h-band@northwestern.edu OI Naramura, Mayumi/0000-0003-3658-0767 FU NCI NIH HHS [R01 CA095221-03, R01 CA096986-04, R01 CA095221-01A1, CA 87986, CA 76118, CA 99900, 1U54 CA 119341-01, R01 CA096986-01A1, R01 CA096986-02, R01 CA096986-05, CA 94143, R01 CA095221-04, R01 CA095221-02, CA 81076, CA 96844, R01 CA096986-03, CA 99163, R01 CA095221-05] NR 50 TC 57 Z9 58 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2007 VL 67 IS 9 BP 4164 EP 4172 DI 10.1158/0008-5472.CAN-06-2580 PG 9 WC Oncology SC Oncology GA 165UC UT WOS:000246330300023 PM 17483327 ER PT J AU Gu, XS Zerbini, LF Otu, HH Bhasin, M Yang, QL Joseph, MG Grall, F Onatunde, T Correa, RG Libermann, TA AF Gu, Xuesong Zerbini, Luiz F. Otu, Hasan H. Bhasin, Manoj Yang, Quanli Joseph, Marie G. Grall, Franck Onatunde, Tomi Correa, Ricardo G. Libermann, Towia A. TI Reduced PDEF expression increases invasion and expression of mesenchymal genes in prostate cancer cells SO CANCER RESEARCH LA English DT Article ID ETS TRANSCRIPTION FACTOR; GROWTH-FACTOR-BETA; E-CADHERIN; EWING SARCOMA; TRANSITION; EPITHELIUM; CARCINOMA; ANTIGEN; TUMORS; FUSION AB The epithelium-specific Ets transcription factor, PDEF, plays a role in prostate and breast cancer, although its precise function has not been established. In prostate cancer, PDEF is involved in regulating prostate-specific antigen expression via interaction with the androgen receptor and NKX3.1, and down-regulation of PDEF by antiproliferative agents has been associated with reduced PDEF expression. We now report that reduced expression of PDEF leads to a morphologic change, increased migration and invasiveness in prostate cancer cells, reminiscent of transforming growth factor beta (TGF beta) function and epithelial-to-mesenchymal transition. Indeed, inhibition of PDEF expression triggers a transcriptional program of genes involved in the TGF beta pathway, migration, invasion, adhesion, and epithelial dedifferentiation. Our results establish PDEF as a critical regulator of genes involved in cell motility, invasion, and adhesion of prostate cancer cells. C1 Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Med Polymer Ctr, Natl Inst Family Planning, Beijing, Peoples R China. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. RP Libermann, TA (reprint author), Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, 4 Blackfan Circle, Boston, MA 02115 USA. EM tliberma@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; Correa, Ricardo/G-7613-2012; Zerbini, Luiz /B-7720-2015; OI Correa, Ricardo/0000-0001-6940-7034; Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NCI NIH HHS [1R01 CA85467] NR 42 TC 53 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2007 VL 67 IS 9 BP 4219 EP 4226 DI 10.1158/0008-5472.CAN-06-3689 PG 8 WC Oncology SC Oncology GA 165UC UT WOS:000246330300029 PM 17483333 ER PT J AU Rocha-Singh, KJ Jaff, MR Crabtree, TR Bloch, DA Ansel, G AF Rocha-Singh, Krishna J. Jaff, Michael R. Crabtree, Tami R. Bloch, Daniel A. Ansel, Gary CA VIVA Physicians TI Performance goals and endpoint assessments for clinical trials of femoropopliteal bare nitinol stents in patients with symptomatic peripheral arterial disease SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE nitinal stents; stenting; femoropopliteal artery; percutaneous transluminal angioplasty; intermittent claudication; peripheral arterial disease ID SUPERFICIAL FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED CONTROLLED-TRIAL; BALLOON ANGIOPLASTY; ENDOVASCULAR BRACHYTHERAPY; MULTICENTER; OBSTRUCTIONS; CLAUDICATION; RESTENOSIS; GUIDELINES AB Objective: This analysis proposes safety and performance goals for prospective single-arm trials of bare nitinol stents to treat patients with debilitating claudication associated with femoropopliteal (FP) atherosclerotic lesions. Background: To date there have been no analyses of clinical trials data to set efficacy and safety benchmarks for new bare nitinol stents in the treatment of claudication from FP disease. Industry has been reluctant to sponsor studies of nitinol stents due to logistical barriers. Methods: VIVA Physician's, Inc. (VPI) analyzed subject-level data from the PTA control arm of three randomized FDA device trials conducted by industry. Subjects with Rutherford category 2-4 claudication and FP lesion lengths 4-15 cm with 12 month duplex ultrasound (DUS) assessment were identified. These data were combined with the results of a survey of the medical literature (1990-2006) for similar subjects. Results: Analysis of the industry derived control arm PTA data identified 116 patients (mean lesion length 8.7 cm) with a 12 month DUS defined FP patency of 28%. A similar cohort of 191 patients was identified from the medical literature in which the 12-month vessel patency equaled 37%; from these combined patient cohorts, expected vessel patency for PTA was estimated to equal 33%. Conclusion: Based on the PTA performance efficacy rate of 33% derived from industry clinical trial data and the medical literature, and the requirement that the bare nitinol stent 12-month efficacy performance goal be set to equal twice this rate, the patency efficacy goal equals 66%. Additional information is provided on safety and other reporting standards and stent integrity evaluation for bare metal stents. (c) 2007 Wiley-Liss, Inc. C1 Prairie Vasc Inst, Springfield, IL 62794 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Stanford, CA 94305 USA. Riverside Hosp, Columbus, OH USA. RP Rocha-Singh, KJ (reprint author), Prairie Vasc Inst, POB 19420, Springfield, IL 62794 USA. EM ksinah@prairieheart.com NR 21 TC 101 Z9 107 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY 1 PY 2007 VL 69 IS 6 BP 910 EP 919 DI 10.1002/ccd.21104 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 164UJ UT WOS:000246259800025 PM 17377972 ER PT J AU Shan, L He, P Sheen, J AF Shan, Libo He, Ping Sheen, Jen TI Intercepting host MAPK signaling cascades by bacterial type III effectors SO CELL HOST & MICROBE LA English DT Review ID NF-KAPPA-B; PROTEIN-TYROSINE-PHOSPHATASE; ARABIDOPSIS INNATE IMMUNITY; SECRETION SYSTEM EFFECTORS; PROGRAMMED CELL-DEATH; PSEUDOMONAS-SYRINGAE; YERSINIA EFFECTOR; PLANT DEFENSE; ACTIVATION; YOPJ AB The evolutionarily conserved MAP kinase (MAPK) cascades play essential roles in plant and animal innate immunity. A recent explosion of research has uncovered a myriad of virulence strategies used by pathogenic bacteria to intercept MAPK signaling through diverse type III effectors injected into host cells. Here, we review the latest literature and discuss the various mechanisms that pathogenic bacteria use to manipulate host MAPK signaling cascades. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM70567] NR 50 TC 42 Z9 44 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD MAY PY 2007 VL 1 IS 3 BP 167 EP 174 DI 10.1016/j.chom.2007.04.008 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 221BU UT WOS:000250203200004 PM 18005696 ER PT J AU Katzin, LW Levine, M Singhal, AB AF Katzin, L. W. Levine, M. Singhal, A. B. TI Dural puncture headache, postpartum angiopathy, pre-eclampsia and cortical vein thrombosis after an uncomplicated pregnancy SO CEPHALALGIA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Katzin, LW (reprint author), Massachusetts Gen Hosp, Dept Neurol, WAC-835,55 Fruit St, Boston, MA 02114 USA. EM lkatzin@partners.org NR 9 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2007 VL 27 IS 5 BP 461 EP 464 DI 10.1111/j.1468-2982.2007.01285.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 158RP UT WOS:000245811800010 PM 17359517 ER PT J AU Jaffer, FA Kim, DE Quinti, L Tung, CH Aikawa, E Pande, AN Kohler, RH Shi, GP Libby, P Weissleder, R AF Jaffer, Farouc A. Kim, Dong-Eog Quinti, Luisa Tung, Ching-Hsuan Aikawa, Elena Pande, Ashvin N. Kohler, Rainer H. Shi, Guo-Ping Libby, Peter Weissleder, Ralph TI Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor SO CIRCULATION LA English DT Article DE atherosclerosis; cathepsin K; fluorescence; imaging; inflammation ID CYSTEINE PROTEINASES; EXPRESSION; PLAQUE; GENE; PYCNODYSOSTOSIS; SPECIFICITY; MACROPHAGES; PROGRESSION; FIBROSIS; DISEASE AB Background - Cathepsin K (CatK), a potent elastinolytic and collagenolytic cysteine protease, likely participates in the evolution and destabilization of atherosclerotic plaques. To assess better the biology of CatK activity in vivo, we developed a novel near-infrared fluorescence (NIRF) probe for imaging of CatK and evaluated it in mouse and human atherosclerosis. Methods and Results - The NIRF imaging agent consists of the CatK peptide substrate GHPGGPQGKC-NH2 linked to an activatable fluorogenic polymer. In vitro, CatK produced a 2- to 14-fold activation of the agent over other cysteine and matrix metalloproteinases ( P < 0.0001), as well as a > 8-fold activation over a control imaging agent ( P < 0.001). Optical imaging of atheroma revealed > 100% NIRF signal increases in apolipoprotein E-/- mice in vivo (n = 13; P < 0.05, CatK imaging agent versus control agent) and in human carotid endarterectomy specimens ex vivo ( n = 14; P < 0.05). Fluorescence microscopy of plaque sections demonstrated that enzymatically active CatK ( positive NIRF signal) localized primarily in the vicinity of CatK-positive macrophages. Augmented NIRF signal ( reflecting CatK activity) colocalized with disrupted elastin fibers within the media underlying plaques. Conclusions - Use of this novel protease-activatable NIRF agent for optical imaging in vivo demonstrated preferential localization of enzymatically active CatK to macrophages, consistent with their known greater elastinolytic capabilities compared with smooth muscle cells. Augmented CatK proteolysis in atheromata further links CatK to vascular remodeling and plaque vulnerability. C1 Massachusetts Gen Hosp, CMIR, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, CMIR, 149 13th St,Room 5406, Boston, MA 02129 USA. EM fjaffer@partners.org; weissleder@helix.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R24-CA92782]; NHLBI NIH HHS [R01-HL080472, U01 HL080731] NR 37 TC 146 Z9 148 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 2007 VL 115 IS 17 BP 2292 EP 2298 DI 10.1161/CIRCULATIONAHA.106.660340 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 162XK UT WOS:000246122600007 PM 17420353 ER PT J AU Goodman, E Daniels, SR Meigs, JB Dolan, LM AF Goodman, Elizabeth Daniels, Stephen R. Meigs, James B. Dolan, Lawrence M. TI Instability in the diagnosis of metabolic syndrome in adolescents SO CIRCULATION LA English DT Article DE adolescents; insulin; obesity; syndrome X ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CARDIOVASCULAR RISK-FACTORS; TREATMENT PANEL-III; SYNDROME PHENOTYPE; YOUNG ADULTHOOD; UNITED-STATES; SYNDROME-X; HEART; PREVALENCE AB Background - Factor analyses suggest that the structure underlying metabolic syndrome is similar in adolescents and adults. However, adolescence is a period of intense physiological change, and therefore stability of the underlying metabolic structure and clinical categorization based on metabolic risk is uncertain. Methods and Results - We analyzed data from 1098 participants in the Princeton School District Study, a school-based study begun in 2001 - 2002, who were followed up for 3 years. We performed factor analyses of 8 metabolic risks at baseline and follow-up to assess stability of factor patterns and clinical categorization of metabolic syndrome. Metabolic syndrome was defined using the current American Heart Association/ National Heart, Lung, and Blood Institute definition for adults (AHA), a modified AHA definition used in prior pediatric metabolic syndrome studies ( pediatric AHA), and the International Diabetes Federation (IDF) guidelines. We found that factor structures were essentially identical at both time points. However, clinical categorization was not stable. Approximately half of adolescents with baseline metabolic syndrome lost the diagnosis at follow-up regardless of the definitions used: pediatric AHA = 56% (95% confidence interval [CI], 42% to 69%), AHA = 49% ( 95% CI, 32% to 66%), IDF = 53% ( 95% CI, 38% to 68%). In addition to loss of the diagnosis, new cases were identified. Cumulative incidence rates were as follows: pediatric AHA = 3.8% ( 95% CI, 2.8% to 5.2%); AHA = 4.4% ( 95% CI, 3.3% to 5.9%); IDF = 5.2% ( 95% CI, 4.0% to 6.8%). Conclusions - During adolescence, metabolic risk factor clustering is consistent. However, marked instability exists in the categorical diagnosis of metabolic syndrome. This instability, which includes both gain and loss of the diagnosis, suggests that the syndrome has reduced clinical utility in adolescence and that metabolic syndrome - specific pharmacotherapy for youth may be premature. C1 Floating Hosp Children, Tufts New England Med Ctr, Boston, MA USA. Denver Childrens Hosp, Dept Pediat, Denver, CO USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cincinnati Childrens Hosp, Med Ctr, Div Endocrinol, Cincinnati, OH USA. RP Goodman, E (reprint author), Gen Pediat & Adolescent Med, 750 Washington St,NEMC Box 351, Boston, MA 02111 USA. EM egoodman@tufts-nemc.org FU NCRR NIH HHS [M01 RR008084, M01RR 08084]; NICHD NIH HHS [HD41527, R01 HD041527, R01 HD041527-06]; NIDDK NIH HHS [DK59183, R01 DK059183] NR 44 TC 108 Z9 118 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 2007 VL 115 IS 17 BP 2316 EP 2322 DI 10.1161/CIRCULATIONAHA.106.669994 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 162XK UT WOS:000246122600010 PM 17420347 ER PT J AU D'Avila, A Ptaszek, LM Yu, PB Walker, JD Wright, C Noseworthy, PA Myers, A Refaat, M Ruskin, JN AF D'Avila, Andre Ptaszek, Leon M. Yu, Paul B. Walker, Jennifer D. Wright, Cameron Noseworthy, Peter A. Myers, Andrea Refaat, Marwan Ruskin, Jeremy N. TI Left atrial-esophageal fistula after pulmonary vein isolation - A cautionary tale SO CIRCULATION LA English DT Editorial Material ID ABLATION C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP D'Avila, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 2 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 2007 VL 115 IS 17 BP E432 EP E433 DI 10.1161/CIRCULATIONAHA.106.680181 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 162XK UT WOS:000246122600020 PM 17470703 ER PT J AU Ernst, CWO Lee, JE Nakanishi, T Karimbux, NY Rezende, TMB Stashenko, P Seki, M Taubman, MA Kawai, T AF Ernst, C. W. O. Lee, J. E. Nakanishi, T. Karimbux, N. Y. Rezende, T. M. B. Stashenko, P. Seki, M. Taubman, M. A. Kawai, T. TI Diminished forkhead box P3/CD25 double-positive T regulatory cells are associated with the increased nuclear factor-kB ligand (RANKL(+)) T cells in bone resorption lesion of periodontal disease SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE FoxP3; periodontal; oral immunology; RANKL; T cells; T-reg cells ID RECURRENT APHTHOUS ULCERATIONS; PORPHYROMONAS-GINGIVALIS; OSTEOPROTEGERIN LIGAND; PERIPHERAL-BLOOD; TISSUES; LYMPHOCYTES; CYTOKINE; FOXP3; DIFFERENTIATION; POPULATIONS AB Periodontal disease involves multi-bacterial infections accompanied by inflammatory bone resorption lesions. The abundant T and B lymphocyte infiltrates are the major sources of the osteoclast differentiation factor, receptor activator for nuclear factor-kB ligand (RANKL) which, in turn, contributes to the development of bone resorption in periodontal disease. In the present study, we found that the concentrations of RANKL and regulatory T cell (T-reg)-associated cytokine, interleukin (IL)-10, in the periodontal tissue homogenates were correlated negatively, whereas RANKL and proinflammatory cytokine, IL-1 beta, showed positive correlation. Also, according to the fluorescent-immunohistochemistry, the frequency of forkhead box P3 (FoxP3)/CD25 double-positive cells was diminished strikingly in the bone resorption lesion of periodontal disease compared to healthy gingival tissue, while CD25 or FoxP3 single positive cells were still observed in lesions where abundant RANKL(+) lymphocytes were present. Very importantly, few or no expressions of FoxP3 by the RANKL(+) lymphocytes were observed in the diseased periodontal tissues. Finally, IL-10 suppressed both soluble RANKL (sRANKL) and membrane RANKL (mRANKL) expression by peripheral blood mononuclear cells (PBMC) activated in vitro in a bacterial antigen-specific manner. Taken together, these results suggested that FoxP3/CD25 double-positive T-reg cells may play a role in the down-regulation of RANKL expression by activated lymphocytes in periodontal diseased tissues. This leads to the conclusion that the phenomenon of diminished CD25(+)FoxP3(+) T-reg cells appears to be associated with the increased RANKL(+) T cells in the bone resorption lesion of periodontal disease. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Mitsubishi Pharma Corp, Div Res & Dev, Tokyo, Japan. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 The Fenway, Boston, MA 02115 USA. EM tkawai@forsyth.org RI Rezende, Taia/D-3732-2015 FU NIDCR NIH HHS [K22 DE014551, DE-14551, R01 DE003420, R37 DE003420, R01 DE009018, DE-03420, DE-09018] NR 34 TC 34 Z9 39 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 2007 VL 148 IS 2 BP 271 EP 280 DI 10.1111/j.1365-2249.2006.03318.x PG 10 WC Immunology SC Immunology GA 155UL UT WOS:000245603800010 PM 17355249 ER PT J AU Porrozzi, R da Costa, MVS Teva, A Falqueto, A Ferreira, AL dos Santos, CD Fernandes, AP Gazzinelli, RT Campos-Neto, A Grimaldi, G AF Porrozzi, Renato Santos da Costa, Marcos V. Teva, Antonio Falqueto, Aloisio Ferreira, Adelson L. dos Santos, Claudiney D. Fernandes, Ana Paula Gazzinelli, Ricardo T. Campos-Neto, Antonio Grimaldi, Gabriel, Jr. TI Comparative evaluation of enzyme-linked immunosorbent assays based on crude and recombinant leishmanial antigens for serodiagnosis of symptomatic and asymptomatic Leishmania infantum visceral infections in dogs SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID DIRECT AGGLUTINATION-TEST; CANINE LEISHMANIASIS; IMMUNOCHROMATOGRAPHIC-DIPSTICK; CHIMERIC ANTIGEN; IMMUNE-RESPONSE; BRAZILIAN DOGS; ENDEMIC AREAS; DIAGNOSIS; ANTIBODY; EPIDEMIOLOGY AB The diagnosis of visceral leishmaniasis remains difficult in rural areas where the disease is endemic, and serologic methods still need assessment, as they are not very sensitive for the detection of asymptomatic infectious dogs. Here we present data on the development of enzyme-linked immunosorbent assay (ELISA)based methods for the detection of antibodies against recombinant leishmanial antigens (namely, the recombinant K26 [rK26] and rK39 antigens from Leishmania infantum and the rA2 protein from Leishmania donovani) in comparison to ELISAs employing crude soluble antigen (CSA). The assays utilized sera from known negative controls (n = 25) and clinically asymptomatic (n = 50) and symptomatic (n = 50) dogs with confirmed L. infantum infections. Additional studies were also done using sera from animals harboring other infections (n = 14) for the evaluation of cross-reactivity. Our study indicated that rK26 and rK39 used in ELISAs provided very high sensitivities for the detection of symptomatic dogs (94% and 100%, respectively), followed by CSA (88%) and rA2 (70%). Conversely, rA2 was more sensitive for asymptomatic dogs (88%) than rK39 and rK26 (both 66%) and CSA (30%). Some cross-reactivity in sera from dogs with other infections (Leishmania braziliensis and Leptospira interrogans) was identified, but the rA2 protein provided the greatest specificity (98%). Data further indicate that all three recombinant proteins must be used in parallel to detect essentially all infected dogs. Efforts should be made to develop a cheap and reliable serologic test based on epitope selection from these diagnostic markers for the sensitive detection of L. infantum-infected dogs. C1 Fiocruz MS, Dept Immunol, Inst Oswaldo Cruz, BR-21045090 Rio De Janeiro, Brazil. Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. Univ Fed Espirito Santo, Vitoria, ES, Brazil. Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. Forsyth Inst, Boston, MA USA. RP Grimaldi, G (reprint author), Fiocruz MS, Dept Immunol, Inst Oswaldo Cruz, Pav Leonidas Deane,5th Floor,Room 509, BR-21045090 Rio De Janeiro, Brazil. EM Grimaldi@ioc.fiocruz.br NR 34 TC 55 Z9 57 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2007 VL 14 IS 5 BP 544 EP 548 DI 10.1128/CVI.00420-06 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 170RN UT WOS:000246681800008 PM 17314229 ER PT J AU Banyard, J Bao, L Hofer, MD Zurakowski, D Spivey, KA Feldman, AS Hutchinson, LM Kuefer, R Rubin, MA Zetter, BR AF Banyard, Jacqueline Bao, Lere Hofer, Matthias D. Zurakowski, David Spivey, Kristin A. Feldman, Adam S. Hutchinson, Lloyd M. Kuefer, Rainer Rubin, Mark A. Zetter, Bruce R. TI Collagen XXIII expression is associated with prostate cancer recurrence and distant metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID RADICAL PROSTATECTOMY; ANTIGEN ERA; PROGRESSION; PROTEIN; CELLS; TRANSFORMATION; CARCINOMA; BIOMARKER; COMPONENT; RACEMASE AB Purpose: We had previously identified a new transmembrane collagen, type XXIII, in metastatic rat prostate carcinoma cells. The purpose of this study was to determine the expression of collagen XXIII in human prostate cancer and investigate its relationship with disease progression. Experimental Design: We investigated collagen XXIII expression in prostate cancer tissue and did a retrospective analysis of association with prostate-specific antigen (PSA)- defined disease recurrence. The presence of collagen XXIII in prostate cancer patient urine was also assessed before and after prostatectomy. Results: Collagen XXIII protein was detected at very low levels in benign prostate tissue and was significantly increased in prostate cancer. Distant metastases exhibited significantly higher collagen XXIII levels compared with either localized prostate cancer or regional (lymph node) metastases. Patients with high collagen XXIII levels had a 2.8-fold higher risk of PSA failure with median time to failure of 8.1 months, compared with low collagen XXIII patients with a median time to failure of 5 years. Multivariate Cox regression showed that the presence of collagen XXIII was significantly associated with time to PSA recurrence, independent of other clinical variables. Collagen XXIII was also detected in prostate cancer patient urine, with reduced levels after prostatectomy, indicating potential as a noninvasive fluid biomarker. Conclusions: We present the first report demonstrating increased collagen XXIII expression in prostate cancer tissue. We show that collagen XXIII level is a significant independent predictor of PSA-defined disease recurrence, suggesting a potential role as a molecular biomarker of prostate cancer progression and metastasis. C1 Harvard Univ, Vasc Biol Program, Dept Surg, Childrens Hosp,Sch Med,Karp Family Res Labs, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthoped Surg & Biostat, Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Univ Hosp, Dept Urol, Ulm, Germany. RP Zetter, BR (reprint author), Harvard Univ, Vasc Biol Program, Dept Surg, Childrens Hosp,Sch Med,Karp Family Res Labs, 11-125,300 Longwood Ave, Boston, MA 02115 USA. EM bruce.zetter@childrens.harvard.edu OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [CA09381-03, CA104973] NR 34 TC 14 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2007 VL 13 IS 9 BP 2634 EP 2642 DI 10.1178/1078-0432.CCR-06-2163 PG 9 WC Oncology SC Oncology GA 162ZW UT WOS:000246129100016 PM 17473194 ER PT J AU Norden-Zfoni, A Desai, J Manola, J Beaudry, P Force, J Maki, R Folkman, J Bello, C Baum, C DePrimo, SE Shalinsky, DR Demetri, GD Heymach, JV AF Norden-Zfoni, Anat Desai, Jayesh Manola, Judith Beaudry, Paul Force, Jeremy Maki, Robert Folkman, Judah Bello, Carlo Baum, Charles DePrimo, Sam E. Shalinsky, David R. Demetri, Goerge D. Heymach, John V. TI Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; MONOCYTE-DERIVED MACROPHAGES; HEMATOPOIETIC STEM-CELLS; BONE-MARROW; PROGENITOR CELLS; FACTOR RECEPTOR; SURROGATE MARKER; CANCER-PATIENTS; FACTOR VEGF AB Purpose: There is an unmet need for noninvasive markers to measure the biological effects of targeted agents, particularly those inhibiting the vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway, and identify patients most likely to benefit from treatment. In this study, we investigated potential blood-based biomarkers for SU11248 (sunitinib malate), a multitargeted tyrosine kinase inhibitor, in patients with metastatic imatinib-refractory gastrointestinal stromal tumors. Experimental Design: Patients (n = 73) enrolled in a phase I/II trial received SU11248 daily for 14 or 28 days followed by 14 days without treatment per cycle. Clinical benefit was defined as progression-free survival of > 6 months. We assessed plasma markers, including VEGF and soluble VEGFR-2 (sVEGFR-2), and two cellular populations bearing VEGF receptors: monocytes and, in a subset of patients, mature circulating endothelial cells (CEC). Results: Compared to patients with progressive disease, patients with clinical benefit had significantly greater increases in CECs (0.52 versus -0.01 CEC/mu L/d, P = 0.03) and smaller decreases in monocyte levels (47% versus 60%, P = 0.007) during cycle 1.VEGF increased by 2.2-fold and sVEGFR-2 decreased 25% during the first 2 weeks of treatment. Neither plasma marker correlated with clinical outcome although a modest inverse correlation was observed between sVEGFR-2 changes and plasma drug levels. Monocytes,VEGF, and sVEGFR-2 all rebounded towards baseline off treatment. Conclusions: Monocytes, VEGF, and sVEGFR-2 were consistently modulated by treatment, suggesting that they may serve as pharmacodynamic markers for SU11248. Changes in CECs and monocytes, but not the plasma markers, differed between the patients with clinical benefit and those with progressive disease. These end points merit further investigation in future trials to determine their utility as markers of SU11248 activity and clinical benefit in gastrointestinal stromal tumors and other tumor types. C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Pfizer Global Res & Dev, La Jolla, CA USA. RP Heymach, JV (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Oncol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jheymach@mdanderson.org FU NCI NIH HHS [P20 CA090578, P50 CA101942] NR 54 TC 163 Z9 169 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2007 VL 13 IS 9 BP 2643 EP 2650 DI 10.1158/1078-0432.CCR-06-0919 PG 8 WC Oncology SC Oncology GA 162ZW UT WOS:000246129100017 PM 17473195 ER PT J AU Ioannou, GN Weiss, NS Kowdley, KV AF Ioannou, George N. Weiss, Noel S. Kowdley, Kris V. TI Relationship between transferrin-iron saturation, alcohol consumption, and the incidence of cirrhosis and liver cancer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID C VIRUS-INFECTION; HEPATITIS-C; HEREDITARY HEMOCHROMATOSIS; HEPATOCELLULAR-CARCINOMA; LIPID-PEROXIDATION; UNITED-STATES; BINDING CAPACITY; OVERLOAD; PREVALENCE; INJURY AB Background & Aims: Excessive alcohol consumption and iron overload might act in synergy to promote hepatic fibrogenesis and carcinogenesis. We examined the relation between baseline serum transferrin-iron saturation (TS) and the incidence of hospitalizations or deaths related to cirrhosis and liver cancer as well as the influence of alcohol consumption on this relationship. Methods: Participants included 8767 persons aged 25-74 years without evidence of cirrhosis at entry into the study or during the first 5 years of follow-up who were subsequently followed for a mean of 13.3 years as part of the first National Health and Nutrition Examination Survey. Results: During 116,656 person-years of follow-up, 115 participants were hospitalized for or died of cirrhosis and 4 more of liver cancer. Compared with persons with low TS (< 40%) and low alcohol consumption (<= 1 drink/day) who had an incidence of cirrhosis/liver cancer of 70/100,000 person-years, the incidence was increased in persons with elevated TS (>= 40%) and low alcohol consumption (154/100,000; adjusted hazard ratio, 2.2; 95% confidence interval, 1.3-3.8) and in persons with low TS and elevated (> 1 drink/day) alcohol consumption (198/100,000; adjusted hazard ratio, 2.9; 95% confidence interval, 1.7-5.0). The incidence of cirrhosis/liver cancer was particularly high among persons with both elevated TS and elevated alcohol consumption (480/100,000; adjusted hazard ratio, 6.8; 95% confidence interval, 3.6-12.9), exceeding the rate predicted by the addition of the separate attributable risks associated with drinking and elevated serum TS. Conclusions: Elevated serum TS is associated with an increased incidence of cirrhosis or liver cancer particularly in the presence of elevated alcohol consumption. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA 98108 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, S-111-GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU NIDDK NIH HHS [DK 02957, DK063996] NR 31 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2007 VL 5 IS 5 BP 624 EP 629 DI 10.1016/j.cgh.2007.01.008 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 165SV UT WOS:000246326800020 PM 17478349 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI Through the looking glass: Anemia guidelines, vested interests, and distortions SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; CLINICAL-PRACTICE GUIDELINES; STAGE RENAL-DISEASE; INDUSTRY; OUTCOMES; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 26 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2007 VL 2 IS 3 BP 415 EP 417 DI 10.2215/CJN.01340307 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 161XB UT WOS:000246049100004 PM 17699445 ER PT J AU Ficociello, LH Perkins, BA Silva, KH Finkelstein, DM Ignatowska-Switalska, H Gaciong, Z Cupples, LA Aschengrau, A Warram, JH Krolewski, AS AF Ficociello, Linda H. Perkins, Bruce A. Silva, Kristen H. Finkelstein, Dianne M. Ignatowska-Switalska, Halina Gaciong, Zbigniew Cupples, L. Adrienne Aschengrau, Ann Warram, James H. Krolewski, Andrzej S. TI Determinants of progression from microalbuminuria to proteinuria in patients who have type 1 diabetes and are treated with angiotensin-converting enzyme inhibitors SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ALBUMIN EXCRETION; IDDM PATIENTS; NEPHROPATHY; CAPTOPRIL; MELLITUS; RISK; SPIRONOLACTONE; HYPERGLYCEMIA; METAANALYSIS; REGRESSION AB The aims of this study were to assess the frequency and determinants of (1) treatment with angiotensin-converting enzyme inhibitors (ACE-I) and (2) progression to proteinuria in the presence of ACE-I treatment in patients with type I diabetes and microalbuminuria. A clinic-based cohort study of patients with type 1 diabetes was begun in 1991. The patients who were included in this study (n=373) are the cohort members who received a diagnosis of microalbuminuria during a 2-yr baseline observation and were followed for 10 yr with frequent assessments of urinary albumin excretion and biennial examinations. Progression to proteinuria occurred when the median urinary albumin excretion during a 2-yr interval exceeded 299 mu g/min. During the decade-long study, the proportion of patients who had a history of microalbuminuria and were treated with ACE-I rose from 17 to 67%. Patients who started this treatment had (on average) higher BP, higher urinary albumin excretion, and longer diabetes duration than those who did not. Microalbuminuria often progressed to proteinuria (6.3/100 person-years) in those who were treated. Poor glycemic control and elevated serum cholesterol were the major determinants/predictors of this progression. Although treatment with ACE-I increased during the past decade, it was not completely effective, because microalbuminuria progressed to proteinuria in many treated patients. Poor glycemic control and elevated serum cholesterol were the major determinants/predictors for progression while on ACE-I treatment. The mechanisms that are responsible for the frequent failure of ACE-I to prevent progression of microalbuminuria to proteinuria in a clinical setting art! not clear. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Univ Toronto, Div Endocrinol & Metab, Toronto, ON, Canada. Warsaw Med Univ, Div Hypertens & Internal Med, Warsaw, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 368, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu OI Aschengrau, Ann/0000-0001-8153-7712; Cupples, L. Adrienne/0000-0003-0273-7965 FU NIDDK NIH HHS [R01-DK41526] NR 34 TC 33 Z9 33 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2007 VL 2 IS 3 BP 461 EP 469 DI 10.2215/CJN.03691106 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 161XB UT WOS:000246049100011 PM 17699452 ER PT J AU Kestenbaum, B Rudser, KD Shlipak, MG Fried, LF Newman, AB Katz, R Sarnak, MJ Seliger, S Stehman-Breen, C Prineas, R Siscovick, DS AF Kestenbaum, Bryan Rudser, Kyle D. Shlipak, Michael G. Fried, Linda F. Newman, Anne B. Katz, Ronit Sarnak, Mark J. Seliger, Stephen Stehman-Breen, Catherine Prineas, Ronald Siscovick, David S. TI Kidney function, electrocardiographic findings, and cardiovascular events among older adults SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CONGESTIVE-HEART-FAILURE; QT INTERVAL PROLONGATION; CORONARY-ARTERY-DISEASE; STAGE RENAL-DISEASE; QRS DURATION; CORRECTED QT; CYSTATIN-C; FOLLOW-UP; HEMODIALYSIS AB Chronic kidney disease (CKD) is associated with cardiovascular (CV) disease and mortality. It is not known whether cardiac rhythm disturbances are more prevalent among individuals with CKD or whether resting electrocardiogram findings predict future CV events in the CKD setting. Data were obtained from the Cardiovascular Health Study, a community-based study of adults aged >= 65 yr. After exclusions for prevalent heart disease, atrial fibrillation, implantable pacemaker, or antiarrhythmic medication use, 3238 participants were analyzed. CKD was defined by an estimated GFR <60 ml/min per 1.73 m(2). Outcomes were adjudicated incident heart failure (HF), incident coronary heart disease (CHD), and mortality. Participants with CKD had longer PR and corrected QT intervals compared with those without CKD; however, differences in electrocardiographic markers were explained by traditional CV risk factors and CV medication use. After adjustment for known risk factors, each 10-ms increase in the QRS interval was associated with a 15% greater risk for incident HF (95% confidence interval [CI] 1.04 to 1.27), a 13% greater risk for CHD (95% CI 1.04 to 1.24), and a 17% greater risk for mortality (95% CI 1.09, 1.25) among CKD participants. Each 5% increase in QTI was associated with a 42% (95% CI 1.23 to 1.65), 22% (95% CI 1.07 to 1.40), and 10% (95% CI 0.98 to 1.22) greater risk for HF, CHD, and mortality, respectively. Associations seemed stronger for participants with CKD; however, no significant interactions were detected. Resting electrocardiographic abnormalities are common in CKD and independently predict future clinical CV events in this setting. C1 Univ Washington, Harborview Med Ctr, Div Nephrol, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA. Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. Univ Calif San Francisco, Gen Internal Med Sect, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Tufts New Englans Med Ctr, Dept Med, Boston, MA USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Epidemiol Sect, Winston Salem, NC 27103 USA. RP Kestenbaum, B (reprint author), Univ Washington, Harborview Med Ctr, Div Nephrol, Room 10EH11,Box 359764, Seattle, WA 98104 USA. EM brk@u.washington.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85083, N01 HC-15103, N01 HC-55222, N01-HC-35129, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85084, N01-HC-85085, N01-HC-85086, U01 HL080295]; NIDDK NIH HHS [K23 DK63274-01] NR 32 TC 13 Z9 14 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2007 VL 2 IS 3 BP 501 EP 508 DI 10.2215/CJN.04231206 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 161XB UT WOS:000246049100016 PM 17699457 ER PT J AU Zivkovic, SA Medsger, TA AF Zivkovic, Sasa A. Medsger, Thomas A., Jr. TI Myasthenia gravis and scleroderma: Two cases and a review of the literature SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Review DE myasthenia gravis; scleroderma; systemic sclerosis; localized scleroderma; D-penicillamine ID PROGRESSIVE SYSTEMIC-SCLEROSIS; MORPHEA LOCALIZED SCLERODERMA; D-PENICILLAMINE; CLASSIFICATION; PATHOGENESIS; DISORDERS; DISEASES; COUNTY; LUPUS AB Myasthenia gravis is uncommon in patients with scleroderma, and when diagnosed is usually associated with previous use of D-penicillamine. Clinically, both myasthenia and scleroderma may present with fatigue, weakness and bulbar symptoms, so one of diagnoses may be delayed. We report two new cases and review clinical features of 12 other reported cases of co-existing scleroderma and myasthenia gravis, unrelated to previous D-penicillamine therapy. Co-occurrence of myasthenia and scleroderma was reported almost exclusively (13/14) in women with a mean latency of 7.03 years. Most patients (10/11) had seropositive generalized myasthenia, and there were no cases with exclusively ocular symptoms. Three patients with pre-existing myasthenia were safely treated with D-penicillamine. Myasthenia and scleroderma occur in the context of an underlying autoimmune diathesis, but their co-occurrence could be underreported as the recognition of either disorder may be delayed by overlapping clinical symptoms. Our findings also suggest that D-penicillamine may be cautiously used in selected patients with pre-existing scleroderma and myasthenia, when potential benefits outweigh the risk of possible myasthenia exacerbation. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Pittsburgh, Dept Neurol, Sch Med, PUH F875, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15213 USA. RP Zivkovic, SA (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, PUH F875, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM zivkovics@upmc.edu NR 30 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD MAY PY 2007 VL 109 IS 4 BP 388 EP 391 DI 10.1016/j.clineuro.2007.01.006 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 159RN UT WOS:000245884100017 PM 17280777 ER PT J AU Decristofaro, S AF Decristofaro, Susan TI The inspiring and regenerative power of the arts SO CLINICAL NURSE SPECIALIST LA English DT Article C1 Dana Farber Canc Inst, Blum Patient Family Resource Ctr, Boston, MA 02115 USA. RP Decristofaro, S (reprint author), Dana Farber Canc Inst, Blum Patient Family Resource Ctr, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAY-JUN PY 2007 VL 21 IS 3 BP 170 EP 171 DI 10.1097/01.NUR.0000270012.51716.2c PG 2 WC Nursing SC Nursing GA 170BD UT WOS:000246635200008 PM 17495554 ER PT J AU Bozic, KJ Smith, AR Hariri, S Adeoye, S Gourville, J Maloney, WJ Parsley, B Rubash, HE AF Bozic, Kevin J. Smith, Amanda R. Hariri, Sanaz Adeoye, Sanjo Gourville, John Maloney, William J. Parsley, Brian Rubash, Harry E. TI The 2007 ABJS Marshall Urist Award - The impact of direct-to-consumer advertising in orthopaedics SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; PRESCRIPTION DRUGS; HOSPITAL COST; PROMOTION; PHYSICIAN; REQUESTS AB Direct-to-consumer advertising (DTCA) has become an influential factor in healthcare delivery in the United States. We evaluated the influence of DTCA on surgeon and patient opinions and behavior in orthopaedics by surveying orthopaedic surgeons who perform hip and knee arthroplasties and patients who were scheduled to have hip or knee arthroplasty. Respondents were asked for their opinions of and experiences with DTCA, including the influence of DTCA on surgeon and patient decision making. Greater than 98% of surgeon respondents had experience with patients who were exposed to DTCA. The majority of surgeon respondents reported DTCA had an overall negative impact on their practice and their interaction with patients (74%), and their patients often were confused or misinformed about the appropriate treatment for their condition based on an advertisement (77%). Fifty-two percent of patient respondents recalled seeing or hearing advertisements related to hip or knee arthroplasty. These patients were more likely to request a specific type of surgery or brand of implant from their surgeon and to see more than one surgeon before deciding to have surgery. Direct-to-consumer advertising seems to play a substantial role in surgeon and patient decision making in orthopaedics. Future efforts should be aimed at improving the quality and accuracy of information contained in consumer-directed advertisements related to orthopaedic implants and procedures. C1 Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Orthopaed Surg, New York, NY USA. Harvard Univ, Sch Business, Boston, MA 02115 USA. Stanford Univ, Dept Orthopaed Surg, Palo Alto, CA 94304 USA. Baylor Coll Med, Dept Orthopaed Surg, Houston, TX 77030 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM bozick@orthosurg.ucsf.edu NR 27 TC 32 Z9 32 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2007 IS 458 BP 202 EP 219 DI 10.1097/BLO.0b013e31804fdd02 PG 18 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 164UE UT WOS:000246259200038 PM 17353799 ER PT J AU Schelleman, H Chen, Z Kealey, C Whitehead, AS Christie, J Price, M Brensinger, CM Newcomb, CW Thorn, CF Samaha, FF Kimmel, SE AF Schelleman, H. Chen, Z. Kealey, C. Whitehead, A. S. Christie, J. Price, M. Brensinger, C. M. Newcomb, C. W. Thorn, C. F. Samaha, F. F. Kimmel, S. E. TI Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID VKORC1 GENE; INTERETHNIC VARIABILITY; ORAL ANTICOAGULANTS; REQUIREMENT; POPULATION; HAPLOTYPES; POLYMORPHISMS AB The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 ( VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans ( -12.10 mg/week +/- 4.93; P = 0.02) and Caucasians ( -14.41 mg/week +/- 3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio 43 ( odds ratio 3.10; 95% confidence interval: 1.73-5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans. C1 Univ Penn, Dept Biostat & Epidemiol, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Pharmacol, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Pharmacogenet, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Vet Affairs Med Ctr, Sch Med, Philadelphia, PA 19104 USA. RP Kimmel, SE (reprint author), Univ Penn, Dept Biostat & Epidemiol, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. EM skimmel@cceb.med.upenn.edu FU NCRR NIH HHS [P20RR020741]; NHLBI NIH HHS [R01HL066176] NR 21 TC 83 Z9 85 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2007 VL 81 IS 5 BP 742 EP 747 DI 10.1038/sj.clpt.6100144 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 160DT UT WOS:000245921500023 PM 17329985 ER PT J AU Cather, C AF Cather, Corinne TI Attention training: A novel treatment approach to auditory hallucinations SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID SYMPTOMS; THERAPY; TRIAL C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Cather, C (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, 25 Staniford St, Boston, MA 02114 USA. EM ccather@partners.org NR 11 TC 1 Z9 1 U1 2 U2 2 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2007 VL 14 IS 2 BP 139 EP 141 DI 10.1016/j.cbpra.2006.09.003 PG 3 WC Psychology, Clinical SC Psychology GA 168UF UT WOS:000246548800003 ER PT J AU Yueh, B Collins, MP Souza, PE Heagerty, PJ Liu, CF Boyko, EJ Loovis, CF Fausti, SA Hedrick, SC AF Yueh, Bevan Collins, Margaret P. Souza, Pamela E. Heagerty, Patrick J. Liu, Chuan-Fen Boyko, Edward J. Loovis, Carl F. Fausti, Stephen A. Hedrick, Susan C. TI Screening for Auditory Impairment - Which Hearing Assessment Test (SAI-WHAT): RCT design and baseline characteristics SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE hearing loss; screening; rehabilitation of hearing impaired; hearing aids; patient compliance; treatment effectiveness; randomized controlled trials; depression; quality of life; patient outcome assessment ID QUALITY-OF-LIFE; RANDOMIZED TRIAL; ELDERLY PEOPLE; HEALTH-STATUS; OLDER-ADULTS; PRIMARY-CARE; VALIDATION; AMPLIFICATION; HANDICAP; AIDS AB Background: Effective screening programs should not merely detect presence of disease, but also lead to long-term benefit. We describe the rationale and design of the first randomized clinical trial to study the long-term effects of routine screening for hearing loss. We also describe the baseline characteristics of the randomized cohort. Methods: We randomized 2305 veterans age 50 years or older to a control arm without screening, or to screening with: physiologic testing (AudioScope), a self-administered questionnaire (Hearing Handicap Inventory for the Elderly-Screening version [HHIE-S]), or both tests. The primary outcome measure will be hearing aid use one year after screening. We will also study a number of secondary outcomes, including appointments made with and visits to an audiologist, cases of aidable hearing loss, hearing aids dispensed, self-rated communication ability, and hearing-related quality of life. Results: Baseline demographic and health status measures were evenly distributed across the screening arms. The percentage of patients who screened positive for hearing loss was 18.6%, 59.2%, and 63.6% for the AudioScope, HHIE-S, and combined screening arms, respectively. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Portland VA Med Ctr, Natl Ctr Rehabiliatat & Auditory Res, Portland, OR USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Yueh, B (reprint author), VA Puget Sound Hlth Care Syst, Surg Serv 1120TO, 1660 S Columbian Way, Seattle, WA 98108 USA. EM byueh@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 NR 53 TC 6 Z9 8 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2007 VL 28 IS 3 BP 303 EP 315 DI 10.1016/j.cct.2006.08.008 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 152DA UT WOS:000245339800010 PM 17030153 ER PT J AU Cicchetti, F Gross, RE Bulte, JWM Owen, M Chen, I Saint-Pierre, M Wang, XK Yu, MX Brownell, AL AF Cicchetti, Francesca Gross, Robert E. Bulte, Jeff W. M. Owen, Mary Chen, Iris Saint-Pierre, Martine Wang, Xukui Yu, Meixiang Brownell, Anna-Liisa TI Dual-modality in vivo monitoring of subventricular zone stem cell migration and metabolism SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE positron emission tomography (PET); magnetic resonance imaging (MRI); superparamagnetic iron oxide particles; transplantation; inflammation; dopamine ID POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE-EXPRESSION; MAGNETICALLY LABELED CELLS; PROGENITOR CELLS; LIVING ANIMALS; IRON-OXIDE; RAT-BRAIN; TRANSPLANTATION; TRACKING; RECEPTOR AB Rat subventricular zone (SVZ) stem cells were labeled with superparamagnetic iron oxide particles (SPIO) to follow their fate and migratory potential with magnetic resonance imaging (MRI) and positron emission tomography (PET). Labeled cells were transplanted into either the right rostral migratory stream (RMS) or striatum of normal adult Sprague-Dawley rats and serially followed for 3 months. Minimal migration of the cells implanted into the striatum was observed after 3 weeks whereas SVZ cells implanted into the RMS migrated toward the olfactory bulb at I week post-transplantation. PET studies of glucose metabolism using F-18-FDG demonstrated enhanced glucose utilization in the striatum of transplanted animals. PET studies conducted 3 months after transplantation showed elevated accumulation of C-11-raclopride (dopamine receptor type 2) and C-11-CFT (dopamine transporter) binding in the striatal grafts. Implanted SVZ cells did not induce significant inflammation as identified by PET using C-11-PK11195, a ligand detecting activated microglia. Histological analysis identified viable SPIO-labeled cells (some of which were nestin-positive) 7 weeks post-transplantation, suggesting a prolonged presence of undifferentiated neural stem cells within transplants. In addition, double immunostaining for neuronal and asttocytic markers (NeuN and GFAP) indicated that differentiation into neuronal and astrocytic phenotypes also occurred. Thus, combining MRI and PET enables monitoring of cell migration and metabolism non-invasively in vivo for extended periods of time. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 CHU Laval, Ctr Rech & Neurosci, Quebec City, PQ G1V 4G2, Canada. Univ Laval, Dept Med, Quebec City, PQ G1K 7P4, Canada. Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. Simmons Coll, Dept Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Cicchetti, F (reprint author), CHU Laval, Ctr Rech & Neurosci, RC-9800,2705 Blvd Laurier, Quebec City, PQ G1V 4G2, Canada. EM Francesca.cicchetti@crchul.ulaval.ca; abrownell@partners.org RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 FU NINDS NIH HHS [R01 NS045062, NS046322-01A1] NR 40 TC 17 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD MAY-JUN PY 2007 VL 2 IS 3 BP 130 EP 138 DI 10.1002/cmmi.138 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 194BQ UT WOS:000248319300003 PM 17583908 ER PT J AU Bajwa, EK Yu, CL Gong, MN Thompson, BT Christiani, DC AF Bajwa, Ednan K. Yu, Chu-Ling Gong, Michelle N. Thompson, B. Taylor Christiani, David C. TI Pre-B-cell colony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; genetic predisposition to disease; genetic polymorphism ID HUMAN FETAL MEMBRANES; ACUTE LUNG INJURY; ASSOCIATION; EXPRESSION; ARDS; CLONING AB Objective: Pre-B-cell colony-enhancing factor (PBEF) levels are elevated in bronchoalveolar lavage fluid and serum of patients with acute lung injury. There are several suspected functional polymorphisms of the corresponding PBEF gene. We hypothesized that variations in PBEF gene polymorphisms alter the risk of developing acute respiratory distress syndrome (ARDS). Design: Nested case-control study. Setting: Tertiary academic medical center. Patients: We studied 375 patents with ARDS and 787 at-risk controls genotyped for the PBEF T-1001G and C-1543T polymorphisms. Interventions: None. Measurements and Main Results: Patients with the -1001G (variant) allele had significantly greater odds of developing ARDS than wild-type homozygotes (odds ratio, 1.35; 95% confidence interval, 1.02-1.78). Patients with the -1543T (variant) allele did not have significantly different odds of developing ARDS than wild-type homozygotes (odds ratio, 0.86; 95% confidence interval, 0.65-1.13). When analysis was stratified by ARDS risk factor, -1543T was associated with decreased odds of developing ARDS in septic shock patients (odds ratio, 0.66; 95% confidence interval, 0.45-0.97). Also, -1001G was associated with increased hazard of intensive care unit mortality, whereas -1543T was associated with decreased hazard of 28-day and 60-day ARDS mortality, as well as shorter duration of mechanical ventilation. Similar results were found in analyses of the related GC (-1001G:-1543C) and TT (-1001T:-1543T) haplotypes. Conclusions: The PBEF T-1001G variant allele and related haplotype are associated with increased odds of developing ARDS and increased hazard of intensive care unit mortality among at-risk patients, whereas the C-1543T variant allele and related haplotype are associated with decreased odds of ARDS among patients with septic shock and better outcomes among patients with ARDS. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Environm Hlth, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Med, Div Pulm & Crit Care Med, New York, NY USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu FU NHLBI NIH HHS [HL07874, HL60710, HL67197] NR 27 TC 56 Z9 63 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2007 VL 35 IS 5 BP 1290 EP 1295 DI 10.1097/01.CCM.0000260243.22758.4F PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 159LR UT WOS:000245867800011 PM 17414088 ER PT J AU Di Stefano, L Ji, JY Moon, NS Herr, A Dyson, N AF Di Stefano, Luisa Ji, Jun-Yuan Moon, Nam-Sung Herr, Anabel Dyson, Nicholas TI Mutation of Drosophila Lsd1 disrupts H3-K4 methylation, resulting in tissue-specific defects during development SO CURRENT BIOLOGY LA English DT Article ID POSITION-EFFECT VARIEGATION; CRYSTAL-STRUCTURE; GENE-EXPRESSION; SWIRM DOMAIN; HISTONE; LSD1; MELANOGASTER; COMPLEX; DEMETHYLATION; PROTEINS AB Histone-tall modifications play a fundamental role in the processes that establish chromatin structure and determine gene expression [1-4]. One such modification, histone methylation, was considered irreversible until the recent discovery of histone demethylases. Lsd1 was the first histone demethylase to be identified [5]. Lsd1 is highly conserved in many species, from yeast to humans, but its function has primarily been studied through biochemical approaches. The mammalian ortholog has been shown to demethylate monomethyl- and dimethyl-K4 and -K9 residues of histone H3 [5, 6]. Here we describe the effects of Lsd1 mutation in Drosophila. The inactivation of dLsd1 strongly affects the global level of monomethyl-and dimethyl-H3-K4 methylation and results in elevated expression of a subset of genes. dLsd1 is not an essential gene, but animal viability is strongly reduced in mutant animals in a gender-specific manner. Interestingly, dLsd1 mutants are sterile and possess defects in ovary development, indicating that dLsd1 has tissue-specific functions. Mutant alleles of dLsd1 suppress positional-effect variegation, suggesting a disruption of the balance between euchromatin and heterochromatin. Taken together, these results show that dLsd1-mediated H3-K4 demethylation has a significant and specific role in Drosophila development. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA064402, CA64402, P01 CA095281, P01 CA095281-01A10001, R01 CA064402-12, R01 CA064402-13]; NIGMS NIH HHS [R01 GM053203, R01 GM053203-11, R01 GM053203-12] NR 27 TC 58 Z9 62 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 1 PY 2007 VL 17 IS 9 BP 808 EP 812 DI 10.1016/j.cub.2007.03.068 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 164QS UT WOS:000246249500028 PM 17462898 ER PT J AU Levine, RA Slaugenhaupt, SA AF Levine, Robert A. Slaugenhaupt, Susan A. TI Molecular genetics of mitral valve prolapse SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE filamin A; genetics; growth factor; mitral regurgitation; mitral valve prolapse ID MARFAN-SYNDROME; HYPERTROPHIC CARDIOMYOPATHY; PSEUDOXANTHOMA ELASTICUM; TRANSCRIPTION FACTOR; VALVULAR DYSTROPHY; CONNECTIVE-TISSUE; CARDIAC VALVES; COLLAGEN GENES; HEART-VALVES; MOUSE MODEL AB Purpose of review Mitral valve prolapse is a common disorder with a strong hereditary component. It is associated with important mitral regurgitation requiring surgical repair and other clinical complications. Genetic studies can provide clues to mechanism and therapy. Recent findings Advances in phenotypic classification have led to linkage to sites on chromosomes 11, 13 and 16 and identification of the first mutation in familial mitral valve prolapse not related to connective tissue syndromes - an X-linked filamin A mutation. New understanding of mechanism based on studies in a mouse Marfan model emphasize the dynamic interplay of differentiating cells and growth factors, with strong potential for therapy. Summary This new knowledge brings us closer to the ultimate goal of preventing the progression of mitral valve disease to the stage of clinical expression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. RP Levine, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5068, Boston, MA 02114 USA. EM rlevine@partners.org NR 56 TC 17 Z9 18 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAY PY 2007 VL 22 IS 3 BP 171 EP 175 DI 10.1097/HCO.0b013e3280f3bfcd PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 163NM UT WOS:000246166600002 PM 17413272 ER PT J AU de Aguilar-Nascimento, JE Kudsk, KA AF de Aguilar-Nascimento, Jose Eduardo Kudsk, Kenneth A. TI Use of small-bore feeding tubes: successes and failures SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE enteral nutrition; feeding tube placement; pneumothorax ID CRITICALLY-ILL PATIENTS; INADVERTENT INTRACRANIAL PLACEMENT; INTENSIVE-CARE-UNIT; NASOGASTRIC TUBE; ENTERAL NUTRITION; SEPTIC MORBIDITY; ESPEN GUIDELINES; ABDOMINAL-TRAUMA; HEAD-INJURIES; METAANALYSIS AB Purpose of review Early enteral nutrition is the preferred option for feeding patients who cannot meet their nutrient requirements orally. This article reviews complications associated with small-bore feeding tube insertion and potential methods to promote safe gastric or postpyloric placement. We review the available bedside methods to check the position of the feeding tube and identify inadvertent misplacements. Recent findings Airway misplacement rates of small feeding tubes are considerable. Bedside methods (auscultation, pH, aspirate appearance, air bubbling, external length of the tube, etc.) to confirm the position of a newly inserted small-bore feeding tube have limited scientific basis. Radiographic confirmation therefore continues to be the most accurate method to ascertain tube position. Fluoroscopic and endoscopic methods are reliable but costly and are not available in many hospitals. Rigid protocols to place feeding tubes along with new emerging technology such as CO2 colorimetric paper and tubes coupled with signaling devices are promising candidates to substitute for the blind placement method. Summary The risk of misplacement with blind bedside methods for small-bore feeding tube insertion requires a change in hospital protocols. C1 Univ Fed Mato Grosso, Dept Surg, Cuiaba, Brazil. William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, Madison, WI 53706 USA. RP de Aguilar-Nascimento, JE (reprint author), Rua Estevao Mendonca 81 Apto 801, BR-78043300 Cuiaba, MT, Brazil. EM aguilar@terra.com.br NR 50 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD MAY PY 2007 VL 10 IS 3 BP 291 EP 296 DI 10.1097/MCO.0b013e3280d64a1d PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 165CJ UT WOS:000246281100005 PM 17414497 ER PT J AU Fanjiang, G Kleinman, RE AF Fanjiang, Gary Kleinman, Ronald E. TI Nutrition and performance in children SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE behavior; children; cognition; nutrition; performance; physical activity ID POLYUNSATURATED FATTY-ACIDS; AUTISM SPECTRUM DISORDERS; COGNITIVE-DEVELOPMENT; MENTAL-DEVELOPMENT; PHYSICAL-ACTIVITY; SCHOOL-CHILDREN; YOUNG-CHILDREN; UNITED-STATES; MICRONUTRIENT SUPPLEMENT; DIETARY INTERVENTION AB Purpose of review Malnutrition in late infancy and childhood remains a significant public health issue in developing nations as well as for those in transition to an industrialized economy. In addition, in these settings and particularly in developed nations, overweight is becoming a very serious threat to both the immediate and the long-term health of children. In this review, we present recent studies that have examined relationships between childhood undernutrition and three general areas of performance: physical activity, cognition and behavior. Recent findings Malnourished children have been shown to have decreased physical activity and endurance, and poorer cognitive function and school performance. Multiple single micronutrient deficiencies, including vitamin B12, thiamin, niacin, zinc and iron, have been associated with poorer cognitive performance. Behavioral problems, including attention deficits, have also been associated with food insufficiency and malnutrition. Summary The effects of impaired nutritional status during childhood may have long-standing consequences for the health and performance of children during their adult years. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Pediat, Pediat Gastroenterol & Nutr Unit,Med Sch, Cambridge, MA 02138 USA. RP Kleinman, RE (reprint author), 175 Cambridge St,CPZS 578, Boston, MA 02114 USA. EM rkleinman@partners.org NR 100 TC 28 Z9 28 U1 3 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD MAY PY 2007 VL 10 IS 3 BP 342 EP 347 DI 10.1097/MCO.0b013e3280523a9e PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 165CJ UT WOS:000246281100013 PM 17414505 ER PT J AU O'Leary, JG Pratt, DS AF O'Leary, Jacqueline G. Pratt, Daniel S. TI Cholestasis and cholestatic syndromes SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE bile acid transport; biliary atresia; cholestasis; intrahepatic cholestasis of pregnancy; primary biliary cirrhosis; primary sclerosing cholangitis ID PRIMARY BILIARY-CIRRHOSIS; INTRAHEPATIC CHOLESTASIS; URSODEOXYCHOLIC ACID; SCLEROSING CHOLANGITIS; PREGNANCY; LIVER; EXPRESSION; ATRESIA; MICE; CELLS AB Purpose of review This review focuses on the recent advances in cholestatic liver diseases. While there is an emphasis placed on translational and treatment-focused studies, basic science studies with the greatest impact on the field are also covered. Recent findings Highlights include new discoveries for the role of the farsenoid X receptor and sodium-dependent taurocholate cotransporting polypeptide; new insights into the pathogenesis of progressive familial intrahepatic cholestasis type 1, biliary atresia, intrahepatic cholestasis of pregnancy, and primary biliary cirrhosis; new information for assessing prognosis in biliary atresia and primary biliary cirrhosis; and important clinical trials in intrahepatic cholestasis of pregnancy, primary biliary cirrhosis and primary sclerosing cholangitis. Summary The studies of 2006 have furthered our understanding of cholestasis and cholestatic syndromes. While we continue to add to our knowledge of pathogenesis and treatment for many of these diseases, much work remains. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. RP Pratt, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM dspratt@partners.org NR 28 TC 12 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD MAY PY 2007 VL 23 IS 3 BP 232 EP 236 DI 10.1097/MOG.0b013e3280d942d8 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 158DK UT WOS:000245771200003 PM 17414837 ER PT J AU Brander, C Self, S Korber, B AF Brander, Christian Self, Steve Korber, Bette TI Capturing viral diversity for in-vitro test reagents and HIV vaccine immunogen design SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE HIV; immunogen; protective cellular immunity; sequence diversity; T cell; vaccine design AB Purpose of review HIV diversity is a major challenge to accurate detection of HIV-specific immunity in vitro and HIV vaccine immunogen design alike. Although achieving extensive coverage of global viral diversity is a common goal for both tasks, different strategies for achieving maximal in-vitro detection of responses and optimal in-vivo induction of immune responses may be needed. This review describes and compares some of the most recently developed approaches. Recent findings Single sequence-based antigen sets as well as polyvalent peptide test reagents have been developed over recent years that are suitable for detection of comprehensive CD4(+) and CD8(+) T-cell immunity in the naturally infected or vaccinated host. These tools permit increasingly accurate assessment of the host immune response, thus providing the basis for identification of immune correlates of controlled HIV infection. Summary These recent findings and newly developed strategies that allow more comprehensive detection of HIV-specific T-cell responses provide the tools necessary to assess vaccine immunogenicity and breadth within genetically different host populations and relative to diverse local viral populations. They will ultimately inform design of vaccine immunogen sequences that can induce broadly protective cellular immunity. C1 [Brander, Christian] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Brander, Christian] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Self, Steve] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Korber, Bette] Los Alamos Natl Lab, Los Alamos, NM USA. [Korber, Bette] Santa Fe Inst, Santa Fe, NM 87501 USA. RP Brander, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, MGH E 5239,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 NR 35 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2007 VL 2 IS 3 BP 183 EP 188 DI 10.1097/COH.0b013e3280f3bfe2 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NT UT WOS:000208417800004 PM 19372885 ER PT J AU Lakshmanan, V Alter, G Altfeld, M Bhardwaj, N AF Lakshmanan, Viswanathan Alter, Galit Altfeld, Marcus Bhardwaj, Nina TI Biology of plasmacytoid dendritic cells and natural killer cells in HIV-1 infection SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE HIV-1; interferon; natural killer cell; plasmacytoid dendritic cell AB Purpose This review summarizes recent literature on the biology of dendritic cells and natural killer cells in HIV-1 infection and the importance of crosstalk between them in the development of strong antiviral immunity. Recent findings Type I interferons produced by dendritic cells in response to HIV-1 have been suggested to act as a double-edged sword, stemming HIV-1 replication on the one hand and causing T-cell loss on the other. Recent epidemiologic evidence demonstrates a strong association between the natural killer cell receptor KIR3DS1 (along with its presumed ligand HLA-B Bw4-80I) in the control of HIV-1 replication. Summary Dendritic and natural killer cells play a central role in the innate immune response to viral infections through both the direct elimination of infected cells and modulation of each other's function. C1 [Lakshmanan, Viswanathan; Bhardwaj, Nina] NYU, Sch Med, New York, NY 10016 USA. [Alter, Galit; Altfeld, Marcus] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Bhardwaj, N (reprint author), NYU, Sch Med, Smilow 1307,522 1st Ave, New York, NY 10016 USA. EM nina.bhardwaj@med.nyu.edu NR 161 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2007 VL 2 IS 3 BP 189 EP 200 DI 10.1097/COH.0b013e32810996db PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NT UT WOS:000208417800005 PM 19372886 ER PT J AU Brawley, OW Jani, AB Kauh, J Berger, MZ Martin, IK Newman, LA Akers, AY Newmann, SJ Smith, JS Flowers, C Glover, R Lonial, S Lund, MJ Master, V Delongchomps, NB Singh, A Haas, GP AF Brawley, Otis W. Jani, Ashesh B. Kauh, John Berger, Mitchell Z. Martin, Iman Kalifa Newman, Lisa A. Akers, Aletha Y. Newmann, Sara J. Smith, Jennifer S. Flowers, Christopher Glover, Roni Lonial, Sagar Lund, Mary Jo Master, Verai Delongchomps, Nicolas B. Singh, Amar Haas, Gabriel P. TI Disparities in cancer care SO CURRENT PROBLEMS IN CANCER LA English DT Review ID AFRICAN-AMERICAN WOMEN; INVASIVE CERVICAL-CANCER; B-CELL LYMPHOMA; ANDROGEN RECEPTOR GENE; NON-HODGKINS-LYMPHOMA; EARLY BREAST-CANCER; HUMAN-PAPILLOMAVIRUS INFECTION; BONE-MARROW-TRANSPLANTATION; LOCALIZED PROSTATE-CANCER; SURGICAL ADJUVANT BREAST C1 Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Clark Atlanta Univ, Sch Social Work, Atlanta, GA USA. SUNY Hlth Sci Ctr, Dept Urol, Syracuse, NY 13210 USA. RP Brawley, OW (reprint author), Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 FU NIMHD NIH HHS [P60MD000525] NR 479 TC 6 Z9 7 U1 9 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2007 VL 31 IS 3 BP 114 EP 236 DI 10.1016/j.currproblcancer.2007.02.001 PG 123 WC Oncology SC Oncology GA 181TB UT WOS:000247457900002 PM 17543943 ER PT J AU Gupta, V Thiagalingam, A Maheswaran, S AF Gupta, Vandana Thiagalingam, Arunthathi Maheswaran, Shyamala TI Smad-signaling in mammary gland development and tumorigenesis SO CURRENT SIGNAL TRANSDUCTION THERAPY LA English DT Review DE TGF beta; activin; inhibin; BMP; MIS; nodal; cripto-1; smads; breast cancer ID TRANSFORMING-GROWTH-FACTOR; BREAST-CANCER CELLS; BONE MORPHOGENETIC PROTEIN-2; TGF-BETA RECEPTOR; HORMONE-RELATED PROTEIN; NF-KAPPA-B; DIFFERENTIAL GENE-EXPRESSION; FACTOR-BINDING PROTEIN-3; HUMAN COLORECTAL-CANCER; EPITHELIAL-CELLS AB The Transforming Growth Factor-beta (TGF beta) superfamily of cytokines regulates a myriad of cellular processes including proliferation, differentiation and tumorigenesis. Signaling by these growth regulatory molecules is propagated by ligand-induced hetero-oligomerization of distinct type II and type I serine/threonine kinase receptors, which result in activation ofreceptor-activated Smad proteins as well as Smad-independent pathways. Disruption of TGF beta induced signaling can contribute to development and progression of human breast cancer. The role of Smad-signaling in mammary gland development and tumorigenesis will be the focus of this review. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA USA. EM maheswaran@helix.mgh.harvard.edu NR 139 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-3624 J9 CURR SIGNAL TRANSD T JI Curr. Signal Transduct. Ther. PD MAY PY 2007 VL 2 IS 2 BP 111 EP 120 DI 10.2174/157436207780619482 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 167YY UT WOS:000246490000002 ER PT J AU Kisgati, M Asmis, R AF Kisgati, Marta Asmis, Reto TI Generation of retroviruses for the overexpression of cytosolic and mitochondrial glutathione reductase in macrophages in vivo SO CYTOTECHNOLOGY LA English DT Article DE retrovirus; gene Transfer; glutathione Reductase; macrophage; atherosclerosis ID LOW-DENSITY LIPOPROTEIN; INDUCED CELL INJURY; GENE-TRANSFER; HEMATOPOIETIC PROGENITOR; APOLIPOPROTEIN-E; LESION FORMATION; DEFICIENT MICE; STEM-CELLS; ATHEROSCLEROSIS; EXPRESSION AB Retroviral gene transfer and bone marrow transplantation has been used by many investigators to study the role of macrophage proteins in different mouse models of human disease. While this approach is faster and less expensive than generating transgenic mice with macrophage-specific promoters and applicable to a wider array of mouse models, it has been hampered by two major drawbacks: labor-intensive cloning procedures involved in generating retroviral vectors for each gene of interest and low viral titers. Here we describe the construction of a MSCV-based retroviral vector that can serve as an acceptor vector for commercially available Cre-lox-compatible donor vectors. Using this new retroviral vector in combination with a FACS approach to enhance viral titers, we generated high-titer retroviruses carrying either EGFP-tagged cytosolic or EGFP-tagged mitochondria-targeted glutathione reductase. We show that the introduction of these constructs via retroviral gene transfer and bone marrow transplantation into atherosclerosis-prone LDL receptor-null mice results in the long-term increase in macrophage glutathione reductase activity. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Kenezy Gyula Hosp, Dept Lab Med, Debrecen, Hungary. RP Asmis, R (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM asmis@uthscsa.edu FU NHLBI NIH HHS [R01 HL070963] NR 32 TC 0 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PD MAY PY 2007 VL 54 IS 1 BP 5 EP 14 DI 10.1007/s10616-007-9046-7 PG 10 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 179ET UT WOS:000247273100002 PM 19003013 ER PT J AU Schlueter, PJ Sang, XP Duan, CM Wood, AW AF Schlueter, Peter J. Sang, Xianpeng Duan, Cunming Wood, Antony W. TI Insulin-like growth factor receptor 1b is required for zebrafish primordial germ cell migration and survival SO DEVELOPMENTAL BIOLOGY LA English DT Article DE germline; insulin-like signaling; cell migration; chemokine; embryo; growth factor; vasa ID FACTOR-II GENE; IGF-I; POSTNATAL-GROWTH; MOUSE; EXPRESSION; CHEMOKINE; PROLIFERATION; APOPTOSIS; DISTINCT; GONADS AB Insulin-like growth factor (IGF) signaling is a critical regulator of somatic growth during fetal and adult development, primarily through its stimulatory effects on cell proliferation and survival. IGF signaling is also required for development of the reproductive system, although its precise role in this regard remains unclear. We have hypothesized that IGF signaling is required for embryonic germline development, which requires the specification and proliferation of primordial germ cells (PGCs) in an extragonadal location, followed by directed migration to the genital ridges. We tested this hypothesis using loss-of-function studies in the zebrafish embryo, which possesses two functional copies of the Type-1 IGF receptor gene (igf1ra, igf1rb). Knockdown of IGF1Rb by morpholino oligonucleotides (MO) results in mismigration and elimination of primordial germ cells (PGCs), resulting in fewer PGCs colonizing the genital ridges. In contrast, knockdown of IGF1Ra has no effect on PGC migration or number despite inducing widespread somatic cell apoptosis. Ablation of both receptors, using combined MO injections or overexpression of a dominant-negative IGF1R, yields embryos with a PGC-deficient phenotype similar to IGF1Rb knockdown. TUNEL analyses revealed that mismigrated PGCs in IGF1Rb-deficient embryos are eliminated by apoptosis; overexpression of an antiapoptotic gene (Bcl21) rescues ectopic PGCs from apoptosis but fails to rescue migration defects. Lastly, we show that suppression of IGF signaling leads to quantitative changes in the expression of genes encoding CXCL-family chemokine ligands and receptors involved in PGC migration. Collectively, these data suggest a novel role for IGF signaling in early germline development, potentially via cross-talk with chemokine signaling pathways. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. RP Wood, AW (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. EM awwood@partners.org FU NINDS NIH HHS [P30 NS045776, P30 NS 045776] NR 52 TC 29 Z9 33 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 2007 VL 305 IS 1 BP 377 EP 387 DI 10.1016/j.ydbio.2007.02.015 PG 11 WC Developmental Biology SC Developmental Biology GA 161QN UT WOS:000246030500029 PM 17362906 ER PT J AU Abdelwahid, E Yokokura, T Krieser, RJ Balasundaram, S Fowle, WH White, K AF Abdelwahid, Eltyeb Yokokura, Takakazu Krieser, Ronald J. Balasundaram, Sujatha Fowle, William H. White, Kristin TI Mitochondrial disruption in Drosophila apoptosis SO DEVELOPMENTAL CELL LA English DT Article ID PROGRAMMED CELL-DEATH; CYTOCHROME-C; CASPASE ACTIVATION; REAPER; ELEGANS; PROTEINS; GENE; INDUCTION; MEMBRANES; DOMAINS AB Mitochondrial disruption is a conserved aspect of apoptosis, seen in many species from mammals to nematodes. Despite significant conservation of other elements of the apoptotic pathway in Drosophila, a broad role for mitochondrial changes in apoptosis in flies remains unconfirmed. Here, we show that Drosophila mitochondria become permeable in response to the expression of Reaper and Hid, endogenous regulators of developmental apoptosis. Caspase activation in the absence of Reaper and Hid is not sufficient to permeabilize mitochondria, but caspases play a role in Reaperand Hid-induced mitochondrial changes. Reaper and Hid rapidly localize to mitochondria, resulting in changes in mitochondrial ultrastructure. The dynamin-related protein, Drp1, is important for Reaper- and DNA-damage-induced mitochondrial disruption. Significantly, we show that inhibition of Reaper or Hid mitochondrial localization or inhibition of Drp1 significantly inhibits apoptosis, indicating a role for mitochondrial disruption in fly apoptosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Northeastern Univ, Electron Microscopy Ctr, Boston, MA 02115 USA. RP White, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kristin.white@cbrc2.mgh.harvard.edu RI White, Kristin/D-7936-2013 FU NIGMS NIH HHS [GM 55568, R01 GM055568] NR 42 TC 115 Z9 117 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY PY 2007 VL 12 IS 5 BP 793 EP 806 DI 10.1016/j.devcel.2007.04.004 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 167OF UT WOS:000246460300015 PM 17488629 ER PT J AU Menzaghi, C Trischitta, V Doria, A AF Menzaghi, Claudia Trischitta, Vincenzo Doria, Alessandro TI Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease SO DIABETES LA English DT Review ID CORONARY-ARTERY-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; SINGLE-NUCLEOTIDE POLYMORPHISMS; ADIPOSE-SPECIFIC PROTEIN; PIMA INDIAN POPULATION; GENOME-WIDE LINKAGE; SERUM ADIPONECTIN; PLASMA ADIPONECTIN; APM1 GENE; ENCODING ADIPONECTIN AB Recent evidence points to molecules secreted by the adipose tissue, or adipokines, as possible links between increased adipose mass and metabolic abnormalities. Among these molecules, adiponectin has drawn much attention because of its insulin-sensitizing and antiatherogenic actions, suggesting that genetic deficits in its production or action may contribute to insulin resistance and coronary artery disease (CAD). A meta-analysis of the data published to date supports this hypothesis. Two independent effects, corresponding to the two linkage disequilibrium blocks that can be identified at the adiponectin locus, appear to be present. In the 5' block, the g.-11391G -> A variant has a modest but significant effect on adiponectinemia, with a mean difference between genotypes of 1.64 ng/ml (95% CI 0.88-2.41). In the 3' block, the g.+2766 -> T variant is a strong determinant of insulin resistance and CAD, with minor allele homozygotes having a lower homeostasis model assessment of insulin resistance (HOMA(IR)) index (-0.36 units, 95% CI 0.24-0.47) and a lower cardiovascular risk (odds ratio (1.55, 95% CI 0.38-0.80) than carriers of other genotypes. No consistent effect on BMI or risk of type 2 diabetes is evident. Polymorphisms in the genes coding for the adiponectin receptors may also influence the risk of insulin resistance and CAD, but data on these genes are still too sparse to draw firm conclusions. In summary, the studies published to date indicate that polymorphisms at the adiponectin locus are indeed predictors of circulating adiponectin levels, insulin sensitivity, and atherosclerosis, highlighting the pivotal role of this adipokine in the modulation of metabolism and atherogenesis. C1 IRCCS Casa Sollievo Sofferenza, Res Unit Diabetol & Endocrinol, San Giovanni Rotondo, Italy. Univ Roma La Sapienza, Dept Clin Sci, I-00185 Rome, Italy. Harvard Univ, Sch Med, Res Div, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM c.menzaghi@operapadrepio.it; alessandro.doria@joslin.harvard.edu RI Trischitta, Vincenzo/K-1487-2016; OI Trischitta, Vincenzo/0000-0003-1174-127X; Menzaghi, Claudia/0000-0002-7438-8955 FU NHLBI NIH HHS [HL73168, HL71981]; NIDDK NIH HHS [DK60837, DK55523, DK36836] NR 112 TC 179 Z9 190 U1 0 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2007 VL 56 IS 5 BP 1198 EP 1209 DI 10.2337/db06-0506 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GG UT WOS:000246291500002 PM 17303804 ER PT J AU Witczak, CA Fujii, N Hirshman, MF Goodyear, LJ AF Witczak, Carol A. Fujii, Nobuharu Hirshman, Michael F. Goodyear, Laurie J. TI Ca2+/calmodulin-dependent protein kinase kinase-alpha regulates skeletal muscle glucose uptake independent of AMP-activated protein kinase and Akt activation SO DIABETES LA English DT Article ID AS160 PHOSPHORYLATION; MOLECULAR-CLONING; IN-VIVO; CONTRACTION; TRANSPORT; CALCIUM; INSULIN; CALMODULIN; PHOSPHATASE; EXERCISE AB Studies in nonmuscle cells have demonstrated that Ca2+/ calmodulin-dependent protein kinase kinases (CaMKKs) are upstream regulators of AMP-activated protein kinase (AMPK) and Akt. In skeletal muscle, activation of AMPK and Akt has been implicated in the regulation of glucose uptake. The objective of this study was to determine whether CaMKK alpha regulates skeletal muscle glucose uptake, and whether it is dependent on AMPK and/or Akt activation. Expression vectors containing constitutively active CaMKK alpha (caCaMKK alpha) or empty vector were transfected into mouse muscles by in vivo electroporation. After 2 weeks, caCaMKK alpha was robustly expressed and increased CaMKI (Thr(177/180)) phosphorylation, a known CaMKK substrate. In muscles from wild-type mice, caCaMKKa increased in vivo [H-3]-2-deoxyglucose uptake 2.5-fold and AMPK alpha 1 and -alpha 2 activities 2.5-fold. However, in muscles from AMPK alpha 2 inactive mice (AMPK alpha 2i), caCaMKK alpha did not increase AMPK alpha 1 or -a2 activities, but it did increase glucose uptake 2.5-fold, demonstrating that caCaMKKa stimulates glucose uptake independent of AMPK. Akt (Thr(308)) phosphorylation was not altered by CaMKK alpha, and caCaMKKa plus insulin stimulation did not increase the insulin-induced phosphorylation of Akt (Thr(308)). These results suggest that caCaMKKa stimulates glucose uptake via insulin-independent signaling mechanisms. To assess the role of CaMKK in contraction-stimulated glucose uptake, isolated muscles were treated with or without the CaMKK inhibitor STO-609 and then electrically stimulated to contract. Contraction increased glucose uptake 3.5-fold in muscles from both wild-type and AMPKa2i mice, but STO-609 significantly decreased glucose uptake (similar to 24%) only in AMPKa2i mice. Collectively, these results implicate CaMKK alpha in the regulation of skeletal muscle glucose uptake independent of AMPK and Akt activation. C1 Joslin Diabet Ctr, Metab Sect, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Sect, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [F32AR051663, R01AR42238, R01AR45670]; NIDDK NIH HHS [DK36836, T32DK07260-27] NR 44 TC 71 Z9 76 U1 2 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2007 VL 56 IS 5 BP 1403 EP 1409 DI 10.2337/db06-1230 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GG UT WOS:000246291500026 PM 17287469 ER PT J AU Arikawa, E Ma, RCW Isshiki, K Luptak, I He, ZH Yasuda, Y Maeno, Y Patti, ME Weir, GC Harris, RA Zammit, VA Tian, R King, GL AF Arikawa, Emi Ma, Ronald C. W. Isshiki, Keiji Luptak, Ivan He, Zhiheng Yasuda, Yutaka Maeno, Yasuhiro Patti, Mary Elizabeth Weir, Gordon C. Harris, Robert A. Zammit, Victor A. Tian, Rong King, George L. TI Effects of insulin replacements, inhibitors of angiotensin, and PKC beta's actions to normalize cardiac gene expression and fuel metabolism in diabetic rats SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; ACTIVATED RECEPTOR-ALPHA; FATTY-ACID-METABOLISM; TISSUE GROWTH-FACTOR; GLUCOSE-TRANSPORT; SUBSTRATE METABOLISM; VENTRICULAR MYOCYTES; SKELETAL-MUSCLE; TROPONIN-I; HEART AB High-density oligonucleotide arrays were used to compare gene expression of rat hearts from control, untreated diabetic, and diabetic groups treated with islet cell transplantation (ICT), protein kinase C (PKC)(3 inhibitor ruboxistaurin, or ACE inhibitor captopril. Among the 376 genes that were differentially expressed between untreated diabetic and control hearts included key metabolic enzymes that account for the decreased glucose and increased free fatty acid utilization in the diabetic heart. ICT or insulin replacements reversed these gene changes with normalization of hyperglycemia, dyslipidemia, and cardiac PKC activation in diabetic rats. Surprisingly, both ruboxistaurin and ACE inhibitors improved the metabolic gene profile (confirmed by real-time RT-PCR and protein analysis) and ameliorated PKC activity in diabetic hearts without altering circulating metabolites. Functional assessments using Langendorff preparations and C-13 nuclear magnetic resonance spectroscopy showed a 36% decrease in glucose utilization and an impairment in diastolic function in diabetic rat hearts, which were normalized by all three treatments. In cardiomyocytes, PKC inhibition attenuated fatty acid-induced increases in the metabolic genes PDK4 and UCP3 and also prevented fatty acid-mediated inhibition of basal and insulin-stimulated glucose oxidation. Thus, PKC(3 or ACE inhibitors may ameliorate cardiac metabolism and function in diabetes partly by normalization of fuel metabolic gene expression directly in the myocardium. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Warwick Med Sch, Coventry, W Midlands, England. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU NHLBI NIH HHS [HL59246]; NIDDK NIH HHS [DK59725, R24 DK58739] NR 49 TC 33 Z9 42 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2007 VL 56 IS 5 BP 1410 EP 1420 DI 10.2337/db06-0655 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GG UT WOS:000246291500027 PM 17363743 ER PT J AU Last, D Alsop, DC Abduljalil, AM Marquis, RP de Bazelaire, C Hu, K Cavallerano, J Novak, V AF Last, David Alsop, David C. Abduljalil, Amir M. Marquis, Robert P. de Bazelaire, Cedric Hu, Kun Cavallerano, Jerry Novak, Vera TI Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity SO DIABETES CARE LA English DT Article ID CARBON-DIOXIDE REACTIVITY; NO CLINICAL HISTORY; BLOOD-FLOW; WHITE-MATTER; CEREBROVASCULAR REACTIVITY; RESERVE CAPACITY; MELLITUS; MRI; DISEASE; HYPOPERFUSION AB OBJECTIVE - The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation. RESEARCH DESIGN AND METHODS - CBF was examined in 26 diabetic (aged 61.6 +/- 6.6 years) and 25 control (aged 60.4 +/- 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla. RESULTS - The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (-13.1 %, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (-3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region. CONCLUSIONS - Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gerontol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Novak, V (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gerontol, 110 Francis St, Boston, MA 02215 USA. EM vnovak@bidmc.harvard.edu RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 FU NCRR NIH HHS [M01 RR001032-316142, M01 RR001032, M01 RR001032-316097, M01 RR001032-30A10856, M01-RR01032]; NIA NIH HHS [P01 AG004390, P60 AG008812, 2P60 AG08812, AG004390]; NINDS NIH HHS [R01 NS045745-04, R01 NS045745, 1R01-NS045745-01A21] NR 40 TC 98 Z9 101 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2007 VL 30 IS 5 BP 1193 EP 1199 DI 10.2337/dc06-2052 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GF UT WOS:000246291400027 PM 17290035 ER PT J AU Meigs, JB Rutter, MK Sullivan, LM Fox, CS D'Agostino, RB Wilson, PWF AF Meigs, James B. Rutter, Martin K. Sullivan, Lisa M. Fox, Caroline S. D'Agostino, Ralph B., Sr. Wilson, Peter W. F. TI Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome SO DIABETES CARE LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; FEDERATION; DEFINITIONS; POPULATION; PREVALENCE; CRITERIA; HEART; STATEMENT; MELLITUS; PROGRAM AB OBJECTIVE - Metabolic syndrome increases the risk for type 2 diabetes and cardiovascular disease (CVD) and may be associated with insulin resistance. RESEARCH DESIGN AND METHODS - We tested the hypothesis that the metabolic syndrome confers risk with or without concomitant insulin resistance among 2,803 Framingham Offspring Study subjects followed up to 11 years for new diabetes (135 cases) or CVD (240 cases). We classified subjects by presence of metabolic syndrome (using the National Cholesterol Education Program's [NCEPs] Third Adult Treatment Panel [ATP III], International Diabetes Federation [IDF], or European Group for the Study of Insulin Resistance [EGIR] criteria) and insulin resistance (homeostasis model assessment of insulin resistance >= 75th percentile) and, used separate risk factor-adjusted proportional hazards models to estimate relative risks (RRs) for diabetes or CVD using as references those without insulin resistance, metabolic syndrome, or without both. RESULTS - Fifty-six percent of individuals with ATP III, 52% with IDF, and 100% with EGIR definitions of metabolic syndrome had insulin resistance. Insulin resistance increased risk for diabetes (RR 2.6 [95% CI 1.7-4.0]) and CVD (1.8 [1.4-2.3]) as did metabolic syndrome for diabetes (ATP III, 3.5 [2.2-5.6]; IDF, 4.6 [2.7-7.7]; and EGIR, 3.3 [2.1-5.1]) and CVD (ATP III, 1.8 [1.4-2.3]; IDF, 1.7 [1.3-2.3]; and EGIR, 2.1 [1.6-2.7]). Relative to those without either I metabolic syndrome or insulin resistance, metabolic syndrome and insulin resistance increased risk for diabetes (ATP III, 6.0 [3.3-10.8] and IDF, 6.9 [3.7-13.0]) and CVD (ATP III, 2.3 [1.7-3.1] and IDF, 2.2 [1.6-3.0]). Any instance of metabolic syndrome without insulin resistance increased risk for diabetes approximately threefold (P < 0.001; IDF metabolic syndrome without insulin resistance (RR 1.6, P = 0.01), but not ATP III metabolic syndrome without insulin resistance (RR 1.3,P = 0.2), increased for CVD. CONCLUSIONS - Metabolic syndrome increased risk for diabetes regardless of insulin resistance. Metabolic syndrome by ATP III criteria may require insulin resistance to increase risk for CVD. The simultaneous presence of metabolic syndrome and insulin resistance identifies an especially high-risk individual. C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Manchester Royal Infirm, Manchester Diabet Ctr, Manchester M13 9WL, Lancs, England. Univ Manchester, Sch Med, Div Cardiovasc & Endocrine Sci, Manchester M13 9PL, Lancs, England. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, Framingham Mass Heart Study, Framingham, MA USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Stanifort St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Rutter, Martin/0000-0001-6380-539X FU NHLBI NIH HHS [N01-HC-25195] NR 30 TC 128 Z9 133 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2007 VL 30 IS 5 BP 1219 EP 1225 DI 10.2337/dc06-2484 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GF UT WOS:000246291400031 PM 17259468 ER PT J AU Beckman, JA Goldfine, AB Dunaif, A Gerhard-Herman, M Creager, MA AF Beckman, Joshua A. Goldfine, Allison B. Dunaif, Andrea Gerhard-Herman, Marie Creager, Mark A. TI Endothelial function varies according to insulin resistance disease type SO DIABETES CARE LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; CORONARY-ARTERY-DISEASE; REACTIVE PROTEIN-LEVELS; DEPENDENT VASODILATION; DIABETES-MELLITUS; VASCULAR FUNCTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; NONDIABETIC SUBJECTS; MAJOR DETERMINANT AB OBJECTIVE - We examined the relationship between insulin resistance and vascular function in three insulin-resistant states (type 2 diabetes, non-HIV lipodystrophic diabetes, and nondiabetic polycystic ovary syndrome [PCOS]) and in healthy control subjects. RESEARCH DESIGN AND METHODS - The population included 12 women with type 2 diabetes, 6 with lipodystrophic diabetes, 10 with PCOS, and 19 healthy female subjects. Metabolic measures included insulin sensitivity by the homeostasis model assessment, lipids, free fatty acids, and adiponectin. High-resolution B-mode ultrasound was used to determine endothelium-dependent and -independent vasodilation. RESULTS - Type 2 diabetic, liposdystrophic, and PCOS subjects were insulin resistant compared with control subjects (P = 0.001). Flow-mediated vasodilation was reduced in diabetic (3.4 +/- 1.3%) compared with control (7.3 +/- 1.1%) subjects but not in lipodystrophic (7.7 +/- 41.2%) or PCOS (9.9 +/- 0.7%) subjects (P = 0.005). Nitroglycerin-mediated vasodilation was attenuated in both diabetic (15.2 +/- 2.0%) andlipodystrophic (16.7 +/- 3.6%) subjects compared with healthy control (24.6 +/- 2.4%) and PCOS (23.2 +/- 1.8%) subjects (P = 0.019). insulin resistance, free fatty acids, adiponectin, or C-reactive protein did not associate with vascular dysfunction. CONCLUSIONS- Among these different types of patients with insulin resistance, we found abnormal endothelium-dependent vasodilation only in the patients with type 2 diabetes. We postulate that variations in the mechanism of insulin resistance may affect endothelial function differently than glucose homeostasis. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Joslin Diabet Ctr, Div Cellular & Mol Physiol, Boston, MA 02215 USA. Northwestern Univ, Div Endocrinol, Chicago, IL 60611 USA. RP Beckman, JA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 FU NHLBI NIH HHS [HL-48743]; NIDDK NIH HHS [K23-DK02795] NR 50 TC 26 Z9 26 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2007 VL 30 IS 5 BP 1226 EP 1232 DI 10.2337/dc06-2142 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GF UT WOS:000246291400032 PM 17261751 ER PT J AU Trief, PM Teresi, JA Izquierdo, R Morin, PC Goland, R Field, L Eimicke, JP Brittain, R Starren, J Shea, S Weinstock, RS AF Trief, Paula M. Teresi, Jeanne A. Izquierdo, Roberto Morin, Philip C. Goland, Robin Field, Leslie Eimicke, Joseph P. Brittain, Rebecca Starren, Justin Shea, Steven Weinstock, Ruth S. TI Psychosocial outcomes of telemedicine case management for elderly patients with diabetes - The randomized IDEATel trial SO DIABETES CARE LA English DT Article ID QUALITY-OF-LIFE; GLYCEMIC CONTROL; CARE MANAGEMENT; SELF-EFFICACY; OLDER-ADULTS; DEPRESSION; MELLITUS C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. Hebrew Home Aged, Div Res, Riverdale, NY USA. SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. Joslin Diabet Ctr, Syracuse, NY USA. Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10027 USA. Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Epidemiol & Biomed Informat, New York, NY 10027 USA. VA Med Ctr, Dept Med, Syracuse, NY USA. RP Trief, PM (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM triefp@upstate.edu NR 26 TC 27 Z9 27 U1 2 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2007 VL 30 IS 5 BP 1266 EP 1268 DI 10.2337/dc06-2476 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GF UT WOS:000246291400039 PM 17325261 ER PT J AU Ingelsson, E Larson, MG Fox, CS Yin, X Wang, TJ Lipinska, I Pou, KM Hoffmann, U Benjamin, EJ Keaney, JF Vasan, RS AF Ingelsson, Erik Larson, Martin G. Fox, Caroline S. Yin, Xiaoyan Wang, Thomas J. Lipinska, Izabella Pou, Karla M. Hoffmann, Udo Benjamin, Emelia J. Keaney, John F., Jr. Vasan, Ramachandran S. TI Clinical correlates of circulating visfatin levels in a community-based sample SO DIABETES CARE LA English DT Article ID GESTATIONAL DIABETES-MELLITUS; COLONY-ENHANCING FACTOR; PLASMA; GLUCOSE; HUMANS; WOMEN; FAT C1 Boston Univ, Sch Med, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Vasan, RS (reprint author), Boston Univ, Sch Med, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24HL4334, N01-HC-25195, R01-HL-076784, K23-HL-074077]; NIDDK NIH HHS [T32 DK007529] NR 14 TC 27 Z9 30 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2007 VL 30 IS 5 BP 1278 EP 1280 DI 10.2337/dc06-2353 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 165GF UT WOS:000246291400043 PM 17261750 ER PT J AU Haines, ST AF Haines, Stuart T. TI Emerging treatments for patients with type 2 diabetes SO DIABETES EDUCATOR LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Diabetes-Educators (AADE 2006) CY AUG 09, 2006 CL Los Angeles, CA SP Amer Assoc Diabetes Educators ID GLUCAGON-LIKE PEPTIDE-1; METFORMIN-TREATED PATIENTS; GLYCEMIC CONTROL; EXENATIDE EXENDIN-4; DOUBLE-BLIND; IV INHIBITOR; SULFONYLUREA; WEIGHT; LIRAGLUTIDE; SITAGLIPTIN C1 Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. Univ Maryland, Joslin Diabet Ctr, Baltimore, MD 21201 USA. RP Haines, ST (reprint author), Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. NR 21 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2007 VL 33 SU 5 BP 105S EP 110S DI 10.1177/0145721707302885 PG 6 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 174WC UT WOS:000246972500003 PM 17548897 ER PT J AU Blonde, L Haines, ST Leahy, JJ Siminerio, L AF Blonde, Lawrence Haines, Stuart T. Leahy, John (Jack) Siminerio, Linda TI Case presentation: A patient with type 2 diabetes SO DIABETES EDUCATOR LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Diabetes-Educators (AADE 2006) CY AUG 09, 2006 CL Los Angeles, CA SP Amer Assoc Diabetes Educators C1 Ochsner Clin Fdn, Ochsner Diabet Clin Res Unit, Dept Endocrinol Diabet & Metab Dis, New Orleans, LA 70121 USA. Univ Maryland Med, Univ Maryland Sch Pharm, Joslin Diabet Ctr, Baltimore, MD 21201 USA. Univ Vermont, Div Endocrinol Diabet & Metab, Burlington, VT USA. Univ Pittsburgh, Inst Diabet, Pittsburgh, PA USA. RP Blonde, L (reprint author), Ochsner Clin Fdn, Ochsner Diabet Clin Res Unit, Dept Endocrinol Diabet & Metab Dis, New Orleans, LA 70121 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2007 VL 33 SU 5 BP 114S EP 116S DI 10.1177/0145721707302888 PG 3 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 174WC UT WOS:000246972500005 PM 17548899 ER PT J AU Oge, A Isganaitis, E Jimenez-Chillaron, J Reamer, C Faucette, R Barry, K Przybyla, R Patti, ME AF Oge, A. Isganaitis, E. Jimenez-Chillaron, J. Reamer, C. Faucette, R. Barry, K. Przybyla, R. Patti, M. E. TI In utero undernutrition reduces diabetes incidence in non-obese diabetic mice SO DIABETOLOGIA LA English DT Article DE apoptosis; leptin; low birthweight; non-obese diabetic mice; NOD; type 1 diabetes mellitus ID RAT PANCREATIC-ISLETS; LOW-BIRTH-WEIGHT; NOD MICE; BETA-CELLS; GENERAL-POPULATION; INCREASED RISK; INSULIN; MELLITUS; APOPTOSIS; LEPTIN AB Aims/hypothesis Observational studies in humans suggest that low birthweight may decrease the risk of type 1 diabetes, but the mechanism is unknown. We hypothesised that antenatal undernutrition would decrease the incidence of type 1 diabetes in non-obese diabetic (NOD) mice. Materials and methods A 40% restriction of energy intake was applied to pregnant NOD dams from day 12.5 to day 18.5 of gestation, resulting in intrauterine growth retardation of offspring. All mice were fed a standard diet after weaning. Control and undernourished female offspring were followed to assess diabetes incidence. Male NOD mice were treated with cyclophosphamide to accelerate development of diabetes. Glucose homeostasis, body composition and pancreatic histology were compared in control and undernourished offspring. Results Mean birthweight was lower in undernourished than in control mice (p=0.00003). At 24 weeks of age, the cumulative incidence of spontaneous diabetes in female mice was 73% in control and 48% in undernourished mice (p=0.003). In cyclophosphamide-treated male mice, antenatal undernutrition also tended to reduce the development of diabetes (p=0.058). Maternal leptin levels were lower in undernourished dams on day 18.5 of pregnancy (p=0.039), while postnatal leptin levels were significantly higher in undernourished offspring at 4, 20 and 27 weeks of life (p < 0.05). Beta cell mass was similar in both groups (control = 0.4 mg; undernourished = 0.54 mg; p=0.24). Histological evidence of apoptosis at 20 weeks was greater in control than in undernourished mice (control = 6.3 +/- 1.4%; undernourished = 4.2 +/- 0.3%, p=0.05). Conclusion/interpretation Antenatal undernutrition reduces the incidence of diabetes in NOD mice, perhaps via alterations in apoptosis. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, Room 620,1 Joslin Plane, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI Biguzzi, Felipe/E-4724-2015 FU NIDDK NIH HHS [DK 062948] NR 49 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2007 VL 50 IS 5 BP 1099 EP 1108 DI 10.1007/s00125-007-0617-0 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 154QC UT WOS:000245521400026 PM 17370059 ER PT J AU Brachtel, EF Iafrate, AJ Mark, EJ Deshpande, V AF Brachtel, Elena F. Iafrate, A. John Mark, Eugene J. Deshpande, Vikram TI Cytomorphological correlates of epidermal growth factor receptor mutations in lung carcinoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE lung carcinoma; cytology; EGFR mutations ID BRONCHIOLOALVEOLAR PATHOLOGICAL SUBTYPE; EGFR MUTATIONS; GENE-MUTATIONS; CANCER; GEFITINIB; SENSITIVITY; FEATURES; ADENOCARCINOMAS; PERFORMANCE AB The initial diagnosis of lung carcinoma is frequently made by fine-needle aspiration biopsy. Novel therapeutic strategies of this disease include. tyrosine kinase inhibitors (TKI), such as g(gefitinih (Iressa (R)) or erlotinib (Tarceva (R)), which target the kinase domain of epidermal growth factor receptor (EGFR). Somatic mutations of this region have been shown to predict a therapeutic response of lung carcinomas to TKI. EGFR mutations have been described in adenocarcinomas of the lung, especially the bronchioloalveolar subtype, which has both cytopathologic and histopathologic definitions. This study investigates whether tumors with EGFR mutations display a characteristic phenotype on fine-needle aspiration biopsy. We identified 37 fine-needle aspiration biopsy of lung masses on which molecular analysis for EGFR mutations was available. Molecular analysis was performed on DNA isolated from formalin-fixed, paraffin-embedded, or frozen tissue from the corresponding core biopsies/cell blocks or resection specimens followed by PCR with primers for the tyrosine kinase region exons 18-24 and nucleotide sequence analysis by gel electrophoresis. Two observers who were blinded to the mutational data assessed several cytomorphological parameters. A semiquantitative analysis included predominant tissue pattern (flat or overlapping), nuclear features (nucleoli, intranuclear inclusions, grooves), cytoplasmic qualities, and extracellular material. All cases were adenocarcinomas primary in the lung. Thirteen cases showed EGFR mutations in exons 18, 19, 20, or 21 of the tyrosine kinase domain. The 24 cases negative for the relevant mutation served as the control group. Tumors with EGFR mutations were statistically more likely to demonstrate a predominantly flat, monolayer architecture (P = 0.04) with nuclear inclusions (P = 0.014) and the absence of macronucleoli (P = 0.001). The predominance of flat monolayers in conjunction with the absence of extracellular mucin and macronucleoli indicated the presence of EGFR mutations with a positive predictive value of 69% and a negative predictive value of 92%. All jour cases with extracellular mucin were negative for the examined mutations. Some of the traditional cytomorphological features of bronchioloalveolar carcinoma, i.e., flat monolayers, intranuclear inclusions, and the absence of macronucleoli, statistically correlated with the presence of mutations within the tyrosine kinase region of EGFR. Cytomorphological features could serve as an adjunctive predictive marker of response to TKIs and possibly to other new therapies in development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Brachtel, EF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Friut St,WRN 2, Boston, MA 02114 USA. EM ebrachtel@partners.org NR 25 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2007 VL 35 IS 5 BP 257 EP 262 DI 10.1002/dc.20617 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 159SC UT WOS:000245885700001 PM 17427221 ER PT J AU Nawgiri, RS Nagle, JA Wilbur, DC Pitman, MB AF Nawgiri, Ranjana S. Nagle, Julie A. Wilbur, David C. Pitman, Martha B. TI Cytomorphology and B72.3 labeling of benign and malignant ductal epithelium in pancreatic lesions compared to gastrointestinal epithelium SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE endoscopic ultrasound-guided fine-needle aspiration biopsy; gastrointestinal contamination; pancreas; pancreatic cancer; B72.3 ID FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; CYTOLOGIC FEATURES; CYSTIC NEOPLASMS; MUCINOUS TUMORS; DIAGNOSIS; EXPRESSION; PATHOLOGY; EUS AB Endoscopic ultrasound-guided pancreatic fine-needle aspiration biopsy very frequently produces gastrointestinal epithelial contamination (GIC). We studied the cytomorphology and B72.3 immunoreactivity of lesional epithelium of benign and malignant ductal lesions of the pancreas and compared the findings to our previously established template of GIC. Air-dried smears, fixed smears, and ThinPrep (R) (TP) specimens were obtained using a cytobrush, directly from benign and malignant ductal lesions of 18 Whipple specimens, to ensure purity of the epithelium studied. Smear background, cell architecture, and cellular features were analyzed. Immunocytochemical staining with B72.3 was performed in 14 cases. Epithelium of ductal carcinoma was distinguished from benign ductal epithelium in chronic pancreatitis and GIC primarily by crowded architecture and atypical cellular features, including high nuclear-to-cytoplasmic ratio, irregular nuclei, nucleoli, and vacuolated cytoplasm. Benign ductal and GIC epithelium were only distinguished by architecture (goblet cells and brush borders), but not consistently, especially gastric epithelium that lacked these features. B72.3 shows promise in the differentiation between GIC and benign and malignant ductal epithelium, with no staining supporting benign ductal cells, fine punctate perinuclear staining correlating with GIC, and strong cytoplasmic staining supporting malignancy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Warren 105-D,55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 19 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2007 VL 35 IS 5 BP 300 EP 305 DI 10.1002/dc.20624 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 159SC UT WOS:000245885700009 PM 17427224 ER PT J AU Nurgalieva, Z Lowrey, A El-Serag, HB AF Nurgalieva, Zhannat Lowrey, Angus El-Serag, Hashem B. TI The use of cytokeratin stain to distinguish Barrett's esophagus from contiguous tissues: A systematic review SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Barrett's esophagus; markers; cardiac; intestinal metaplasia; cytokeratins; microarray ID GASTROESOPHAGEAL-REFLUX-DISEASE; GASTRIC INTESTINAL METAPLASIA; DISTAL ESOPHAGUS; IMMUNOREACTIVITY PATTERNS; ESOPHAGOGASTRIC JUNCTION; EXPRESSION; CARDIA; ADENOCARCINOMA; EPITHELIUM; DIAGNOSIS AB Our objective was to systematically review the existing literature regarding the use of cytokeratin (CK) stain in differentiating Barrett's esophagus (BE) from tissues of the gastric cardia, corpus, or antrum, with or without intestinal metaplasia (IM). Pubmed was searched for full publications in English (1983-2005) addressing the use of CK for differentiation of BE from contiguous tissues. Information was collected on the study sample, blinding, the methods used for CK staining, and for defining and applying the gold standard tests. Test characteristics were obtained or calculated. Sixteen studies (containing 46 comparisons) met the inclusion and exclusion criteria. Immunostaining for CK 7 and 20 was generally highly specific in distinguishing long-segment BE from antrum IM, fundus IM, or noncardiac gastric IM; 27 comparisons showed statistically significant differences. However, only 8 of 15 comparisons (6 of 12 studies) reported significant differences in CK staining patterns between BE and gastric cardia IM with a high sensitivity (89%-100%) and specificity (83%-100%) for long-segment BE and lower estimates for short-segment BE, while the other seven comparisons showed no significant differences and a very low sensitivity. Examination by a blinded pathologist was reported in five of six positive studies and in only one of six of the negative studies. In addition, variation in the patient populations, use of surgical resection versus endoscopic biopsies, and biopsy sampling technique in endoscopic studies may have accounted for these differences. Finally, two studies did not find significant differences in CK staining patterns between BE and normal cardiac mucosa. In conclusions, CK immunostaining has not performed well in differentiating BE, especially short-segment BE, from cardia IM. There seems to be a spectrum bias where the accuracy varies with different tested populations. CK immunostaining distinguished well between BE and IM in noncardiac segments of the stomach; however, these comparisons are not clinically relevant. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU NIDDK NIH HHS [R21 DK067366-02] NR 40 TC 14 Z9 17 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2007 VL 52 IS 5 BP 1345 EP 1354 DI 10.1007/s10620-006-9399-3 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 158VL UT WOS:000245823100035 PM 17373588 ER PT J AU Rosenberg, ES Davidian, M Banks, HT AF Rosenberg, Eric S. Davidian, Marie Banks, H. Thomas TI Using mathematical modeling and control to develop structured treatment interruption strategies for HIV infection SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE STI; CD4; HIV dynamics; drug resistance; viral load ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; LONG-TERM CONTROL; CONCEPTUAL-FRAMEWORK; COMBINATION THERAPY; PROTEASE INHIBITORS; PROSPECTIVE COHORT; FOLLOW-UP; RESISTANCE AB The goal of this article is to suggest that mathematical models describing biological processes taking place within a patient over time can be used to design adaptive treatment strategies. We demonstrate using the key example of treatment strategies for human immunodeficiency virus type-1 (HIV) infection. Although there has been considerable progress in management of HIV infection using highly active antiretroviral therapies, continuous treatment with these agents involves significant cost and burden, toxicities, development of drug resistance, and problems with adherence; these latter complications are of particular concern in substance-abusing individuals. This has inspired interest in structured or supervised treatment interruption (STI) strategies, which involve cycles of treatment withdrawal and re-initiation. We argue that the most promising STI strategies are adaptive treatment strategies. We then describe how biological mechanisms governing the interaction over time between HIV and a patient's immune system may be represented by mathematical models and how control methods applied to these models can be used to design adaptive STI strategies seeking to maintain long-term suppression of the virus. We advocate that, when such mathematical representations of processes underlying a disease or disorder are available, they can be an important tool for suggesting adaptive treatment strategies for clinical study. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol & Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Dept Pathol & Med, Gray J-504 55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org FU NCI NIH HHS [R01 CA-085848, R01 CA085848]; NIAID NIH HHS [R01 AI071915, R21AI-040873, R37 AI031789, R21 AI040873, R01 AI-071915, R37 AI-031789]; NIGMS NIH HHS [R01 GM-67299, R01 GM067299] NR 73 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY PY 2007 VL 88 SU 2 BP S41 EP S51 DI 10.1016/j.drugalcdep.2006.12.024 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 166OE UT WOS:000246387600006 PM 17276624 ER PT J AU Movahed, MR Ebrahimi, R AF Movahed, Mohammad-Reza Ebrahimi, Ramin TI The prevalence of valvular abnormalities in patients who were referred for echocardiographic examination with a primary diagnosis of "Heart murmur" SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE echocardiography; murmur; valvular heart disease; valvular abnormalities; mitral regurgitation; mitral stenosis; aortic regurgitation; aortic stenosis ID SYSTOLIC MURMURS; DOPPLER ECHOCARDIOGRAPHY; AORTIC REGURGITATION; AUSCULTATION AB Introduction: The prevalence of valvular abnormality and innocent murmur in patients who are referred for echocardiographic evaluation with the diagnosis of "murmur" is not known. The goal of this study was to evaluate the prevalence of valvular abnormalities in such patients. Methods: We retrospectively reviewed the echocardiograms that were referred with the primary ordering diagnosis of "murmur," for the presence of valvular abnormalities. For comparison, we used other documented primary reasons for echocardiographic referral, such as chest pain, shortness of breath, etc. Results: In this cohort, 7,684 echocardiogram reports documented primary diagnostic reasons for echocardiographic referral. A total of 3,460 echocardiogram reports (45%) were coded "murmur" as the primary reason for the study referral. There was a higher prevalence of female patient referrals for heart murmur evaluation (61.8% vs. 38.2%). Although, patients with murmur had a higher prevalence of valvular abnormalities, compared to other reasons for echocardiographic examination, the prevalence of valvular abnormality was less than 50% (48.6% vs. 35.5%) in both groups. Despite the higher number of female patients referred with the diagnosis of murmur, the percentage of abnormal valves was lower in women (45.6% vs. 53.4% in men). Conclusion: The prevalence of valvular abnormalities in patients who were referred with the diagnosis of murmur for echocardiographic examination was less than 50%, with a lesser degree found in women. Routine utilization of echocardiography for evaluation of all murmurs may be unwarranted. C1 Univ Arizona, Coronary Care Unit, Sarver Heart Ctr, Dept Med,Sect Cardiol, Tucson, AZ 85724 USA. Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Movahed, MR (reprint author), Univ Arizona, Coronary Care Unit, Sarver Heart Ctr, Dept Med,Sect Cardiol, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM rmovahed@email.arizona.edu NR 19 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD MAY PY 2007 VL 24 IS 5 BP 447 EP 451 DI 10.1111/j.1540-8175.2007.00425.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 160KT UT WOS:000245940100001 PM 17456061 ER PT J AU Kelly, MM Forsyth, JP AF Kelly, Megan M. Forsyth, John P. TI Observational fear conditioning in the acquisition and extinction of attentional bias for threat: An experimental evaluation SO EMOTION LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV 22, 2003 CL Boston, MA SP Assoc Advancement Behav Therapy DE fear conditioning; observational learning; emotional Stroop; anxiety; threat bias ID LEARNING-THEORY PERSPECTIVE; ANXIETY RESPONSE PATTERNS; EMOTIONAL STROOP TASK; COLOR-NAMING TASK; SELECTIVE ATTENTION; SOCIAL PHOBIA; PANIC DISORDER; COGNITIVE AVOIDANCE; SPATIAL ATTENTION; CLINICAL PATIENTS AB Anxious persons show automatic and strategic attentional biases for threatening information. Yet, the mechanisms and processes that underlie such biases remain unclear. The central aim of the present study was to elucidate the relation between observational threat learning and the acquisition and extinction of biased threat processing by integrating emotional Stroup color naming tasks within an observational differential fear conditioning procedure. Forty-three healthy female participants underwent several consecutive observational fear conditioning phases. During acquisition, participants watched a confederate displaying mock panic attacks (UCS) paired with a verbal stimulus (CS+), but not with a second nonreinforced verbal stimulus (CS-). As expected, participants showed greater magnitude electrodermal and verbal-evaluative (e.g., distress, fear) conditioned responses to the CS+ over the CS- word. Participants also demonstrated slower color-naming latencies to CS+ compared to the CS- word following acquisition and showed attenuation of this preferential processing bias for threat following extinction. Findings are discussed broadly in the context of the interplay between fear learning and processing biases for threat as observed in persons suffering from anxiety disorders. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. SUNY Albany, Albany, NY 12222 USA. RP Kelly, MM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-5,150 Huntington Ave, Boston, MA 02130 USA. EM Megan.Kelly@va.gov FU NIMH NIH HHS [MH6010701] NR 92 TC 20 Z9 20 U1 6 U2 15 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD MAY PY 2007 VL 7 IS 2 BP 324 EP 335 DI 10.1037/1528-3542.7.2.324 PG 12 WC Psychology, Experimental SC Psychology GA 166WT UT WOS:000246412200010 PM 17516811 ER PT J AU Lorenz, S Frenzel, R Paschke, R Breitwieser, GE Miedlich, SU AF Lorenz, Stephan Frenzel, Romy Paschke, Ralf Breitwieser, Gerda E. Miedlich, Susanne U. TI Functional desensitization of the extracellular calcium-sensing receptor is regulated via distinct mechanisms: Role of G protein-coupled receptor kinases, protein kinase C and beta-arrestins SO ENDOCRINOLOGY LA English DT Article ID AGONIST-INDUCED INTERNALIZATION; PHOSPHORYLATION; ACTIVATION; FILAMIN; CA2+; EXPRESSION; BINDS; 1A AB The extracellular calcium-sensing receptor (CaR) senses small fluctuations of the extracellular calcium (Ca-e(2+)) concentration and translates them into potent changes in parathyroid hormone secretion. Dissecting the regulatory mechanisms of CaR-mediated signal transduction may provide insights into the physiology of the receptor and identify new molecules as potential drug targets for the treatment of osteoporosis and/or hyperparathyroidism. CaR can be phosphorylated by protein kinase C (PKC) and G protein-coupled receptor kinases (GRKs), and has been shown to bind to beta-arrestins, potentially contributing to desensitization of CaR, although the mechanisms by which CaR-mediated signal transduction is terminated are not known. We used a PKC phosphorylation site-deficient CaR, GRK and beta-arrestin overexpression or down-regulation to delineate CaR-mediated desensitization. Fluorescence-activated cell sorting was used to determine whether receptor internalization contributed to desensitization. Overexpression of GRK 2 or 3 reduced Ca-e(2+) dependent inositol phosphate accumulation by more than 70%, whereas a GRK2 mutant deficient in G alpha(q) binding (D110A) was without major effect. Overexpression of GRK 4 - 6 did not reduce Ca-e(2+)-dependent inositol phosphate accumulation. Overexpression of beta-arrestin 1 or 2 revealed a modest inhibitory effect on Ca-e(2+)-dependent inositol phosphate production ( 20 - 30%), which was not observed for the PKC phosphorylation site-deficient CaR. Agonist-dependent receptor internalization ( 10 - 15%) did not account for the described effects. Thus, we conclude that PKC phosphorylation of CaR contributes to beta-arrestin-dependent desensitization of CaR coupling to G proteins. In contrast, GRK 2 predominantly interferes with G protein-mediated inositol-1,4,5-trisphosphate formation by binding to G alpha(q). C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Leipzig, Dept Med 2, D-04109 Leipzig, Germany. Geisinger Med Clin, Weis Ctr Res, Danville, PA 17822 USA. RP Miedlich, SU (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM smiedlich@partners.org FU NIGMS NIH HHS [GM58578, R01 GM077563, R01 GM077563-03, R01 GM077563-04] NR 32 TC 36 Z9 37 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2007 VL 148 IS 5 BP 2398 EP 2404 DI 10.1210/en.2006-1035 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 158RG UT WOS:000245810600050 PM 17255208 ER PT J AU Gonzalez-Heydrich, J Dodds, A Whitney, J MacMillan, C Waber, D Faraone, SV Boyer, K Mrakotsky, C DeMaso, D Bourgeois, B Biederman, J AF Gonzalez-Heydrich, Joseph Dodds, Alice Whitney, Jane MacMillan, Carlene Waber, Deborah Faraone, Stephen V. Boyer, Katrina Mrakotsky, Christine DeMaso, David Bourgeois, Blaise Biederman, Joseph TI Psychiatric disorders and behavioral characteristics of pediatric patients with both epilepsy and attention-deficit hyperactivity disorder SO EPILEPSY & BEHAVIOR LA English DT Article DE attention-deficit hyperactivity disorder; epilepsy; comorbid psychiatric disorders; anxiety disorders; etiology ID TEMPORAL-LOBE EPILEPSY; DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; ADHD; SEIZURES; CHILDHOOD; SCHIZOPHRENIA; ADOLESCENTS; POPULATION; INHIBITION AB Objective. Attention-deficit hyperactivity disorder (ADHD) coexisting with epilepsy is poorly understood; thus, we compared the clinical correlates and psychiatric comorbid conditions of 36 children with epilepsy and ADHD aged 6 to 17 years enrolled in an ADHD treatment trial, with those reported in the literature on children with ADHD without epilepsy. Methods. Measures included the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), the Wechsler Abbreviated Scale of Intelligence (WASI), and the Scales for Independent Behavior-Revised (SIB-R). Results. Mean IQ was 86 +/- 19, and SIB-R Standard Score was 72 +/- 26. The ADHD-Combined subtype, composed of both inattentive and hyperactive symptoms, was most frequent (58%). Sixty-one percent exhibited a comorbid disorder, including anxiety disorders (36%) and oppositional defiant disorder (31%). Conclusions. Comorbidity in ADHD with epilepsy is similar to that in ADHD without epilepsy reported in the literature. These preliminary data argue that the pathophysiology of ADHD has common components in both populations. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Childrens Hosp, Psychopharmacol Program, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Harvard Univ, Sch Med, Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02115 USA. RP Gonzalez-Heydrich, J (reprint author), Childrens Hosp, Pediat Psychopharmacol Program, 300 Longwood Ave,Fegan 8, Boston, MA 02115 USA. EM joseph.gonzalez-heydrich@tch.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K23 MH066835, K23 MH066835-01, K23 MH066835-02, K23 MH066835-03, K23 MH066835-04] NR 40 TC 43 Z9 49 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2007 VL 10 IS 3 BP 384 EP 388 DI 10.1016/j.yebeh.2007.01.010 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 165RD UT WOS:000246322200005 PM 17368109 ER PT J AU Pulsifer, MB Winterkorn, EB Thiele, EA AF Pulsifer, Margaret B. Winterkorn, Elisabeth B. Thiele, Elizabeth A. TI Psychological profile of adults with tuberous sclerosis complex SO EPILEPSY & BEHAVIOR LA English DT Article DE tuberous sclerosis complex; epilepsy; seizure disorder; psychological functioning ID EPILEPSY; SAMPLE AB The Symptom Checklist-90-Revised, a standardized self-report measure of psychological symptoms, was administered to 42 adults with tuberous sclerosis complex (TSC). Approximately 45% reported high overall psychological distress, most commonly involving interpersonal sensitivity, psychoticism, depression, and obsessive-compulsive symptoms. Symptoms were related to number of organ systems affected by TSC and, in some cases, to seizure history, but not to genotype, IQ, education, severity of epilepsy, or use of anticonvulsant or psychiatric medication. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Herscot Ctr Tuberous Sclerosis Complex, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Pulsifer, MB (reprint author), Massachusetts Gen Hosp, Herscot Ctr Tuberous Sclerosis Complex, Dept Psychiat, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM mpulsifer@partners.org NR 15 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2007 VL 10 IS 3 BP 402 EP 406 DI 10.1016/j.yebeh.2007.02.004 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 165RD UT WOS:000246322200008 PM 17392032 ER PT J AU Salinsky, M Storzbach, D Oken, B Spencer, D AF Salinsky, Martin Storzbach, Daniel Oken, Barry Spencer, David TI Topiramate effects on the EEG and alertness in healthy volunteers: A different profile of antiepileptic drug neurotoxicity SO EPILEPSY & BEHAVIOR LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophysiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc DE antiepileptic drugs; electroencephalogram; cognition; neurotoxicity; gabapentin; topiramate ID COGNITIVE PERFORMANCE; DOUBLE-BLIND; CARBAMAZEPINE; EPILEPSY; GABAPENTIN; PHENYTOIN; LAMOTRIGINE; ADULTS; ABILITIES; THERAPY AB Objective. Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness. Methods. Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400 mg/day for TPM or 3600 mg/day for GBP, over a 10-week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test re-test changes for all measures were scored against similar test retest distributions previously obtained from untreated healthy volunteers. Results. TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT. Conclusions. TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP. (C) 2007 Elsevier Inc. All rights reserved. C1 Oregon Hlth & Sci Univ, Epilepsy Ctr, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Salinsky, M (reprint author), Oregon Hlth & Sci Univ, Epilepsy Ctr, 3181 SW Sam Jackson Pk Rd,CDW-3, Portland, OR 97201 USA. EM Salinsky@OHSU.edu NR 43 TC 9 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2007 VL 10 IS 3 BP 463 EP 469 DI 10.1016/j.yebeh.2006.12.011 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 165RD UT WOS:000246322200018 PM 17337249 ER PT J AU Blum, A Tremont, G Donahue, J Tung, G Duncan, J Buchbinder, B Gascon, G AF Blum, A. Tremont, G. Donahue, J. Tung, G. Duncan, J. Buchbinder, B. Gascon, G. TI Landau-Kleffner syndrome with lateral temporal focal cortical dysplasia and mesial temporal sclerosis: A 30-year follow-up SO EPILEPSY & BEHAVIOR LA English DT Article DE Landau-Kleffner syndrome; mesial temporal lobe epilepsy; cortical dysplasia ID ACQUIRED EPILEPTIC APHASIA; LATE-ONSET SEIZURES; CONVULSIVE DISORDER; SIGN LANGUAGE; LOBE EPILEPSY; CORTICOSTEROID-THERAPY; HIPPOCAMPAL SCLEROSIS; LEFT HEMISPHERECTOMY; CHILDREN; CHILDHOOD AB A 39-year-old man, who presented at age 32 with Landau-Kleffner syndrome, had persisting oral and written language deficits into adulthood. Seizures were easily controlled in childhood, but reemerged in adulthood as medication-refractory complex partial seizures. Abnormal T2 signal hyperintensity was seen in the left mesial temporal area on brain MRI. Later, left temporal lobectomy revealed focal cortical dysplasia in the lateral temporal neocortex and gliosis plus neuronal loss in the hippocampus. This case suggests that focal cortical microdysgenesis may be a cause of the Landau-Kleffner syndrome. Persistent seizures in this illustrative case may have led to the evolution of dual-temporal-lobe pathology with mesial temporal sclerosis. (C) 2007 Elsevier Inc. All rights reserved. C1 Rhode Isl Hosp, Dept Neurol, Comprehens Epilepsy Program, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Neuropsychol, Comprehens Epilepsy Program, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Neuropathol, Comprehens Epilepsy Program, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Neuroradiol, Comprehens Epilepsy Program, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Neurosurg, Comprehens Epilepsy Program, Providence, RI 02903 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Jeddah, Saudi Arabia. RP Blum, A (reprint author), Rhode Isl Hosp, Dept Neurol, Comprehens Epilepsy Program, 110 Lockwood St,Suite 342, Providence, RI 02903 USA. EM ablum@lifespan.org RI Donahue, John/A-3000-2008 OI Donahue, John/0000-0001-7186-2562 NR 39 TC 5 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2007 VL 10 IS 3 BP 495 EP 503 DI 10.1016/j.yebeh.2007.01.015 PG 9 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 165RD UT WOS:000246322200022 PM 17347054 ER PT J AU White, HD Braunwald, E Murphy, SA Jacob, AJ Gotcheva, N Polonetsky, L Antman, EM AF White, Harvey D. Braunwald, Eugene Murphy, Sabina A. Jacob, Ashok J. Gotcheva, Nina Polonetsky, Leonid Antman, Elliott M. TI Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25 SO EUROPEAN HEART JOURNAL LA English DT Article DE ExTRACT-TIMI 25; enoxaparin; unfractionated heparin; age ID RANDOMIZED-TRIAL; UNSTABLE ANGINA; TENECTEPLASE; COMBINATION; EFFICACY; ASSENT-3; THERAPY; SAFETY AB Aims To determine the effects of age on outcomes in patients with STEMI treated with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). Methods and results In the ExTRACT-TIMI 25 trial, 20 479 patients with STEMI were randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX was administered to patients >= 75 years, and a reduced dose in those with an estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a subset of patients (n = 73). The exposure to anti-Xa over time was lower in the elderly (AUC(0-12h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal recurrent myocardial infarction, was greater in patients < 75 years (20%) than >= 75 years (6%), but the absolute benefits were similar. When compared with UFH, ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of the excess risk tended to be lower (RR = 1. 15) in patients >= 75 years assigned to ENOX. Conclusion A dose reduction of ENOX in the elderly appears to be helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in both young and elderly patients with STEMI treated with fibrinolysis. C1 Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1030, New Zealand. Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. St Johns Hosp, SE Scotland Plast Surg Unit, Livingston EH54 6PP, Scotland. Natl Heart Ctr, Dept Cardiol, Sofia, Bulgaria. Republ Res Pract Ctr, Minsk, Byelarus. RP White, HD (reprint author), Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1030, New Zealand. EM harveyw@adhb.govt.nz NR 12 TC 51 Z9 60 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2007 VL 28 IS 9 BP 1066 EP 1071 DI 10.1093/eurheartj/ehm081 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176FW UT WOS:000247071200010 PM 17456482 ER PT J AU Tournoux, FB Alabiad, C Fan, D Chen, AA Chaput, M Heist, EK Mela, T Mansour, M Reddy, V Ruskin, JN Picard, MH Singh, JP AF Tournoux, Francois B. Alabiad, Chrisfouad Fan, Dali Chen, Annabel A. Chaput, Miguel Heist, Edwin Kevin Mela, Theofanie Mansour, Moussa Reddy, Vivek Ruskin, Jeremy N. Picard, Michael H. Singh, Jagmeet P. TI Echocardiographic measures of acute haemodynamic response after cardiac resynchronization therapy predict long-term clinical outcome SO EUROPEAN HEART JOURNAL LA English DT Article DE dP/dt; resynchronization; Doppler; long-term outcome; cardiomyopathy; heart failure ID CHRONIC HEART-FAILURE; INTRAVENTRICULAR-CONDUCTION DELAY; PRESSURE-VOLUME LOOPS; MITRAL REGURGITATION; DILATED CARDIOMYOPATHY; ASYNCHRONY PREDICTS; PACING SITES; TISSUE; IMPROVEMENT; SYNCHRONICITY AB Aims Although acute haemodynamic improvement in response to cardiac resynchronization therapy (CRT) is reflective of a favourable cardiac contractile response, there is limited information regarding not only its ability to predict long-term clinical outcome but also ca rdi ac -substrate -specific differences in the prognostic value of this measure. Methods and results Fifty-three heart failure patients (69 +/- 11 years) with low left ventricle ejection fraction (LVEF) (22 +/- 6%), wide QRS (169 +/- 31 ms), and indications for CRT were included. There were no significant differences in age, New York Heart Association (NYHA) class, medications, QRS width, or LVEF between ischaemic (n = 37) and non-ischaemic (n = 16) groups. Echocardiograms were performed within 24 h of implantation with device OFF and ON. Acute haemodynamic response was measured as LV dP/dt derived from the CW Doppler of mitral regurgitation. Percentage change in dP/dt was used to classify patients: high- (HR: Delta dP/dt > 25%) or poor-responders (PR: Delta dP/dt < 25%). Clinical response to CRT was defined by a combined endpoint of hospitalizations and at[-cause mortality at 12 months. HR group had a significantly better outcome compared to the PR group (P-value = 0.004) irrespective of the aetiology of the cardiomyopathy. Conclusion Echocardiographic assessment of the acute haemodynamic response to CRT predicts longterm clinical outcome in both ischaemic and non-ischaemic cardiomyopathy. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 40 TC 38 Z9 41 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2007 VL 28 IS 9 BP 1143 EP 1148 DI 10.1093/eurheartj/ehm050 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176FW UT WOS:000247071200021 PM 17449877 ER PT J AU Joseph, J AF Joseph, Jacob TI The stem cell army in heart failure: do we mobilize or pave the way home? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material C1 VA Boston Healthcare Syst, Cardiol Sect 111, W Roxbury, MA 02132 USA. Boston Univ, Sch Med, Boston, MA USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, W Roxbury, MA 02132 USA. EM jacob.joseph@med.va.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2007 VL 28 IS 10 BP 1180 EP 1181 DI 10.1093/eurheartj/ehm011 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 181II UT WOS:000247430000004 PM 17483525 ER PT J AU Giedraitis, V Irizarry, MC Sundelof, J Gunnarsson, MD Kilander, L Glaser, A Ingelsson, M Hyman, BT Basun, H Lannfelt, L AF Giedraitis, V. Irizarry, M. C. Sundelof, J. Gunnarsson, M. Degermann Kilander, L. Glaser, A. Ingelsson, M. Hyman, B. T. Basun, H. Lannfelt, L. TI Regulation of A beta levels in human plasma SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 Univ Uppsala, Dept Publ Hlth Geriatr, Uppsala, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Astra Zeneca, Sodertalje, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2007 VL 37 SU 1 MA 218 BP 72 EP 72 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 166BM UT WOS:000246352100221 ER PT J AU Sawalha, AH Jeffries, M AF Sawalha, Amr H. Jeffries, Matlock TI Defective DNA methylation and CD70 overexpression in CD4(+) T cells in MRL/lpr lupus-prone mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD70; DNA methylation; lupus; mouse ID SYNGENEIC MICE; ERYTHEMATOSUS; ACTIVATION; DISEASE; CD27; DEMETHYLATION; 5-AZACYTIDINE; MECHANISMS; EXPRESSION; INHIBITORS AB We have determined that abnormal DNA methylation in T cells coincides with the development of autoimmunity, using a mouse model that exhibits an age-dependent lupus-like disease (MRL/1pr mice). Splenic CD4(+) T cells were isolated from these mice at 5 and 16 wk of age (before and after autoimmunity is established) and the expression of DNA methyltransferase 1 (Dnmt1) and the methylation-sensitive gene Tnfsf7 (CD70) was measured. Bisulfite DNA sequencing was used to monitor the methylation status of the Tnfsf7 gene. We found that Dnmt1 steady-state mRNA levels were significantly lower in 16-wk-old MRL/1pr mice, which had established autoimmunity, compared to the 5-wk-old MRL/1pr mice. Furthermore, the expression of CD70 was higher in MRL/1pr mice at 16 wk. CD70 was overexpressed in MRL/1pr mice compared to age- and sexmatched MRL+/+ controls. Bisulfite DNA sequencing of the Tnfsf7 gene in MRL/1pr mice revealed that at 16 wk, CG pairs were hypomethylated compared to 5-wk-old mice, and that Tnfsf7 from MRL/lpr mice was hypomethylated at 16 wk relative to age-matched MRL+/+ controls. Our data indicate that decreased expression of Dnmt1 and the corresponding T cell DNA hypomethylation correlate with the development of age-dependent autoimmunity in MRL/lpr mice. C1 US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. RP Sawalha, AH (reprint author), 825 NE 13th St MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu OI Jeffries, Matlock/0000-0001-9516-4312 FU NCRR NIH HHS [P20-RR015577]; NIAMS NIH HHS [P30 AR053483] NR 25 TC 37 Z9 40 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2007 VL 37 IS 5 BP 1407 EP 1413 DI 10.1002/eji.200636872 PG 7 WC Immunology SC Immunology GA 168XY UT WOS:000246558500029 PM 17429846 ER PT J AU Wozniak, J Biederman, J Mick, E Waxmonsky, J Hantsoo, L Best, C Cluette-Brown, JE Laposata, M AF Wozniak, Janet Biederman, Joseph Mick, Eric Waxmonsky, James Hantsoo, Liisa Best, Catherine Cluette-Brown, Joanne E. Laposata, Michael TI Omega-3 fatty acid monotherapy for pediatric bipolar disorder: A prospective open-label trial SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE pediatric; mania; bipolar disorder; treatment; omega-3 fatty acid; children ID FATTY-ACID COMPOSITION; BLOOD-CELL MEMBRANES; MANIA RATING-SCALE; DOUBLE-BLIND; SCHIZOPHRENIC-PATIENTS; EICOSAPENTAENOIC ACID; DIVALPROEX SODIUM; MAJOR DEPRESSION; CHILDREN; ADOLESCENTS AB Background: To test the effectiveness and safety of omega-3 fatty acids (Omegabrite (R)) brand) in the treatment of pediatric bipolar disorder (BPD). Method: Subjects (N=20) were outpatients of both sexes, 6 to 17 years of age, with a DSM-1V diagnosis of BPD and Young Mania Rating Scale (YMRS) score of > 15 treated over an 8-week period in open-label trial with omega-3 fatty acids 1290 mg-4300 mg combined EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Results: Subjects experienced a statistically significant but modest 8.9 2.9 point reduction in the YMRS scores (baseline YMRS=28.9 +/- 10.1; endpoint YMRS=19.1 +/- 2.6, p < 0.001). Adverse events were few and mild. Red blood cell membrane levels of EPA and DHA increased in treated subjects. Conclusions: As only 35% of these subjects had a response by the usual accepted criteria of > 50% decrease on the YMRS, omega-3 fatty acids treatment was associated with a very modest improvement in manic symptoms in children with BPD. (c) 2007 Elsevier B. V. and ECNP. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM jwozniak@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 42 TC 69 Z9 71 U1 4 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY-JUN PY 2007 VL 17 IS 6-7 BP 440 EP 447 DI 10.1016/j.euroneuro.2006.11.006 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 163YT UT WOS:000246200000008 PM 17258897 ER PT J AU Moran-Gates, T Grady, C Park, YS Baldessarini, RJ Tarazi, FI AF Moran-Gates, Taylor Grady, Christopher Park, Young Shik Baldessarini, Ross J. Tarazi, Frank I. TI Effects of risperidone on dopamine receptor subtypes in developing rat brain SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE autoradiography; caudate-putamen; childhood-onset schizophrenia; dopamine receptors; frontal cortex; risperidone ID ATYPICAL ANTIPSYCHOTIC-DRUGS; SEROTONIN 5-HT2A; SCHIZOPHRENIA; CHILDREN; D-3; ADOLESCENTS; EXPRESSION; DISORDER; HALOPERIDOL; SENSITIVITY AB The atypical antipsychotic risperidone is often prescribed to pediatric patients with neuropsychiatric disorders, though its effects on the developing brain remain unclear. Accordingly, we studied the effects of repeated treatment of risperidone on dopamine receptors in brain regions of juvenile rat. Levels of dopamine receptors (D-1, D-2, D-3, D-4) in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0 mg/kg) and compared findings to those in adult rats treated with risperidone (3.0 mg/kg/day) previously. Risperidone (at 1.0 and 3.0 mg/kg/day) increased levels of D-1 receptors in nucleus accumbens and caudate-putamen of juvenile, but not adult rats. Conversely, all three doses of risperidone dose-dependently increased D2 labeling in media[ prefrontal cortex and hippocampus, and D4 receptor in nucleus accumbens, caudate-putamen and hippocampus of juvenile animals as well as in adults. Only the high dose of risperidone (3.0 mg/kg) increased D2 receptors in caudate-putamen in both juvenile and adult brain. D3 receptors were not altered by risperidone in any brain region at any dose or age. The findings indicate dose-dependent effects of risperidone on dopamine receptors in developing animals, and that juvenile animals are more sensitive than adults to the cerebral effects of risperidone. (C) 2006 Elsevier B. V. and ECNP. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Inje Univ, Sch Biotechnol & Biomed Sci, Kimhae 621749, South Korea. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Lab Psychiat Neurosci, 115 Mill St, Belmont, MA 02478 USA. EM ftarazi@hms.harvard.edu FU NIMH NIH HHS [R03 MH068359-02, MH-068359, R03 MH068359, R03 MH068359-01A1] NR 47 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY-JUN PY 2007 VL 17 IS 6-7 BP 448 EP 455 DI 10.1016/j.euroneuro.2006.10.004 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 163YT UT WOS:000246200000009 PM 17175142 ER PT J AU Meeran, SM Katiyar, SK AF Meeran, Syed M. Katiyar, Santosh K. TI Grape seed proanthocyanidins promote apoptosis in human epidermoid carcinoma A431 cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation via loss of mitochondrial membrane potential SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE apoptosis; cell cycle; grape seed proanthocyanidins; skin cancer ID DEPENDENT KINASE INHIBITORS; CYTOCHROME-C RELEASE; NF-KAPPA-B; POLYPHENOLIC FRACTION; INK4 INHIBITORS; SKIN-CANCER; GROWTH; BCL-2; KERATINOCYTES; INDUCTION AB Dietary grape seed proanthocyanidins (GSPs) prevent photocarcinogenesis in mice. Here, we report that in vitro treatment of human epidermoid carcinoma A431 cells with GSPs inhibited cellular proliferation (13-89%) and induced cell death (1-48%) in a dose (5-100 mu g/ml)- and time (24, 48 and 72 h)-dependent manner. GSP-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest at 24 h, which was mediated through the inhibition of cyclin-dependent kinases (Cdk) Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and simultaneous increase in protein expression of cyclin-dependent kinase inhibitors (Cdki), Cip1/p21 and Kip1/p27, and enhanced binding of Cdki-Cdk. The treatment of A431 cells with GSPs (20-80 mu g/ml) resulted in a dose-dependent increase in apoptotic cell death (26-58%), which was associated with an increased protein expression of proapoptotic Bax, decreased expression of antiapoptotic Bcl-2 and Bcl-xl, loss of mitochondrial membrane potential, and cleavage of caspase-9, caspase-3 and PARP. Pretreatment with the pan-caspase inhibitor (z-VAD-fmk) blocked the GSP-induced apoptosis in A431 cells suggesting that GSP-induced apoptosis is associated primarily with the caspase-3-dependent pathway. Together, our study suggests that GSPs possess chemotherapeutic potential against human epidermoid carcinoma cells in vitro, further in vivo mechanistic studies are required to verify the chemotherapeutic effect of GSPs in skin cancers. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCI NIH HHS [CA 104428]; NIAMS NIH HHS [AR 050948-01] NR 41 TC 39 Z9 46 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAY PY 2007 VL 16 IS 5 BP 405 EP 415 DI 10.1111/j.1600-0625.2007.00542.x PG 11 WC Dermatology SC Dermatology GA 155VC UT WOS:000245605500003 PM 17437483 ER PT J AU Barabino, S Rolando, M Chen, L Dana, MR AF Barabino, Stefano Rolando, Maurizio Chen, Lu Dana, M. Reza TI Exposure to a dry environment induces strain-specific responses in mice SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE animal model; dry eye; T cell response ID OCULAR SURFACE; KERATOCONJUNCTIVITIS SICCA; CONJUNCTIVAL EPITHELIUM; ANIMAL-MODELS; C57BL/6 MICE; EYE SYNDROME; MOUSE MODEL; TEAR FILM; T-CELLS; EXPRESSION AB Most current animal models of dry eye have a single causative mechanism and do not take into consideration the influence of environmental conditions on tear secretion and associated ocular surface signs. Since immunity and inflammation have been implicated in dry eye pathogenesis, and different mouse strains are known to have differentially biased immune responses, we conducted the present study to test the hypothesis that strains with specifically polarized T cell responses (T helper-1 [Th1] vs. T helper-2 [Th2]) develop differential signs of dry eye when exposed to a controlled low humidity setting. Eight to 12-week-old BALB/c (Th2 biased) and C57BL/6 (Th1 biased) mice were placed in a controlled environment chamber (CEC) where relative humidity (RH), temperature (T), and air flow (AF) were continuously regulated and monitored. Mice were exposed to specific environmental controlled conditions (RH = 15.5 3.8%, AF = 15 1/min, T = 21-23 degrees C for 3 to 7 days. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (NEI grading scheme, score 0-15) and goblet cell density in the superior and inferior conjunctivae were measured by a masked observer. No statistically significant differences between the groups were found at baseline. Statistically significant decreases in tear secretion were seen after exposure to the CEC environment. Mean cotton thread wetting was 1.9 +/- 0.2 (baseline), 1.4 +/- 0.3 (day 3), and 0.9 +/- 0.2 mm (day 7) for BALB/c mice, and 1.7 +/- 0.3 (baseline), 0.9 +/- 0.3 (day 3), and 0.4 +/- 0.2 mm (day 7) for C57BL/6 mice. These mice showed reduced tear secretion as compared to BALB/C at each time point tested (P < .005, t-test). Both BALB/c and C57BL/6 mice showed a significant increase in corneal fluorescein staining at both day 3 and day 7 as compared to baseline. With exposure to the CEC goblet cell density significantly decreased in the superior and inferior conjunctivae in BALB/c mice, while it remained unchanged in C57BL/6 mice. This study indicates that exposure of non-pharmacologically modified mice to a low humidity environment in the CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs which are strain-specific. () 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Ophthalmol,Lab Immunol, Massachusetts Eye & Ear Infrim,Schepens Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Cornea Serv, Boston, MA 02114 USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, Ocular Surface Res Ctr, I-16126 Genoa, Italy. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol,Lab Immunol, Massachusetts Eye & Ear Infrim,Schepens Res Inst, 20 Stanford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu OI ROLANDO, MAURIZIO/0000-0002-4982-1462 NR 25 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 2007 VL 84 IS 5 BP 973 EP 977 DI 10.1016/j.exer.2007.02.003 PG 5 WC Ophthalmology SC Ophthalmology GA 168ON UT WOS:000246534000020 PM 17397831 ER PT J AU Hadlock, T Kowaleski, J Mackinnon, S Heaton, JT AF Hadlock, Tessa Kowaleski, Jeffrey Mackinnon, Susan Heaton, James T. TI A novel method of head fixation for the study of rodent facial function SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CONDITIONED WHISKING; AWAKE RAT; NERVE; MOVEMENTS; RECOVERY; ANATOMY; INJURY; BRAIN AB The rodent vibrissial system offers an excellent model for the study of both sensory and motor function. It has been widely employed to gather data pertaining to sensory and motor function involving the 5th and 7th cranial nerves and the central nervous system. Existing methods of head fixation for precise measurements of ocular and vibrissial function involve exposing the cranium and applying dental cement from which two or more threaded rods emerge. This common approach is suboptimal, requiring a relatively complicated implantation procedure, and results in a large, chronic interface between the scalp and environmentally exposed implant material attached to the skull. Here we describe a head fixation device that is inexpensive, easy to build, less prone to infection, preserves access to the cranial midline, and permits repeated measurements over many months. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Washington, Sch Med, Div Plast & Reconstruct Surg, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu FU NIDCR NIH HHS [K08 DE015665-01A2, K08 DE015665] NR 22 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2007 VL 205 IS 1 BP 279 EP 282 DI 10.1016/j.expneurol.2007.02.014 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 166TO UT WOS:000246403400031 PM 17397835 ER PT J AU Bedlack, RS Traynor, BJ Cudkowicz, ME AF Bedlack, Richard S. Traynor, Bryan J. Cudkowicz, Merit E. TI Emerging disease-modifying therapies for the treatment of motor neuron diseasd/amyotropic lateral sclerosis SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE ALS; amyotropic lateral sclerosis; MND; motor neuron disease; neuroprotection ID TRANSGENIC MOUSE MODEL; CU/ZN SUPEROXIDE-DISMUTASE; GULF-WAR VETERANS; MUTANT SOD1; CLINICAL-TRIALS; CYCLOOXYGENASE-2 INHIBITORS; NEURODEGENERATIVE DISEASE; PROTEIN AGGREGATION; EXTEND SURVIVAL; SPINAL-CORDS AB It has been > 130 years since the first description of the upper and lower motor neuron disease called amyotropic lateral sclerosis (ALS). Sadly, there has been little change in the long interval over which this disease is diagnosed, or in its poor prognosis. Significant gains have been made, however, in understanding its pathophysiology and in symptomatic care. Disease-causing mutations have been identified and used to create animal models. Other identified mutations may increase susceptibility and cause disease only in a particular environment and at a particular age. A number of 'downstream' molecular pathways have been implicated, including transcriptional disturbances, protein aggregation, excitotoxicity, mitochondrial dysfunction, oxidative stress, neuroinflammation, cytoskeletal and axonal transport derangements, growth factor dysregulation and apoptosis. This knowledge has led to an impressive pipeline of candidate therapies that offer hope for finally being able to alter ALS disease progression. These are described and prioritized herein, and suggestions are offered for efficiently sifting through them. C1 Duke Univ, Med Ctr, Durham, NC 27705 USA. NIMH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Bedlack, RS (reprint author), Duke Univ, Med Ctr, Box 3333, Durham, NC 27705 USA. EM bedla001@mc.duke.edu RI Traynor, Bryan/G-5690-2010 FU Intramural NIH HHS NR 147 TC 13 Z9 14 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD MAY PY 2007 VL 12 IS 2 BP 229 EP 252 DI 10.1517/14728214.12.2.229 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 187CY UT WOS:000247826100006 PM 17604499 ER PT J AU Chan, JA Kulke, MH AF Chan, Jennifer A. Kulke, Matthew H. TI Emerging therapies for the treatment of patients with advanced neuroendocrine tumors SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE bevacizumab; carcinoid; mTOR; neuroendocrine tumor; pancreatic neuroendocrine tumor; radiolabeled somatostatin; sunitinib ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR RADIONUCLIDE THERAPY; ADVANCED CARCINOID-TUMORS; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; HEPATIC ARTERIAL CHEMOEMBOLIZATION; ACTING SOMATOSTATIN ANALOG; ISLET-CELL CARCINOMAS; PHASE-II; LIVER METASTASES; GASTROINTESTINAL TUMORS AB Patients with neuroendocrine tumors may pursue a number of treatment options, but there is little consensus on a single, standard treatment approach. Somatostatin analogs are generally administered to patients with symptoms of hormonal secretion, and are often highly effective in this regard. However, the administration of somatostatin analogs is only rarely associated with tumor regression, and randomized trials demonstrating a survival benefit associated with their use have not been performed. Selected patients with hepatic metastases may undergo surgical debulking, embolization or other ablative therapies. The clinical benefit associated with administration of systemic agents such as IFN-alpha or cytotoxic chemotherapy has been limited. With the possible exception of streptozocin-based therapy in patients with pancreatic neuroenclocrine tumors, the widespread use of standard cytotoxic regimens has been limited by their relatively modest antitumor activity, as well as concerns regarding their potential toxicity. The modest efficacy seen with these agents in patients with advanced neuroenclocrine tumors has led to great interest in the development of novel treatment approaches. One such approach is the use of radiolabeled somatostatin analogs. Recently, agents targeting the VEGF pathway and mammalian target of rapamycin have also shown promise in patients with advanced neuroenclocrine tumors. Ongoing randomized studies should help better define the role these agents will play in the future treatment of patients with this disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jang@partners.org NR 102 TC 11 Z9 11 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD MAY PY 2007 VL 12 IS 2 BP 253 EP 270 DI 10.1517/14728214.12.2.253 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 187CY UT WOS:000247826100007 PM 17604500 ER PT J AU Seltzer, B AF Seltzer, Ben TI Donepezil: an update SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE alzheimer's disease; cholinergic system; cholinesterase inhibitors; dementia; donepezil ID MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIAL; SEVERE ALZHEIMERS-DISEASE; CORTICAL ACETYLCHOLINESTERASE ACTIVITY; CHOLINE-ACETYLTRANSFERASE ACTIVITY; STEADY-STATE PHARMACOKINETICS; TRAUMATIC BRAIN-INJURY; SCALE CLINICAL-TRIALS; DOUBLE-BLIND; VASCULAR DEMENTIA AB Donepezil hydrochloride is the most widely prescribed drug for Alzheimer's disease (AD). The main mechanism of action through which it influences cognition and function is presumed to be the inhibition of acetylcholinesterase enzyme in the brain; however, donepezil may also impact the pathophysiology of AD at several other points. Officially approved for mild-to-moderate and severe AD, donepezil has also been shown to be effective in early-stage AD, vascular dementia, Parkinson's disease dementia/Lewy body disease and cognitive symptoms associated with multiple sclerosis. In addition, one study suggested that donepezil may delay the onset of AD in subjects with mild cognitive impairment, a prodrome to AD. The pharmacokinetics, pharmacodynamics, safety/tolerability profile and drug interaction properties of donepezil make it an easy and safe agent to use. However, in general, the efficacy of donepezil is limited, and ongoing studies are investigating other agents that may ultimately overtake its present position as the mainstay of anti-AD therapy. C1 Harvard Univ, Sch Med, Geriatr Res Ctr, VA Boston Healthcare Syst,Dept Neurol, Boston, MA 02130 USA. RP Seltzer, B (reprint author), Harvard Univ, Sch Med, Geriatr Res Ctr, VA Boston Healthcare Syst,Dept Neurol, 150 S Huntington Ave, Boston, MA 02130 USA. EM bseltzer@partners.org NR 171 TC 53 Z9 54 U1 4 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD MAY PY 2007 VL 8 IS 7 BP 1011 EP 1023 DI 10.1517/14656566.8.7.1011 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 161MM UT WOS:000246019400012 PM 17472546 ER PT J AU Gerstner, E Batchelor, T AF Gerstner, Elizabeth Batchelor, Tracy TI Primary CNS lymphoma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE chemotherapy; CNS lymphoma; diagnosis; neurotoxicity; prognosis; radiation; salvage therapy ID NERVOUS-SYSTEM LYMPHOMA; HIGH-DOSE METHOTREXATE; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; POLYMERASE-CHAIN-REACTION; RADIATION-THERAPY; PHASE-II; IMMUNOCOMPETENT PATIENTS; DEFERRED RADIOTHERAPY AB Primary CNS lymphoma, an uncommon form of extranodal non-Hodgkin's lymphoma, has increased in incidence and occurs in both immunocompromised and immunocompetent hosts. Primary CNS lymphoma in immunocompetent patients is associated with unique diagnostic, prognostic and therapeutic issues and the management of this malignancy is different from other forms of extranodal non-Hodgkin's lymphoma. Characteristic imaging features should lead to suspicion of the diagnosis, avoidance of corticosteroids (if possible) and early neurosurgical consultation for stereotactic biopsy. Since primary CNS lymphoma may involve the brain, cerebrospinal fluid and eyes, diagnostic evaluation should include assessment of all of these regions as well as screening for the possibility of occult systemic disease. Resection provides no therapeutic benefit and should be reserved for the rare patient with neurological deterioration due to brain herniation. Whole-brain radiation therapy alone is insufficient for durable tumor control and is associated with a high risk of neurotoxicity in patients over 60 years of age. Neurotoxicity is typically associated with significant cognitive, motor and autonomic dysfunction and has a negative impact on quality of life. Chemotherapy and whole-brain radiation therapy together improve tumor response rates and survival compared with whole-brain radiation therapy alone. Methotrexate-based multiagent chemotherapy without whole-brain radiation therapy is associated with similar tumor response rates and survival compared with regimens that include whole-brain radiation therapy, although controlled trials have not been performed. The risk of neurotoxicity is lower in patients treated with chemotherapy alone. The incidence of HIV-related primary CNS lymphoma has decreased in the era of highly active antiretroviral therapy. Patients with HIV-associated primary CNS lymphoma have a worse prognosis but may respond to highly active antiretroviral therapy, whole-brain radiation therapy or therapies directed against the Epstein-Barr virus. C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 70 TC 21 Z9 28 U1 0 U2 2 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAY PY 2007 VL 7 IS 5 BP 689 EP 700 DI 10.1586/14737140.7.5.689 PG 12 WC Oncology SC Oncology GA 170HX UT WOS:000246654900009 PM 17492932 ER PT J AU Levy, V Lindon, C Zheng, Y Harfe, BD Morgan, BA AF Levy, Vered Lindon, Catherine Zheng, Ying Harfe, Brian D. Morgan, Bruce A. TI Epidermal stem cells arise from the hair follicle after wounding SO FASEB JOURNAL LA English DT Article DE infundibulum; epidermis; follicular bulge; wound healing ID LABEL-RETAINING CELLS; MOUSE EPIDERMIS; PROLIFERATIVE UNIT; SKIN; IDENTIFICATION; EPITHELIA; KINETICS; BEHAVIOR; HEDGEHOG AB During normal development, the epidermis and hair follicle are distinct lineage compartments maintained by independent stem cell populations. Both epidermal and follicular keratinocytes are recruited to participate in epidermal repair in response to injury. However, it is generally thought that follicular cells contribute to the wound epidermis only transiently and are ultimately replaced by the progeny of stem cells derived from the original epidermal compartment prior to wounding. Here we use inducible and constitutive cre recombinase expressed from the Sonic hedgehog locus ( Shh) for in vivo lineage tracing. This analysis confirms that follicular cells participate in the initial resurfacing of the wound but also reveals that their progeny persist in wound epidermis for months after the wound is healed. It further demonstrates that Shh is not induced in keratinocytes during the wound healing process. We conclude that follicular cells can undergo reprogramming to become long-term repopulating epidermal progenitors following wounding. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu NR 28 TC 187 Z9 200 U1 2 U2 15 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2007 VL 21 IS 7 BP 1358 EP 1366 DI 10.1096/fj.06-6926com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 162VG UT WOS:000246117000011 PM 17255473 ER PT J AU Novgorodov, AS El-Alwani, M Bielawski, J Obeid, LM Gudz, TI AF Novgorodov, Alexander S. El-Alwani, Mazen Bielawski, Jacek Obeid, Lina M. Gudz, Tatyana I. TI Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration SO FASEB JOURNAL LA English DT Article DE brain development; S1P2 receptor; FTY720; directional guidance cue ID PROTEIN-COUPLED RECEPTORS; SPHINGOSINE 1-PHOSPHATE RECEPTOR; RHO FAMILY GTPASES; CELL-MIGRATION; AXON GUIDANCE; PROLIFERATION; MECHANISMS; FTY720; LYSOPHOSPHOLIPIDS; ANGIOGENESIS AB Sphingosine-1-phosphate (S1P) acts as an extracellular ligand for a family of G-protein coupled receptors that are crucial in cell migration. S1P5 is exclusively expressed in oligodendrocytes and oligodendrocyte precursor cells (OPCs), which migrate considerable distances during brain development. The current studies suggest a physiological role for S1P and S1P5 in regulation of OPC migration. mRNA expression levels of S1P2 and S1P5 are comparable in OPCs, but S1P binding specifically to the S1P5 receptor blocked OPC migration (IC50 = 29 nM). Thus, knocking down S1P5 using siRNA prevented the S1P-induced decrease in OPC migration, whereas knocking down S1P2 did not have any effect. S1P-induced modulation of OPC migration was insensitive to pertussis toxin, suggesting that S1P5-initiated signaling is not mediated by the G alpha(i)-protein coupled pathway. Furthermore, S1P5 appears to engage the G alpha(12/13) protein coupled Rho/ROCK signaling pathway to impede OPC migration. To modulate OPC motility, extracellular S1P could be derived from the export of intracellular S1P generated in response to glutamate treatment of OPCs. These studies suggest that S1P could be a part of the neuron-oligodendroglial communication network regulating OPC migration and may provide directional guidance cues for migrating OPCs in the developing brain. C1 Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Gudz, TI (reprint author), Med Univ S Carolina, Dept Neurosci, 114 Doughty St, Charleston, SC 29425 USA. EM gudz@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCRR NIH HHS [P20 RR 17677-04]; NIGMS NIH HHS [GM062887] NR 66 TC 80 Z9 84 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2007 VL 21 IS 7 BP 1503 EP 1514 DI 10.1096/fj.06-7420com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 162VG UT WOS:000246117000025 PM 17255471 ER PT J AU Huang, W Yang, SY Shao, JZ Li, YP AF Huang, Wei Yang, Shuying Shao, Jianzhong Li, Yi-Ping TI Signaling and transcriptional regulation in osteoblast commitment and differentiation SO FRONTIERS IN BIOSCIENCE LA English DT Review DE osteoblast; Runx2; Osterix; ATF4; SATB2; Wnt signaling; TGF-Beta signaling; hedgehog signaling; fgf signaling; ephrin signaling; sympathetic signaling; review ID MESENCHYMAL STEM-CELLS; BONE MORPHOGENETIC PROTEIN-2; RECEPTOR-RELATED PROTEIN-5; GROWTH-FACTOR-BETA; SYMPATHETIC-NERVOUS-SYSTEM; UBIQUITIN-MEDIATED DEGRADATION; HISTONE DEACETYLASE INHIBITORS; OSTEOPETROTIC RAT MUTATIONS; GLYCOGEN-SYNTHASE KINASE-3; GENE ARRAY ANALYSIS AB The major event that triggers osteogenesis is the transition of mesenchymal stem cells into bone forming, differentiating osteoblast cells. Osteoblast differentiation is the primary component of bone formation, exemplified by the synthesis, deposition and mineralization of extracellular matrix. Although not well understood, osteoblast differentiation from mesenchymal stem cells is a well-orchestrated process. Recent advances in molecular and genetic studies using gene targeting in mouse enable a better understanding of the multiple factors and signaling networks that control the differentiation process at a molecular level. Osteoblast commitment and differentiation are controlled by complex activities involving signal transduction and transcriptional regulation of gene expression. We review Wnt signaling pathway and Runx2 regulation network, which are critical for osteoblast differentiation. Many other factors and signaling pathways have been implicated in regulation of osteoblast differentiation in a network manner, such as the factors Osterix, ATF4, and SATB2 and the TGF- beta, Hedgehog, FGF, ephrin, and sympathetic signaling pathways. This review summarizes the recent advances in the studies of signaling transduction pathways and transcriptional regulation of osteoblast cell lineage commitment and differentiation. The knowledge of osteoblast commitment and differentiation should be applied towards the development of new diagnostic and therapeutic alternatives for human bone diseases. C1 Harvard Univ, Dept Cytokine Biol, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. Zhejiang Univ, Coll Life Sci, Hangzhou 310027, Peoples R China. Harvard Univ, Dept Dev Biol, Sch Dent Med, Boston, MA 02115 USA. RP Li, YP (reprint author), Harvard Univ, Dept Cytokine Biol, Sch Dent Med, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM ypli@forsyth.org RI Yang, Shuying/G-4599-2011 FU NIAMS NIH HHS [AR-48133, AR44741, R01 AR044741, R01 AR048133]; NIDCR NIH HHS [R03 DE016857] NR 264 TC 125 Z9 130 U1 0 U2 37 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2007 VL 12 BP 3068 EP 3092 DI 10.2741/2296 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 163KG UT WOS:000246157900026 PM 17485283 ER PT J AU LeGuern, C AF LeGuern, Christian TI Tolerogenic property of MHC class I and class II molecules: lessons from a gene therapy approach SO FRONTIERS IN BIOSCIENCE LA English DT Article DE major histocompatibility complex; MHC; gene therapy; regulatory T cells; T cell tolerance; peptides; review ID DENDRITIC CELLS; BONE-MARROW; BETA-GLOBIN; T-CELLS; PEPTIDES; SELF; COMPLEX; TOLERANCE; ANTIGEN; MICE AB Conditions allowing the development of a stable state of hematopoietic chimerism, i.e., the coexistence of foreign and recipient hematopoietic cells in the same individual, remain the most effective means to produce immune tolerance to antigens expressed by foreign cells/ grafts. However, heavy immunosuppression is required to achieve chimerism and as such has limited clinical application. MHC antigens being the primary targets of immune responses, we pioneered an innovative approach in which foreign MHC genes were first introduced in bone marrow cells of recipients of subsequent grafts expressing the same MHC antigens. This strategy produced MHC class I ( MHC I) or class II ( MHC II) molecular chimerism, did not require heavy conditioning, and enabled long-term transplant acceptance in rodents as well as large animals. However, recent developments have indicated, that although the outcomes of gene transfer were similar, the mechanism of tolerance induction by MHC I and MHC II gene transfer were markedly different. This review examines the tolerance mechanism arising after MHC gene transfer to infer that MHC II gene therapy is clinically more relevant since the transfer of a single gene enables broad tolerance to all graft antigens via the production of MHC II peptides for selective activation of regulatory T cells (T-regs). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, TBRC,Lab Mol Biol, Boston, MA 02115 USA. RP LeGuern, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, TBRC,Lab Mol Biol, Boston, MA 02115 USA. EM leguern@helix.mgh.harvard.edu FU NIAID NIH HHS [R01AI064344, R01AI063408] NR 47 TC 7 Z9 7 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2007 VL 12 BP 3133 EP 3139 DI 10.2741/2301 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 163KG UT WOS:000246157900031 PM 17485288 ER PT J AU Benichou, G Kant, CD Madsen, J Tocco, G AF Benichou, Gilles Kant, Cavit D. Madsen, Joren Tocco, Georges TI Modulation of alloreactivity to MHC-derived peptides and transplantation tolerance SO FRONTIERS IN BIOSCIENCE LA English DT Article DE T cells; transplantation; MHC peptides; tolerance; allorecognition; review ID MAJOR HISTOCOMPATIBILITY COMPLEX; SKIN-GRAFT REJECTION; PERSISTENT ALLOPEPTIDE REACTIVITY; RAT CARDIAC ALLOGRAFTS; T-CELL ALLOREACTIVITY; CLASS-I ANTIGENS; ACQUIRED THYMIC TOLERANCE; HLA-DR PEPTIDES; INDIRECT RECOGNITION; INDIRECT ALLORECOGNITION AB The recognition by T cells of intact foreign MHC molecules at the surface of transplanted cells ( direct pathway) was originally thought to represent the driving force behind acute rejection of allogeneic transplants. Over the past decade, however, a body of evidence has been provided demonstrating that T cell recognition of donor peptides presented by recipient APCs ( indirect pathway) is sufficient on its own to ensure both acute and chronic rejection of allografts. While the direct allorecognition leads to an exceptionally vigorous inflammatory T cell response, it is thought to be short lived due to the rapid depletion of donor professional APCs and it can be controlled with a short course of immunosuppressive drugs including calcineurin inhibitors. In contrast, while the indirect alloresponse is oligoclonal and much weaker, it is long-lived and tends to spread to formerly cryptic determinants on donor and self-tissue specific antigens. This feature of indirect alloreactivity is presumably associated with the sustained presence of recipient professional APCs that can maintain a chronic inflammatory response similar to that observed in autoimmune diseases. Consequently, the indirect alloresponse may be more difficult to suppress than its direct counterpart. On the other hand, there is accumulating evidence showing that administration of alloantigen in a "tolerogenic fashion" mediates allograft acceptance via the activation of regulatory T cells recognizing donor antigens via the indirect allorecognition pathway. Apparently, these regulatory T cells can suppress both direct and indirect inflammatory T cell responses to donor antigens. This suggests that modulation of indirect alloreactivity may represent the best strategy to achieve long-term donor-specific tolerance to allotransplants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit,Cellular & Mol Immuno, Boston, MA 02114 USA. RP Benichou, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit,Cellular & Mol Immuno, 55 Fruit St,Their 807, Boston, MA 02114 USA. EM gbenichou@partners.org FU NIAID NIH HHS [K02-AI53103, AI-1066705]; NICHD NIH HHS [R01-HD050484] NR 95 TC 4 Z9 6 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2007 VL 12 BP 4239 EP 4247 DI 10.2741/2383 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 163KG UT WOS:000246157900113 PM 17485370 ER PT J AU Ochiai, T Benichou, G Cosimi, AB Kawai, T AF Ochiai, Takanori Benichou, Gilles Cosimi, A. Benedict Kawai, Tatsuo TI Induction of allograft tolerance in nonhuman primates and humans SO FRONTIERS IN BIOSCIENCE LA English DT Article DE transplantation; immune tolerance; chimerism; costimulatory blockade; non-human primates; review ID DONOR BONE-MARROW; STAGE RENAL-DISEASE; REGULATORY T-CELLS; ORGAN-TRANSPLANTATION; LYMPHOHEMATOPOIETIC CHIMERISM; OPERATIONAL TOLERANCE; MONOCLONAL-ANTIBODIES; CYNOMOLGUS MONKEYS; KIDNEY ALLOGRAFTS; MULTIPLE-MYELOMA AB Despite remarkable improvement in short-term survival following organ transplantation, long-term results have been less satisfactory, mainly due to chronic rejection or toxicities induced by immunosuppressive drugs. Therefore, induction of specific immunologic tolerance remains an important goal in organ transplantation. Although numerous regimens for the induction of allograft tolerance have been developed in rodents, their application to large animal models has been limited. The mechanisms of action of the approaches that have been successfully applied in monkey models can be divided into three major categories: 1) deletion, 2) co-stimulatory blockade and 3) regulation. Long-term allograft survival has now been achieved in several nonhuman primate models; however, late- onset chronic rejection as well as the toxicity of some of these regimens remain as significant limitations that hamper clinical application. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, White 510,55 Fruit St, Boston, MA 02114 USA. EM tkawai@partners.org FU NHLBI NIH HHS [5P01 HL 1864625]; NIAID NIH HHS [R01 AI037692, R01 AI037692-09, 2R01 AI37692006A1, R21 AI037692, R21 AI037692-06, R01 AI037692-10] NR 44 TC 8 Z9 8 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2007 VL 12 BP 4248 EP 4253 DI 10.2741/2384 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 163KG UT WOS:000246157900114 PM 17485371 ER PT J AU Benichou, G Alessandrini, A Charrad, RS Wilkes, DS AF Benichou, Gilles Alessandrini, Alessandro Charrad, Rachida-Sihem Wilkes, David S. TI Induction of autoimmunity after allotransplantation SO FRONTIERS IN BIOSCIENCE LA English DT Article DE autoimmune disease; transplantation; T cells; allorecognition; lung; heart; review ID MINOR HISTOCOMPATIBILITY ANTIGENS; LUNG ALLOGRAFT-REJECTION; T-CELL REPERTOIRE; CARDIAC MYOSIN; HEART-TRANSPLANTATION; INDIRECT RECOGNITION; COMPLEX PEPTIDES; GRAFT-REJECTION; ORAL TOLERANCE; SELF-ANTIGEN AB Our studies show that activated autoreactive inflammatory T cells specific and autoantibodies to collagen ( V) and cardiac myosin are consistently detected after lung and heart transplantation, respectively. Clonal expansion of these T cells occurs only after an alloresponse, but once activated they can induce on their own rejection of allogeneic and even syngeneic transplants. Indirect rather than indirect alloresponse triggers autoimmunity after transplantation presumably via antigen mimicry between autoantigen peptides and donor MHC peptides. Also, it is plausible that inflammation and tissue damage associated with initial alloresponse to donor MHC antigens causes the release of formerly sequestered autoantigens. This may result in the presentation of some cryptic self- determinants thereby triggering an autoimmune process at the site of the graft. Finally, tolerance induction to cardiac myosin and collagen ( V) results in long- term survival and reduced pathogenesis of heart and lung allografts, respectively. This suggests that, after transplantation, the inflammatory alloresponse to donor MHC triggers a cascade of events including autoimmunity to tissue antigens, a phenomenon that is essential to the actual rejection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, Boston, MA 02114 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA. Indiana Univ, Sch Med, Ctr Immunobiol, Indianapolis, IN USA. RP Benichou, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, 55 Fruit St,Their 807, Boston, MA 02114 USA. EM gbenichou@partners.org FU NHLBI NIH HHS [R01HL/AL67177, R01HL60797]; NIAID NIH HHS [AI-1066705, KO2-AI53103]; NICHD NIH HHS [R01-HD050484] NR 56 TC 11 Z9 11 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2007 VL 12 BP 4362 EP 4369 DI 10.2741/2393 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 163KG UT WOS:000246157900123 PM 17485380 ER PT J AU Sykes, M AF Sykes, Megan TI Mechanisms of tolerance induced via mixed chimerism SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE tolerance; mixed chimerism; costimulatory; blockade; anti-CD154; review ID BONE-MARROW-TRANSPLANTATION; TOTAL LYMPHOID IRRADIATION; ANTI-CD154 MONOCLONAL-ANTIBODY; TERM ALLOGRAFT SURVIVAL; REGULATORY T-CELLS; DONOR-SPECIFIC TRANSFUSION; HEMATOPOIETIC STEM-CELLS; MAJOR HISTOCOMPATIBILITY BARRIERS; WHOLE-BODY IRRADIATION; NATURAL-KILLER-CELLS AB Mixed hematopoietic chimerism provides a powerful means of inducing robust, donor-specific tolerance. In this article, the minimal requirements for achieving mixed chimerism, the development of new reagents that promote its achievement, and the mechanisms by which peripheral and intrathymic tolerance are achieved via mixed chimerism are discussed. An emerging understanding of these mechanisms, along with the development of new immunosuppressive reagents, is allowing advancement toward clinical application of this approach. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Biol Res Ctr, MGH E,Bldg 149-5102 13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL18646, R01 HL49915] NR 143 TC 19 Z9 19 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD MAY 1 PY 2007 VL 12 BP 2922 EP 2934 DI 10.2741/2282 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 163KG UT WOS:000246157900012 PM 17485269 ER PT J AU Shoelson, SE Herrero, L Naaz, A AF Shoelson, Steven E. Herrero, Laura Naaz, Afia TI Obesity, inflammation, and insulin resistance SO GASTROENTEROLOGY LA English DT Review ID NECROSIS-FACTOR-ALPHA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; TYPE-2 DIABETES-MELLITUS; C-REACTIVE PROTEIN; FACTOR-KAPPA-B; IMPAIRED GLUCOSE-TOLERANCE; INNATE IMMUNE-SYSTEM; ADIPOSE-TISSUE; WEIGHT-LOSS; METABOLIC SYNDROME AB Weight gain and obesity are major risk factors for conditions and diseases ranging from insulin resistance and type 2 diabetes mellitus to atherosclerosis and the sequelae of nonalcoholic fatty liver disease. A chronic, subacute state of inflammation often accompanies the accumulation of excess lipid in adipose tissue and liver (hepatic steatosis), evidenced by changes in both inflammatory cells and biochemical markers of inflammation. These changes can be seen in the involved tissues and systemically, in terms of elevated circulating levels of inflammatory markers. The link between obesity and inflammation has therefore raised the important question of whether obesity-induced inflammation plays a pathogenic role in the development and progression of these disorders. We review the rapidly expanding body of animal and clinical data that support potential roles for inflammation in the pathogenesis of insulin resistance and type 2 diabetes mellitus. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM steven.shoelson@joslin.harvard.edu RI Herrero, Laura/D-4011-2014 OI Herrero, Laura/0000-0003-4244-4673 FU NHLBI NIH HHS [HL83813]; NIDDK NIH HHS [DK43123, DK45943, DK51729, DK73547, DK74556] NR 137 TC 733 Z9 763 U1 23 U2 120 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2007 VL 132 IS 6 BP 2169 EP 2180 DI 10.1053/j.gastro.2007.03.059 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 166UA UT WOS:000246404700007 PM 17498510 ER PT J AU Kaplan, LM Klein, S Boden, G Brenner, DA Gostout, CJ Lavine, JE Popkin, BM Schirmer, BD Seeley, RJ Yanovski, SZ Cominelli, F AF Kaplan, Lee M. Klein, Samuel Boden, Guenther Brenner, David A. Gostout, Christopher J. Lavine, Joel E. Popkin, Barry M. Schirmer, Bruce D. Seeley, Randy J. Yanovski, Susan Z. Cominelli, Fabio TI Report of the American Gastroenterological Association (AGA) Institute Obesity Task Force SO GASTROENTEROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Washington Univ, Div Geriatr, St Louis, MO USA. Temple Univ, Div Endocrinol & Metab, Philadelphia, PA 19122 USA. Columbia Univ, Dept Med, New York, NY 10027 USA. Mayo Clin, Rochester, MN USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Univ N Carolina, Div Nutr Epidemiol, Chapel Hill, NC 27515 USA. Univ Virginia, Laparoscop Inst, Charlottesville, VA 22903 USA. Univ Cincinnati, Genome Res Ctr, Cincinnati, OH 45221 USA. NIDDKD, Bethesda, MD 20892 USA. Univ Virginia, Dept Gastroenterol & Hepatol, Charlottesville, VA 22903 USA. RP Kaplan, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. OI popkin, barry/0000-0001-9495-9324; Seeley, Randy/0000-0002-3721-5625 NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2007 VL 132 IS 6 BP 2272 EP 2275 DI 10.1053/j.gastro.2007.03.061 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 166UA UT WOS:000246404700014 PM 17498517 ER PT J AU Lieberman, D Nadel, M Smith, RA Atkin, W Duggirala, SB Fletcher, R Glick, SN Johnson, CD Levin, TR Pope, JB Potter, MB Ransohoff, D Rex, D Schoen, R Schroy, P Winawer, S AF Lieberman, David Nadel, Marion Smith, Robert A. Atkin, Wendy Duggirala, Subash B. Fletcher, Robert Glick, Seth N. Johnson, C. Daniel Levin, Theodore R. Pope, John B. Potter, Michael B. Ransohoff, David Rex, Douglas Schoen, Robert Schroy, Paul Winawer, Sidney TI Standardized colonoscopy reporting and data system: report of the Quality Assurance Task Group of the National Colorectal Cancer Roundtable SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID FLEXIBLE SIGMOIDOSCOPY; ASA CLASSIFICATION; ADENOMA DETECTION; CT COLONOGRAPHY; AVERAGE-RISK; SURVEILLANCE; POLYPECTOMY; GUIDELINES; SOCIETY; UPDATE AB Background: Standardized reporting systems for diagnostic and screening tests facilitate quality improvement programs and clear communication among health care providers. Although colonoscopy is commonly used for screening, diagnosis, and therapy, no standardized reporting system for this procedure currently exists. The Quality Assurance Task Group of the National Colorectal Cancer Roundtable developed a reporting and data system for colonoscopy based on continuous quality improvement indicators. Design: The Task Group systematically reviewed quality indicators recommended by the Multi-Society Task Force on Colorectal Cancer and developed consensus-based terminology for reporting and data systems to capture these data elements. The Task Group included experts in several disciplines: gastroenterology, primary care, diagnostic imaging, and health care delivery. Results and Conclusions: The standardized colonoscopy reporting and data system provides a tool that can be used for efforts in continuous quality improvement within and across practices that use colonoscopy. C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. Amer Canc Soc, Atlanta, GA 30329 USA. Ctr Medicare Serv, Chron Care Policy Grp, Baltimore, MD USA. Ctr Medicaid Serv, Chron Care Policy Grp, Baltimore, MD USA. Harvard Univ, Sch Med, Dept Ambulatory Care, Boston, MA USA. Harvard Univ, Sch Med, Dept Prevent Epidemiol & Social Med, Boston, MA USA. Univ Penn, Penn Presbyterian Med Ctr, Dept Med Imaging, Philadelphia, PA 19104 USA. Mayo Clin, Dept Radiol, Rochester, MN USA. Kaiser Permanente Med Ctr, Dept Gastroenterol, Walnut Creek, CA USA. Louisiana State Univ, Hlth Sci Ctr, Dept Family Med, Shreveport, LA 71105 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Indiana Univ, Sch Med, Div Gastroenterol, Indianapolis, IN USA. Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. Boston Univ, Sch Med, Gastroenterol Sect, Boston, MA 02118 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Serv Gastroenterol & Nutr, New York, NY 10021 USA. St Marks Hosp, Canc Res UK, Colorectal Canc Unit, Harrow, Middx, England. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97239 USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-GI,POB 1034, Portland, OR 97239 USA. OI Atkin, Wendy/0000-0001-9073-9658 NR 32 TC 158 Z9 159 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2007 VL 65 IS 6 BP 757 EP 766 DI 10.1016/j.gie.2006.12.055 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164EW UT WOS:000246217300003 PM 17466195 ER PT J AU Vosburgh, KG Stylopoulos, N Estepar, RSJ Ellis, RE Samset, E Thompson, CC AF Vosburgh, Kirby G. Stylopoulos, Nicholas Estepar, Raul San Jose Ellis, Randy E. Samset, Eigil Thompson, Christopher C. TI EUS with CT improves efficiency and structure identification over conventional EUS SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID PANCREATIC MASSES; ULTRASOUND AB Background: EUS is complicated because of the subtleties of US interpretation, small fields of observation, and uncertainty of probe position and orientation. Objective: Improved EUS performance is sought by providing contextual information to support US probe positioning and identification of features in US images. Our aims were to demonstrate the feasibility of the image registered gastroscopic US (IRGUS) system in a porcine model and to compare the effectiveness and the efficiency of IRGUS with traditional EUS. Design: Animal feasibility study. Interventions: The IRGUS system uses preprocedure CT and miniature US probe trackers to create real-time synthetic displays of the position of the probe tip and a matched slice of CT data for comparison with the US image. Participants used EUS and IRGUS systems in a porcine model to evaluate the speed and accuracy of structure identification. Main Outcome Measurements: The performance and utility of lRGUS were determined by the number of correctly identified structures in a timed trial, kinematic variables, and a structured survey Results: IRGUS was twice as effective as EUS in localizing and identifying individual structures. In timed trials, IRGUS users identified over 25% more structures than EUS users. Improvement in examination efficiency and accuracy of feature identification was statistically significant, and 90% of the users preferred IRGUS to EUS for these tasks. Conclusions: IRGUS appears feasible and may be superior to conventional EUS in efficiency and accuracy of probe positioning and in image interpretation. IRGUS has the potential to shorten the EUS learning curve and to broaden the adoption of EUS techniques by gastroenterologists. C1 Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Vosburgh, KG (reprint author), Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Dept Surg, 165 Cambridge St,Ste 702, Boston, MA 02114 USA. NR 10 TC 15 Z9 15 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2007 VL 65 IS 6 BP 866 EP 870 DI 10.1016/j.gie.2006.09.021 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164EW UT WOS:000246217300018 PM 17466206 ER PT J AU Vakoc, BJ Shishko, M Yun, SH Oh, WY Suter, MJ Desjardins, AE Evans, JA Nishioka, NS Tearney, GJ Bouma, BE AF Vakoc, Benjamin J. Shishko, Milen Yun, Seok H. Oh, Wang-Yuhl Suter, Melissa J. Desjardins, Adrien E. Evans, John A. Nishioka, Norman S. Tearney, Guillermo J. Bouma, Brett E. TI Comprehensive esophageal microscopy by using optical frequency-domain imaging (with video) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COHERENCE TOMOGRAPHY; GI TRACT; BARRETTS-ESOPHAGUS; DYSPLASIA; DIAGNOSIS AB Background: Optical coherence tomography (OCT) has been used for high-resolution endoscopic imaging and diagnosis of specialized intestinal metaplasia, dysplasia, and intramucosal carcinoma of the esophagus. However, the relatively slow image-acquisition rate of the present OCT systems inhibits wide-field imaging and limits the clinical utility of OCT for diagnostic imaging in patients with Barrett's esophagus. Objective: This study describes a new optical imaging technology optical frequency-domain imaging (OFDI), derived from OCT, that enables comprehensive imaging of large esophageal segments with microscopic resolution. Design: A prototype OFDI system was developed for endoscopic imaging. The system was used in combination with a balloon-centering catheter to comprehensively image the distal esophagus in swine. Results: Volumetric images of the mucosa and portions of the muscularis propria were obtained for 4.5-cm-long segments. Image resolution was 7 mu m in depth and 30 mu m parallel to the lumen, and provided clear delineation of each mucosal layer. The 3-dimensional data sets were used to create cross-sectional microscopic images, as well as vascular maps of the esophagus. Submucosal vessels and capillaries were visualized by using Doppler-flow processing. Conclusions: Comprehensive microscopic imaging of the distal esophagus in vivo by using OFDI is feasible. The unique capabilities of this technology for obtaining detailed information of tissue microstructure over large mucosal areas may open up new possibilities for improving the management of patients with Barrett's esophagus. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. Duke Univ, Med Ctr, GI Div, Durham, NC USA. RP Bouma, BE (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard MIT Div Hlth Sci & Technol, 55 Fruit St, Boston, MA 02114 USA. RI Oh, Wang-Yuhl/C-2055-2011 FU NCI NIH HHS [R01 CA103769, R01 CA103769-03, R33 CA110130, R33 CA110130-02]; NCRR NIH HHS [R01 RR0119768, R01 RR019768-03] NR 19 TC 83 Z9 83 U1 2 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2007 VL 65 IS 6 BP 898 EP 905 DI 10.1016/j.gie.2006.08.009 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164EW UT WOS:000246217300024 PM 17383652 ER PT J AU Capito, RM Spector, M AF Capito, R. M. Spector, M. TI Collagen scaffolds for nonviral IGF-1 gene delivery in articular cartilage tissue engineering SO GENE THERAPY LA English DT Article DE nonviral gene delivery; collagen scaffolds; cartilage tissue engineering ID GROWTH-FACTOR-I; MESENCHYMAL STEM-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; MATRIX SYNTHESIS; PLASMID DNA; CHONDROCYTES; INSULIN; REPAIR; VIVO; PROLIFERATION AB This study investigated the use of a type II collagen-glycosaminoglycan (CG) scaffold as a nonviral gene delivery vehicle for facilitating gene transfer to seeded adult articular chondrocytes to produce an elevated, prolonged and local expression of insulin-like growth factor (IGF)-1 for enhancing cartilage regeneration. Gene-supplemented CG (GSCG) scaffolds were synthesized by two methods: (1) soaking a pre-cross-linked CG scaffold in a plasmid solution followed by a freeze-drying process, and (2) chemically cross-linking the plasmid DNA to the scaffold. Two different plasmid solutions were also compared: (1) naked plasmid IGF-1 alone, and (2) plasmid IGF-1 with a lipid transfection reagent. Plasmid release studies revealed that cross-linking the plasmid to the CG scaffold prevented passive bolus release of plasmid and resulted in vector release controlled by scaffold degradation. In chondrocyte-seeded GSCG scaffolds, prolonged and elevated IGF-1 expression was enhanced by using the cross-linking method of plasmid incorporation along with the addition of the transfection reagent. The sustained level of IGF-1 overexpression resulted in significantly higher amounts of tissue formation, chondrocyte-like cells, GAG accumulation, and type II collagen production, compared to control scaffolds. These findings demonstrate that CG scaffolds can serve as nonviral gene delivery vehicles of microgram amounts of IGF-1 plasmid (< 10 mg per scaffold) to provide a locally sustained therapeutic level of overexpressed IGF-1, resulting in enhanced cartilage formation. C1 VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, 150 S Huntington Ave,MS 151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Shah, Ramille/E-3737-2010 NR 37 TC 71 Z9 75 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 2007 VL 14 IS 9 BP 721 EP 732 DI 10.1038/sj.gt.3302918 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 157SU UT WOS:000245742000002 PM 17315042 ER PT J AU Nowak, J Kalinka-Warzocha, E Juszczynski, P Bilinski, P Mika-Witkowska, R Zajko, M Bienvenu, J Coiffier, B Salles, G Warzocha, K AF Nowak, Jacek Kalinka-Warzocha, Ewa Juszczynski, Przemyslaw Bilinski, Przemyslaw Mika-Witkowska, Renata Zajko, Malgorzata Bienvenu, Jacques Coiffier, Bertrand Salles, Gilles Warzocha, Krzysztof TI Association of human leukocyte antigen ancestral haplotype 8.1 with adverse outcome of non-Hodgkin's lymphoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID TUMOR-NECROSIS-FACTOR; B-CELL-LYMPHOMA; LIGAND-RECEPTOR SYSTEM; NF-KAPPA-B; GENETIC POLYMORPHISMS; FOLLICULAR LYMPHOMA; LYMPHOTOXIN-ALPHA; FACTOR FAMILY; CLASS-II; ALLELES AB Previous reports have implicated the tumor necrosis factor (TNF-308) locus to non-Hodgkin's lymphoma (NHL) outcome. The purpose of the study was to examine other chromosome components of the HILA 8.1 ancestral haplotype (AH) and their relation to the clinical course of INHL. HLA class I, II, TNF-308, and lymphotoxin alpha (LTA(+252)) alleles were analyzed in 154 newly diagnosed NHL patients. Three locus haplotypes were inferred from the unphased genotypes by a Bayesian implementation of the expectation maximization (EM) algorithm using the PHASE 2.1 program. TNF-308A was the only allele associated with fever, poor performance status, elevated beta 2-microglobulin, TNIF and its p75 receptor plasma levels. Although TNF-308A was in strong linkage disequilibrium with the remaining alleles of 8.1 AH, only HLA-A*01 and HLA-B*08 showed association with prognostic variables. A part of 8.1 AH (A*01-B*08-TNF-308A) was predictive for shorter freedom from progression and overall survival (RR = 2.47, P = 0.04 1; RR = 3.15; P = 0.0049), an association that was stronger than TIN F-308A alone and independent from International Prognostic Index (IRR = 1.55, P < 0.001; RR = 2.36; P < 0.0001). A*01-B*08-TNF-308A fragment of 8.IAH remained an independent predictive factor in a multivariate model. We conclude that 8.1 AH is an important contributor to NHL outcome. In contrast to A*01-8*08-TNF-308A, the remaining alleles (Cw*07, DRBI*03, LTA(+252G)) associated with the 8.1 AH seem to be its passive components. (c) 2007 Wiley-Liss, Inc. C1 Inst Hematol & Blood Transfus, PL-02776 Warsaw, Poland. Reg Oncol Ctr, Lodz, Poland. Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Hosp Lyon Sud, Hospices Civils Lyon, Immunol Lab, F-69310 Pierre Benite, France. Hematol Serv, Pierre Benite, France. RP Warzocha, K (reprint author), Inst Hematol & Blood Transfus, 14 Indira Gandhi St, PL-02776 Warsaw, Poland. EM warzocha@ihit.waw.pl RI Bilinski, Przemyslaw/K-5055-2012; Nowak, Jacek/B-8045-2009; OI Nowak, Jacek/0000-0002-3474-7597 NR 30 TC 16 Z9 18 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2007 VL 46 IS 5 BP 500 EP 507 DI 10.1002/gcc.20436 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 145ZO UT WOS:000244904500010 PM 17311253 ER PT J AU Chiaretti, S Tavolaro, S Ghia, EM Ariola, C Matteucci, C Elia, L Maggio, R Messina, M Ricciardi, MR Vitale, A Ritz, J Mecucci, C Guarini, A Foa, R AF Chiaretti, Sabina Tavolaro, Simona Ghia, Emanuela Maria Ariola, Cristina Matteucci, Caterina Elia, Loredana Maggio, Roberta Messina, Monica Ricciardi, Maria Rosaria Vitale, Antonella Ritz, Jerome Mecucci, Cristina Guarini, Anna Foa, Robin TI Characterization of ABL1 expression in adult T-cell acute lymphoblastic leukemia by oligonucleotide array analysis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE NUP214/ABL1; T-lineage acute lymphoblastic leukemia; gene expression profile; ABL1 expression ID COMPARATIVE GENOMIC HYBRIDIZATION; ACUTE MYELOID-LEUKEMIA; GENE; AMPLIFICATION; TRANSFORMATION; REARRANGEMENT; PROTEIN; FUSION; CLASSIFICATION; NUP214-ABL1 AB Background and Objectives Recent data have highlighted an involvement of ABL1 in T-cell acute lymphoblastic leukemia (T-ALL). Specifically, the presence of a fusion gene involving ABL1 and NUP214, both located at 9q34, has been reported. We sought to evaluate whether TALL patients with overexpression of ABL showed a peculiar gene expression pattern and were characterized by having specific rearrangements. Design and Methods We previously assessed the expression profile of 128 adults with ALL by oligonucleotide arrays: 33 had T-ALL. In the current study, we evaluated the expression levels of ABL1 in T-ALL cases and found three patients who had ABL1 levels comparable to those detected in BCR/ABL(+) cases and one who had a significantly higher level of ABL1 expression. In order to establish the incidence of ABL1 overexpression in TALL, we evaluated 17 additional patients by quantitative (Q)-polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. Results The three cases with ABL1 expression levels comparable to those found in BCR/ABL1 cases had a specific signature characterized by a high expression of genes involved in regulation of transcription. The fourth case, with the highest levels of ABL1, harbored the NUP214-ABL1 rearrangement, which was confirmed by fluorescence in situ hybridization (FISH). Three of the four patients were refractory to induction chemotherapy. Of the 17 additional patients evaluated by Q-PCR and RT-PCR, none showed ABL1 overexpression. Interpretation and Conclusions Overall, overexpression of ABL1 was found in 8% of T-ALL cases. These results underline the value of microarray analyses for the identification of specific signatures associated with ABL1 overexpression, as well as rearrangements, e.g. NUP214-ABL1, in adult T-ALL. C1 Univ Roma La Sapienza, Div Hematol, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy. Univ Perugia, Policlin Monteluce, Hematol & Bone Marrow Transplantat Unit, I-06100 Perugia, Italy. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Foa, R (reprint author), Univ Roma La Sapienza, Div Hematol, Dept Cellular Biotechnol & Hematol, Via Benevento 6, I-00161 Rome, Italy. EM rfoa@bce.uniroma1.it NR 35 TC 8 Z9 8 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAY PY 2007 VL 92 IS 5 BP 619 EP 626 DI 10.3324/haematol.10865 PG 8 WC Hematology SC Hematology GA 165YD UT WOS:000246342800008 PM 17488685 ER PT J AU Eathiraju, S Mudgal, CS Jupiter, JB AF Eathiraju, Srikanth Mudgal, Chaitanya S. Jupiter, Jesse B. TI Monteggia fracture-dislocations SO HAND CLINICS LA English DT Article ID RADIO-ULNAR JOINT; ROTATORY INSTABILITY; INTERNAL-FIXATION; NERVE ENTRAPMENT; GALEAZZI LESIONS; OPEN REDUCTION; ELBOW; HEAD; STABILITY; FOREARM AB Monteggia fracture-dislocations remain a relatively uncommon injury. Prompt recognition of this injury is imperative. The character of the ulnar fracture is useful in determining optimal treatment. It is imperative to look for associated injuries of the radial head and coronoid, which alter the management and lead to altered outcomes. C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 56 TC 19 Z9 19 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD MAY PY 2007 VL 23 IS 2 BP 165 EP + DI 10.1016/j.hcl.2007.01.008 PG 14 WC Orthopedics SC Orthopedics GA 182XF UT WOS:000247536600004 PM 17548008 ER PT J AU O'Connor, AM Wennberg, JE Legare, F Llewellyn-Thomas, HA Moulton, BW Sepucha, KR Sodano, AG King, JS AF O'Connor, Annette M. Wennberg, John E. Legare, France Llewellyn-Thomas, Hilary A. Moulton, Benjamin W. Sepucha, Karen R. Sodano, Andrea G. King, Jaime S. TI Toward the 'tipping point': Decision aids and informed patient choice SO HEALTH AFFAIRS LA English DT Article ID TRIAL; OUTCOMES AB Preference-sensitive treatment decisions involve making value trade-offs between benefits and harms that should depend on informed patient choice. There is strong evidence that patient decision aids not only improve decision quality but also prevent the overuse of options that informed patients do not value. This paper discusses progress in implementing decision aids and the policy prospects for reaching a "tipping point" in the adoption of "informed patient choice" as a standard of practice. C1 Univ Ottawa, Sch Nursing, Ottawa, ON K1N 6N5, Canada. Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1N 6N5, Canada. Univ Ottawa, Tier Canada Res Chair 1, Ottawa, ON K1N 6N5, Canada. Dartmouth Coll Sch Med, CECS, Hanover, NH USA. Univ Laval, Tier Canada Res Chair 2, Quebec City, PQ G1K 7P4, Canada. Univ Laval, Dept Family Med, Quebec City, PQ G1K 7P4, Canada. Amer Soc Law Med & Eth, Boston, MA USA. Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP O'Connor, AM (reprint author), Univ Ottawa, Sch Nursing, Ottawa, ON K1N 6N5, Canada. EM aoconnor@ohri.ca NR 23 TC 201 Z9 202 U1 5 U2 17 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2007 VL 26 IS 3 BP 716 EP 725 DI 10.1377/hlthaff.26.3.716 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 167NL UT WOS:000246458300015 PM 17485749 ER PT J AU Buerhaus, PI Donelan, K Ulrich, BT Norman, L DesRoches, C Dittus, R AF Buerhaus, Peter I. Donelan, Karen Ulrich, Beth T. Norman, Linda DesRoches, Catherine Dittus, Robert TI Impact of the nurse shortage on hospital patient care: Comparative perspectives - Physicians and hospital executives often do not associate nurses with patient safety and early detection of complications. SO HEALTH AFFAIRS LA English DT Article AB National surveys of registered nurses, physicians, and hospital executives document considerable concern about the U.S. nurse shortage. Substantial proportions of respondents perceived negative impacts on care processes, hospital capacity, nursing practice, and the Institute of Medicine's six aims for improving health care systems. There were also many areas of divergent opinion within and among these groups, including the impact of the shortage on safety and early detection of patient complications. These divergences in perceptions could be important barriers to resolving the current nurse shortage and improving the quality and safety of patient care. C1 Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Gannett Healthcare Grp, Dallas, TX USA. Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37240 USA. Vet Affairs Tennessee Valley Healthcare, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN 37240 USA. EM Peter.Buerhaus@vanderbilt.edu NR 14 TC 40 Z9 40 U1 0 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2007 VL 26 IS 3 BP 853 EP 862 DI 10.1377/hlthaff.26.3.853 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 167NL UT WOS:000246458300032 PM 17485766 ER PT J AU Jaradat, AK Biggs, PJ AF Jaradat, Adnan K. Biggs, Peter J. TI Tenth value layers for Co-60 gamma rays and for 4, 6, 10, 15, and 18 MV X rays in concrete for beams of cone angles between 0 degrees and 14 degrees calculated by Monte Carlo simulation SO HEALTH PHYSICS LA English DT Article DE shielding; accelerators; medical; Monte Carlo; photons ID SCATTERING ANGLES; PHOTON BEAMS; LEAD; ACCELERATORS; FACILITIES; FRACTIONS; SPECTRA; PROGRAM; CODE AB The calculation of shielding barrier thicknesses for radiation therapy facilities according to the NCRP formalism is based on the use of broad beams (that is, the maximum possible field sizes). However, in practice, treatment fields used in radiation therapy are, on average, less than half the maximum size. Indeed, many contemporary treatment techniques call for reduced field sizes to reduce co-morbidity and the risk of second cancers. Therefore, published tenth value layers (TVLs) for shielding materials do not apply to these very small fields. There is, hence, a need to determine the TVLs for various beam modalities as a function of field size. The attenuation of Co-60 gamma rays and photons of 4, 6, 10, 15, and 18 MV bremsstrahlung x ray beams by concrete has been studied using the Monte Carlo technique (MCNP version 4C2) for beams of half-opening angles of 0 degrees, 3 degrees, 6 degrees, 9 degrees, 12 degrees, and 14 degrees. The distance between the x-ray source and the distal surface of the shielding wall was fixed at 600 cm, a distance that is typical for modern radiation therapy rooms. The maximum concrete thickness varied between 76.5 cm and 151.5 cm for Co-60 and 18 MV x rays, respectively. Detectors were placed at 630 cm, 700 cm, and 800 cm from the source. TVLs have been determined down to the third TVL. Energy spectra for 4, 6, 109 15, and 18 MV x rays for 10 X 10 cm(2) and 40 X 40 cm(2) field sizes were used to generate depth dose curves in water that were compared with experimentally measured values. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Massachusetts, Dept Phys, Lowell, MA 01854 USA. RP Biggs, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM pjbiggs@partners.org NR 25 TC 4 Z9 4 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2007 VL 92 IS 5 BP 456 EP 463 DI 10.1097/01.HP.0000254920.02129.fd PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 159IM UT WOS:000245859000005 PM 17429304 ER PT J AU Martinez-Monedero, R Oshima, K Heller, S Edge, ASB AF Martinez-Monedero, Rodrigo Oshima, Kazuo Heller, Stefan Edge, Albert S. B. TI The potential role of endogenous stem cells in regeneration of the inner ear SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT Inner Ear Biology Workshop Symposium on Terminal Differentiation - A Challenge in regeneration CY SEP 17, 2005 CL Tubingen, GERMANY DE stem cells; hair cells; spiral ganglion; regeneration ID NEURAL PROGENITOR CELLS; PANCREATIC BETA-CELLS; HAIR-CELLS; COCHLEAR NERVE; AUDITORY NEUROPATHY; SUPPORTING CELLS; SPIRAL GANGLION; ACOUSTIC TRAUMA; HEARING-LOSS; DEGENERATION AB Stem cells in various mammalian organs retain the capacity to renew themselves and may be able to restore damaged tissue. Their existence has been proven by genetic tracer studies that demonstrate their differentiation into multiple tissue types and by their ability to self-renew through proliferation. Stem cells from the adult nervous system proliferate to form clonal floating colonies called spheres in vitro, and recent studies have demonstrated sphere formation by cells in the cochlea in addition to the vestibular system and the auditory ganglia, indicating that these tissues contain cells with stem cell properties. The presence of stem cells in the inner ear raises the hope of regeneration of mammalian inner ear cells but is difficult to correlate with the lack of spontaneous regeneration seen in the inner ear after tissue damage. Loss of stem cells postnatally in the cochlea may correlate with the loss of regenerative capacity and may limit our ability to stimulate regeneration. Retention of sphere forming ability in adult vestibular tissues suggests that the limited capacity for repair may be attributed to the continued presence of progenitor cells. Future strategies for regeneration must consider the distribution of endogenous stem cells in the inner ear and whether the tissue retains cells with the capacity for regeneration. (C) 2007 Elsevier B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Tillotson Unit Cell Biol, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Div Hlth Sci & Technol, Program Speech & Hearing Biosci, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Stanford Univ, Sch Med, Dept Otolaryngol HNS & Mol Cellular Physiol, Stanford, CA 94305 USA. RP Edge, ASB (reprint author), Massachusetts Eye & Ear Infirm, Tillotson Unit Cell Biol, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM albert_edge@meei.harvard.edu FU NIDCD NIH HHS [P30 DC005209, R01 DC007174, F33 DC006789, P30 DC05209, R01 DC007174-03, R01 DC007174-01A1, R01 DC006167, DC006167, R01 DC007174-02] NR 42 TC 21 Z9 26 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2007 VL 227 IS 1-2 SI SI BP 48 EP 52 DI 10.1016/j.heares.2006.12.015 PG 5 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 169ZP UT WOS:000246630900008 PM 17321086 ER PT J AU Ho, ICK Neuzil, P Mraz, T Beldova, Z Gross, D Formanek, P Taborsky, M Niederle, P Ruskin, JN Reddy, VY AF Ho, Ivan C. K. Neuzil, Petr Mraz, Tomas Beldova, Zuzana Gross, Dan Formanek, Pavel Taborsky, Milos Niederle, Petr Ruskin, Jeremy N. Reddy, Vivek Y. TI Use of intracardiac echocardiography to guide implantation of a left atrial appendage occlusion device (PLAATO) SO HEART RHYTHM LA English DT Article DE atrial fibrillation; intracardiac echocardiography; left atrial appendage occlusion; transesophageal echocardiography ID HIGH-RISK PATIENTS; TRANSCATHETER OCCLUSION; PREVENT STROKE; FIBRILLATION; EXPERIENCE AB BACKGROUND Over 90% of thrombi in atrial fibrillation (AF) originate from the Left atrial appendage (LAA). Patients with contraindications to anticoagulation are potential candidates for LAA occlusion using the Percutaneous Left Atrial Appendage Transcatheter Occlusion system (PLAATO, ev3 Inc., Plymouth, MN). Transesophageal echocardiography (TEE) is typically used to guide implantation. OBJECTIVE This study sought to examine the utility of intracardiac echocardiography (ICE) in providing adequate imaging guidance as an alternative to TEE during PLAATO implantation. METHODS The study group consisted of 10 patients who underwent PLAATO implantation with simultaneous TEE and ICE imaging guidance. ICE was used to perform the following tasks typically fulfilled by TEE: (1) verification of the absence of LAA thrombus, (2) identification of the LAA ostial dimension for device sizing, (3) guidance of transseptal puncture, (4) verification of the delivery sheath position, and (5) confirmation of location and stability of device before its irrecoverable release. The ability of ICE to perform these tasks was assessed from three separate positions: the standard right atrial (RA) position, within the coronary sinus (CS), and the right ventricular outflow tract. RESULTS ICE imaging of the LAA was optimal from within the CS, although imaging from the proximal pulmonary artery provided better visualization of the distal LAA in cross-section. The LAA dimensions, confirmation of the absence of LAA thrombus, proper positioning of the delivery sheath, verification of Location and stability of the device obtained by ICE were consistent with findings from TEE. CONCLUSION Using nonconventional imaging planes, ICE imaging was able to perform the intraprocedural functions provided by TEE during implantation of the PLAATO Left atrial appendage occlusion device. C1 Massachusetts Gen Hosp, Cardiav Arrhythmia Serv, Boston, MA 02114 USA. Na Homolce Hosp, Prague, Czech Republic. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiav Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org NR 10 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAY PY 2007 VL 4 IS 5 BP 567 EP 571 DI 10.1016/j.hrthm.2007.01.014 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 163UN UT WOS:000246188800001 PM 17467621 ER PT J AU Chen, Y Yang, Y Miller, ML Shen, DX Shertzer, HG Stringer, KF Wang, B Schneider, SN Nebert, DW Dalton, TP AF Chen, Ying Yang, Yi Miller, Marian L. Shen, Dongxiao Shertzer, Howard G. Stringer, Keith F. Wang, Bin Schneider, Scott N. Nebert, Daniel W. Dalton, Timothy P. TI Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure SO HEPATOLOGY LA English DT Article ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; REACTIVE OXYGEN PRODUCTION; LIGASE MODIFIER SUBUNIT; GLUTATHIONE HOMEOSTASIS; HEPATIC GLUTATHIONE; LIPID-PEROXIDATION; OXIDATIVE STRESS; MOUSE; RAT; GENE AB Oxidative stress is considered to be a critical mediator in liver injury of various etiologies. Depletion of glutathione (GSH), the major antioxidant in liver, has been associated with numerous liver diseases. To explore the specific role of hepatic GSH in vivo, we targeted Gclc, a gene essential for GSH synthesis, so that it was flanked by loxP sites and used the albumin-cyclization recombination (Alb-Cre) transgene to disrupt the Gclc gene specifically in hepatocytes. Deletion within the Gclc gene neared completion by postnatal day (PND)14, and loss of GCLC protein was complete by PND21. Cellular GSH was progressively depleted between PND14 and PND28 - although loss of mitochondrial GSH was less severe. Nevertheless, ultrastructural examination of liver revealed dramatic changes in mitochondrial morphology, these alterations were accompanied by striking decreases in mitochondrial function in vitro, cellular ATP, and a marked increase in lipid peroxidation. Plasma fiver biochemistry tests from these mice were consistent with progressive severe parenchymal damage. Starting at PND21, livers from hepatocyte-specific Gclc knockout [Gclc(h/h)] mice showed histological features of hepatic steatosis; this included inflammation and hepatocyte death, which progressed in severity such that mice died at approximately I month of age due to complications from liver failure. Conclusion: GSH is essential for hepatic function and loss of hepatocyte GSH synthesis leads to steatosis with mitochondrial injury and hepatic failure. C1 Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis & Cardiovasc Res C, Boston, MA 02114 USA. Cincinnati Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH USA. RP Dalton, TP (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA. EM tim.dalton@uc.edu FU NIEHS NIH HHS [R01 ES012463, R01 ES10133, P30 ES06096] NR 44 TC 45 Z9 50 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2007 VL 45 IS 5 BP 1118 EP 1128 DI 10.1002/hep.21635 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 163UC UT WOS:000246187700005 PM 17464988 ER PT J AU Hadjikhani, N Joseph, RM Snyder, J Tager-Flusberg, H AF Hadjikhani, Nouchine Joseph, Robert M. Snyder, Josh Tager-Flusberg, Helen TI Abnormal activation of the social brain during face perception in autism SO HUMAN BRAIN MAPPING LA English DT Article DE autism spectrum disorder; face perception; fusiform gyrus; amygdala; mirror neuron system; social brain; visual processing ID PERVASIVE DEVELOPMENTAL DISORDERS; EMOTIONAL FACIAL EXPRESSIONS; SUPERIOR TEMPORAL SULCUS; HUMAN AMYGDALA; NEURAL BASIS; ASPERGER-SYNDROME; CORTICAL SURFACE; SPECTRUM DISORDER; COORDINATE SYSTEM; FUSIFORM ACTIVITY AB ASD involves a fundamental impairment in processing social-communicative information from faces. Several recent studies have challenged earlier findings that individuals with autism spectrum disorder (ASD) have no activation of the fusiform gyrus (fusiform face area, FFA) when viewing faces. In this study, we examined activation to faces in the broader network of face-processing modules that comprise what is known as the social brain. Using 3T functional resonance imaging, we measured BOLD signal changes in 10 ASD subjects and 7 healthy controls passively viewing nonemotional faces. We replicated our original findings of significant activation of face identity-processing areas (FFA and inferior occipital gyrus, IOG) in ASD. However, in addition, we identified hypoactivation in a more widely distributed network of brain areas involved in face processing [including the right amygdala, inferior frontal cortex (IFC), superior temporal sulcus (STS), and face-related somatosensory and premotor cortex]. In ASD, we found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (IFC, STS) and other face-processing areas. The severity of the social symptoms measured by the Autism Diagnostic Observation Schedule was correlated with the right IFC cortical thickness and with functional activation in that area. When viewing faces, adults with ASD show atypical patterns of activation in regions forming the broader face-processing network and social brain, outside the core FFA and IOG regions. These patterns suggest that areas belonging to the mirror neuron system are involved in the face-processing disturbances in ASD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Hadjikhani, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Bldg 120,110 6th St,Room 217, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Tager-Flusberg, Helen/D-5265-2009 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NIDCD NIH HHS [U19 DC 03610]; NIMH NIH HHS [K01 MH073944-01]; NINDS NIH HHS [R01 NS44824-01] NR 68 TC 131 Z9 134 U1 8 U2 27 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2007 VL 28 IS 5 BP 441 EP 449 DI 10.1002/hbm.20283 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 159HW UT WOS:000245857200008 PM 17133386 ER PT J AU Yang, J Pawlyk, B Wen, XH Adamian, M Soloviev, M Michaud, N Zhao, Y Sandberg, MA Makino, CL Li, T AF Yang, Jun Pawlyk, Basil Wen, Xiao-Hong Adamian, Michael Soloviev, Maria Michaud, Norman Zhao, Yun Sandberg, Michael A. Makino, Clint L. Li, Tiansen TI Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals SO HUMAN MOLECULAR GENETICS LA English DT Article ID FUNCTIONAL ABNORMALITIES; MAMMALIAN RETINA; RIBBON SYNAPSES; NIGHT BLINDNESS; INNER SEGMENTS; MAGUK PROTEINS; MOUSE RETINA; EXPRESSION; GENE; OUTER AB Membrane palmitoylated protein 4 (Mpp4) is a member of the membrane-associated guanylate kinase family. We show that Mpp4 localizes specifically to the plasma membrane of photoreceptor synaptic terminals. Plasma membrane Ca2+ ATPases (PMCAs), the Ca2+ extrusion pumps, interact with an Mpp4-dependent presynaptic membrane protein complex that includes Veli3 and PSD95. In mice lacking Mpp4, PMCAs were lost from rod photoreceptor presynaptic membranes. Synaptic ribbons were enlarged, a phenomenon known to correlate with higher Ca2+. SERCA2 (sarcoplasmic-endoplasmic reticulum Ca2+ ATPase, type 2), which pumps cytosolic Ca2+ into intracellular Ca+2 Stores and localizes next to the ribbons, was increased. The distribution Of IP3RII (InsP(3) receptor, type 2), which releases Ca2+ from the stores, was shifted away from the synaptic terminals. Synaptic transmission to second-order neurons was maintained but was reduced in amplitude. These data suggest that loss of Mpp4 disrupts a Ca2+ extrusion mechanism at the presynaptic membranes, with ensuing adaptive responses by the photoreceptor to restore Ca2+ homeostasis. We propose that Mpp4 organizes a presynaptic protein complex that includes PMCAs and has a role in modulating Ca2+ homeostasis and synaptic transmission in rod photoreceptors. C1 Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA. RP Li, T (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM tli@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [EY12944, EY14104, EY10309] NR 46 TC 24 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2007 VL 16 IS 9 BP 1017 EP 1029 DI 10.1093/hmg/ddm047 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 181ZR UT WOS:000247475400002 PM 17341488 ER PT J AU Horowitz, RE Naritoku, WY AF Horowitz, Richard E. Naritoku, Wesley Y. TI The autopsy as a performance measure and teaching tool SO HUMAN PATHOLOGY LA English DT Article DE autopsy; medical student education; pathology resident training; performance measurement ID ACCURACY AB A survey of pathology training programs about current operations and attitudes revealed that the autopsy is underused in medical student and pathology resident teaching, is inadequately reported, often does not have a dedicated faculty, is not championed by pathologists or clinicians, is not valued as a performance measure, and is barely used as a resource for medical research. The autopsy can be reestablished as a teaching too] and performance measure, but this will require that the autopsy be recognized as a credible and valuable medical procedure. The autopsy must then be funded; and new sources of both volume and funding, such as incorporating autopsies into payment schedules, into clinical trials, and in pay-for-performance initiatives, must be solicited. Once there is reimbursement for autopsies, pathologists, clinicians, and health care administrators will embrace the autopsy as a new source of revenue and as a valid measure of physician, hospital, and health system performance. Pathologists and the pathology specialty societies must take the lead in the reestablishment of the autopsy and must, at the same time, encourage innovations such as centralization, greater use of Pathology Assistants, and application of molecular techniques. New tools for using the autopsy in medical student teaching should be embraced, and the role of the autopsy in pathology residency programs must be reevaluated. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. W Los Angeles Vet Affairs Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. RP Horowitz, RE (reprint author), VA Hlth Care Ctr, Mail Code 691-113, Los Angeles, CA 90073 USA. EM rehorwtz@ucla.edu NR 16 TC 23 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2007 VL 38 IS 5 BP 688 EP 695 DI 10.1016/j.humpath.2007.01.001 PG 8 WC Pathology SC Pathology GA 162UJ UT WOS:000246114700002 PM 17376512 ER PT J AU Perner, S Hofer, MD Kim, R Shah, RB Li, HJ Moller, P Hautmann, RE Gschwend, JE Kuefer, R Rubin, MA AF Perner, Sven Hofer, Matthias D. Kim, Robert Shah, Rajal B. Li, Haojie Moeller, Peter Hautmann, Richard E. Gschwend, Juergen E. Kuefer, Rainer Rubin, Mark A. TI Prostate-specific membrane antigen expression as a predictor of prostate cancer progression SO HUMAN PATHOLOGY LA English DT Article DE PSMA; prostate cancer; progression; tissue microarray (TMA) ID QUANTITATIVE-ANALYSIS AQUA; RADICAL PROSTATECTOMY; RECURRENCE; ANTIBODIES; ADENOCARCINOMA; POTENT AB Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, because current therapy may lead to overtreatment of men with limited disease. The prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein that is highly restricted to the prostate. Previously, studies analyzing the expression of PSMA have found an up-regulation in correlation with prostate cancer, particularly in advanced cancer. This association is ideal for an application as a prognostic marker. In the current study, we characterized PSMA expression in a high-risk cohort and evaluated its potential use as predictive marker of prostate-specific antigen (PSA) recurrence. PSMA expression was analyzed by immunohistochemistry using tissue microarrays composed of tumor samples from 450 patients. Protein intensity was recorded using a semiautomated quantitative microscope system (ACIS II; Clarient Chromavision Medical Systems, San Juan Capistrano, CA). PSMA expression levels differed significantly (P <.001) between benign prostatic tissue, localized prostate cancer, and lymph node metastases. Dividing the cohort into high- and low- PSMA expressing cancers based on the median area of positive staining, we found that high PSMA levels were associated with significant increase of PSA recurrence (P =.004). This was independent of clinical parameters such as lymph node tumor burden (lymph node density, > 20%; P < .001), extraprostatic extension (P =.017), seminal vesicle invasion (P <.001), and high Gleason score (8-10, P =.006). In a multivariate model, PSMA expression and metastases to pelvic lymph nodes were significantly associated with time to PSA recurrence (HR, 1.4; 95% confidence interval, C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Ulm, Dept Urol, D-89075 Ulm, Germany. Univ Hosp Ulm, Inst Pathol, D-89081 Ulm, Germany. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. RP Rubin, MA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM marubin@partners.org OI Rubin, Mark/0000-0002-8321-9950 NR 29 TC 128 Z9 139 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2007 VL 38 IS 5 BP 696 EP 701 DI 10.1016/j.humpath.2006.11.012 PG 6 WC Pathology SC Pathology GA 162UJ UT WOS:000246114700003 PM 17320151 ER PT J AU Nyby, MD Abedi, K Smutko, V Eslami, P Tuck, ML AF Nyby, Michael D. Abedi, Karolin Smutko, Victoria Eslami, Pirooz Tuck, Michael L. TI Vascular angiotensin type 1 receptor expression is associated with vascular dysfunction, oxidative stress and inflammation in fructose-fed rats SO HYPERTENSION RESEARCH LA English DT Article DE angiotensin; hypertension; oxidative stress; vascular; insulin resistance ID CONVERTING ENZYME-INHIBITOR; NITRIC-OXIDE SYNTHASE; AORTIC SMOOTH-MUSCLE; INSULIN-RESISTANCE; HYPERINSULINEMIC RATS; BLOOD-PRESSURE; HYPERTENSION; IMPROVEMENT; SYSTEM; MECHANISMS AB This study determined whether or not oxidative stress and vascular dysfunction in fructose-induced hyper-insulinernic rats are associated with activation of the vascular renin-angiotensin system (RAS). Four groups of rats were used. CONT rats were fed normal rat chow, CONT+CAP were fed normal rat chow and given 500 mg/L captopril in their drinking water, fructose-fed rats (FFR) were fed a high-fructose diet and FFR+CAP were fed the high-fructose diet plus captopril in water. After 8 weeks, the vascular reactivity of mesenteric artery segments was measured. Blood was analyzed for insulin, glucose, hydrogen peroxide and 8-isoprostane. Aortic and heart tissue were used for subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Systolic blood pressure was significantly higher in FFR (p<0.05), and captopril treatment inhibited the blood pressure increase. Mesenteric artery dose-response curves to acetylcholine were shifted to the right in FFR (p<0.05) and were normal in FFR+CAP. Plasma insulin (p<0.05), hydrogen peroxide (p<0.02) and 8-isoprostane (p<0.05) were increased in FFR. Captopril treatment reducd hydrogen peroxide and 8-isoprostane concentrations. Aortic tissue mRNA expression levels were increased for angiotensin-converting enzyme (ACE, p<0.05), angiotensin type 1 receptor (AT1R, p<0.02), NOX4 (p<0.02) and VCAM-1 (p<0.05) in FFR aortic samples. Captopril treatment reduced AT1R, NOX4 and VCAM-1 expression in FFR to levels not different from CONT. Similar changes in heart tissue mRNA expression for angiotensinogen, AT1R and NOX4 were also observed. These results demonstrate that vascular RAS is upregulated in FFR and support the hypothesis that vascular RAS mediates vascular dysfunction and vascular oxidative stress in FFR. C1 VA Greater Los Angles Healthcare Syst, Dept Med, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Nyby, MD (reprint author), VA Greater Los Angles Healthcare Syst, Dept Med, Sepulveda 111E,16111 Plummer St, Sepulveda, CA 91343 USA. EM mnyby@ucla.edu NR 25 TC 48 Z9 51 U1 0 U2 2 PU JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE PI TOYONAKA PA SENRI ASAHI HANKYU BLDG, 13TH FLOOR, 1-5-3 SHINSENRIHIGASHI-MACHI, TOYONAKA, 560-0082, JAPAN SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD MAY PY 2007 VL 30 IS 5 BP 451 EP 457 DI 10.1291/hypres.30.451 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 189GQ UT WOS:000247977800010 PM 17587757 ER PT J AU Lu, LR Ikizawa, K Hu, D Werneck, MBF Wucherpfennig, KW Cantor, H AF Lu, Linrong Ikizawa, Koichi Hu, Dan Werneck, Miriam B. F. Wucherpfennig, Kai W. Cantor, Harvey TI Regulation of activated CD4(+) T cells by NK cells via the Qa-1-NKG2A inhibitory pathway SO IMMUNITY LA English DT Article ID NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CLASS IB MOLECULES; IFN-GAMMA; RECEPTOR CD94/NKG2A; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; SELF-TOLERANCE; IN-VIVO AB The ability of natural-killer cells to regulate adaptive immunity is not well understood. Here we define an interaction between the class Ib major histocompatibility complex (MHC) molecule Qa-1-Qdm on activated T cells responsible for adaptive immunity and CD94-NKG2A inhibitory receptors expressed by natural-killer cells by using Qa-1-deficient and Qa-1 knockin mice containing a point mutation that selectively abolishes Qa-1-Qdm binding to CD94-NKG2A receptors. The Qa-1-NKG2A interaction protected activated CD4(+) T cells from lysis by a subset of NKG2A(+) NK cells and was essential for T cell expansion and development of immunologic memory. Antibody-dependent blockade of this Qa-1-NKG2A interaction resulted in potent NK-dependent elimination of activated autoreactive T cells and amelioration of experimental autoimmune encephalomyelitis. These findings extend the functional reach of the NK system to include regulation of adaptive T cell responses and suggest a new clinical strategy for elimination of antigen-activated T cells in the context of autoimmune disease and transplantation. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu RI Werneck, Miriam/H-5802-2012; Lu, Linrong/A-1429-2013; Hu, Dan/D-9642-2015; OI Lu, Linrong/0000-0002-0171-4115 FU NIAID NIH HHS [AI 37562, R01 AI037562] NR 41 TC 113 Z9 120 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2007 VL 26 IS 5 BP 593 EP 604 DI 10.1016/j.immuni.2007.03.017 PG 12 WC Immunology SC Immunology GA 173TR UT WOS:000246895900012 PM 17509909 ER PT J AU Clark, S Camargo, CA AF Clark, Sunday Camargo, Carlos A., Jr. TI Epidemiology of anaphylaxis SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; DIAL TELEPHONE SURVEY; BEE STING ALLERGY; TREE NUT ALLERGY; UNITED-STATES; FOOD ALLERGIES; PREVALENCE; CHILDREN; POPULATION; PEANUT AB Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Understanding the epidemiology of anaphylaxis has important implications for preventing anaphylaxis and managing patients. Unfortunately, estimates of the prevalence and incidence of anaphylaxis vary widely. Inconsistent definitions of anaphylaxis contribute to these divergent estimates. The implementation of a simple clinical definition to diagnose anaphylaxis not only would help in the management of patients but also would advance epidemiologic research on the distribution and determinants of this potentially life-threatening disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 54 TC 46 Z9 46 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2007 VL 27 IS 2 BP 145 EP + DI 10.1016/j.iac.2007.03.002 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA 175AK UT WOS:000246984100003 PM 17493495 ER PT J AU Choy, HA Kelley, MM Chen, TL Moller, AK Matsunaga, J Haake, DA AF Choy, Henry A. Kelley, Melissa M. Chen, Tammy L. Moller, Annette K. Matsunaga, James Haake, David A. TI Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; TANDEM BETA-ZIPPER; FIBRONECTIN-BINDING; STAPHYLOCOCCUS-AUREUS; BORRELIA-BURGDORFERI; GENE-EXPRESSION; MAMMALIAN-CELLS; HOST-CELLS; IDENTIFICATION; BBK32 AB Transmission of leptospirosis occurs through contact of mucous membranes and abraded skin with freshwater contaminated by pathogenic Leptospira spp. Exposure to physiological osmolarity induces leptospires to express high levels of the Lig surface proteins containing imperfect immunoglobulin-like repeats that are shared or differ between LigA and LigB. We report that osmotic induction of Lig is accompanied by 1.6- to 2.5-fold increases in leptospiral adhesion to immobilized extracellular matrix and plasma proteins, including collagens I and IV, laminin, and especially fibronectin and fibrinogen. Recombinant LigA-unique and LigB-unique repeat proteins bind to these same host ligands. We found that the avidity of LigB in binding fibronectin is comparable to that of the Staphylococcus aureus FnBPA D repeats. Both LigA- and LigB-unique repeats interact with the amino-terminal fibrin- and gelatin-binding domains of fibronectin, which are also recognized by fibronectin-binding proteins mediating the adhesion of other microbial pathogens. In contrast, repeats common to both LigA and LigB do not bind these host proteins, and nonrepeat sequences in the carboxyterminal domain of LigB show only weak interaction with fibronectin and fibrinogen. A functional role for the binding activity of LigA and LigB is suggested by the ability of the recombinants to inhibit leptospiral adhesion to fibronectin by 28% and 21%, respectively. The binding of LigA and LigB; to multiple ligands present in different tissues suggests that these adhesins may be involved in the initial colonization and dissemination stages of leptospirosis. The characterization of the Lig adhesin function should aid the design of Lig-based vaccines and serodiagnostic tests. C1 VA Greater LA Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. RP Choy, HA (reprint author), VA Greater LA Healthcare Syst, Div Infect Dis, Bldg 113,Room 225,111F, Los Angeles, CA 90073 USA. EM hachoy@ucla.edu FU NIAID NIH HHS [R01 AI034431, AI-34431, R01 AI034431-10A1, R21 AI034431, R29 AI034431] NR 68 TC 143 Z9 148 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2007 VL 75 IS 5 BP 2441 EP 2450 DI 10.1128/IAI.01635-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 165YY UT WOS:000246345000042 PM 17296754 ER PT J AU Maadani, A Fox, KA Mylonakis, E Garsin, DA AF Maadani, Arash Fox, Kristina A. Mylonakis, Elftherios Garsin, Danielle A. TI Enterococcus faecalis mutations affecting virulence in the Caenorhabditis elegans model host SO INFECTION AND IMMUNITY LA English DT Article ID STREPTOCOCCUS-MUTANS; GENE-EXPRESSION; SERINE-PROTEASE; BIOLOGY; CARIOGENICITY; GELATINASE; INFECTION; SYSTEM; DNA AB Enterococcus faecalis transposon insertion mutants were screened for attenuated killing of the nematode model host Caenorhabditis elegans. The genes disrupted in the attenuated mutants encode a variety of factors including transcriptional regulators, transporters, and damage control and repair systems. Five of nine mutants tested were attenuated in a mouse peritonitis model. C1 Univ Texas, Hlth Sci Ctr, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Garsin, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Microbiol & Mol Genet, 6431 Fannin St,MSB 1-174, Houston, TX 77030 USA. EM Danielle.A.Garsin@uth.tmc.edu FU NIAID NIH HHS [AI603084, AI064332, AI064470, R01 AI064332, R21 AI064470] NR 22 TC 34 Z9 34 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2007 VL 75 IS 5 BP 2634 EP 2637 DI 10.1128/IAI.01372-06 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 165YY UT WOS:000246345000064 PM 17307944 ER PT J AU Pazos, M Siccardi, D Mumy, K Shi, H Mrsny, R McCormick, B AF Pazos, M. Siccardi, D. Mumy, K. Shi, H. Mrsny, R. McCormick, B. TI Novel methods to treat inflammation by disrupting hepoxilin A3 synthesis or secretion SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT CCFA National Research and Clinical Conference/5th Annual Advances in the Inflammatory Bowel Diseases CY DEC 01-03, 2006 CL Miami, FL SP CCFA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Wales Coll Cardiff, Cardiff, Wales. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2007 VL 13 IS 5 SU S BP 643 EP 643 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164HY UT WOS:000246225600003 ER PT J AU Weng, M Huntley, D Foye-Jackson, O Wang, J Walker, W Cherayil, B Shi, H AF Weng, M. Huntley, D. Foye-Jackson, O. Wang, J. Walker, W. Cherayil, B. Shi, H. TI Alternatively activated macrophages in intestinal helminth infection: Effects on concurrent bacterial enteritis SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT CCFA National Research and Clinical Conference/5th Annual Advances in the Inflammatory Bowel Diseases CY DEC 01-03, 2006 CL Miami, FL SP CCFA C1 Massachusetts Gen Hosp, Mucosal Immun Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2007 VL 13 IS 5 SU S BP 644 EP 644 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164HY UT WOS:000246225600006 ER PT J AU Sands, B Feagan, B Yan, S Sandborn, W Rutgeerts, P Eisenberg, D Bala, M Johanns, J Hanauer, S Reinisch, W AF Sands, B. Feagan, B. Yan, S. Sandborn, W. Rutgeerts, P. Eisenberg, D. Bala, M. Johanns, J. Hanauer, S. Reinisch, W. TI Improvement in health related quality of life in infliximab-treated moderate-tosevere active ulcerative colitis patients: Improvement overall and by baseline disease activity SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT CCFA National Research and Clinical Conference/5th Annual Advances in the Inflammatory Bowel Diseases CY DEC 01-03, 2006 CL Miami, FL SP CCFA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Robarts Clin Trials, London, ON, Canada. Centocor Res & Dev Inc, Malvern, PA USA. Mayo Clin, Rochester, MN USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Chicago, Chicago, IL 60637 USA. Univ Hosp Vienna, Vienna, Austria. RI Feagan, Brian/M-4283-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2007 VL 13 IS 5 SU S BP 648 EP 648 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164HY UT WOS:000246225600019 ER PT J AU Mora, J Iwata, M Eksteen, B Junt, T Adams, D von Andrian, U AF Mora, J. Iwata, M. Eksteen, B. Junt, T. Adams, D. von Andrian, U. TI Imprinting of gut-homing IgA-secreting cells via a synergistic mechanism SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT CCFA National Research and Clinical Conference/5th Annual Advances in the Inflammatory Bowel Diseases CY DEC 01-03, 2006 CL Miami, FL SP CCFA C1 Harvard Univ, Sch Med, CBRI, Boston, MA USA. Univ Birmingham, Birmingham, W Midlands, England. Tokushima Bunri Univ, Kagawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2007 VL 13 IS 5 SU S BP 652 EP 652 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 164HY UT WOS:000246225600034 ER PT J AU Kaz, A Kim, YH Dzieciatkowskil, S Lynch, H Watson, P Washington, MK Lin, L Grady, WM AF Kaz, Andrew Kim, Young-Ho Dzieciatkowskil, Slavomir Lynch, Henry Watson, Patrice Washington, Mary Kay Lin, Li Grady, William M. TI Evidence for the role of aberrant DNA methylation in the pathogenesis of Lynch syndrome adenomas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Lynch syndrome; HNPCC; DNA methylation; colon cancer; adenoma ID NONPOLYPOSIS COLORECTAL-CANCER; CPG ISLAND METHYLATION; MISMATCH REPAIR DEFICIENCY; HMLH1 PROMOTER; COLON-CANCER; MICROSATELLITE INSTABILITY; BREAST-CANCER; WILD-TYPE; SOMATIC INACTIVATION; MOLECULAR ANALYSIS AB Colorectal cancer (CRC) forms through a series of histologic steps that are accompanied by mutations and epigenetic alterations, which is called the polyp-cancer sequence. The role of epigenetic alterations, such as aberrant DNA methylation, in the polyp-cancer sequence in sporadic CRC and particularly in hereditary colon cancer is not well understood. Consequently, we assessed the methylation status of CDKN2A/p16, MGMT, MLH1 and p14(ARF) in adenomas arising in the Lynch syndrome, a familial colon cancer syndrome caused by MLH1 and MSH2 mutations, to determine if DNA methylation is a "second hit" mechanism in CRC and to characterize the role of DNA methylation in the polyp phase of the Lynch syndrome. We found MLH1 and p14(ARF) are methylated in 53 and 60% of the Lynch syndrome adenomas and in 4 and 20% of sporadic adenomas, whereas CDKN2A/p16 and MGMT are methylated in 6 and 14% of the Lynch syndrome adenomas versus 50 and 64% of sporadic adenomas. Therefore, the frequency and pattern of gene methylation varies between the Lynch syndrome and sporadic colon adenomas, implying differences in the molecular pathogenesis of the tumors. MLH1 methylation in the Lynch syndrome adenomas suggests gene methylation might have a role in the initiation of these neoplasms. (c) 2007 Wiley-Liss, Inc. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Samsung Med Ctr, Dept Med, Seoul, South Korea. Sungkyunkwan Univ, Sch Med, Dept Med, Seoul, South Korea. Creighton Univ, Sch Med, Dept Prevent Med, Omaha, NE 68178 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. VA Puget Sound Healthcare Syst, R&D Serv, Seattle, WA USA. RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA. EM wgrady@fhcrc.org NR 53 TC 21 Z9 21 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2007 VL 120 IS 9 BP 1922 EP 1929 DI 10.1002/ijc.22544 PG 8 WC Oncology SC Oncology GA 146ZA UT WOS:000244972000012 PM 17278092 ER PT J AU Lopez-Varela, E Oliva, E McIntyre, JF Fuller, AF AF Lopez-Varela, E. Oliva, E. McIntyre, J. F. Fuller, A. F., Jr. TI Primary treatment of Bartholin's gland carcinoma with radiation and chemoradiation: a report on ten consecutive cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Bartholin's gland carcinoma; vulva carcinoma; radiation therapy ID ADENOID CYSTIC CARCINOMA; THERAPY AB We reviewed our experience with primary radiation therapy for Bartholin's gland carcinoma (BGC) as an alternative to traditional surgical treatment. A retrospective study reviewed records from the Cancer Data Registry and Research Patient Data Registry from 1986 to 2002. Charts of ten women identified with BGC were reviewed for demographic information, presenting symptoms, tumor characteristics, treatment modalities, and complications, as well as for recurrence and survival. The incidence of BGC was 2.13% of all invasive vulvar cancer cases at the Massachusetts General Hospital (MGH). Four patients presented with clinical stage I disease, one with stage II, three with stage III, and two with stage IV. The median age at diagnosis was 63.5 years. There were five squamous cell carcinomas, two adenoid cystic carcinomas, two mucinous adenocarcinomas, and one small-cell carcinoma. After a change in treatment policy in 1986 from primary surgery that had often required postoperative radiation therapy, ten consecutive patients were treated with primary radiotherapy or chemoradiation therapy. Treatment included teletherapy combined with a boost to the primary site, regional nodes and/or interstitial brachytherapy. Short-term complications were mild and well tolerated; one patient developed late radiation-associated pelvic fractures. Four tumors recurred with a mean time to recurrence of 31.2 months. The median follow-up was 87.2 months (45-142). Three- and 5-year survivals were 71.5% and 66%, comparable to outcomes after surgery and postoperative radiation therapy. We conclude that primary radiation or chemoradiation therapy offers an effective alternative to surgery in the treatment of BGC with preservation of genital function and low morbidity. C1 Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Lopez-Varela, E (reprint author), Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. EM elopezvarela@partners.org NR 19 TC 11 Z9 11 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY-JUN PY 2007 VL 17 IS 3 BP 661 EP 667 DI 10.1111/j.1525-1438.2006.00781.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 167CX UT WOS:000246429600016 PM 17504379 ER PT J AU Balboni, TA Chen, MH Harris, JR Recht, A Stevenson, MA D'Amico, AV AF Balboni, Tracy A. Chen, Ming-Hui Harris, Jay R. Recht, Abram Stevenson, Mary Ann D'Amico, Anthony V. TI Academic career selection and retention in radiation oncology: The Joint Center for Radiation Therapy experience SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE graduate medical education; radiation oncology; residency; academic medicine ID US MEDICAL-STUDENTS; CLINICAL-RESEARCH; UNITED-STATES; MANAGED CARE; ARRO SURVEYS; LIFE-STYLE; RESIDENTS; FACULTY; ASSOCIATION; SCHOOLS AB Purpose: The United States healthcare system has witnessed declining reimbursement and increasing documentation requirements for longer than 10 years. These have decreased the time available to academic faculty for teaching and mentorship. The impact of these changes on the career choices of residents is unknown. The purpose of this report was to determine whether changes have occurred during the past decade in the proportion of radiation oncology trainees from a single institution entering and staying in academic medicine. Methods and Materials: We performed a review of the resident employment experience of Harvard Joint Center for Radiation Therapy residents graduating during 13 recent consecutive years (n = 48 residents). The outcomes analyzed were the initial selection of an academic vs. nonacademic career and career changes during the first 3 years after graduation. Results: Of the 48 residents, 65% pursued an academic career immediately after graduation, and 44% remained in academics at the last follow-up, after a median of 6 years. A later graduation year was associated with a decrease in the proportion of graduates immediately entering academic medicine (odds ratio, 0.78; 95% confidence interval, 0.65-0.94). However, the retention rate at 3 years of those who did immediately enter academics increased with a later graduation year (p = 0.03). Conclusion: During a period marked by notable changes in the academic healthcare environment, the proportion of graduating Harvard Joint Center for Radiation Therapy residents pursuing academic careers has been declining; however, despite this decline, the retention rates in academia have increased. (c) 2007 Elsevier Inc. C1 Harvard Radiat Oncol Residency Program, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT USA. Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Balboni, TA (reprint author), Harvard Radiat Oncol Residency Program, 375 Longwood Ave, Boston, MA 02115 USA. EM tbalboni@partners.org NR 25 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2007 VL 68 IS 1 BP 183 EP 186 DI 10.1016/j.ijrobp.2006.11.044 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 161WA UT WOS:000246046000025 PM 17276610 ER PT J AU Tennstedt, SL Fitzgerald, MP Nager, CW Xu, Y Zimmern, P Kraus, S Goode, PS Kusek, JW Borello-France, D Mallett, V AF Tennstedt, Sharon L. Fitzgerald, Mary Pat Nager, Charles W. Xu, Yan Zimmern, Philippe Kraus, Stephen Goode, Patricia S. Kusek, John W. Borello-France, Diane Mallett, Veronica CA Urinary Incontinence Treatment TI Quality of life in women with stress urinary incontinence SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE quality of life; urinary incontinence ID UROGENITAL DISTRESS INVENTORY; PELVIC ORGAN PROLAPSE; IMPACT QUESTIONNAIRE; DYSFUNCTION; PREVALENCE; INSTRUMENT; WHITE; URGE AB The objective of this study was to identify clinical and demographic factors associated with incontinence-related quality of life (QoL) in 655 women with stress urinary incontinence who elected surgical treatment. The following factors were examined for their association with QoL as measured with the Incontinence Impact Questionnaire (IIQ): number of incontinence (UI) episodes/day; self-reported type of UI symptoms (stress and urge); sexual function as measured by the Prolapse/Urinary Incontinence Sexual Questionnaire; symptom bother as measured by the Urogenital Distress Inventory; as well as other clinical and sociodemographic factors. A stepwise least-squares regression analysis was used to identify factors significantly associated with QoL. Lower QoL was related to the greater frequency of stress UI symptoms, increasing severity, greater symptom bother, prior UI surgery or treatment, and sexual dysfunction (if sexually active). Health and sociodemographic factors associated with lower incontinence-related QoL included current tobacco use, younger age, lower socioeconomic status, and Hispanic ethnicity. C1 New England Res Inst, Watertown, MA 02472 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Duquesne Univ, Pittsburgh, PA 15219 USA. Univ Tennessee, Knoxville, TN USA. RP Tennstedt, SL (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM stennstedt@neriscience.com FU NIDDK NIH HHS [U01 DK, U01 DK 58225, U01 DK 58229, U01 DK 58231, U01 DK 58234, U01 DK 60379, U01 DK 60380, U01 DK 60393, U01 DK 60395, U01 DK 60397, U01 DK 60401] NR 22 TC 38 Z9 40 U1 2 U2 5 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD MAY PY 2007 VL 18 IS 5 BP 543 EP 549 DI 10.1007/s00192-006-0188-5 PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 153TK UT WOS:000245457900011 PM 17036169 ER PT J AU She, HC Nakazawa, T Matsubara, A Hisatomi, T Young, TA Michaud, N Connolly, E Hafezi-Moghadam, A Gragoudas, ES Miller, JW AF She, Haicheng Nakazawa, Toru Matsubara, Akihisa Hisatomi, Toshio Young, Tara A. Michaud, Norman Connolly, Edward Hafezi-Moghadam, Ali Gragoudas, Evangelos S. Miller, Joan W. TI Reduced photoreceptor damage after photodynamic therapy through blockade of nitric oxide synthase in a model of choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; MACULAR DEGENERATION; CELL-DEATH; RETINAL-DETACHMENT; RAT MODEL; IN-VIVO; VERTEPORFIN; APOPTOSIS; BENZOPORPHYRIN; MACROPHAGES AB PURPOSE. To investigate the role of nitric oxide synthase (NOS) in photoreceptor degeneration associated with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV). METHODS PDT was performed in monkey and Brown Norway rats with laser-induced CNV. L-NAME, a NOS inhibitor, or saline was injected intraperitoneally in rats with CNV. An NO donor or saline, was injected intravitreously into normal rats. Photoreceptor apoptosis was evaluated by TUNEL and electron microscopy. NOS, ED-1, and cleaved-caspase-3 (c-casp-3) expression were determined by immunohistochemistry. CNV lesions were examined by fluorescence angiography and choroidal flat mount. RESULTS. TUNEL and electron microscopy showed photoreceptor apoptosis after PDT. In rats, there were significantly more TUNEL-positive cells in the photoreceptors 24 hours after PDT, whereas in the CNV lesions there were more TUNEL-positive cells 6 hours after PDT. C-casp-3 was detected in the CNV lesions but not in the photoreceptors after PDT. There was no difference in the numbers of ED-1-positive macrophages before and after PDT. However, inducible NOS (iNOS) was increased after PDT in macrophages. Intravitreous injection of the NO donor without PDT also induced substantial photoreceptor apoptosis. L-NAME-treated animals had significantly fewer TUNEL-positive cells in the photoreceptors than saline-treated animals after PDT (P < 0.05). There were no differences in CNV size and leakage between L-NAME- and saline-treated groups. CONCLUSIONS. iNOS expression in macrophages contributes to PDT-induced photoreceptor degeneration. NOS inhibition reduces PDT-induced photoreceptor degeneration without compromising the treatment effect of PDT in an experimental model of CNV. C1 Harvard Univ, Sch Med, Angiogenesis & Laser Labs, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Angiogenesis & Laser Labs, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu OI Hisatomi, Toshio/0000-0003-2552-9595; Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NEI NIH HHS [P30 EY014104]; NIAID NIH HHS [AI050775] NR 43 TC 17 Z9 18 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2007 VL 48 IS 5 BP 2268 EP 2277 DI 10.1167/iovs.06-0979 PG 10 WC Ophthalmology SC Ophthalmology GA 162DU UT WOS:000246067800053 PM 17460290 ER PT J AU Anastos, K Lu, DL Shi, QH Tien, PC Kaplan, RC Hessol, NA Cole, S Vigen, C Cohen, M Young, M Justman, J AF Anastos, Kathryn Lu, Dalian Shi, Qiuhu Tien, Phyllis C. Kaplan, Robert C. Hessol, Nancy A. Cole, Steven Vigen, Cheryl Cohen, Mardge Young, Mary Justman, Jessica TI Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE high-density lipoprotein; highly active antiretroviral therapy; lipids; low-density lipoprotein; women ID DENSITY-LIPOPROTEIN CHOLESTEROL; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; WOMENS INTERAGENCY HIV; HIGH BLOOD CHOLESTEROL; ADULT TREATMENT PANEL; PLASMA-CONCENTRATIONS; PROTEASE INHIBITORS; INFECTED PATIENTS; INSULIN SENSITIVITY; DIABETES-MELLITUS AB Background: The effects of HIV infection, highly active antiretroviral therapy (HAART), and specific antiretroviral agents on lipoproteins in women are not well described. Methods: In a cross-sectional substudy of the Women's Interagency HIV Study with 623 HIV-negative and 1556 HIV-positive women (636 untreated, 419 on non-protease inhibitor [PI] HAART, and 501 on PI-containing HAART), we performed multivariate analyses of associations among fasting lipoprotein levels, HIV infection, and HAART. Results: Untreated HIV-positive women had lower high-density lipoprotein cholesterol (HDL-C and higher triglycerides (TGs) but not lower low-density lipoprotein cholesterol (LDL-C) than HIV-negative women and were the most likely to have unfavorable HDL-C by National Cholesterol Education Program (NCEP) guidelines. PI HAART users had higher LDL-C than untreated HIV-infected women (107 vs. 100 mg/dL, P = 0.0006) and were the most likely to have unfavorable LDL-C and TGs by NCEP guidelines. HIV-negative women and non-PI HAART users had similar HDL-C levels (55 and 53 mg/dL, respectively), which were higher than those in untreated HIV-infected women and PI HAART users (42 and 49 mg/dL, respectively; P < 0.001 for all). Lamivudinc, didanosine, nevirapine, and efavirenz were independently associated with higher HDL-C (P < 0.001 for all). Ritonavir, indinavir/ritonavir, and nelfinavir were associated with higher LDL-C (P < 0.01 for all). Stavudine, abacavir, and all ritonavir- containing regimens were associated with higher TGs (P < 0.05 for all), and tenofovir was associated with lower TGs (P = 0.009). Conclusions: A dyslipidemic pattern was associated with HIV infection itself, was more severe in users of PI-containing HAART, but was not present in women taking non-PI HAART. C1 Montefiore Med Ctr, Womens Interagcy HIV Study, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Data Solut LLC, Bronx, NY USA. New York Med Coll, Valhalla, NY 10595 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ So Calif, Los Angeles, CA USA. Cook Cty Hosp, Chicago, IL 60612 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Anastos, K (reprint author), Montefiore Med Ctr, Womens Interagcy HIV Study, 3311 Bainbridge Ave, Bronx, NY 10467 USA. EM kanastos@montefiore.org RI Kaplan, Robert/A-2526-2011 FU NCRR NIH HHS [M01-RR-00079, M01-RR-00083]; NIAID NIH HHS [AI-51519, N01-AI-35161, U01-AI-31834, U01-AI-34989, U01-AI-34994, U01-AI-35004, U01-AI-42590, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632]; NIDDK NIH HHS [DK-54615] NR 55 TC 64 Z9 66 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2007 VL 45 IS 1 BP 34 EP 42 DI 10.1097/QAI.0b013e318042d5fe PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 160TA UT WOS:000245964000006 PM 17460470 ER PT J AU Pole, N Neylan, TC Otte, C Metzler, TJ Best, SR Henn-Haase, C Marmar, CR AF Pole, Nnamdi Neylan, Thomas C. Otte, Christian Metzler, Thomas J. Best, Suzanne R. Henn-Haase, Clare Marmar, Charles R. TI Associations between childhood trauma and emotion-modulated psychophysiological responses to startling sounds: A study of police cadets SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE childhood trauma; startle; police stress; psychophysiology ID POSTTRAUMATIC-STRESS-DISORDER; SEXUALLY ABUSED GIRLS; ACOUSTIC STARTLE; NEUROENDOCRINE ACTIVITY; MATERNAL-DEPRIVATION; VIETNAM VETERANS; WOMEN; SYMPTOMS; PSYCHOPATHOLOGY; MALTREATMENT AB Childhood trauma may confer risk for adult psychopathology by altering emotional and physiological responses to subsequent stressors. Few studies have distinguished effects of childhood trauma from effects of current Axis I psychopathology on adult psychophysiological reactivity. The authors exposed 90 psychiatrically healthy police cadets to startling sounds under increasing threat of shock while assessing their eyeblink electromyogram (EMG), skin conductance (SC), and heart rate responses. When compared with those who did not endorse early trauma (n = 65), cadets reporting childhood trauma (n = 25) reported less positive emotion and showed greater SC responses across all threat levels. They also showed threat-dependent elevations in reported negative emotions and EMG responses. Results suggest that childhood trauma may lead to long-lasting alterations in emotional and psychophysiological reactivity even in the absence of current Axis I psychopathology. C1 Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Pole, N (reprint author), Univ Michigan, Dept Psychol, 2260 E Hall,530 Church St, Ann Arbor, MI 48109 USA. EM nnamdi@umich.edu FU NIMH NIH HHS [R01-MH056350-06] NR 49 TC 30 Z9 31 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2007 VL 116 IS 2 BP 352 EP 361 DI 10.1037/0021-843X.116.2.352 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 168DL UT WOS:000246502900012 PM 17516767 ER PT J AU Peden, DB Bush, RK AF Peden, David B. Bush, Robert K. TI Advances in environmental and occupational disorders 2006 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE hygiene hypothesis; endotoxin; dendritic cell; Toll receptors; air pollution; allergens; fungi; occupational; indoor exposures; exposure reduction ID HUMAN DENDRITIC CELLS; AIRWAY INFLAMMATION; ENDOTOXIN EXPOSURE; HYGIENE HYPOTHESIS; BIRTH COHORT; ASTHMA; ALLERGEN; IGE; SENSITIZATION; DISEASE AB In 2006, there continued to be significant contributions to the Journal in the area of environmental and occupational allergy. In addition to very strong clinical observations, there were a number of studies that examined the effect of environmental agents on cellular and molecular processes in allergy, and molecular approaches were also used in investigations of allergen structure and biology. The Journal also received a number of very strong epidemiologic studies examining several aspects of environmental and occupational allergy. Thus, this particular area of our specialty thrives as a result of clinical, mechanistic, epidemiologic, and translational observations. This article reviews a number of these papers presented in the journal in 2006. C1 Univ N Carolina, Sch Med, Div Pediat Immunol & Infect Dis, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Univ Wisconsin, Sch Med & Publ Hlth, Sect Allergy Immunol Pulm Crit Care & Sleep Med, Madison, WI 53706 USA. RP Peden, DB (reprint author), Univ N Carolina, Sch Med, Div Pediat Immunol & Infect Dis, CB 7310,104 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM David_Peden@med.unc.edu NR 61 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2007 VL 119 IS 5 BP 1127 EP 1132 DI 10.1016/j.jaci.2007.03.030 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 167CB UT WOS:000246427200012 PM 17472812 ER PT J AU Streeter, CC Jensen, JE Perlmutter, RM Cabral, HJ Tian, H Terhune, DB Ciraulo, DA Renshaw, PF AF Streeter, Chris C. Jensen, J. Eric Perlmutter, Ruth M. Cabral, Howard J. Tian, Hua Terhune, Devin B. Ciraulo, Domenic A. Renshaw, Perry F. TI Yoga asana sessions increase brain GABA levels: A pilot study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; MAGNETIC-RESONANCE SPECTROSCOPY; DEPRESSED-PATIENTS; PANIC DISORDER; ANXIETY; EPILEPSY; THERAPY; RECEPTOR; SPECTRA; MATTER AB Objectives: The aim of this study was to compare changes in brain gamma-aminobutyric (GABA) levels associated with an acute yoga session versus a reading session. It was hypothesized that an individual yoga session would be associated with an increase in brain GABA levels. Design: This is a parallel-groups design. Settings/location: Screenings, scan acquisitions, and interventions took place at medical school-affiliated centers. Subjects: The sample comprised 8 yoga practitioners and 11 comparison subjects. Interventions: Yoga practitioners completed a 60-minute yoga session and comparison subjects completed a 60-minute reading session. Outcome measures: GABA-to-creatine ratios were measured in a 2-cm axial slab using magnetic resonance spectroscopic imaging immediately prior to and immediately after interventions. Results: There was a 27% increase in GABA levels in the yoga practitioner group after the yoga session (0.20 mmol/kg) but no change in the comparison subject group after the reading session (-0.001 mmol/kg) (t = -2.99, df = 7.87, p = 0.018). Conclusions: These findings demonstrate that in experienced yoga practitioners, brain GABA levels increase after a session of yoga. This suggests that the practice of yoga should be explored as a treatment for disorders with low GABA levels such as depression and anxiety disorders. Future studies should compare yoga to other forms of exercise to help determine whether yoga or exercise alone can alter GABA levels. C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston VA Healthcare Syst, Boston, MA USA. RP Streeter, CC (reprint author), Boston Univ, Sch Med, Div Psychiat, 85 E Newton St M912E, Boston, MA 02118 USA. EM streeter@bu.edu RI Emidio, Fernando/H-2015-2011; OI Cabral, Howard/0000-0002-1185-8331; Ciraulo, Domenic/0000-0001-7706-8765; Terhune, Devin/0000-0002-6792-4975 FU NCRR NIH HHS [M01RR00533]; NIAAA NIH HHS [AA013727, K23AA13149]; NIDA NIH HHS [DA09448, DA15116, DA50038] NR 39 TC 66 Z9 66 U1 3 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD MAY PY 2007 VL 13 IS 4 BP 419 EP 426 DI 10.1089/acm.2007.6338 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 170AC UT WOS:000246632200007 PM 17532734 ER PT J AU Meeker, JD Godfrey-Bailey, L Hauser, R AF Meeker, John D. Godfrey-Bailey, Linda Hauser, Russ TI Relationships between serum hormone levels and semen quality among men from an infertility clinic SO JOURNAL OF ANDROLOGY LA English DT Article DE epidemiology; human; male; reproduction; sperm; thyroid ID FOLLICLE-STIMULATING-HORMONE; INHIBIN-B; REPRODUCTIVE HORMONES; LUTEINIZING-HORMONE; DANISH MEN; SPERMATOGENESIS; TESTOSTERONE; MARKER AB Participation rates in epidemiologic studies on semen quality are generally very low, raising concerns as to the potential for selection bias. Since hormones both initiate and maintain spermatogenesis, they may serve as surrogates of semen quality in epidemiologic studies. For this reason, in the present study, we explored the influence and predictive ability of reproductive and thyroid hormones on semen quality among men who were partners in an infertile couple. Between 1999 and 2003, 388 men were recruited from Massachusetts General Hospital Andrology Laboratory for clinical evaluation of fertility status. Fresh semen samples were assessed for quality (concentration, motility and morphology) and the serum levels of hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, sex hormone-binding globulin (SHBG), testosterone, free androgen index, free T-4, total T-3, and thyroid-stimulating hormone (TSH), were measured. Multiple logistic regression revealed increased odds for below-reference sperm concentration and morphology in men with increased FSH, and decreased odds for below-reference sperm concentration and motility in men with increased inhibin B. When FSH and inhibin B were divided into quintiles, the relationships with sperm concentration showed evidence of a threshold value. However, the ability of specific FSH (10 IU/L) and/or inhibin B (80 pg/mL) cutoff values to predict semen quality was lower than in previous reports. In multiple linear regression analysis, FSH and LH were inversely associated with sperm concentration, motility, and morphology. Inhibin B and free T-4 were positively associated with sperm concentration, while there was a suggestive positive association between testosterone and sperm motility. In conclusion, we have found that FSH, LH, inhibin B, testosterone and free T-4 levels are associated with human semen parameters. Additional consideration should be given to the utility of serum hormone levels as a surrogate for semen quality in epidermiologic studies in which the collection of semen is difficult due to logistical and/or volunteer rate constraints. C1 Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Fertil Ctr, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, M6226 SPH II,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Meeker, John/0000-0001-8357-5085 NR 23 TC 85 Z9 89 U1 1 U2 4 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAY-JUN PY 2007 VL 28 IS 3 BP 397 EP 406 DI 10.2164/jandrol.106.001545 PG 10 WC Andrology SC Endocrinology & Metabolism GA 159ND UT WOS:000245871900009 PM 17135633 ER PT J AU Yeo, Y Geng, WL Ito, T Kohane, DS Burdick, JA Radisic, M AF Yeo, Yoon Geng, Wenliang Ito, Taichi Kohane, Daniel S. Burdick, Jason A. Radisic, Milica TI Photocrosslinkable hydrogel for myocyte cell culture and injection SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE heart; cell injection; cardiomyocyte; myocardial infarction; RGD; photocrosslinkable hydrogel ID FIBROBLAST-GROWTH-FACTOR; NEONATAL RAT CARDIOMYOCYTES; STEM-CELLS; ISCHEMIC-MYOCARDIUM; SKELETAL MYOBLASTS; ENDOTHELIAL-CELLS; CARDIAC-FUNCTION; CHITOSAN; HEART; SURVIVAL AB Conventional treatment options for myocardial infarction are limited by the inability of mature myocardium to regenerate after injury. Although functional improvements after injection of cells and growth factors have been demonstrated, the clinical utility of this procedure has been hampered by poor cell localization, low survival, and rapid clearance of injected growth factors. The main objective of this study was to evaluate the applicability of a hydrogel, based on photocrosslinkable chitosan and acryloyl-poly (ethylene glycol)-RGDS (Az-chitosan/Acr-PEG-RGD) for myocyte cell culture and myocardial injection. Chitosan was modified with photoreactive azidobenzoic acid and Acr-PEG-RGD was synthesized by reacting YRGDS with an equimolar amount of acryloyl-PEG-N-hydroxysuccinimide. For injection and encapsulation each polymer was dissolved in Di-H2O (pH 6.4), the solutions were mixed and crosslinked by UV application (4 mW/cm(2)). C2C12 myoblasts proliferated and differentiated on hydrogels containing 5 mM RGD but not on the pure photocrosslinked chitosan. In vitro, the crosslinked hydrogels retained 80% of encapsulated VEGF for 24 days. Live/dead staining of neonatal rat cardiomyocytes encapsulated into Az-chitosan/Acr-PEG-RGD hydrogels indicated high cell viability upon UV crosslinking. Ex vivo, we localized the hydrogel on the surface and in the ventricle wall of an adult rat heart by brief (2 min) UV light application. (c) 2006 Wiley Periodicals, Inc. C1 Univ Toronto, Inst Biomat & Biomed Engn, Dept Chem Engn & Appl Chem, Toronto, ON, Canada. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA USA. Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. RP Radisic, M (reprint author), Univ Toronto, Inst Biomat & Biomed Engn, Dept Chem Engn & Appl Chem, Toronto, ON, Canada. EM milica@chem-eng.utoronto.ca NR 34 TC 68 Z9 70 U1 0 U2 25 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2007 VL 81B IS 2 BP 312 EP 322 DI 10.1002/jbm.b.30667 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 161HC UT WOS:000246004400004 PM 16969828 ER PT J AU Winter, JO Cogan, SF Rizzo, JF AF Winter, Jessica O. Cogan, Stuart F. Rizzo, Joseph F., III TI Neurotrophin-eluting hydrogel coatings for neural stimulating electrodes SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE neural prostheses; hydrogel; NGF; nerve regeneration; electrical stimulation ID SPINAL-CORD-INJURY; PEPTIDE DRUG-DELIVERY; IRIDIUM OXIDE AIROF; NERVE GROWTH-FACTOR; ELECTRICAL-STIMULATION; RETINAL DEGENERATION; SURFACE MODIFICATION; CHARGE-INJECTION; GANGLION-CELLS; IN-VIVO AB Improved sensory and motor prostheses for the central nervous system will require large numbers of electrodes with low electrical thresholds for neural excitation. With the eventual goal of reducing stimulation thresholds, we have investigated the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging from 1.5 to 3 weeks were synthesized. These hydrogels were applied to multielectrode arrays with sputtered iridium oxide charge-injection sites. The coatings had little impact on the iridium oxide electrochemical properties, including charge storage capacity, impedance, and voltage transients during current pulsing. Additionally, we quantitatively examined the ability of neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth factor, NGF) for at least I week, with neurite extension near that of an NGF positive control and much higher than extension seen from sham, bovine serum albumin-releasing boluses, and a negative control. These results show that neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and suggest a method to improve neuron,electrode proximity, which could result in lowered electrical stimulation thresholds. Reduced thresholds support the creation of smaller electrode structures and high density electrode prostheses, greatly enhancing prosthesis control and function. (C) 2006 Wiley Periodicals, Inc. C1 Boston VA Hosp, Ctr Innovat Visual Rehabil, Boston, MA USA. Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. EIC Labs, Norwood, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Winter, JO (reprint author), Boston VA Hosp, Ctr Innovat Visual Rehabil, Boston, MA USA. EM winter.63@osu.edu FU NINDS NIH HHS [R43 NS04968701] NR 71 TC 50 Z9 51 U1 2 U2 19 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2007 VL 81B IS 2 BP 551 EP 563 DI 10.1002/jbm.b.30696 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 161HC UT WOS:000246004400033 PM 17041927 ER PT J AU Doornberg, JN Parisien, R van Duijn, PJ Ring, D AF Doornberg, Job N. Parisien, Robert van Duijn, P. Joppe Ring, David TI Radial head arthroplasty with a modular metal spacer to treat acute traumatic elbow instability SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID VALGUS STABILITY; FRACTURES; REPLACEMENT; PROSTHESIS; DISLOCATIONS; MANAGEMENT; MORPHOLOGY; DESIGN; ADULTS AB Background: The use of a metal radial head prosthesis to help stabilize an elbow with traumatic instability is appealing because internal fixation of multifragment, displaced fractures of the radial head is susceptible to either early or late failure. The newer modular prostheses are easier to size and implant, but their effectiveness has not been investigated, to our knowledge. Methods: Twenty-seven patients in whom a radial head replacement with a modular metal spacer prosthesis had been performed to treat traumatic elbow instability were evaluated with use of the Mayo Elbow Performance Index (MEPI), the American Shoulder and Elbow Surgeons Elbow Evaluation Instrument (ASES), and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Radiographs were evaluated for arthrosis, periprosthetic radiolucency, and heterotopic ossification. Results: Seven patients underwent one or more subsequent operations to treat residual instability, heterotopic ossification and elbow contracture, ulnar neuropathy, or a misplaced screw. In two of these patients, the prosthesis was removed as part of an elbow contracture release or to treat infection. At an average of forty months postoperatively, elbow motion in the entire group of twenty-seven patients averaged 131 degrees of flexion with a 20 degrees flexion contracture, 73 degrees of pronation, and 57 degrees of supination. Stability was restored to all twenty-seven elbows, and twenty-two patients had a good or excellent result according to the MEPI. Seventeen patients had radiographic evidence of lucency around the neck of the prosthesis that was not associated with increased pain, thirteen patients had clinically inconsequential heterotopic ossification anterior to the radial neck, and nine patients had radiographic changes in the capitellum. Conclusions: An intentionally loosely placed modular metal radial head prosthesis can help to restore stability in conjunction with repair of other fractures and reattachment of the lateral collateral ligament to the epicondyle in the setting of traumatic elbow instability with a comminuted fracture of the radial head. While a prosthesis that is too large can cause problems, lucencies around the stem of the intentionally loose prosthesis and most changes in the capitellum do not appear to cause problems, at least in the short term. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Doornberg, JN (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM jdoornberg@partners.org; dring@partners.org NR 49 TC 67 Z9 71 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2007 VL 89A IS 5 BP 1075 EP 1080 DI 10.2106/JBJS.E.01340 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 166KK UT WOS:000246377400021 PM 17473146 ER PT J AU Shanbhag, AS Kaufman, AM Hayata, K Rubash, HE AF Shanbhag, Arun S. Kaufman, Adam M. Hayata, Koichiro Rubash, Harry E. TI Assessing osteolysis with use of high-throughput protein chips SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-ARTHROPLASTY; SYNOVIAL-LIKE MEMBRANE; BONE-CEMENT INTERFACE; RHEUMATOID-ARTHRITIS; WEAR DEBRIS; MATRIX-METALLOPROTEINASE; INFLAMMATORY REACTIONS; ACETABULAR COMPONENTS; CHEMOKINE RECEPTORS; JOINT PROSTHESES AB Background: Previous studies of bone resorption around failed joint replacements have focused on a limited number of cytokines, primarily tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, with use of enzyme-linked immunosorbent assay and immunohistochemistry techniques. In this study, we utilized high-throughput protein chips to profile twenty-nine inflammatory cytokines around failed total joint replacements. Methods: Peri-implant granulomatous tissues were harvested from around the failed total hip prostheses of thirteen patients. Synovial lining capsular tissues from thirteen patients with end-stage degenerative joint disease were used as controls. After homogenization, twenty-nine cytokines were quantified with use of high-throughput protein chips. Results: IL-6 and IL-8 were found consistently in failed joint replacement tissues, reaffirming their prominent role in osteoclastogenesis and end-stage bone resorption. High levels of interferon-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by interferon-gamma (MIG), both chemoattractants of activated Th1 lymphocytes, were also detected. Soluble intercellular adhesion molecule (sICAM) and transforming growth factor-beta 1 (TGF-beta(1)) were not detected universally, nor were TNF-alpha or IL-1. After a twenty-four-hour organ culture, IL-1 beta levels increased substantially along with those of other mediators. We measured but did not detect any activators of cytotoxic T-cells, antibody-producing B-cells, or eosinophils involved in delayed-type hypersensitivity. Variations from patient to patient were seen across all cytokines and highlight the unique response of individual patients to their joint replacements. Conclusions: In failed total joint replacements in patients with end-stage osteolysis, IL-6 and IL-8 may be the primary drivers of osteoclastogenesis. The presence of IP-10 and MIG imply a role for T-cells, while TGF-beta(1), and sICAM may represent a systemic attempt to modulate the inflammation. TNF-alpha and IL-1 do not appear to play a major role in the end stages of the disease. Clinical Relevance: These results demonstrate that proteomic tools can provide a foundation for understanding the cytokine-driven osteolysis cascade and a base from which to identify and evaluate potential targets for blockage or augmentation. C1 Harvard Univ, Sch Med, Biomat Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shanbhag, AS (reprint author), Harvard Univ, Sch Med, Biomat Lab, Massachusetts Gen Hosp, GRJ 1115,55 Fruit St, Boston, MA 02114 USA. EM shanbhag@helix.mgh.harvard.edu NR 72 TC 27 Z9 29 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2007 VL 89A IS 5 BP 1081 EP 1089 DI 10.2106/JBJS.F.00330 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 166KK UT WOS:000246377400022 PM 17473147 ER PT J AU Shin, R Ring, D AF Shin, Robert Ring, David TI Current concepts review - The ulnar nerve in elbow trauma SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID CUBITAL TUNNEL-SYNDROME; DISTAL HUMERAL FRACTURES; SURGICAL-TREATMENT; INTRAARTICULAR FRACTURES; INTERCONDYLAR FRACTURES; HETEROTOPIC OSSIFICATION; FAILED DECOMPRESSION; RHEUMATOID-ARTHRITIS; OPERATIVE APPROACH; INTERNAL-FIXATION AB The prevalence of ulnar nerve dysfunction after elbow injury is unknown because authors of published investigations have inadequately differentiated among acute injury-related, acute surgery-related, and delayed (subacute or chronic) ulnar neuropathies and these retrospective case series have not included careful evaluation of ulnar nerve function. Ulnar neuropathy is well documented after distal humeral fracture, but it can also develop following any complex elbow trauma. The ulnar nerve should be identified and protected during the treatment of a bicolumnar fracture of the distal part of the humerus, but current data are inconclusive regarding the value of routine anterior transposition of the nerve. Although most delayed ulnar neuropathies present at a relatively late stage with weakness, with or without muscle atrophy, improved motor strength may be observed in some patients many years after ulnar nerve decompression. Ulnar nerve decompression and transposition are becoming an integral part of many posttraumatic reconstructive elbow procedures, but most recommendations for management of the ulnar nerve are based on retrospective reviews, anecdotal reports, and expert opinion. C1 Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP Shin, R (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 113 TC 35 Z9 38 U1 0 U2 8 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2007 VL 89A IS 5 BP 1108 EP 1116 DI 10.2106/JBJS.F.00594 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 166KK UT WOS:000246377400027 PM 17473151 ER PT J AU Snyder, PJ Biller, BMK Zagar, A Jackson, I Arafah, BM Nippoldt, TB Cook, DM Mooradian, AD Kwan, A Scism-Bacon, J Chipman, JJ Hartman, ML AF Snyder, Peter J. Biller, Beverly M. K. Zagar, Anthony Jackson, Ivor Arafah, Baha M. Nippoldt, Todd B. Cook, David M. Mooradian, Arshag D. Kwan, Anita Scism-Bacon, Jamie Chipman, John J. Hartman, Mark L. TI Effect of growth hormone replacement on BMD in adult-onset growth hormone deficiency SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BMD; bone turnover markers; growth hormone; hypopituitarism; IGF-I ID BONE-MINERAL DENSITY; GH DEFICIENCY; DOUBLE-BLIND; THERAPY; METABOLISM; TURNOVER; FRACTURE; TRIAL; HYPOPITUITARISM; WOMEN AB To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. Introduction: Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. Materials and Methods: We randomized 67 men and women to receive GH (n = 33) or placebo (n = 34) for 2 yr. The GH dose was initially 2 mu g/kg body weight/d, increased gradually to a maximum of 12 mu g/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. Results: BMD of the lumbar spine in the entire group increased by 2.9 +/- 3.9% above baseline in the GH-treated subjects, which was significantly (p = 0.037) greater than the 1.4 +/- 4.5% increase in the placebotreated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 +/- 4.3% above baseline, which was significantly (p = 0.001) greater than that in placebo-treated men (0.4 +/- 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. Conclusions: We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw my conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD. C1 Univ Penn, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Rhode Isl Hosp, Brown Med Sch, Providence, RI USA. Case Western Reserve Univ, Div Endocrinol, Cleveland, OH 44106 USA. Mayo Clin, Div Endocrinol & Metab, Rochester, MN USA. Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. St Louis Univ, Div Endocrinol, St Louis, MO 63103 USA. RP Snyder, PJ (reprint author), Univ Penn, Div Endocrinol Diabet & Metab, 778 Clin Res Bldg 415 Curie Blvd, Philadelphia, PA 19104 USA. EM pjs@pobox.upenn.edu OI Snyder, Peter/0000-0003-0555-4654 NR 29 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2007 VL 22 IS 5 BP 762 EP 770 DI 10.1359/JBMR.070205 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160IL UT WOS:000245934000016 PM 17280527 ER PT J AU Goverman, J Weber, JM Keaney, TJ Sheridan, RL AF Goverman, Jeremy Weber, Joan M. Keaney, Timothy J. Sheridan, Robert L. TI Intravenous colistin for the treatment of multi-drug resistant, gram-negative infection in the pediatric burn population SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID QUALITY-CONTROL GUIDELINES; CRITICALLY-ILL PATIENTS; PSEUDOMONAS-AERUGINOSA; POLYMYXIN-B; ACINETOBACTER-BAUMANNII; NOSOCOMIAL INFECTIONS; TOXICITY; BACTERIA; OLD; ANTIBIOTICS AB The rising incidence of multi-drug resistant (MDR) gram-negative infections in the intensive care unit (ICU) continues to challenge clinicians and has resulted in reemergence of the glycopeptide antibiotic colistin. Over the past 11 years, 14 patients at a tertiary pediatric burn center were treated with colistin for gram-negative infections resistant to all tested antibiotics. This study reviews the safety of such treatment and the outcome for this cohort of patients. All hospitalized patients treated with intravenous colistin between 1990 and 2005 were identified. A retrospective chart review was performed for each patient. Demographic data, along with information regarding the type and severity of injury, were collected. Data with respect to microbiology, renal status, and neurological events were also noted. Over an 11-year period, we identified 14 children infected with pan-resistant gram-negative organisms requiring 16 courses of colistin. Two children (14.3%) developed significant rises in serum creatinine concentration; however, no child required renal replacement therapy or developed neurologic complications attributable to colistin. Favorable response rate was 78.6% (11/14), and overall mortality was 14.3% (2/14); both deaths were attributed to sepsis. In our experience with 14 children treated with intravenous colistin, two developed a significant elevation in serum creatinine concentration during the course of therapy and neurotoxicity was not reported. Colistin should be dispensed with great caution, but it appears to have an acceptable safety profile in children and may be used in select cases of infection with highly resistant gram-negative organisms. C1 Massachusetts Gen Hosp, Burns Serv, Boston, MA 02114 USA. Shriners Hosp Burned Children, Burns Serv, Boston, MA USA. RP Goverman, J (reprint author), Massachusetts Gen Hosp, Burns Serv, Bigelow 13,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 34 Z9 35 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2007 VL 28 IS 3 BP 421 EP 426 DI 10.1097/BCR.0B013E318053D346 PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 166ZG UT WOS:000246419500008 PM 17438490 ER PT J AU Becker, ER McPherson, MA Rahimi, A AF Becker, Edmund R. McPherson, Marie A. Rahimi, Ali TI Influence of source and type of admission on in-hospital mortality for coronary artery bypass surgery patients: National results from 1.7 million CABG patients, 1998 to 2002 SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID OUTCOMES AB Background: Hospitals identify the type of coronary artery bypass graft (CABG) surgery admission as routine, urgent, or emergency, and identify CABG admissions as elective, from another hospital, from a long-term healthcare facility, and an admission that results from an emergency room visit. No research has analyzed the importance of these admission characteristics on CABG outcomes. Methods: Using the Nationwide Inpatient Sample data from the Healthcare Cost and Utilization Project database for 1998 through 2002, 1.7 million CABG admissions are analyzed using descriptive and logistic regression techniques to evaluate the extent of differences in in-hospital CABG mortality rates by the type of admission and the source of admission. Results: While there has been 22% decline over our 5-year study period regardless of the source or type of admission, we find that a 2.5-fold difference exists in the in-hospital CABG mortality rates among categories that distinguish the type of admission and the source of admission in the nation's hospital. In 2002, CABG admissions that are routine elective-surgeries have a CABG mortality rate of 1.49%, while urgent CABG admissions from a long-term care facility have an in-hospital mortality rate that is 3.64%. Conclusions: While significant progress has been made lowering in-hospital CABG mortality, sizable differences still remain among the types and sources of CABG admissions. Clinical trial research on CABG patients where the end points include mortality need to be especially mindful of the potential differences and distortions in their data that can be generated due to these various sources of hospital admissions. C1 Emory Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston Heart Fdn, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Becker, ER (reprint author), Emory Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 1518 Clifton Rd,NE, Atlanta, GA 30322 USA. EM ebeck01@sph.emory.edu NR 11 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAY-JUN PY 2007 VL 22 IS 3 BP 203 EP 210 DI 10.1111/j.1540-8191.2007.00386.x PG 8 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 163HP UT WOS:000246151000007 PM 17488415 ER PT J AU Ray, IB Dukkipati, S Houghtaling, C McPherson, CD Kastelein, N Ruskin, JN Reddy, VY AF Ray, Indranill Basu Dukkipati, Srinivas Houghtaling, Christopher McPherson, Christina D. Kastelein, Nathan Ruskin, Jeremy N. Reddy, Vivek Y. TI Initial experience with a novel remote-guided magnetic catheter navigation system for left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Scientific Session of the Heart-Rhythm-Society CY MAY 05, 2005 CL New Orleans, LA SP Heart Rhythm Soc DE electrophysiology; remote navigation; catheter ablation; mapping; infarction ID SINUS RHYTHM; TACHYCARDIA; LESIONS AB Objective: This study examined the feasibility of using a remote magnetic catheter navigation system (MNS) in concert with an EAM system to perform detailed left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction. Background: Substrate-based catheter ablation of ventricular tachycardia (VT) involves detailed electroanatomical mapping (EAM) of the ventricles. While a safe and effective procedure, VT ablation is nonetheless uncommonly performed, due in part to the technical challenges related to ventricular mapping. Methods: Using a prototype EAM system (CARTO-RMT), seven chronically infarcted swine were mapped using either: (i) a standard manually manipulated catheter or (ii) a magnetic remotely manipulated (Niobe) catheter. A total of 191 +/- 54 and 221 +/- 64 points were acquired to map the chamber either manually or remotely, respectively. Results: Procedure times were longer remotely (94 +/- 22 vs. 59 +/- 19 minute, P = 0.004; and 27 +/- 8 vs. 18 +/- 3 sec/point, P = 0.04), but this became less apparent with increased operator experience. However, the fluoroscopy time was significantly shorter with remote mapping (56 +/- 56 vs. 244 +/- 67 sec/map, P = 0.03). The calculated scar size was comparable between the two methods (16.3 +/- 4.9 vs. 16.4 +/- 4.8 cm(2), P = 0.37). Pathologic examination confirmed that the MNS was able to precisely deliver radiofrequency lesions to the scar borders. Using the MNS, the error to reach an evenly distributed set of endocardial targets was 6.6 +/- 3.6 mm and 4.6 +/- 2.0 mm, using transseptal and retrograde approaches, respectively. Conclusions: Ventricular mapping using this remote navigation paradigm is technically possible and requires minimal fluoroscopy exposure, potentially facilitating ventricular substrate mapping and ablation. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Stereotaxis Inc, St Louis, MO USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org RI Basu Ray, Indranill/D-3794-2011 FU NHLBI NIH HHS [K23 HL68064-01A1] NR 16 TC 17 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2007 VL 18 IS 5 BP 520 EP 525 DI 10.1111/j.1540-8167.2007.00794.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 160LM UT WOS:000245942200016 PM 17388912 ER PT J AU Cianferotti, L Demay, MB AF Cianferotti, Luisella Demay, Marie B. TI VDR-mediated inhibition of DKK1 and SFRP2 suppresses adipogenic differentiation of murine bone marrow stromal cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE 1,25(OH)(2)D-3; PPAR gamma; osteoblast differentiation; adipocyte differentiation; Wnt signaling ID VITAMIN-D-RECEPTOR; PPAR-GAMMA INSUFFICIENCY; MINERAL ION HOMEOSTASIS; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; IN-VITRO; SIGNALING PATHWAY; 3T3-L1 CELLS; ABLATED MICE; CULTURES AB Osteoblasts and adipocytes are thought to derive from a common bone marrow stromal cell (BMSC) precursor. Activation of the canonical Wnt signaling pathway plays a pivotal role in the differentiation of BMSCs along either of these two lineages, promoting osteogenesis and inhibiting adipogenesis. Liganded nuclear receptors, including the vitamin D receptor WDR) and peroxisomal proliferator-activated receptor gamma (PPAR gamma), can also affect BMSCs differentiation. To address whether VDR ablation modulates the differentiation of BMSCs into the osteoblast or adipogenic lineages, BMSCs were isolated from VDR null mice and from their wild-type littermates. VDR ablation did not alter osteoblastic differentiation. However, when cultured under adipogenic conditions, BMSCs from the VDR null mice expressed higher mRNA levels of PPAR gamma and of markers of adipogenic differentiation. An increase in the size and number of mature adipocyte foci was also observed in cultures isolated from VDR null mice relative to those isolated from wildtype mice. To address whether the increased adipogenesis observed in the VDR null cultures was associated with inhibition of the canonical Wnt signaling pathway, mRNA levels for DKK1 and SFRP2 were examined. Cultures from the VDR null mice expressed higher levels of mRNA encoding DKK1 and SFRP2 than did the wild-type cultures. This difference is, at least in part, due to ligand-dependent actions of the VDR, since 1,25-dihydroxyvitamin D-3 suppressed DKK1 and SFRP2 expression in wild-type cultures. Thus, the VDR inhibits adipogenesis of BMSCs at least in part by suppressing the expression of inhibitors of the canonical Wnt signaling pathway. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 501,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 46974, R01 DK046974] NR 45 TC 31 Z9 35 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 2007 VL 101 IS 1 BP 80 EP 88 DI 10.1002/jcb.21151 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 160AM UT WOS:000245909200007 PM 17212358 ER PT J AU Venkatesan, B Mahimainathan, L Das, F Ghosh-Choudhury, N Choudhury, GG AF Venkatesan, Balachandar Mahimainathan, Lenin Das, Falguni Ghosh-Choudhury, Nandini Choudhury, Goutam Ghosh TI Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID AKT/PROTEIN KINASE-B; TRANSCRIPTION FACTOR FOXO3A; ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR PTEN; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; PHOSPHATIDYLINOSITOL 3-KINASE; LIFE-SPAN; C-FOS AB Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen peroxide (H2O2) reduced the expression of catalase. H2O2 increased phosphorylation of Akt kinase in a dose-dependent and sustained manner with a concomitant increase in the phosphorylation of FoxOI transcription factor. Further analysis revealed that H2O2 promoted rapid activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase activity, resulting in the attenuation of FoxOI phosphorylation and preventing the downregulating effect of H2O2 on catalase protein level. Dominant negative Akt attenuated the inhibitory effect of H2O2 on expression of catalase. Constitutively active FoxOI increased the expression of catalase. However, dominant negative FoxOI inhibited catalase protein level. Catalase transcription was reduced by H2O2 treatment. Furthermore, expression of dominant negative Akt and constitutively active FoxOI increased catalase transcription, respectively. These results demonstrate that ROS downregulate the expression of catalase in mesangial cells by PI3 kinase/Akt signaling via FoxOI as a target. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu OI /0000-0001-5077-3552 FU NIAMS NIH HHS [R01 AR52425]; NIDDK NIH HHS [R01 DK55815, R01 DK50190] NR 51 TC 49 Z9 52 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 2007 VL 211 IS 2 BP 457 EP 467 DI 10.1002/jcp.20953 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 152ET UT WOS:000245344500021 PM 17186497 ER PT J AU Shin, HK Salomone, S Potts, EM Lee, SW Millican, E Noma, K Huang, PL Boas, DA Liao, JK Moskowitz, MA Ayata, C AF Shin, Hwa Kyoung Salomone, Salvatore Potts, E. Michelle Lee, Sae-Won Millican, Eric Noma, Kensuke Huang, Paul L. Boas, David A. Liao, James K. Moskowitz, Michael A. Ayata, Cenk TI Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE focal cerebral ischemia; hydroxyfasudil; hypoxia; isolated vessels; laser speckle flowmetry; Rho-kinase ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE; MYOSIN PHOSPHATASE; STROKE PROTECTION; SMOOTH-MUSCLE; ACTIVATION; HYPERTENSION; DAMAGE; MICE; PHOSPHORYLATION AB Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient ( eNOS(-/-)) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS(-/-) mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS(-/-) mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke. C1 Harvard Univ, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biomed Imaging,Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Stroke Serv, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Neurosci Intens Care Unit, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, Sch Med,Dept Radiol, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011; OI Salomone, Salvatore/0000-0001-5307-6103 FU NHLBI NIH HHS [R01 HL052233, R01 HL052233-10, R01 HL052233-11, R01 HL052233-12, R01 HL057818, R01 HL057818-09, R01 HL070274, R01 HL070274-03, R01 HL070274-04, R01 HL070274-05, R01 HL080187, R01 HL080187-01A1, R01 HL080187-02, R01 HL080187-03]; NIBIB NIH HHS [R01 EB000790, R01EB00790-01A2]; NIDDK NIH HHS [R01 DK062729, R01 DK062729-03, R01 DK062729-04, R01 DK062729-05]; NINDS NIH HHS [P01 NS010828-330036, P01 NS010828, P01 NS035611, P01 NS35611, P50 NS010828, P50 NS010828-320037, P50 NS10828, R01 NS033335, R01 NS033335-13, R01 NS048426, R01 NS048426-04] NR 38 TC 63 Z9 64 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2007 VL 27 IS 5 BP 998 EP 1009 DI 10.1038/sj.jcbfm.9600406 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 161FG UT WOS:000245999300011 PM 17033691 ER PT J AU Amory, JK Wang, C Swerdloff, RS Anawalt, BD Matsumoto, AM Bremner, WJ Walker, SE Haberer, LJ Clark, RV AF Amory, John K. Wang, Christina Swerdloff, Ronald S. Anawalt, Bradley D. Matsumoto, Alvin M. Bremner, William J. Walker, Susan E. Haberer, Lynda J. Clark, Richard V. TI The effect of 5 alpha reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; DUAL 5-ALPHA-REDUCTASE INHIBITOR; PLACEBO-CONTROLLED TRIAL; STEROID 5-ALPHA-REDUCTASE; SPERM CONCENTRATION; DIHYDROTESTOSTERONE; EFFICACY; SAFETY; TESTOSTERONE; TYPE-1 AB Context: Dutasteride and finasteride are 5 alpha-reductase inhibitors (5ARIs) that dramatically reduce serum levels of dihydrotestosterone (DHT). Objective: Because androgens are essential for fertility, we sought to determine the impact of 5ARI administration on serum testosterone (T), DHT, and spermatogenesis. Design, Setting, Subjects, and Intervention: We conducted a randomized, double-blinded, placebo-controlled trial in 99 healthy men randomly assigned to receive dutasteride (D; 0.5 mg) (n = 33), finasteride (F; 5 mg) (n = 34), or placebo (n = 32) once daily for 1 yr. Main Outcome Measures: Blood and semen samples were collected at baseline and 26 and 52 wk of treatment and 24 wk after treatment and were assessed for T, DHT, and semen parameters. Results: D and F significantly (P < 0.001) suppressed serum DHT, compared with placebo (D, 94%; F, 73%) and transiently increased serum T. In both treatment groups, total sperm count, compared with baseline, was significantly decreased at 26 wk (D, -28.6%; F, -34.3%) but not at 52 wk (D, -24.9%; F, -16.2%) or the 24-wk follow-up (D, -23.3%; F, -6.2%). At 52 wk, semen volume was decreased (D, -29.7%; F, -14.5%, significantly for D) as was sperm concentration (D, -13.2%; F, -7.4%, neither significant). There was a significant reduction of -6 to 12% in sperm motility during treatment with both D and F and at follow-up. Neither treatment had any effect on sperm morphology. Conclusions: This study demonstrates that the decrease in DHT induced by 5ARIs is associated with mild decreases in semen parameters that appear reversible after discontinuation. C1 Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA. GlaxoSmithKline Res & Dev Ltd, Dept Clin Pharmacol, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Med, Torrance, CA 90509 USA. Univ Calif Los Angeles, Harbor Med Ctr, Gen Clin Res Ctr, Torrance, CA 90509 USA. RP Clark, RV (reprint author), Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 42 TC 88 Z9 91 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2007 VL 92 IS 5 BP 1659 EP 1665 DI 10.1210/jc.2006-2203 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164GI UT WOS:000246221200017 PM 17299062 ER PT J AU Leong, CO Vidnovic, N DeYoung, MP Sgroi, D Ellisen, LW AF Leong, Chee-Onn Vidnovic, Nick DeYoung, Maurice Phillip Sgroi, Dennis Ellisen, Leif W. TI The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; YES-ASSOCIATED PROTEIN; KINASE C-ABL; DNA-DAMAGE; TYROSINE KINASE; P73-DEPENDENT APOPTOSIS; EXPRESSION PROFILES; P73 FUNCTION; P53 HOMOLOG; P63 AB Breast cancers lacking estrogen and progesterone receptor expression and HER2 amplification exhibit distinct gene expression profiles and clinical features, and they comprise the majority of BRCA1-associated tumors. Here we demonstrated that the p53 family member p63 controls a pathway for p73-dependent cisplatin sensitivity specific to these "triple-negative" tumors. In vivo, Delta Np63 and TAp73 isoforms were coexpressed exclusively within a subset of triple-negative primary breast cancers that commonly exhibited mutational inactivation of p53. The Delta Np63 alpha isoform promoted survival of breast cancer cells by binding TAp73 and thereby inhibiting its proapoptotic activity. Consequently, inhibition of p63 by RNA interference led to TAp73-dependent induction of proapoptotic Bcl-2 family members and apoptosis. Breast cancer cells expressing Delta Np63 alpha and TAp73 exhibited cisplatin sensitivity that was uniquely dependent on TAp73. Thus, in response to treatment with cisplatin, but not other chemotherapeutic agents, TAp73 underwent c-Abl-dependent phosphorylation, which promoted dissociation of the Delta Np63 alpha/TAp73 protein complex, TAp73-dependent transcription of proapoptotic Bcl-2 family members, and apoptosis. These findings define p63 as a survival factor in a subset of breast cancers; furthermore, they provide what we believe to be a novel mechanism for cisplatin sensitivity in these triple-negative cancers, and they suggest that such cancers may share the cisplatin sensitivity of BRCA1-associated tumors. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ-904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA122589]; NIDCR NIH HHS [DE 15945, R01 DE015945] NR 52 TC 185 Z9 194 U1 1 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2007 VL 117 IS 5 BP 1370 EP 1380 DI 10.1172/JCI30866 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 165ZS UT WOS:000246347000031 PM 17446929 ER PT J AU Luptak, I Shen, M He, HM Hirshman, MF Musi, N Goodyear, LJ Yan, J Wakimoto, H Morita, H Arad, M Seidman, CE Seidman, JG Ingwall, JS Balschi, JA Tian, R AF Luptak, Ivan Shen, Mei He, Huamei Hirshman, Michael F. Musi, Nicolas Goodyear, Laurie J. Yan, Jie Wakimoto, Hiroko Morita, Hiroyuki Arad, Michael Seidman, Christine E. Seidman, J. G. Ingwall, Joanne S. Balschi, James A. Tian, Rong TI Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PARKINSON-WHITE-SYNDROME; RAT SKELETAL-MUSCLE; HYPERTROPHIC CARDIOMYOPATHY; PRESSURE-OVERLOAD; GLUCOSE-TRANSPORT; ALPHA-2 SUBUNIT; TRANSGENIC MICE; ACID CYCLE; HEART; MUTATION AB AMP-activated protein kinase (AMPK) responds to impaired cellular energy status by stimulating substrate metabolism for ATP generation. Mutation of the gamma 2 regulatory subunit of AMPK in humans renders the kinase insensitive to energy status and causes glycogen storage cardiomyopathy via unknown mechanisms. Using transgenic mice expressing one of the mutant gamma 2 subunits (N488I) in the heart, we found that aberrant high activity of AMPK in the absence of energy deficit caused extensive remodeling of the substrate metabolism pathways to accommodate increases in both glucose uptake and fatty acid oxidation in the hearts of gamma 2 mutant mice via distinct, yet synergistic mechanisms resulting in selective fuel storage as glycogen. Increased glucose entry in the gamma 2 mutant mouse hearts was directed through the remodeled metabolic network toward glycogen synthesis and, at a substantially higher glycogen level, recycled through the glycogen pool to enter glycolysis. Thus, the metabolic consequences of chronic activation of AMPK in the absence of energy deficiency is distinct from those previously reported during stress conditions. These findings are of particular importance in considering AMPK as a target for the treatment of metabolic diseases. C1 Brigham & Womens Hosp, Div Cardiovasc Med, NMR Lab Cardiovasc Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Joslin Diabet Ctr, Metab Unit, Boston, MA 02215 USA. RP Tian, R (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, NMR Lab Cardiovasc Med, 221 Longwood Ave,Room 252, Boston, MA 02115 USA. EM rtian@rics.bwh.harvard.edu OI Tian, Rong/0000-0002-3676-3830; Luptak, Ivan/0000-0001-7498-7694 FU NHLBI NIH HHS [HL 46033, HL 52320, HL 59246, HL 67970, P50 HL052320, R01 HL046033, R01 HL059246, R01 HL067970, R29 HL046033]; NIAMS NIH HHS [AR 45670, R01 AR045670]; NIDDK NIH HHS [DK 68626, R01 DK068626] NR 50 TC 58 Z9 59 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2007 VL 117 IS 5 BP 1432 EP 1439 DI 10.1172/JCI30658 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 165ZS UT WOS:000246347000037 PM 17431505 ER PT J AU Kennedy, RD Chen, CC Stuckert, P Archila, EM De la Vega, MA Moreau, LA Shimamura, A D'Andrea, AD AF Kennedy, Richard D. Chen, Clark C. Stuckert, Patricia Archila, Elyse M. De la Vega, Michelle A. Moreau, Lisa A. Shimamura, Akiko D'Andrea, Alan D. TI Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE MYELOID-LEUKEMIA; DNA-DAMAGE RESPONSE; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; THERAPEUTIC STRATEGY; NUCLEAR ACCUMULATION; PANCREATIC-CANCER; PROTEINS FANCA; OVARIAN-CANCER; BRCA PATHWAY AB The Fanconi anemia (FA) pathway maintains genomic stability in replicating cells. Some sporadic breast, ovarian, pancreatic, and hematological. tumors are deficient in FA pathway function, resulting in sensitivity to DNA-damaging agents. FA pathway dysfunction in these tumors may result in hyperdependence on alternative DNA repair pathways that could be targeted as a treatment strategy. We used a high-throughput siRNA screening approach that identified ataxia telangiectasia mutated (ATM) as a critical kinase for FA pathway-deficient human fibroblasts. Human fibroblasts and murine embryonic fibroblasts deficient for the FA pathway were observed to have constitutive ATM activation and Fancg(-/-)Atm(-/-) mice were found to be nonviable. Abrogation of ATM function in FA pathway-deficient cells resulted in DNA breakage, cell cycle arrest, and apoptotic cell death. Moreover, Fanconi anemia complementation group G- (FANCG-) and FANCC-deficient pancreatic tumor lines were more sensitive to the ATM inhibitor KU-55933 than isogenic corrected lines. These data suggest that ATM and FA genes function in parallel and compensatory roles to maintain genomic integrity and cell viability. Pharmaceutical inhibition of ATM may have a role in the treatment of FA pathway-deficient human cancers. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Kennedy, Richard/J-3489-2012; Chen, Clark/C-8714-2013 OI Kennedy, Richard/0000-0003-4737-6163; Chen, Clark/0000-0001-6258-9277 FU NCI NIH HHS [P50 CA 105009-01, P50 CA105009]; NHLBI NIH HHS [K23 HL 068632-03, K23 HL068632, P01 HL 54785, P50 HL054785, R01 HL 52725, R01 HL052725, R37 HL052725]; NIAID NIH HHS [AI 067751, U19 AI067751]; NIDDK NIH HHS [R01 DK 43889, R01 DK043889]; PHS HHS [P01 150654] NR 54 TC 98 Z9 98 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2007 VL 117 IS 5 BP 1440 EP 1449 DI 10.1172/JCI31245 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 165ZS UT WOS:000246347000038 PM 17431503 ER PT J AU Croda, J Ramos, JGR Matsunaga, J Queiroz, A Homma, A Riley, LW Haake, DA Reis, MG Ko, AI AF Croda, Julio Ramos, Joao G. R. Matsunaga, James Queiroz, Adriano Homma, Akira Riley, Lee W. Haake, David A. Reis, Mitermayer G. Ko, Albert I. TI Leptospira immunoglobulin-like proteins as a serodiagnostic marker for acute leptospirosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINKED IMMUNOSORBENT ASSAYS; HUMAN IMMUNE-RESPONSE; POLYMERASE-CHAIN-REACTION; OUTER-MEMBRANE PROTEIN; URBAN EPIDEMIC; BOVINE LEPTOSPIROSIS; RAPID SERODIAGNOSIS; DIPSTICK ASSAY; M ANTIBODIES; IGM-ELISA AB There is an urgent need for improved diagnosis of leptospirosis, an emerging infectious disease which imparts a large disease burden in developing countries. We evaluated the use of Leptospira immunoglobulin (Ig)-like (Lig) proteins as a serodiagnostic marker for leptospirosis. Lig proteins have bacterial immunoglobulin-like (Big) tandem repeat domains, a moiety found in virulence factors in other pathogens. Sera from patients identified during urban outbreaks in Brazil reacted strongly with immunoblots of a recombinant fragment comprised of the second to sixth Big domains of LigB from L. interrogans serovar Copenhageni, the principal agent for transmission in this setting. Furthermore, the sera recognized an analogous LigB fragment derived from L. kirschneri serovar Grippotyphosa, a pathogenic serovar which is not endemic to the study area. The immunoblot assay detected anti-LigB IgM antibodies in sera from 92% (95% confidence interval, 85 to 96%) of patients during acute-phase leptospirosis. The assay had a sensitivity of 81% for sera from patients with less than 7 days of illness. Anti-LigB antibodies were found in sera from 57% of the patients who did not have detectable anti-whole-Leptospira responses as detected by IgM enzyme-linked immunosorbent assay and microagglutination test. The specificities of the assay were 93 to 100% and 90 to 97% among sera from healthy individuals and patients with diseases that have clinical presentations that overlap with those of leptospirosis, respectively. These findings indicate that the antibody response to this putative virulence determinant is a sensitive and specific marker for acute infection. The use of this marker may aid the prompt and timely diagnosis required to reduce the high mortality associated with severe forms of the disease. C1 Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Brazilian Minist Hlth, Oswaldo Cruz Fdn, Biomanguinhos, Rio De Janeiro, Brazil. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, Ithaca, NY USA. RP Ko, AI (reprint author), Fdn OSwaldo Cruz MS, Ctr Pesquisas Goncalo Moniz, Rua Waldemar Falcao 121, BR-40295001 Salvador, BA, Brazil. EM aik2001@med.cornell.edu RI Ko, Albert/P-2343-2015 FU FIC NIH HHS [TW-00919, D43 TW000905, D43 TW000919, TW-00905]; NIAID NIH HHS [AI-034431, AI-052473, R01 AI034431, R01 AI034431-10A1, R01 AI052473, R21 AI034431, R29 AI034431] NR 63 TC 51 Z9 54 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2007 VL 45 IS 5 BP 1528 EP 1534 DI 10.1128/JCM.02344-06 PG 7 WC Microbiology SC Microbiology GA 169OA UT WOS:000246600300023 PM 17360842 ER PT J AU Bahrani-Mougeot, FK Paster, BJ Coleman, S Barbuto, S Brennan, MT Noll, J Kennedy, T Fox, PC Lockhart, PB AF Bahrani-Mougeot, Farah K. Paster, Bruce J. Coleman, Shirley Barbuto, Sara Brennan, Michael T. Noll, Jenene Kennedy, Thomas Fox, Philip C. Lockhart, Peter B. TI Molecular analysis of oral and respiratory bacterial species associated with ventilator-associated pneumonia SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GRAM-NEGATIVE BACILLI; CARE-UNIT PATIENTS; NOSOCOMIAL PNEUMONIA; DENTAL PLAQUE; COLONIZATION; DIVERSITY; OROPHARYNGEAL; BRUSH AB Trauma intensive care unit (TICU) patients requiring mechanical respiratory support frequently develop ventilator-associated pneumonia (VAP). Oral and oropharyngeal bacteria are believed to be responsible for many cases of VAP, but definitive evidence of this relationship is lacking. Earlier studies used conventional culture-based methods for identification of bacterial pathogens, but these methods are insufficient, as some bacteria may be uncultivable or difficult to grow. The purpose of this study was to use a culture-independent molecular approach to analyze and compare the bacterial species colonizing the oral cavity and the lungs of TICU patients who developed VAP. Bacterial samples were acquired from the dorsal tongue and bronchoalveolar lavage fluid of 16 patients. Bacterial DNA was extracted, and the 16S rRNA genes were PCR amplified, cloned into Escherichia coli, and sequenced. The sequencing data revealed the following: (i) a wide diversity of bacterial species in both the oral and pulmonary sites, some of them novel; (ii) known and putative respiratory pathogens colonizing both the oral cavity and lungs of 14 patients; and (iii) a number of bacterial pathogens (e.g., Dialister pneumosintes, Haemophilus segnis, Gemella morbillorum, and Pseudomonas fluorescens) in lung samples that had not been reported previously at this site when culture-based methods were used. Our data indicate that the dorsal surface of the tongue serves as a potential reservoir for bacterial species involved in VAP. Furthermore, it is clear that the diversity of bacterial pathogens for VAP is far more complex than the current literature suggests. C1 Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28232 USA. Forsyth Inst, Dept Mol Genet, Boston, MA USA. Univ Utah, Med Ctr, Div Resp Crit Care & Occupat Pulm Med, Salt Lake City, UT USA. RP Bahrani-Mougeot, FK (reprint author), Carolinas Med Ctr, Dept Oral Med, POB 32861, Charlotte, NC 28232 USA. EM farah.bahrani-mougeot@carolinas.org NR 22 TC 83 Z9 87 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2007 VL 45 IS 5 BP 1588 EP 1593 DI 10.1128/JCM.01963-06 PG 6 WC Microbiology SC Microbiology GA 169OA UT WOS:000246600300032 PM 17301280 ER PT J AU Sader, HS Ferraro, MJ Reller, LB Schreckenberger, PC Swenson, JM Jones, RN AF Sader, Helio S. Ferraro, Mary J. Reller, L. Barth Schreckenberger, Paul C. Swenson, Jana M. Jones, Ronald N. TI Reevaluation of clinical and laboratory standards institute disk diffusion breakpoints for tetracyclines for testing Enterobacteriaceae SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB We reevaluated Enterobacteriaceae disk diffusion breakpoints for the tetracyclines published in the Clinical and Laboratory Standards Institute (CLSI) document M100-S16, which were (susceptible/resistant) >= 19 mm/<= 14 mm for tetracycline, >= 16 mm/<= 12 mm for doxycycline, and >= 19 mm/<= 14 mm for minocycline. A collection of 504 recent clinical isolates of Enterobacteriaceae were tested against these tetracycline compounds by disk diffusion and broth microdilution methods according to CLSI guidelines. Regression line and scattergram plot analyses determined intermethod accuracy for current disk diffusion breakpoints and showed excellent r values of 0.91 to 0.95. However, error rates (minor/major [false-resistant]/very major [false-susceptible]) were 14.9/0.8/0.0% for tetracycline, 11.5/10.4/0.0% for doxycycline, and 30.6/0.7/0.0% for minocycline and only 4.4/0.0/0.0% for tetracycline, 5.6/0.0/0.2% for doxycycline, and 8.3/0.0/0.3% for minocycline when proposed breakpoints were modified to (susceptible/resistant) >= 15 mm/<= 11 mm for tetracycline, >= 14 mm/<= 10 nun for doxycycline, and 16 mm/<= 12 mm for minocycline. Listed modifications were recently approved by the CLSI (M100-S17). C1 JMI Labs, N Liberty, IA 52317 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Durham, NC USA. Loyola Univ, Chicago, IL 60611 USA. CDC, Atlanta, GA 30333 USA. RP Sader, HS (reprint author), JMI Labs, 345 Beaver Kreek Ctr,Suite A, N Liberty, IA 52317 USA. EM helio-sader@jmilabs.com NR 19 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2007 VL 45 IS 5 BP 1640 EP 1643 DI 10.1128/JCM.00143-07 PG 4 WC Microbiology SC Microbiology GA 169OA UT WOS:000246600300044 PM 17360844 ER PT J AU Robertson, MJ Kahl, BS Vose, JM de Vos, S Laughlin, M Flynn, PJ Rowland, K Cruz, JC Goldberg, SL Musib, L Darstein, C Enas, N Kutok, JL Aster, JC Neuberg, D Savage, KJ LaCasce, A Thornton, D Slapak, CA Shipp, MA AF Robertson, Michael J. Kahl, Brad S. Vose, Julie M. de Vos, Sven Laughlin, Mary Flynn, Patrick J. Rowland, Kendrith Cruz, Jose C. Goldberg, Stuart L. Musib, Luna Darstein, Christelle Enas, Nathan Kutok, Jeffery L. Aster, Jon C. Neuberg, Donna Savage, Kerry J. LaCasce, Ann Thornton, Donald Slapak, Christopher A. Shipp, Margaret A. TI Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol ID NON-HODGKINS-LYMPHOMA; PKC-BETA; SELECTIVE INHIBITOR; GROWTH; ACTIVATION; PHOSPHORYLATION; CARMA1; XENOGRAFTS; CARCINOMA; PATHWAY AB Purpose Protein kinase C beta (PKC beta) was identified by gene-expression profiling, preclinical evaluation, and independent immunohistochemical analysis as a rational therapeutic target in diffuse large B-cell lymphoma (DLBCL). We conducted a multicenter phase II study of a potent inhibitor of PKC beta, enzastaurin, in patients with relapsed or refractory DLBCL. Patients and Methods Enzastaurin was taken orally once daily until disease progression or unacceptable toxicity occurred. Study end points included freedom from progression (FFP) for >= two cycles ( one cycle = 28 days), objective response, and toxicity. Results Fifty-five patients ( median age, 68 years) were enrolled. Patients had received a median number of two prior therapies ( range, one to five); six patients relapsed after high-dose therapy and autologous stem-cell transplantation. Only one grade 4 toxicity (hypomagnesemia) occurred. Grade 3 toxicities included fatigue ( n = 2), edema ( n = 1), headache ( n = 1), motor neuropathy ( n = 1), and thrombocytopenia ( n = 1). No grade 3 or 4 neutropenia occurred. No deaths or discontinuations due to toxicity were reported. Fifteen patients completed less than one cycle of therapy. Twelve of 55 patients (22%; 95% CI, 13% to 46%) experienced FFP for >= two cycles, and eight patients remained free from progression for >= four cycles (15%; 95% CI, 6% to 27%). Four patients (7%; 95% CI, 2% to 18%), including three complete responders and one patient with stable disease, continue to experience FFP 20 + to 50 + months after study entry. Conclusion Treatment with enzastaurin was well-tolerated and associated with prolonged FFP in a small subset of patients with relapsed or refractory DLBCL. Further studies of enzastaurin in DLBCL are warranted. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Univ Nebraska Med Ctr, Omaha, NE USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Minnesota Oncol Hematol PA, Minneapolis, MN USA. Carle Clin Associates, Urbana, IL USA. Joe Arrington Res & Canc Ctr, Lubbock, TX USA. HAckensack Univ, Med Ctr, Ctr Canc, Hackensack, NJ USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu FU NCRR NIH HHS [RR00750-27S3] NR 23 TC 169 Z9 179 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2007 VL 25 IS 13 BP 1741 EP 1746 DI 10.1200/JCO.2006.09.3146 PG 6 WC Oncology SC Oncology GA 165IY UT WOS:000246299500018 PM 17389337 ER PT J AU Taubman, MA Kawai, T Han, XZ AF Taubman, Martin A. Kawai, Toshihisa Han, Xiaozhe TI The new concept of periodontal disease pathogenesis requires new and novel therapeutic strategies SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Editorial Material ID KAPPA-B LIGAND; INFLAMMATORY BONE-RESORPTION; GINGIVAL CREVICULAR FLUID; OSTEOCLAST DIFFERENTIATION; RECEPTOR ACTIVATOR; OSTEOPROTEGERIN LIGAND; PROTEIN EXPRESSION; RANKL; DESTRUCTION; LYMPHOCYTE AB In this issue Bostanci et al. (2007) demonstrate that receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin (OPG) were oppositely regulated in gingival crevice fluid (GCF) from periodontitis patients. RANKL, RANK and OPG are key molecules that regulate osteoclast recruitment, differentiation and activation. New concepts of the pathogenesis of periodontitis have implicated inflammation triggered by host immune response to periodontal biofilm microorganisms(s) in disease. Host response to bacteria involves activation of T and B cells in the inflammatory infiltrate which bear abundant RANKL that promotes osteoclastic bone resorption. Periodontal tissue destruction can be ameliorated by immunobiological interference with immune cell RANKL expression or function. The new disease concepts provide a foundation to build biological approaches to target RANKL production in periodontal lesions. C1 Forsyth Inst, Dept Immunol, Boston, MA USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, Boston, MA USA. EM MTaubman@forsyth.org FU NIDCR NIH HHS [R01 DE003420] NR 24 TC 45 Z9 49 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAY PY 2007 VL 34 IS 5 BP 367 EP 369 DI 10.1111/j.1600-051X.2007.01065.x PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 157SO UT WOS:000245741400001 PM 17448041 ER PT J AU Marder, SR West, B Lau, GS Pultz, JA Pikalov, A Marcus, RN Gutierrez-Esteinou, R Crandall, DT AF Marder, Stephen R. West, Britt Lau, Gina S. Pultz, Joseph A. Pikalov, Andrei Marcus, Ronald N. Gutierrez-Esteinou, Rolando Crandall, David T. TI Aripiprazole effects in patients with acute schizophrenia experiencing higher or lower agitation: A post Hoc analysis of 4 randomized, placebo-controlled clinical trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; INTRAMUSCULAR HALOPERIDOL; SCHIZOAFFECTIVE DISORDER; PHARMACOLOGICAL MANAGEMENT; PARTIAL AGONIST; SHORT-TERM; OLANZAPINE; EFFICACY; ZIPRASIDONE; RISPERIDONE AB Objective: Patients with acute schizophrenia who are agitated typically manifest worse overall symptomatology and are generally more challenging to treat than nonagitated patients. In order to determine whether baseline agitation level influences treatment response, the effects of oral aripiprazole in acute patients with schizophrenia experiencing either higher or lower levels of agitation were examined. Method: A post hoc analysis of pooled data from the first 4 or 6 weeks of 4 randomized, double-blind, placebo-controlled aripiprazole trials was conducted. Patients with a DSM-IV diagnosis of acute schizophrenia randomly assigned to treatment with either aripiprazole 10, 15, 20, or 30 mg/day (N = 790) or placebo (N = 397) were divided into groups experiencing higher or lower agitation at baseline. Higher agitation was defined as a baseline Positive and Negative Syndrome Scale (PANSS)-Excited Component (PEC) score of >= 14 and a score of >= 4 on at least 1 PEC item (excitement, hostility, tension, uncooperativeness, or poor impulse control). Analysis of covariance was used to evaluate PANSS total, Clinical Global Impressions-Improvement scale (CGI-I), and PEC scores between aripiprazole and placebo within the higher and lower agitation groups. Results: In both the higher and lower agitation groups, aripiprazole treatment produced significantly lower PANSS total, CGI-I, and PEC scores at weeks 2 to 6, compared with placebo (p < .05 for each measure). Percentage of concomitant benzodiazepine use was similar at end point for aripiprazole and placebo, and adverse events were generally mild across groups. Conclusions: Aripiprazole significantly improved the core symptoms of acute schizophrenia regardless of baseline agitation level. In particular, agitation symptoms were significantly decreased in patients with higher baseline agitation. Improvements appeared to be independent of benzodiazepine use or excessive sedation effects. These results suggest that oral aripiprazole is an effective and safe treatment option for patients with acute schizophrenia who manifest agitation symptoms. C1 Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA. Bristol Myers Squibb, Columbia, SC USA. Bristol Myers Squibb, Los Angeles, CA USA. Otsuka Amer Pharmaceut Inc, Princeton, NJ USA. Bristol Myers Squibb, Lawrenceville, NJ USA. Bristol Myers Squibb, Plainsboro, NJ USA. RP Marder, SR (reprint author), Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Bldg 210,Rm 130,11301 Wilshire Blvd, Los Angeles, CA USA. EM marder@ucla.edu NR 35 TC 15 Z9 18 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2007 VL 68 IS 5 BP 662 EP 668 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171MO UT WOS:000246740300021 PM 17503974 ER PT J AU Pierre, JM Peloian, JH Wirshing, DA Wirshing, WC Marder, SR AF Pierre, Joseph M. Peloian, John H. Wirshing, Donna A. Wirshing, William C. Marder, Stephen R. TI A randomized, double-blind, placebo-controlled trial on modafinil for negative symptoms in schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT SYNDROME; RATING-SCALE; FATIGUE; CLOZAPINE; EFFICACY; AUGMENTATION; MEDICATIONS; SOMNOLENCE; NARCOLEPSY; OLANZAPINE AB Objective: Negative symptoms are core features of schizophrenia that are functionally debilitating, associated with poor outcomes, and resistant to existing pharmacotherapies. We performed a randomized, double-blind, placebo-controlled study of modafinil, a medication approved for the treatment of excessive daytime sleepiness, to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia. Method: Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned to double-blind treatment with modafinil or placebo for 8 weeks. The study ran from March 2002 through March 2006. Outcome measures included the Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI) scale, Quality of Life Interview, neurocognitive assessments (California Verbal Learning Test, Degraded Performance-Continuous Performance Test, Trail-Making Test B), and somatic measures (sleep, weight, side effects). Results: Modafinil treatment was associated with a greater rate (CGI-Improvement [CGI-I] score <= 3, 7/10 vs. 1/10) and degree (mean CGI-I score, 3.2 vs. 4.1) of global improvement at study endpoint compared with placebo. However, modafinil did not significantly improve global negative symptoms as measured by the total SANS or SANS individual global items. Modafinil did not significantly worsen psychopathology (according to the BPRS), compared with placebo, and was well tolerated. Conclusions: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms. C1 Vet Adm Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Pierre, JM (reprint author), 11301 Wilshire Blvd,Bldg 210 B-151H, Los Angeles, CA 90073 USA. EM drjoe@ucla.edu NR 52 TC 35 Z9 35 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2007 VL 68 IS 5 BP 705 EP 710 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171MO UT WOS:000246740300026 PM 17503979 ER PT J AU Granholm, E McQuaid, JR McClure, FS Link, PC Perivoliotis, D Gottlieb, JD Patterson, TL Jeste, DV AF Granholm, Eric McQuaid, John R. McClure, Fauzia Simjee Link, Peter C. Perivoliotis, Dimitri Gottlieb, Jennifer D. Patterson, Thomas L. Jeste, Dilip V. TI Randomized controlled trial of cognitive behavioral social skills training for older people with schizophrenia: 12 month follow-up SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RESIDUAL PSYCHOTIC SYMPTOMS; AUDITORY HALLUCINATIONS; PSYCHOSOCIAL TREATMENT; MENTAL-ILLNESS; THERAPY; RESISTANT; PSYCHOTHERAPY; INTERVENTION; METAANALYSIS; MEDICATION AB Objective: There is an increasing need for empirically validated psychotherapy interventions that improve functioning in older people with schizophrenia. We developed a 24-session weekly group therapy intervention labeled Cognitive Behavioral Social Skills Training (CBSST), which combined cognitive-behavioral therapy with social skills and problem-solving training to improve functioning. Method: We previously reported end-of-treatment findings from a randomized controlled trial that compared treatment as usual (TAU) with TAU plus group CBSST in 76 outpatients, 42 to 74 years of age, with schizophrenia or schizoaffective disorder (DSM-IV criteria). Twelve-month follow-up results of that trial (conducted from October 1999 to September 2004) are reported here. Blind raters obtained assessments of CBSST skill mastery, functioning, psychotic and depressive symptoms, and cognitive insight (belief flexibility). Results: The significantly greater skill acquisition and self-reported performance of living skills in the community seen in CBSST versus TAU patients at the end of treatment were maintained at 12-month follow-up (p <= .05). Participants in CBSST also showed significantly greater cognitive insight at the end of treatment relative to TAU, but this improvement was not maintained at follow-up. The treatment-group effect was not significant for symptoms at any assessment point; however, symptoms were not the primary treatment target in this stable outpatient sample. Conclusion: Older people with very chronic schizophrenia were able to learn and maintain new skills with CBSST and showed improved self-reported functioning 1 year after the treatment ended. Longer treatment and/or booster sessions may be required to maintain gains in cognitive insight. C1 VA San Diego Healthcare Syst, San Diego, CA 92161 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA USA. SDSU UCSD, Joint Doctoral Program Clin Psychol, San Diego, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Granholm, E (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM egranholm@ucsd.edu RI Granholm, Eric/P-7680-2014 FU NIMH NIH HHS [P30MH66248, R01MH071410] NR 56 TC 41 Z9 47 U1 4 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2007 VL 68 IS 5 BP 730 EP 737 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171MO UT WOS:000246740300029 PM 17503982 ER PT J AU Zhang, XY Tan, YL Zhou, DF Cao, LY Wu, GY Haile, CN Kosten, TA Kosten, TR AF Zhang, Xiang Yang Tan, Yun Long Zhou, Dong Feng Cao, Lian Yuan Wu, Gui Ying Haile, Colin N. Kosten, Theresa A. Kosten, Thomas R. TI Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenia patients with tardive dyskinesia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID VITAMIN-E TREATMENT; MANGANESE SUPEROXIDE-DISMUTASE; INDUCED OROFACIAL DYSKINESIA; FREE-RADICAL PATHOLOGY; OXIDATIVE STRESS; POLYMORPHISM; INVOLVEMENT; PLASMA AB Background: Free radical-mediated pathology has been implicated in the development of tardive dyskinesia (TD). Antioxidant defense system alterations and increased lipid peroxidation have been postulated as a possible mechanism for neuronal damage associated with TD. However, the relationship between antioxidant enzymes, lipid peroxidation products, and the severity of TD symptoms has not been determined within a single patient group. Method: Plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation, superoxide dismutase, glutathione peroxidase, and catalase were examined in 80 patients with schizophrenia (DSM-IV criteria) and TD (Schooler-Kane criteria) and 45 schizophrenia patients without TD. Results were compared to those of 50 age-, sex-, and smoking status-matched controls. Tardive dyskinesia severity was assessed using the Abnormal Involuntary Movement Scale, and patient psychopathology was assessed using the Positive and Negative Syndrome Scale. Results: Patients with TD had lower plasma superoxide dismutase, glutathione peroxidase, and catalase levels but higher MDA levels than those without TD. In the patients with TD, MDA levels were positively correlated with Abnormal Involuntary Movement Scale total score and with Positive and Negative Syndrome Scale negative subscore. Superoxide dismutase and catalase activities were inversely correlated with MDA levels. Conclusions: Our data support the hypothesis that oxidative stress is involved in the pathophysiology of TD. These data also suggest a relationship between oxidative stress and the severity of dyskinesia in TD patients. Increased lipid peroxidation may likely be a result of decreased endogenous antioxidant enzyme activities in TD. C1 Baylor Coll Med, VA Med Ctr, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Peking Univ, Inst Mental Hlth, Beijing, Peoples R China. Beijing Hui Long Guan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. RP Zhang, XY (reprint author), Baylor Coll Med, VA Med Ctr, Dept Psychiat & Behav Sci, Res Bldg 109,room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu FU NIDA NIH HHS [K05-DA0454, P50-DA18827] NR 36 TC 45 Z9 46 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2007 VL 68 IS 5 BP 754 EP 760 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171MO UT WOS:000246740300032 PM 17503985 ER PT J AU Gilman, MD Fischman, AJ Krishnasetty, V Halpern, EF Aquino, SL AF Gilman, Matthew D. Fischman, Alan J. Krishnasetty, Vikram Halpern, Elkan F. Aquino, Suzanne L. TI Hybrid PET/CT of the thorax: When is computer registration necessary? SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE PET scan; helical CT; image reconstruction; tomography; positron emission; image analysis; computer assisted ID CELL LUNG-CANCER; POSITRON-EMISSION-TOMOGRAPHY; DUAL-MODALITY PET/CT; BREATHING PROTOCOL; DATA SETS; CT; LESIONS AB Objective: To determine if computer registration improves the image fusion of hybrid positron emission tomography (PET)/ computed tomography (CT) data sets in the thorax acquired during different breathing maneuvers. Methods: Hybrid PET/CT scans were acquired with varying CT respiratory instructions. The scans of 64 patients with 5 different breathing maneuvers were reviewed, including expiration, suspended breath hold, quiet breathing, small breath in, and regular breath in. The PET/CT data sets were reviewed before registration, after linear registration, and combined linear/nonlinear registration. Each PET/CT data set was graded for the quality of alignment at 5 anatomical locations (diaphragm, aortic arch, heart, thoracic spine, and lung apices) and rated from 1 (very poor) to 5 (excellent). The Kruskal-Wallis test was used to compare alignment between the breathing protocols, and Wilcoxon signed rank test was used to compare the registration techniques. Results: The quality of anatomical alignment between superimposed (nonregistered) PET and attenuation correction CT (CTAC) acquired during expiration, suspended breath hold, and quiet breathing was excellent, with no significant changes in alignment following registration. The quality of anatomical alignment between superimposed (nonregistered) PET and CTAC acquired during inspiration showed significant misalignment at the heart (P = 0.001, P < 0.0001) and diaphragm (P = 0.0001, P < 0.000 1) which did not correct with linear registration. Alignment significantly improved with additional nonlinear registration at the diaphragm (P = 0.008, P = 0.0002), although cardiac misalignment remained. Conclusions: With hybrid PET/CT, excellent anatomical alignment between PET and CTAC scans can be achieved with CT acquisition during expiration, suspended breath hold, or quiet breathing, and additional software registration is not necessary. Nonlinear registration significantly improves alignment discrepancies at the diaphragm if inspiratory methods are used, however, cardiac misalignment remains. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Gilman, MD (reprint author), Univ Hosp, Dept Radiol, ML 0761,234 Goodman St, Cincinnati, OH 45267 USA. EM matthewgilman@hotmail.com NR 13 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2007 VL 31 IS 3 BP 395 EP 401 DI 10.1097/01.rct.0000237817.18678.9c PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 175PF UT WOS:000247024800013 PM 17538286 ER PT J AU Neuman, MI Kelley, M Harper, MB File, TM Camargo, CA AF Neuman, Mark I. Kelley, Meera Harper, Marvin B. File, Thomas M., Jr. Camargo, Carlos A., Jr. CA EMNet Investigators TI Factors associated with antimicrobial resistance and mortality in pneumococcal bacteremia SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Streptococcus pneumoniae; antibiotic resistance; mortality; bacteremia ID STREPTOCOCCUS-PNEUMONIAE BACTEREMIA; COMMUNITY-ACQUIRED PNEUMONIA; MACROLIDE RESISTANCE; UNITED-STATES; PENICILLIN; CLARITHROMYCIN; SURVEILLANCE; ERYTHROMYCIN; AZITHROMYCIN; OUTPATIENTS AB We conducted a multicenter, retrospective cohort study of patients with Streptococcus pneumoniae bacteremia to determine factors associated with antibiotic resistance and mortality. Risk factors were identified using multivariate logistic regression. There were 1574 patients at 34 sites enrolled. Compared to isolates from patients not receiving an antibiotic before the index blood culture, patients receiving an antibiotic were less likely to harbor an antibiotic susceptible organism. Susceptibility to penicillin decreased from 78% (95% confidence interval [CI] 75-80) to 49% (95% CI 39-59); to cefotaxime/ceftriaxone, from 92% (95% CI 90-93) to 82% (95% CI 72-89); and to macrolide, from 84% (95% CI 82-87) to 55% (95% CI 41-68). Factors associated with macrolide non-susceptibility include: > 24 h of antibiotic therapy at time of the index culture (odds ratio [OR] 4.0), residing in southern U.S. (OR 1.7), and having an antibiotic allergy (OR 1.7). Harboring an antibiotic non-susceptible strain (OR 1.4) and male sex (OR 1.4) were associated with increased risk of mortality, whereas black race (OR 0.6) and evidence of focal infection (OR 0.6) were associated with decreased risk. (c) 2007 Elsevier Inc. C1 Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27515 USA. Northeastern Ohio Univ Coll Med & Pharm, Rootstown, OH 44272 USA. Summa Hlth Syst, Infect Dis Serv, Akron, OH USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Neuman, MI (reprint author), Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL63841, R01 HL063841-01A1, R01 HL063841]; NICHD NIH HHS [T32 HD040128, T32 HD040128-01, T32 HD40128-01] NR 27 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2007 VL 32 IS 4 BP 349 EP 357 DI 10.1016/j.jemermed.2006.08.014 PG 9 WC Emergency Medicine SC Emergency Medicine GA 171DX UT WOS:000246716200003 PM 17499686 ER PT J AU Sacco, D McDougal, WS Schwarz, A AF Sacco, Dianne McDougal, W. Scott Schwarz, Alexander TI Preventing migration of stones during fragmentation with thermosensitive polymer SO JOURNAL OF ENDOUROLOGY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; BASKET AB Purpose: To define a method of stabilizing stones during extracorporeal (SWL) and intracorporeal lithotripsy with a thermosensitive polymer. Materials and Methods: Using a thermosensitive polymer that is either a liquid or a gel, depending on the temperature, both calcium oxalate and plaster of Paris phantom stones were placed in the polymer gel or saline, and SWL was performed. Comparisons were made between the effectiveness of the fragmentation in the two media. Also, in-vivo studies using the polymer to prevent migration of ureteral stones were performed in swine. Electrohydraulic lithotripsy was used on a small stone implanted in the distal ureter with the polymer instilled proximally. Once in the ureter, the polymer converted to a gel. After completion of the procedure, the polymer was restored to a liquid form by infusion of cold saline and expelled from the ureter. Three of the pigs underwent treatment of the stone, convalesced for 7 days, and then had urine collections from both ureters to compare the glomerular filtration rates, fractional sodium excretion, urine/plasma creatinine ratio, and urine/plasma urea ratio on the treated and the contralateral ( control) sides. Results: The polymer did not enhance fragmentation when used with SWL but prevented stone migration in the in-vivo studies. The physiologic parameters were not significantly different on the treated and the control sides. The polymer was easily removed from the ureter by infusing cold water. Conclusion: The use of this thermosensitive polymer proximal to ureteral stones prevents migration and is not traumatic to the ureter. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Pluromed, Boston, MA USA. RP Sacco, D (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM dsacco@partners.org NR 6 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD MAY PY 2007 VL 21 IS 5 BP 504 EP 507 DI 10.1089/end.2006.0324 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 172WH UT WOS:000246834700010 PM 17523903 ER PT J AU Quackenbush, J AF Quackenbush, John TI Extracting biology from high-dimensional biological data SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Review DE 'omic data analysis; microarray; bioinformatics; computational biology ID GENE-EXPRESSION; MICROARRAY DATA; SINGLE-CELL; ALZHEIMERS-DISEASE; CANCER; CLASSIFICATION; PREDICTION; STANDARDS; NETWORKS; GENOMES AB The promise of the genome project was that a complete sequence would provide us with information that would transform biology and medicine. But the `parts list' that has emerged from the genome project is far from the `wiring diagram' and `circuit logic' we need to understand the link between genotype, environment and phenotype. While genomic technologies such as DNA microarrays, proteomics and metabolomics have given us new tools and new sources of data to address these problems, a number of crucial elements remain to be addressed before we can begin to close the loop and develop a predictive quantitative biology that is the stated goal of so much of current biological research, including systems biology. Our approach to this problem has largely been one of integration, bringing together a vast wealth of information to better interpret the experimental data we are generating in genomic assays and creating publicly available databases and software tools to facilitate the work of others. Recently, we have used a similar approach to trying to understand the biological networks that underlie the phenotypic responses we observe and starting us on the road to developing a predictive biology. C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu NR 49 TC 33 Z9 34 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD MAY 1 PY 2007 VL 210 IS 9 BP 1507 EP 1517 DI 10.1242/jeb.004432 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 165JN UT WOS:000246301900010 PM 17449816 ER PT J AU Panuzio, J Taft, CT Black, DA Koenen, KC Murphy, CM AF Panuzio, Jillian Taft, Casey T. Black, Danielle A. Koenen, Karestan C. Murphy, Christopher M. TI Relationship abuse and victims' posttraumatic stress disorder symptoms: Associations with child behavior problems SO JOURNAL OF FAMILY VIOLENCE LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 2004 CL New Orleans, LA SP Assoc Advancement Behav Therapy DE relationship abuse; child behavior; posttraumatic stress disorder; psychological aggression ID INTIMATE PARTNER VIOLENCE; BATTERED WOMEN; DOMESTIC VIOLENCE; FAMILY VIOLENCE; PSYCHOSOCIAL DYSFUNCTION; PHYSICAL VIOLENCE; VIETNAM VETERANS; MARITAL CONFLICT; CONDUCT PROBLEMS; SOCIAL SUPPORT AB This study examined associations among male-to-female physical and psychological relationship aggression, female partners' PTSD symptoms, and behavior problems among the children (n=62) of men enrolled in a treatment program for relationship abuse perpetration. Psychological aggression was a stronger predictor of child behavior problems than physical assault. Restrictive engulfment and hostile withdrawal behaviors evidenced the strongest bivariate associations with child behavior problems, and were the strongest predictors of this outcome when considering four distinct forms of psychological aggression together. Victim PTSD symptoms largely mediated the effects of psychological aggression on child behavior. Findings suggest that male-to-female psychological aggression and victim PTSD symptoms play an important role in understanding behavior problems among children living with male relationship abuse perpetrators. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov NR 80 TC 11 Z9 11 U1 5 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD MAY PY 2007 VL 22 IS 4 BP 177 EP 185 DI 10.1007/s10896-007-9069-z PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 169UU UT WOS:000246618400001 ER PT J AU Pratt, JSA Van Noord, M Christison-Lagay, E AF Pratt, Janey S. A. Van Noord, Michael Christison-Lagay, Emily TI The tethered bezoar as a delayed complication of laparoscopic Roux-en-Y gastric bypass: A case report SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE bezoar; gastric bypass; postoperative complication ID MORBID-OBESITY; OUTCOMES AB Known complications of Roux-en-Y gastric bypass causing abdominal pain and obstructive symptoms include biliary colic, anastomotic ulcer, anastomotic stenosis, or internal hernia. This case report describes a new complication in a patient 15 months post-bypass: a bezoar at the gastrojejunal anastomosis, the nidus of which was a length of permanent suture material which had eroded through the gastric wall. We include endoscopic images of the bezoar, a review of the related gastric bypass literature, and describe the changes made in our practice as a result of this complication. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Kaiser Permanente, Vallejo Med Ctr, Dept Surg, Vallejo, CA 94589 USA. RP Pratt, JSA (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC Suite 460, Boston, MA 02114 USA. EM jpratt@partners.org NR 8 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2007 VL 11 IS 5 BP 690 EP 692 DI 10.1007/s11605-007-0098-y PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 163SR UT WOS:000246184000020 PM 17468931 ER PT J AU Grande, D Asch, DA Armstrong, K AF Grande, David Asch, David A. Armstrong, Katrina TI Do doctors vote? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE professionalism; social science; community health; health policy ID MEDICAL PROFESSIONALISM; PUBLIC ROLES AB Background: Organizational leaders and scholars have issued calls for the medical profession to refocus its efforts on fulfilling the core tenets of professionalism. A key element of professionalism is participation in community affairs. Objective: To measure physician voting rates as an indicator of civic participation. Design: Cross-sectional survey of a subgroup of physicians from a nationally representative household survey of civilian, noninstitutionalized adult citizens. Participants: A total of 350,870 participants in the Current Population Survey (CPS) November Voter Supplement from 1996-2002, including 1,274 physicians and 1,886 lawyers; 414,989 participants in the CPS survey from 1976-1982, including 2,033 health professionals. Measurements: Multivariate logistic regression models were used to compare adjusted physician voting rates in the 1996-2002 congressional and presidential elections with those of lawyers and the general population and to compare voting rates of health professionals in 1996-2002 with those in 1976-1992. Results: After multivariate adjustment for characteristics known to be associated with voting rates, physicians were less likely to vote than the general population in 1998 (odds ratio 0.76; 95% confidence interval [CI] 0.59-0.99), 2000 (odds ratio 0.64; 95% CI 0.44-0.93), and 2002 (odds ratio 0.62; 95% CI 0.48-0.80) but not 1996 (odds ratio 0.83; 95% CI 0.59-1.17). Lawyers voted at higher rates than the general population and doctors in all four elections (P <.001). The pooled adjusted odds ratio for physician voting across the four elections was 0.70 (CI 0.61-0.81). No substantial changes in voting rates for health professionals were observed between 1976-1982 and 1996-2002. Conclusions: Physicians have lower adjusted voting rates than lawyers and the general population, suggesting reduced civic participation. C1 Univ Penn, Robert Wood Johnson Hlth & Soc Scholars Program, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Grande, D (reprint author), Univ Penn, Robert Wood Johnson Hlth & Soc Scholars Program, 3641 Locust Walk, Philadelphia, PA 19104 USA. EM dgrande@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X NR 35 TC 8 Z9 8 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2007 VL 22 IS 5 BP 585 EP 589 DI 10.1007/s11606-007-0105-8 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 158YL UT WOS:000245831500005 PM 17443365 ER PT J AU Steinman, MA Chren, MM Landefeld, CS AF Steinman, Michael A. Chren, Mary-Margaret Landefeld, C. Seth TI What's in a name? Use of brand versus generic drug names in United States outpatient practice SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE drug labeling; drug industry; prescriptions; drug; drugs; generic; names; prescription fees; ambulatory care ID TRADE NAMES; POTENTIAL SAVINGS; SUBSTITUTION; INFORMATION; PHYSICIAN; MEDICAID; BENEFIT AB Background: The use of brand rather than generic names for medications can increase health care costs. However, little is known at a national level about how often physicians refer to drugs using their brand or generic names. Objective: To evaluate how often physicians refer to drugs using brand or generic terminology. Design and Participants: We used data from the 2003 National Ambulatory Medical Care Survey (NAMCS), a nationally representative survey of 25,288 community-based outpatient visits in the United States. After each visit, patient medications were recorded on a survey encounter form by the treating physician or transcribed from office notes. Measurements: Our main outcome measure was the frequency with which medications were recorded on the encounter form using their brand or generic names. Results: For 20 commonly used drugs, the median frequency of brand name use was 98% (interquartile range, 81-100%). Among 12 medications with no generic competition at the time of the survey, the median frequency of brand name use was 100% (range 92-100%). Among 8 medications with generic competition at the time of the survey ("multisource" drugs), the median frequency of brand name use was 79% (range 0-98%; P < .001 for difference between drugs with and without generic competition). Conclusions: Physicians refer to most medications by their brand names, including drugs with generic formulations. This may lead to higher health care costs by promoting the use of brand-name products when generic alternatives are available. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. San Francisco VA Med Ctr, Dept Dermatol, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [Z01 AG000912, K07 AG000912]; NIAMS NIH HHS [K02 AR002203, AR02203] NR 19 TC 28 Z9 28 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2007 VL 22 IS 5 BP 645 EP 648 DI 10.1007/s11606-006-0074-3 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 158YL UT WOS:000245831500014 PM 17443372 ER PT J AU Egede, LE AF Egede, Leonard E. TI Failure to recognize depression in primary care: Issues and challenges SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID INTERNATIONAL PRIMARY-CARE; LATE-LIFE DEPRESSION; COLLABORATIVE CARE; MAJOR DEPRESSION; MENTAL-DISORDERS; GENERAL-PRACTICE; ANTIDEPRESSANT TREATMENT; COST-EFFECTIVENESS; RANDOMIZED-TRIAL; FOLLOW-UP C1 Charleston VA TREP, Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Ctr Hlth Dispar Res, Div Gen Internal Med, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Charleston VA TREP, Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM egedel@musc.edu NR 43 TC 27 Z9 27 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2007 VL 22 IS 5 BP 701 EP 703 DI 10.1007/s11606-007-0170-z PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 158YL UT WOS:000245831500025 PM 17370030 ER PT J AU Lindenhovius, ALC Felsch, Q Doornberg, JN Ring, D Kloen, P AF Lindenhovius, Anneluuk L. C. Felsch, Quinten Doornberg, Job N. Ring, David Kloen, Peter TI Open reduction and internal fixation compared with excision for unstable displaced fractures of the radial head SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE elbow; long-term follow-up; Mason; trauma; radial head ID ELBOW; DISLOCATIONS; RESECTION AB Purpose: To determine if excision of the radial head for treatment of an unstable, displaced fracture is associated with a higher rate of early complications or late arthrosis as compared with open reduction and internal fixation (ORIF). Methods: Unstable, displaced fractures of the radial head treated with either excision (15 patients) or ORIF (13 patients) were compared. Implants were removed routinely during the study period. Three patients had instability after radial head excision: 2 were treated in a cast and 1 had temporary pinning of the ulnohumeral joint. Two patients in the ORIF cohort had failure of fixation that subsequently was treated with radial head excision: I had early hardware loosening and 1 developed a nonunion. Results: At the 1-year follow-up evaluation there were no significant differences in the flexion or rotation arc. An average of 17 years after injury there was no significant difference in the flexion arc or rotation arc. One result was rated as unsatisfactory in each cohort according to the Mayo Elbow Performing Index. The average Disabilities of the Arm, Shoulder, and Hand (DASH) score was 5 points in the ORIF cohort and 15 points in the excision cohort. Eight patients in the excision cohort had arthrosis (5 mild, 2 moderate, 1 severe) compared with 2 patients in the ORIF cohort (I mild, I moderate). Conclusions: Open reduction and internal fixation of an unstable, displaced fracture of the radial head occasionally fails, but it seems to reduce the risk of subsequent elbow dislocation and to protect against long-term arthrosis. (J Hand Surg 2007;32A:630-636. Copyright (C) 2007 by the American Society for Surgery of the Hand.) C1 Harvard Univ, Sch Med, Orthopaed Hand & Upper Extrem Serv, Massachusetts Gen Hosp, Boston, MA 02115 USA. Orthotrauma Res Ctr, Amsterdam, Netherlands. Univ Amsterdam, Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 32 TC 31 Z9 34 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY-JUN PY 2007 VL 32A IS 5 BP 630 EP 636 DI 10.1016/j.jhsa.2007.02.016 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 167ZG UT WOS:000246490800007 PM 17482000 ER PT J AU Cordasco, KM Eisenman, DP Glik, DC Golden, JF Asch, SM AF Cordasco, Kristina M. Eisenman, David P. Glik, Deborah C. Golden, Joya F. Asch, Steven M. TI "They blew the levee": Distrust of authorities among hurricane Katrina evacuees SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Hurricane Katrina; disaster planning; trust; qualitative research ID RISK COMMUNICATION; AFRICAN-AMERICANS; TRUST; TRUSTWORTHINESS; BIOTERRORISM; CHALLENGES; PHYSICIANS; ANTHRAX; LESSONS C1 Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Cordasco, KM (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90024 USA. EM kcordasco@mednet.ucla.edu FU ODCDC CDC HHS [K01 CD 000049-02] NR 28 TC 25 Z9 25 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2007 VL 18 IS 2 BP 277 EP 282 DI 10.1353/hpu.2007.0028 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 163LY UT WOS:000246162500009 PM 17483557 ER PT J AU Ferencik, M Gregory, SA Butler, J Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K McNulty, IA Healy, JA Brady, TJ Semigran, MJ Jang, IK AF Ferencik, Maros Gregory, Shawn A. Butler, Javed Achenbach, Stephan Yeh, Robert W. Hoffmann, Udo Inglessis, Ignacio Cury, Ricardo C. Nieman, Koen McNulty, Iris A. Healy, Josephine A. Brady, Thomas J. Semigran, Marc J. Jang, Ik-Kyung TI Analysis of cardiac dimensions, mass and function in heart transplant recipients using 64-slice multi-detector computed tomography SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID LEFT-VENTRICULAR FUNCTION; INTRAVASCULAR ULTRASOUND; CORONARY-ANGIOGRAPHY; 3-DIMENSIONAL ECHOCARDIOGRAPHY; EJECTION FRACTION; 2-DIMENSIONAL ECHOCARDIOGRAPHY; NONINVASIVE DETECTION; MYOCARDIAL-FUNCTION; UNSTABLE ANGINA; REAL-TIME AB Background: Heart transplant recipients present a challenge to cardiac multi-detector computed tomography (MDCT) imaging due to high resting heart rates and body mass indices. Previous studies demonstrated the feasibility of coronary allograft vasculopathy detection by MDCT in heart transplant recipients. However, its performance in assessing cardiac structure and function in these patients has not been evaluated. The aim of this study was to compare 64-slice MDCT analysis of cardiac structure and function to 2-dimensional echocardiography in heart transplant recipients. Methods: Two independent observers used both semi-automated and automated software to measure chamber dimensions and left ventricular ejection fraction and mass in 20 heart transplant recipients by 64-slice MDCT. Inter-observer variability was determined. The results were compared with echocardiographic measurements provided by another blinded observer. Results: There was moderate agreement between MDCT and echocardiography for chamber dimension measurements, except for left atrial diameter. Ejection fraction by MDCT was slightly lower (mean difference: -2 +/- 9%, p = 0.29) than that obtained by echocardiography and the correlation was moderate (R = 0.49 to 0.54). Left ventricular mass measurements were significantly lower by MDCT (mean difference: -87 +/- 44 g, p < 0.001). Inter-observer agreement for MDCT analysis of left ventricular function (R = 0.90) and mass (R = 0.83) were excellent. Conclusions: These findings demonstrate moderate agreement between 64-slice MDCT and echocardiography in the assessment of chamber dimensions as well as left ventricular mass and function in heart transplant recipients with low inter-observer variability. Also, the addition of cardiac structural and functional analysis to MDCT coronary angiography requires no additional scan time, contrast administration or radiation exposure. J Heart Lung Transplant 2007;26:478-84. Copyright (C) 2007 by the International Society for Heart and Lung Transplantation. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Med 2, Erlangen, Germany. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, GRB 843,55 Fruit St, Boston, MA 02114 USA. EM jang.ik@mgh.harvard.edu FU NHLBI NIH HHS [5K30HL004095-06, 5K24HL004021-05, 1T32 HL076136-02]; NIBIB NIH HHS [1T32EB001632-01] NR 31 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAY PY 2007 VL 26 IS 5 BP 478 EP 484 DI 10.1016/j.healun.2007.01.041 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 165DN UT WOS:000246284200009 PM 17449417 ER PT J AU Christofi, S Strouthos, C AF Christofi, Stavros Strouthos, Costas TI Three dimensional four-fermion models - A Monte Carlo study SO JOURNAL OF HIGH ENERGY PHYSICS LA English DT Article DE lattice quantum field theory; field theories in lower dimensions; nonperturbative effects ID GROSS-NEVEU MODEL; JONA-LASINIO MODEL; CRITICAL EXPONENTS; BETA-FUNCTION; 4 DIMENSIONS; PHASE; O(1/N2); SUPERCONDUCTIVITY; VIOLATION; SYMMETRY AB We present results from numerical simulations of three different 3d four-fermion models that exhibit Z(2), U(1), and SU(2) x SU(2) chiral symmetries, respectively. We performed the simulations by using the hybrid Monte Carlo algorithm. We employed finite size scaling methods on lattices ranging from 8(3) to 40(3) to study the properties of the second order chiral phase transition in each model. The corresponding critical coupling defines an ultraviolet fixed point of the renormalization group. In our high precision simulations, we detected next-to-leading order corrections for various critical exponents and we found them to be in good agreement with existing analytical large-N-f calculations. C1 Frederick Inst Technol, CY-1303 Nicosia, Cyprus. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard MIT HST Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Christofi, S (reprint author), Frederick Inst Technol, CY-1303 Nicosia, Cyprus. EM eng.cs@fit.ac.cy; cstrouth@deas.harvard.edu NR 33 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8479 J9 J HIGH ENERGY PHYS JI J. High Energy Phys. PD MAY PY 2007 IS 5 AR 088 PG 12 WC Physics, Particles & Fields SC Physics GA 175RJ UT WOS:000247030800088 ER PT J AU Louis, KS Holdsworth, JM Anderson, MS Campbell, EG AF Louis, Karen Seashore Holdsworth, Janet M. Anderson, Melissa S. Campbell, Eric G. TI Becoming a scientist: The effects of work-group size and organizational climate SO JOURNAL OF HIGHER EDUCATION LA English DT Article ID RESEARCH PRODUCTIVITY; SCIENCE; COMPETITION; SECRECY; COOPERATION; UNIVERSITY; COLLABORATION; CONSEQUENCES; DETERMINANTS; INDIVIDUALS AB The future of the scientific enterprise is vested in the next generation of scientists who are currently enrolled in doctoral programs and fellowships in the nation's universities. Because scientific education occurs in the scientific milieu, graduate students and post-doctoral fellows are directly influenced by the organizational and contextual forces driving the conduct of scientific research. The purpose of this research was to examine the impact of industrial research support, work-group size, and organizational climate on the productivity of graduate students and postdocs and their subsequent willingness to share their research with the scientific community. In order to address this issue, we conducted a national survey of a random sample of 2,000 graduate students and postdoctoral fellows in the life sciences, chemical engineering, and computer science. The results of this survey show that organizational climate (as measured by multi-item scales reflecting the amount of collaboration, competition, individualism, and openness) and work-group size are significantly related to the productivity of students as well as to their willingness to share their research results with others. In addition, we found significant differences and similarities between scientific fields and between doctoral students and postdoctoral fellows. Finally, our data suggest that the presence of industrial funding enhances productivity and does not detract from willingness to share. C1 Univ Minnesota, Dept Educ Policy & Adm, Sch Kinesiol, Minneapolis, MN 55455 USA. Univ Minnesota, Postsecondary Educ Res Inst, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Inst Hlth Policy, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Louis, KS (reprint author), Univ Minnesota, Dept Educ Policy & Adm, Sch Kinesiol, Minneapolis, MN 55455 USA. NR 67 TC 24 Z9 25 U1 3 U2 30 PU OHIO STATE UNIV PRESS PI COLUMBUS PA 1050 CARMACK RD, COLUMBUS, OH 43210 USA SN 0022-1546 J9 J HIGH EDUC JI J. High. Educ. PD MAY-JUN PY 2007 VL 78 IS 3 BP 311 EP + DI 10.1353/jhe.2007.0017 PG 28 WC Education & Educational Research SC Education & Educational Research GA 159KV UT WOS:000245865500003 ER PT J AU Williams, LH Raugi, GJ Dhaliwal, G Saint, S Lipsky, BA AF Williams, Lisa H. Raugi, Gregory J. Dhaliwal, Gurpreet Saint, Sanjay Lipsky, Benjamin A. TI "Are we there yet?" SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID POPULATION-BASED COHORT; INFLAMMATORY MYOPATHIES; DERMATOMYOSITIS; POLYMYOSITIS; CANCER; MYOSITIS; MALIGNANCY; FEATURES C1 [Williams, Lisa H.; Raugi, Gregory J.; Lipsky, Benjamin A.] VA Puget Sound Hlth Care Syst, Primary & Special Med Serv, Dept Pediat, Seattle, WA 98108 USA. [Williams, Lisa H.; Raugi, Gregory J.; Lipsky, Benjamin A.] Univ Washington, Sch Med, Seattle, WA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Saint, Sanjay] Univ Michigan Hlth Syst, Ann Arbor Vet Affairs Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. [Saint, Sanjay] Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI 48109 USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Primary & Special Med Serv, Dept Pediat, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Benjamin.Lipsky@med.va.gov OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 23 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAY-JUN PY 2007 VL 2 IS 3 BP 181 EP 188 DI 10.1002/jhm.210 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 292HP UT WOS:000255257400011 PM 17551950 ER PT J AU Mummidi, S Adams, LM VanCompernolle, SE Kalkonde, M Camargo, JF Kulkarni, H Bellinger, AS Bonello, G Tagoh, H Ahuja, SS Unutmaz, D Ahnja, SK AF Mummidi, Srinivas Adams, Lisa M. VanCompernolle, Scott E. Kalkonde, Mrunal Camargo, Jose F. Kulkarni, Hemant Bellinger, Adam S. Bonello, Gregory Tagoh, Hiromi Ahuja, Seema S. Unutmaz, Derya Ahnja, Sunil K. TI Production of specific mRNA transcripts, usage of an alternate promoter, and octamer-binding transcription factors influence the surface expression levels of the HIV cereceptor CCR5 on primary T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR 5 CCR5; DISEASE PROGRESSION; IN-VITRO; CHEMOKINE RECEPTORS; INTERLEUKIN-2 GENE; INFECTION; TYPE-1; CORECEPTOR; ENTRY AB Surface levels of CCR5 on memory CD4+ T cells influence HIV-1/AIDS susceptibility. Alternative promoter usage results in the generation of CCR5 mRNA isoforms that differ based on whether they contain or lack the untranslated exon 1. The impact of exon 1-containing transcripts on CCR5 surface expression is unknown. In this study, we show that the increased cell surface expression of CCR5 on primary T cells is associated with selective enrichment of exon 1-containing transcripts. The promoter that drives exon I-containing transcripts is highly active in primary human T cells but not in transformed T cell lines. The transcription factors Oct-1 and -2 inhibit and enhance, respectively, the expression of exon 1-containing transcripts and CCR5 surface levels. However, polymorphisms at homologous octamer-binding sites in the CCR5 promoter of nonhuman primates abrogate the binding of these transcription factors. These results identify exon 1-containing transcripts, and the cis-trans factors that regulate the expression levels of these mRNA isoforms as key parameters that affect CCR5 surface expression levels, and by extension, susceptibility to HIV/AIDS among humans, and possibly, the observed interspecies differences in susceptibility to lentiviral infection. The Journal of Immunology, 2007, 178: 5668-.5681. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, Vet Adm Ctr AIDS & HIV Infect, San Antonio, TX 78229 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Univ Leeds, St Jamess Univ Hosp, Mol Med Unit, Leeds, W Yorkshire, England. NYU, Sch Med, Dept Microbiol, Joan & Joel Smilow Res Ctr, New York, NY 10016 USA. RP Ahnja, SK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM derya.unutmaz@med.nyu.edu; ahujas@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008; Tagoh, Hiromi/B-2954-2009 OI Mummidi, Srinivas/0000-0002-4068-6380; Tagoh, Hiromi/0000-0001-9905-6992 FU NIAID NIH HHS [AI 054206, AI 043279, AI 049131, F32 AI 063975]; NIMH NIH HHS [MH 069270]; PHS HHS [NIH R37 046326] NR 57 TC 10 Z9 11 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2007 VL 178 IS 9 BP 5668 EP 5681 PG 14 WC Immunology SC Immunology GA 161YZ UT WOS:000246054400032 PM 17442950 ER PT J AU Reckamp, KL Figlin, RA Moldawer, N Pantuck, AJ Belldegrun, AS Burdick, MD Strieter, RM AF Reckamp, Karen L. Figlin, Robcrt A. Moldawer, Nancy Pantuck, Allan J. Belldegrun, Arie S. Burdick, Marie D. Strieter, Robert M. TI Expression of CXCR3 on mononuclear cells and CXCR3 ligands in patients with metastatic renal cell carcinoma in response to systemic IL-2 therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE chemokines; renal cell carcinoma; cytokine therapy ID TUMOR-SUPPRESSOR GENE; PHASE-II TRIAL; T-CELLS; SUBCUTANEOUS INTERLEUKIN-2; CHEMOKINE RECEPTORS; DOSE INTERLEUKIN-2; BIOLOGICAL AXIS; RENCA TUMOR; CANCER; BEVACIZUMAB AB Chemokines play an important role in regulating tumor-mediated immunity, angiogenesis, and tumor cell inetastasis. The chemokine receptor, CXCR3, is expressed in various human tumors, including renal cell carcinoma (RCC). CXCR3 is also associated with antiangiogenic effects in multiple tumors, and we hypothesized that interleukin-2 (IL-2) treatment of patients with metastatic clear cell RCC could augment CXCR3 levels on circulating mononuclear cells and correlate to outcome. The kinetics of CXCR3 expression on circulating mononuclear cells and its ligands (CXCL9, CXCL10, and CXCL11) in plasma were evaluated in 20 patients with metastatic clear cell RCC during cycles I and 2 of high dose IL-2 therapy. Subpopulations of peripheral blood mononuclear cells (PBMCs) were studied by dual color flow cytometry. Angiogenic ligands were measured and an "angiogenic ratio" was calculated prehigh and posthigh dose IL-2. CXCR3 expression on PBMC at baseline was similar in patients with metastatic RCC and normal controls. PBMC CXCR3 expression increased during treatment, and peaked during cycle 2. Plasma from RCC patients displayed similar baseline levels of CXCR3 ligands to normal controls. however, the angiogenic ratio was significantly increased in patients with metastatic RCC at baseline. Plasma levels of CXCR3 ligands increased during treatment, resulting in a reversal in the angiogenic ratio to favor angiostatic chemokines. The CXCR3/CXCR3 ligand biologic axis and angiogenic ratio may be important biomarkers in clear cell RCC patients who are undergoing high dose IL-2 therapy. C1 City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA USA. Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22901 USA. Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90024 USA. RP Reckamp, KL (reprint author), City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, 1500 E Duarte Rd,MOB 1001, Duarte, CA 91010 USA. EM kreckamp@coh.org OI Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [CA87879, P50CA90388] NR 39 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2007 VL 30 IS 4 BP 417 EP 424 DI 10.1097/CJI.0b013e31802e089a PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 161QE UT WOS:000246029600006 PM 17457216 ER PT J AU Borghaei, H Alpaugh, RK Bernardo, P Palazzo, IE Dutcher, JP Venkatraj, U Wood, WC Goldstein, L Weiner, LM AF Borghaei, Hossein Alpaugh, R. Katherine Bernardo, Patricia Palazzo, Irma E. Dutcher, Janice P. Venkatraj, Usha Wood, William C. Goldstein, Lori Weiner, Louis M. TI Induction of adaptive anti-HER2/neu immune responses in a phase 1B/2 trial of 2B1 bispecific murine monoclonal antibody in metastatic breast cancer (E3194): A trial coordinated by the Eastern Cooperative Oncology Group SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE HER2/neu; bispecific antibody; immunization ID NON-HODGKINS-LYMPHOMA; TARGETING C-ERBB-2; 1ST-LINE TREATMENT; COLORECTAL-CANCER; HYBRID HYBRIDOMAS; PLUS IRINOTECAN; OVARIAN-CANCER; II TRIAL; IN-VIVO; CELLS AB 2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and Fc gamma RIII. 2BI efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the Fc gamma RIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2BI therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but I patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m(2)/d to 1 mg/m(2)/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate anti body-directed cellular cytotoxicity may exert their clinical antitumor effects. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Our Lady Mercy Med Ctr, Bronx, NY USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Hope Canc Clin, Bryan, TX USA. Emory Univ, Atlanta, GA 30322 USA. RP Weiner, LM (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Louis.Weiner@fccc.edu FU NCI NIH HHS [CA58262, CA66636, CA50633, CA23318, CA27525, CA14958, CA21115, CA-23318] NR 55 TC 17 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2007 VL 30 IS 4 BP 455 EP 467 DI 10.1097/CJI.0b013e31803bb421 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 161QE UT WOS:000246029600010 PM 17457220 ER PT J AU Chen, CC Taniguchi, T D'Andrea, A AF Chen, Clark C. Taniguchi, Toshiyasu D'Andrea, Alan TI The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE temozolomide (TMZ); 1,3-bis[2-chloroethyl]-1-nitroso-urea (BCNU); Fanconi anemia (FA); DNA repair; glioma therapeutics ID MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; MISMATCH REPAIR SYSTEM; HUMAN TUMOR-CELLS; DRUG-RESISTANCE; LOCAL CHEMOTHERAPY; METHYLATING AGENTS; MALIGNANT GLIOMAS; G(2) CHECKPOINT; CARCINOMA-CELLS; OVARIAN-TUMORS AB DNA alkylating agents including temozolomide (TMZ) and 1,3-bis[2-chloroethyl]-1-nitroso-urea (BCNU) are the most common form of chemotherapy in the treatment of gliomas. Despite their frequent use, the therapeutic efficacy of these agents is limited by the development of resistance. Previous studies suggest that the mechanism of this resistance is complex and involves multiple DNA repair pathways. To better define the pathways contributing to the mechanisms underlying glioma resistance, we tested the contribution of the Fanconi anemia (FA) DNA repair pathway. TMZ and BCNU treatment of FA-proficient cell lines led to a dose- and time-dependent increase in FANCD2 mono-ubiquitination and FANCD2 nuclear foci formation, both hallmarks of FA pathway activation. The FA-deficient cells were more sensitive to TMZ/BCNU relative to their corrected, isogenic counterparts. To test whether these observations were pertinent to glioma biology, we screened a panel of glioma cell lines and identified one (HT16) that was deficient in the FA repair pathway. This cell line exhibited increased sensitivity to TMZ and BCNU relative to the FA-proficient glioma cell lines. Moreover, inhibition of FA pathway activation by a small molecule inhibitor (curcumin) or by small interference RNA suppression caused increased sensitivity to TMZ/BCNU in the U87 glioma cell line. The BCNU sensitizing effect of FA inhibition appeared additive to that of methyl-guanine methyl transferase inhibition. The results presented in this paper underscore the complexity of cellular resistance to DNA alkylating agents and implicate the FA repair pathway as a determinant of this resistance. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol & Publ Hlth Sci, Seattle, WA 98109 USA. RP Chen, CC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,Mayer 642, Boston, MA 02114 USA. EM cchen1@partners.org RI Chen, Clark/C-8714-2013 OI Chen, Clark/0000-0001-6258-9277 FU NHLBI NIH HHS [R01 HL52725] NR 61 TC 43 Z9 43 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD MAY PY 2007 VL 85 IS 5 BP 497 EP 509 DI 10.1007/s00109-006-0153-2 PG 13 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 164AD UT WOS:000246204100009 PM 17221219 ER PT J AU Lee-Kirsch, MA Chowdhury, D Harvey, S Gong, ML Senenko, L Engel, K Pfeiffer, C Hollis, T Gahr, M Perrino, FW Lieberman, J Hubner, N AF Lee-Kirsch, Min Ae Chowdhury, Dipanjan Harvey, Scott Gong, Maoliang Senenko, Lydia Engel, Kerstin Pfeiffer, Christiane Hollis, Thomas Gahr, Manfred Perrino, Fred W. Lieberman, Judy Hubner, Norbert TI A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE familial chilblain lupus; systemic lupus erythematosus; TREX1; genetics; apoptosis; autoimmune disease ID AICARDI-GOUTIERES-SYNDROME; EXONUCLEASE TREX1; ERYTHEMATOSUS; DNA; CLASSIFICATION; ANTIBODIES; INFECTION; MICE AB We recently described a novel autosomal-dominant genodermatosis, termed familial chilblain lupus, and mapped its genetic locus to chromosome 3p21. Familial chilblain lupus manifests in early childhood with ulcerating acral skin lesions and is associated with arthralgias and circulating antinuclear antibodies. In this study, we report the identification of a heterozygous missense mutation (D18N) in TREX1 encoding the 3 '-5 ' repair exonuclease 1 in affected individuals of the family with chilblain lupus. The homodimeric TREX1 is the most abundant intracellular DNase in mammalian cells. We have recently shown that TREX1 plays a role in apoptotic single-stranded DNA damage induced by the killer lymphocyte protease granzyme A. D18N affects a highly conserved amino acid residue critical for catalytic activity. Recombinant mutant TREX1 homodimers are enzymatically inactive, while wild type/mutant heterodimers show residual exonucleolytic activity, suggesting a heterozygous loss of function. Lymphoblastoid cells carrying the D18N mutation are significantly less sensitive to granzyme A-mediated cell death, suggesting a novel role for this caspase-independent form of apoptosis in the pathogenesis of familial chilblain lupus. Our findings also warrant further investigation of TREX1 in common forms of lupus erythematosus. C1 Tech Univ Dresden, Klin Kinder & Jugendmed, D-01307 Dresden, Germany. Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, Boston, MA 02115 USA. Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA. Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. Tech Univ Dresden, Dermatol Klin, D-01307 Dresden, Germany. RP Lee-Kirsch, MA (reprint author), Tech Univ Dresden, Klin Kinder & Jugendmed, Fetscherstasse 74, D-01307 Dresden, Germany. EM minae.lee-kirsch@uniklinikum-dresden.de RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45587]; NIGMS NIH HHS [GM069962] NR 26 TC 114 Z9 117 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD MAY PY 2007 VL 85 IS 5 BP 531 EP 537 DI 10.1007/s00109-007-0199-9 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 164AD UT WOS:000246204100012 PM 17440703 ER PT J AU Santagata, S van Horne, C Sallan, SE McLaughlin, ME Ramakrishna, NR AF Santagata, Sandro van Horne, Craig Sallan, Stephen E. McLaughlin, Margaret E. Ramakrishna, Naren R. TI Post-irradiation meningioma with sarcoidosis SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE meningioma; sarcoid; sarcoidosis; post-irradiation C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Caritas St Elizabeth Hosp, Dept Neurosurg, Brighton, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ramakrishna, NR (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM nramakrishna@lroc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2007 VL 82 IS 3 BP 271 EP 272 DI 10.1007/s11060-006-9297-8 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 158QL UT WOS:000245807200006 PM 17361337 ER PT J AU Korutla, L Degnan, R Wang, PJ Mackler, SA AF Korutla, Laxminarayana Degnan, Ryan Wang, Peijie Mackler, Scott A. TI NAC1, a cocaine-regulated POZ/BTB protein interacts with CoREST SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE coimmunoprecipitation; gene expression; homodimers; mammalian two-hybrids; nucleus accumbens; transcriptional repressor ID TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; GENE-EXPRESSION; BTB/POZ DOMAIN; DNA-BINDING; N-COR; REST; RECRUITMENT; ADDICTION; COMPLEXES AB In this report, CoREST was identified as a protein that interacts with NAC1. NAC1 is a cocaine-regulated Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex (POZ/BTB) repressor protein, which mediates interactions among several other transcriptional regulators. In the present study, an interaction between NAC1 and CoREST was detected in neuro-2A cells and HEK293T cells. We found that the POZ/BTB domain is necessary and sufficient for interaction with CoREST. Surprisingly, only one of five mutations in the POZ/BTB domain that disrupts homodimer assembly interfered with NAC1 and CoREST interactions. These results indicate that POZ/BTB homodimer formation is not required for NAC1-CoREST interaction. CoREST demonstrated protein-protein interactions with both isoforms of NAC1, sNAC1, and lNAC1. Coimmunoprecipitation studies show that NAC1 and CoREST are physically bound together. To further support the results, a direct interaction was demonstrated in glutathione-S-transferase pull down assays. siRNA directed against NAC1 mRNA significantly reduced NAC1 protein expression and resulted in reversal of CoREST-mediated repression in cells. This interaction between NAC1 and CoREST was not found for other POZ/BTB proteins tested. Endogenous interaction was demonstrated in lysates from rat brain samples. This is the first report to demonstrate that a POZ/BTB protein interacts with CoREST. Taken together, the results indicate that CoREST may be part of the NAC1 repressor mechanism. C1 Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Mackler, SA (reprint author), Univ Penn, Sch Med, Dept Pharmacol, 67 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM smackler@mail.med.upenn.edu FU NIDA NIH HHS [DA 11809] NR 23 TC 21 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2007 VL 101 IS 3 BP 611 EP 618 DI 10.1111/j.1471-4159.2006.04387.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 158SA UT WOS:000245813600003 PM 17254023 ER PT J AU Bourguignon, LYW Gilad, E Peyrollier, K Brightman, A Swanson, RA AF Bourguignon, Lilly Y. W. Gilad, Eli Peyrollier, Karine Brightman, Amy Swanson, Raymond A. TI Hyaluronan-CD44 interaction stimulates Rac1 signaling and PKN gamma kinase activation leading to cytoskeleton function and cell migration in astrocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE astrocyte; CD44; cytoskeleton; hyaluronan; migration; PKN gamma; Rac1 ID SPINAL-CORD-INJURY; FIBRILLARY ACIDIC PROTEIN; HYALURONIC-ACID; EXTRACELLULAR-MATRIX; TYROSINE PHOSPHORYLATION; REACTIVE ASTROCYTES; POTENTIAL EFFECTOR; NERVE REGENERATION; ADHESION MOLECULE; CD44 INTERACTION AB Both hyaluronan [HA, the major glycosaminoglycans in the extracellular matrix (ECM)] and CD44 (a primary HA receptor) are associated with astrocyte activation and tissue repair following central nervous system (CNS) injury. In this study we investigated the question of whether HA-CD44 interaction influences astrocyte signaling and migration. Our data indicated that HA binding to the cultured astrocytes stimulated Rac1 signaling and cytoskeleton-mediated migration. To determine the cellular and molecular basis of these events, we focused on PKN gamma, a Rac1-activated serine/threonine kinase in astrocytes. We determined that HA binding to astrocytes stimulated Rac1-dependent PKN gamma kinase activity which, in turn, up-regulated the phosphorylation of the cytoskeletal protein, cortactin, and attenuated the ability of cortactin to cross-link F-actin. Further analyses indicated that the N-terminal antiparallel coiled-coil (ACC) domains of PKN gamma interacted with Rac1, and transfection of astrocytes with PKN gamma-ACCcDNA inhibited PKN gamma activity. Over-expression of the PKN gamma-ACC domain also functions as a dominant-negative mutant to block HA/CD44-mediated PKN gamma activation of cortactin and astrocyte migration. Taken together, these findings strongly suggest that hyaluronan/CD44 interaction with Rac1-PKN gamma plays a pivotal role in cytoskeleton activation and astrocyte migration. These newly discovered HA/CD44-induced astrocyte function may provide important insight into novel therapeutic treatments for tissue repair following CNS injury. C1 Univ Calif San Francisco, Dept Med, Endocrine Unit, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, Endocrine Unit, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Bourguignon, LYW (reprint author), Univ Calif San Francisco, Dept Med, Endocrine Unit, San Francisco VA Med Ctr, 111 N,4150 Clement St, San Francisco, CA 94121 USA. EM lilly.bourguignon@ucsf.edu FU NCI NIH HHS [R01 CA66163, R01 CA78633]; NIAMS NIH HHS [P01 AR39448] NR 62 TC 47 Z9 52 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2007 VL 101 IS 4 BP 1002 EP 1017 DI 10.1111/j.1471-4159.2007.04485.x PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 161RB UT WOS:000246032000014 PM 17403031 ER PT J AU Rahimian, E Tahsini, M Vossough, A Ohadi, B AF Rahimian, E. Tahsini, M. Vossough, A. Ohadi, B. TI Volumetric measurement of human red nucleus with 3D fast spin echo T2-weighted sequence magnetic resonance imaging SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 17th Meeting of the European-Neurological-Society CY JUN 16-20, 2007 CL Rhodes, GREECE SP European Neurolog Soc C1 Dr Athari Ctr, Tehran, Iran. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2007 VL 254 SU 3 BP 107 EP 107 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 175SN UT WOS:000247034400399 ER PT J AU Vandenbark, A Burrows, G Offner, H Link, J AF Vandenbark, A. Burrows, G. Offner, H. Link, J. TI From EAE to an MS clinical trial: DR 2/MOG-35-55 recombinant T cell receptor ligand treats relapses of experimental encephalomyelitis in DR 2 transgenic mice SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 17th Meeting of the European-Neurological-Society CY JUN 16-20, 2007 CL Rhodes, GREECE SP European Neurolog Soc C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2007 VL 254 SU 3 BP 163 EP 163 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 175SN UT WOS:000247034400624 ER PT J AU Frosch, MP Prada, CM Betensky, RA Garcia-Alloza, M Greenberg, SM Bacskai, BJ AF Frosch, Matthew P. Prada, Claudia M. Betensky, Rebecca A. Garcia-Alloza, Monica Greenberg, Steven M. Bacskai, Brian J. TI Effect of passive immunotherapy on the rate of progression of cerebral amyloid angiopathy (caa) in transgenic mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 83rd Annual Meeting of the American-Association-of-Neuropathologists CY APR 27-30, 2007 CL Washington, DC SP Amer Assoc Neuropathologists C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2007 VL 66 IS 5 BP 434 EP 435 DI 10.1097/01.jnen.0000268872.45065.c2 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 173DE UT WOS:000246852900082 ER PT J AU Lawlor, MW Plotkin, SR Hasserjian, RP Hedley-Whytel, ET AF Lawlor, Michael William Plotkin, Scott R. Hasserjian, Robert P. Hedley-Whytel, E. Tessa TI Precursor B lymphoblastic lymphoma restricted to the central nervous system: a case report SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 83rd Annual Meeting of the American-Association-of-Neuropathologists CY APR 27-30, 2007 CL Washington, DC SP Amer Assoc Neuropathologists C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2007 VL 66 IS 5 BP 441 EP 441 DI 10.1097/01.jnen.0000268901.49117.8b PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 173DE UT WOS:000246852900110 ER PT J AU Auluck, PK Barnett, SM Eichler, FS Hedley-Whyte, ET AF Auluck, Pavan Kumar Barnett, Sarah M. Eichler, Florian S. Hedley-Whyte, E. Tessa TI Neonatal adrenoleukodystrophy with long-term survival SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 83rd Annual Meeting of the American-Association-of-Neuropathologists CY APR 27-30, 2007 CL Washington, DC SP Amer Assoc Neuropathologists C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners Neurol Program, Boston, MA 02114 USA. RI Auluck, Pavan/A-1160-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2007 VL 66 IS 5 BP 452 EP 452 DI 10.1097/01.jnen.0000268950.31191.63 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 173DE UT WOS:000246852900157 ER PT J AU Romero, VA Fernandez-Vina, M Encinales, L Almeciga, I Awad, C Collazos, V Clavijo, OP Zuniga, J Yunis, EJ AF Romero, Viviana A. Fernandez-Vina, Marcelo Encinales, Liliana Almeciga, Ingrid Awad, Carlos Collazos, Vilma Clavijo, Olga P. Zuniga, Joaquin Yunis, Edmond J. TI Tuberculin anergy mediated by Immoral immunity SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 83rd Annual Meeting of the American-Association-of-Neuropathologists CY APR 27-30, 2007 CL Washington, DC SP Amer Assoc Neuropathologists C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Hosp Santa Clara, Bogota, Colombia. Hosp La Tebaida, Quindio, Colombia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2007 VL 66 IS 5 BP 454 EP 454 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 173DE UT WOS:000246852900165 ER PT J AU Maison, SF Vetter, DE Liberman, MC AF Maison, Stephane F. Vetter, Douglas E. Liberman, M. Charles TI A novel effect of cochlear efferents: In vivo response enhancement does not require alpha 9 cholinergic receptors SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OUTER HAIR-CELLS; GUINEA-PIG COCHLEA; NICOTINIC ACETYLCHOLINE-RECEPTOR; BASILAR-MEMBRANE DISPLACEMENT; CROSSED OLIVOCOCHLEAR BUNDLE; AUDITORY-NERVE FIBERS; ELECTRICAL-STIMULATION; RAT COCHLEA; INNERVATION; SYNAPSES AB Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by alpha 9/alpha 10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of similar to 100 s. In mice with targeted deletion of the alpha 9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA USA. MIT, Div Hlth Sci & Technol, Cambridge, MA USA. Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu FU NIDCD NIH HHS [P30 DC005209, P30 DC-05029, R01 DC-00188, R01 DC000188, R01 DC000188-27, R01 DC006258] NR 57 TC 29 Z9 29 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2007 VL 97 IS 5 BP 3269 EP 3278 DI 10.1152/jn.00067.2007 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188QD UT WOS:000247933500011 PM 17344378 ER PT J AU Jones, J Stubblefield, EA Benke, TA Staley, KJ AF Jones, Jethro Stubblefield, Elizabeth A. Benke, Timothy A. Staley, Kevin J. TI Desynchronization of glutamate release prolongs synchronous CA3 network activity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RECURRENT COLLATERAL SYNAPSES; PRESYNAPTIC MODULATION; SYNAPTIC-TRANSMISSION; EPILEPTIFORM ACTIVITY; TRANSMITTER RELEASE; POPULATION BURSTS; HIPPOCAMPAL SLICE; NEURONAL NETWORKS; RAT HIPPOCAMPUS; CA2+ CHANNEL AB Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca2+ with Sr2+. Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr2+ substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 +/- 7.6 (SE) times the duration in control conditions. Sr2+ also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat & Pharmacol, Denver, CO 80262 USA. RP Staley, KJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, VBK 910,55 Fruit St, Boston, MA 02114 USA. EM kstaley@partners.org NR 38 TC 26 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2007 VL 97 IS 5 BP 3812 EP 3818 DI 10.1152/jn.01310.2006 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188QD UT WOS:000247933500060 PM 17344368 ER PT J AU Ulrich, BT Buerhaus, PI Donean, K Norman, L Dittus, R AF Ulrich, Beth T. Buerhaus, Peter I. Donean, Karen Norman, Linda Dittus, Robert TI Magnet status and registered nurse views of the work environment and nursing as a career SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID RECOGNITION PROGRAM; SATISFACTION; HOSPITALS; MORTALITY; BURNOUT; RNS AB Objectives: To compare how registered nurses view the work environment and the nursing shortage based on the Magnet status of their organizations. Background: The upsurge in organizations pursuing and obtaining Magnet recognition provides increased opportunities to investigate whether and how registered nurses who are employed in Magnet organizations and organizations pursuing Magnet status perceive differences in the nursing shortage, hospitals' responses to the shortage, characteristics of the work environment, and professional relationships. Methods: A nationally representative sample of registered nurses licensed to practice in the United States was surveyed. The views of registered nurses who worked in Magnet organizations, organizations in the process of applying for Magnet status, and non-Magnet organizations were analyzed as independent groups. Results: Significant differences were found. Although there is a clear Magnet difference, there are also identifiable differences that occur during the pursuit of Magnet recognition. Conclusion: Many organizations in the process of applying for Magnet status rated higher than Magnet organizations, indicating that there is much to do to maintain the comparative advantages for Magnet hospitals. C1 Gannett Healthcare Grp, Dallas, TX 75234 USA. Vanderbilt Univ, Sch Nursing, Inst Med & Publ Hlth, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA USA. RP Ulrich, BT (reprint author), Gannett Healthcare Grp, 2655 Villa Creek Dr,Suite 250, Dallas, TX 75234 USA. EM BUlrich@GannettHG.com NR 17 TC 41 Z9 41 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2007 VL 37 IS 5 BP 212 EP 220 DI 10.1097/01.NNA.0000269745.24889.c6 PG 9 WC Nursing SC Nursing GA 176XK UT WOS:000247118000002 PM 17479039 ER PT J AU Fonteyn, M AF Fonteyn, Marsha TI Concept mapping: An easy teaching strategy that contributes to understanding and may improve critical thinking SO JOURNAL OF NURSING EDUCATION LA English DT Editorial Material C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Fonteyn, M (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. NR 4 TC 3 Z9 3 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD MAY PY 2007 VL 46 IS 5 BP 199 EP 200 PG 2 WC Nursing SC Nursing GA 164JY UT WOS:000246231200001 ER PT J AU Wengreen, HJ Munger, RG Corcoran, CD Zandi, P Hayden, KM Fotuhi, M Skoog, I Norton, MC Tschanz, J Breitner, JCS Welsh-Bohmer, KA AF Wengreen, H. J. Munger, R. G. Corcoran, C. D. Zandi, P. Hayden, K. M. Fotuhi, M. Skoog, I. Norton, M. C. Tschanz, J. Breitner, J. C. S. Welsh-Bohmer, K. A. TI Antioxidant intake and cognitive function of elderly men and women: The cache county study SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE antioxidants; cognition; elderly; dementia-prevention ID FOOD FREQUENCY QUESTIONNAIRE; SYSTEMIC OXIDATIVE STRESS; ALZHEIMERS-DISEASE; DIETARY-INTAKE; OLDER PERSONS; VITAMIN-E; DEMENTIA; POPULATION; DECLINE; RISK AB Objective: We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and, Aging in Utah. Participants and Design: In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. Results: Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. Conclusion: High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly. C1 Utah State Univ, Dept Nutr & Food Sci, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Res, Logan, UT 84322 USA. Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch publ Hlth, Baltimore, MD 21215 USA. Duke Univ, Ctr Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Sinai Hosp, Div Neurol, Baltimore, MD 21215 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21215 USA. Gothenburg Univ, Sahlgrenska Hosp, Sect Psuchiat, Inst Clin Neurosci, S-41124 Gothenburg, Sweden. Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Ctr Epidemiol Res, Logan, UT 84322 USA. Dept Psychol, Logan, UT 84322 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. RP Wengreen, HJ (reprint author), Utah State Univ, Dept Nutr & Food Sci, Logan, UT 84322 USA. RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012; OI Hayden, Kathleen/0000-0002-7745-3513; Fotuhi, Majid/0000-0002-0980-1176 FU NIA NIH HHS [AG-11380] NR 42 TC 62 Z9 62 U1 2 U2 8 PU SERDI EDITION PI PARIS PA 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD MAY-JUN PY 2007 VL 11 IS 3 BP 230 EP 237 PG 8 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 175ZR UT WOS:000247053000004 PM 17508099 ER PT J AU Katiyar, S Elmets, CA Katiyar, SK AF Katiyar, Suchitra Elmets, Craig A. Katiyar, Santosh K. TI Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE green tea polyphenols; photocarcinogenesis; DNA repair; cyclobutane pyrimidine dimer; immunosuppression; contact hypersensitivity; angiogenesis; IL-10; IL-12 ID ULTRAVIOLET-B RADIATION; ANTIGEN-PRESENTING CELL; CONTACT HYPERSENSITIVITY; INDUCED IMMUNOSUPPRESSION; HAIRLESS MICE; T-CELLS; PREVENTS PHOTOCARCINOGENESIS; CYTOKINE PRODUCTION; IMMUNE SUPPRESSION; PYRIMIDINE DIMERS AB Human skin is constantly exposed to numerous noxious physical, chemical and environmental agents. Some of these agents directly or indirectly adversely affect the skin. Cutaneous overexposure to environmental solar ultraviolet (UV) radiation (290-400 nm) has a variety of adverse effects on human health, including the development of melanoma and nonmelanoma skin cancers. Therefore, there is a need to develop measures or strategies, and nutritional components are increasingly being explored for this purpose. The polyphenols present in green tea (Camellia sinensis) have been shown to have numerous health benefits, including protection from UV carcinogenesis. (-)-Epigallocatechin-3-gallate (EGCG) is the major and most photoprotective polyphenolic component of green tea. In this review article, we have discussed the most recent investigations and mechanistic studies that define and support the photoprotective efficacy of green tea polyphenols (GTPs) against UV carcinogenesis. The oral administration of GTPs in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in mice, and this prevention is mediated through: (a) the induction of immunoregulatory cytokine interleukin (IL) 12; (b) IL-12-dependent DNA repair following nucleotide excision repair mechanism; (c) the inhibition of UVinduced immunosuppression through IL-12-dependent DNA repair; (d) the inhibition of angiogenic factors; and (e) the stimulation of cytotoxic T cells in a tumor microenvironment. New mechanistic information strongly supports and explains the chemopreventive activity of GTPs against photocarcinogenesis. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCI NIH HHS [CA104428, CA105368, CA089738]; NIAMS NIH HHS [AR050948-01]; NIEHS NIH HHS [ES11421] NR 68 TC 104 Z9 110 U1 0 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAY PY 2007 VL 18 IS 5 BP 287 EP 296 DI 10.1016/j.jnutbio.2006.08.004 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 164LY UT WOS:000246236500001 PM 17049833 ER PT J AU De Lima, L Krakauer, EL Lorenz, K Praill, D MacDonald, N Doyle, D AF De Lima, Liliana Krakauer, Eric L. Lorenz, Karl Praill, David MacDonald, Neil Doyle, Derek TI Ensuring palliative medicine availability: The development of the IAHPC list of Essential Medicines for Palliative Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE essential medicines; palliative care; efficacy; safety; cost-effectiveness AB In response to a request from the World Health Organization (WHO), the International Association for Hospice and Palliative Care (IAHPC) developed a List of Essential Medicines for Palliative Care based on the consensus of palliative care workers from around the world. IAHPC designed a Process of five steps, which included developing a set of ethical guidelines; identifying the most common symptoms in palliative care; identifying a list of medications to treat those symptoms; carrying out a survey using a modified Delphi process with participants from developed and developing countries; and convening a meeting of representatives from regional, international, and scientific organizations to develop the final list. Twenty-one symptoms were identified as the most common in palliative care, and an initial list of 120 medications resulted from the initial survey. Seventy-one participants from developing and developed countries responded to the Delphi survey and agreed on the effectiveness and safety of 48 medicationsfor 18 of the 21 symptoms. The final step included discussions among representatives from 26 organizations, which led to the finalization of the list. The IAHPC List of Essential Medicines for Palliative Care includes 33 medications, of which 14 are already included in the WHO Model List. The participants agreed that there is too little evidence to recommend medications for five of the symptoms and suggested that further research be carried out to solve this need. The IAHPC and all the organizations involved in this process welcome suggestions on ways to continue to improve the List of Essential Medicines for Palliative care and to improve access to medications for patients in need. C1 Int Assoc Hospice & Palliat Care, Houston, TX USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Vet Adm Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. Help Hospices, London, England. Worldwide Care Alliance, London, England. McGill Univ, Dept Oncol, McGill Canc Nutr Rehabil Program, Montreal, PQ, Canada. Natl Council Palliat Care England Wales & N Irela, London, England. Scottish Partnership Palliat Care, Edinburgh, Midlothian, Scotland. RP De Lima, L (reprint author), 5535 Mem Dr,Suite F,PMB 509, Houston, TX 77007 USA. EM ldelima@iahpc.com OI De Lima, Liliana/0000-0002-0435-1620 NR 3 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2007 VL 33 IS 5 BP 521 EP 526 DI 10.1016/j.jpainsymman.2007.02.006 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 171OO UT WOS:000246745500008 PM 17482041 ER PT J AU Kang, W Kudsk, KA AF Kang, Woodae Kudsk, Kenneth A. TI Is there evidence that the gut contributes to mucosal immunity in humans? SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Review ID ANTIBODY-FORMING-CELLS; POLYMERIC IMMUNOGLOBULIN-A; ESCHERICHIA-COLI VACCINE; UPPER RESPIRATORY-TRACT; MAJOR ABDOMINAL-TRAUMA; HUMAN PERIPHERAL-BLOOD; ILL ADULT PATIENTS; ORAL IMMUNIZATION; PARENTERAL-NUTRITION; ENTERAL NUTRITION AB Background: Our understanding of the common mucosal immune system derives from animal studies. Antigen-sensitized lymphocytes in the gut-associated lymphoid tissue (GALT) migrate via the blood to mucosal tissues to generate the mucosal-associated lymphoid tissue (MALT). In these sites, B cells differentiate into plasma cells and produce antigen-specific secretory IgA, the principal specific immune antiviral and antibacterial defense of moist mucosal surfaces. Responses to oral intake seem necessary to actively maintain this system in health. Experimentally, lack of enteral stimulation with parenteral feeding alters GALT and MALT size and function. These alterations disturb intestinal and extraintestinal mucosal immunity. Methods: This review is an overview of current and classical studies demonstrating the human mucosal immune system and interactions with nutrition. Results: Human evidence of the mucosal immune system exists, although most data are indirect. Gut stimulation after oral intake induces a generalized immune response in the human MALT through a mucosal-immune network. Examples include neonatal development of GALT influenced by enteral feeding, the presence of antigen-specific IgA and antigen-specific IgA-secreting plasma cells in distant mucosal effector sites such as the breast after gut luminal antigen exposure, and isolation of IgA-producing cells from circulating blood. Conclusions: It is unlikely that clinical studies will ever completely define the effect of route of feeding in all patient populations. This may be possible, however, if investigators understand, define and characterize nutrition-dependent immunologic mechanisms, allowing clinicians to examine clinical responses to nutrition in specific patient populations. This might allow generation of new approaches to protect mucosal immunity. C1 William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. Univ Wisconsin, Dept Surg, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu NR 77 TC 41 Z9 43 U1 0 U2 2 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAY-JUN PY 2007 VL 31 IS 3 BP 246 EP 258 DI 10.1177/0148607107031003246 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 195XG UT WOS:000248445100015 PM 17463152 ER PT J AU Mosquera, JM Perner, S Demichelis, F Kim, R Hofer, MD Mertz, KD Paris, PL Simko, J Collins, C Bismar, TA Chinnaiyan, AM Rubin, MA AF Mosquera, J-M Perner, S. Demichelis, F. Kim, R. Hofer, M. D. Mertz, K. D. Paris, P. L. Simko, J. Collins, C. Bismar, T. A. Chinnaiyan, A. M. Rubin, M. A. TI Morphological features of TMPRSS2-ERG gene fusion prostate cancer SO JOURNAL OF PATHOLOGY LA English DT Article DE fluorescence in situ hybridization (FISH); translocation; gene fusion; blue-tinged mucin; cribriform growth pattern; intraductal tumour spread; signet-ring cell features; collagenous micronodules; macronucleoli ID FOAMY GLAND CARCINOMA; SMALL CELL-CARCINOMA; NEEDLE-BIOPSY; CLINICAL STAGE; MICROSATELLITE INSTABILITY; LIMITED ADENOCARCINOMA; ENDOMETRIOID FEATURES; INTRADUCTAL CARCINOMA; DIAGNOSTIC FEATURES; EXPRESSION AB The TMPRSS2-ETS fusion prostate cancers comprise 50-70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2-ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this, study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2-ERG fusion statu's using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2-ERG fusion status. Five morphological features were associated with TMPRSS2-ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p-values <0.05. Only 24% (n = 30/125) of tumours without any of these features displayed the TMPRSS2-ERG fusion. By comparison, 55% (n = 38/69) of cases with one feature (RR = 3.88), 86% (n = 38/44) of cases with two features (RR = 20.06), and 93% (n = 14115) of cases with three or more features (RR = 44.33) were fusion positive (p < 0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2-ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2-ERG fusion prostate cancer, which may have both prognostic and therapeutic implications. Copyright (C) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Ulm, Dept Pathol, Ulm, Germany. ITC Irst, SRA Div, Bioinformat Grp, Trento, Italy. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. McGill Univ, Fac Med, Dept Pathol, Montreal, PQ, Canada. McGill Univ, Fac Med, Dept Oncol, Montreal, PQ, Canada. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. RP Rubin, MA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave,EBRC 442A, Boston, MA 02115 USA. EM marubin@partners.org OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU NCI NIH HHS [P50 CA090381, P50 CA89520, U01 CA113913]; NIA NIH HHS [R01AG21404] NR 63 TC 81 Z9 87 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 2007 VL 212 IS 1 BP 91 EP 101 DI 10.1002/path.2154 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 166XV UT WOS:000246415200011 PM 17385188 ER PT J AU Kletter, GB Sweetser, DA Wallace, SF Sawin, RS Rutledge, JC Geyerb, JR AF Kletter, Gad B. Sweetser, David A. Wallace, Steven F. Sawin, Robert S. Rutledge, Joe C. Geyerb, J. Russell TI Adrenocorticotropin-secreting pancreatoblastoma SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article ID ISLET-CELL-CARCINOMA; ECTOPIC ACTH SYNDROME; CUSHINGS-SYNDROME; PANCREAS; HORMONE; KETOCONAZOLE; ADRENALECTOMY; MANAGEMENT; OCTREOTIDE; TUMORS AB We present a 3 year-old child with Cushing's syndrome due to an ACTH-secreting metastatic pancreatoblastoma. This malignancy is a rare cause of Cushing's syndrome, particularly at pediatric age. We describe her course including the use of ketoconazole to alleviate hypercortisolemia. C1 Swedish Phys Div, Pediat Endocrine Div, Seattle, WA 98104 USA. MassGen Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Pediat Surg, Seattle, WA USA. Childrens Hosp, Med Labs, Seattle, WA USA. RP Kletter, GB (reprint author), Swedish Phys Div, Pediat Endocrine Div, 1101 Madison,Suite 800, Seattle, WA 98104 USA. EM gad.kletter@swedish.org NR 22 TC 7 Z9 7 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD MAY PY 2007 VL 20 IS 5 BP 639 EP 642 PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 181QT UT WOS:000247451900012 PM 17642425 ER PT J AU Leverich, GS Post, RM Keck, PE Altshuler, LL Frye, MA Kupka, RW Nolen, WA Suppes, T McElroy, SL Grunze, H Denicoff, K Moravec, MKM Luckenbaugh, D AF Leverich, Gabriele S. Post, Robert M. Keck, Paul E., Jr. Altshuler, Lori L. Frye, Mark A. Kupka, Ralph W. Nolen, Willem A. Suppes, Trisha McElroy, Susan L. Grunze, Heinz Denicoff, Kirk Moravec, Maria K. M. Luckenbaugh, David TI The poor prognosis of childhood-onset bipolar disorder SO JOURNAL OF PEDIATRICS LA English DT Article ID SUBSTANCE USE DISORDERS; MENTAL-DISORDERS; CLINICAL-COURSE; I-DISORDER; NETWORK I; CHILDREN; ADOLESCENTS; ILLNESS; GUIDELINES; MANIA AB Objective We examined age of onset of bipolar disorder as a potential course-of-iflness modifier with the hypothesis that early onset will engender more severe illness. Study design A total of 480 carefully diagnosed adult outpatients with bipolar disorder (mean age, 42.5 +/- 11.6 years) were retrospectively rated for age of illness onset, time to first pharmacotherapy, and course of illness. Clinicians prospectively rated daily mood fluctuations over I year. Results Of the 480 patients, 14% experienced onset in childhood (12 years or younger); 36% in adolescence (13 to 18 years); 32% in early adulthood (19 to 29 years); and 19% in late adulthood (after 30 years). Childhood-onset bipolar illness was associated with long delays to first treatment, averaging more than 16 years. The patients with childhood or adolescent onset reported more episodes, more comorbidities, and rapid cycling retrospectively; prospectively, they demonstrated more severe mania, depression, and fewer days wen. Conclusions This study demonstrates that childhood onset of bipolar disorder is common and is associated with long delays to first treatment. Physicians and clinicians should be alert to a possible bipolar diagnosis in children in hopes of shortening the time to initiating treatment and perhaps ameliorating the otherwise adverse course of illness. C1 NIMH, DHHS, NIH, Biol Psychiat Branch,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Cincinnati, Psychopharmacol Res Program, Dept Psychiat, Coll Med, Cincinnati, OH 45221 USA. Cincinnati VA Med Ctr, Ment Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehv Sci, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. Altrecht Inst Ment Hlth Care, Utrecht, Netherlands. Univ Groningen Hosp, Dept Psychiat, Groningen, Netherlands. Univ Texas, SW Med Ctr, Dallas, TX USA. LMU, Psychiat Klin, Munich, Germany. RP Leverich, GS (reprint author), NIMH, DHHS, NIH, Biol Psychiat Branch,Dept Hlth & Human Serv, Bldg 10,Room 3S239,10 Ctr Dr,MSC-1272, Bethesda, MD 20892 USA. EM levericg@mail.nih.gov RI Nolen, Willem/E-9006-2014; OI Grunze, Heinz/0000-0003-4712-8979 NR 45 TC 120 Z9 121 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2007 VL 150 IS 5 BP 485 EP 490 DI 10.1016/j.jpeds.2006.10.070 PG 6 WC Pediatrics SC Pediatrics GA 164PH UT WOS:000246245600012 PM 17452221 ER PT J AU Furst, D Khanna, D Matucci-Cerinic, M Clements, P Steen, V Pope, J Merkel, P Foeldvari, I Seibold, J Pittrow, D Polisson, R Strand, V AF Furst, Daniel Khanna, Dinesh Matucci-Cerinic, Marco Clements, Philip Steen, Virginia Pope, Janet Merkel, Peter Foeldvari, Ivan Seibold, James Pittrow, David Polisson, Richard Strand, Vibeke TI Systemic sclerosis - Continuing progress in developing clinical measures of response SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 38th Laurentian Conference of Rheumatology CY MAY 12-14, 2007 CL Mt Tremblant, CANADA DE omeract; systemic sclerosis; combined response; renal; lung; cardiovascular ID RESOLUTION COMPUTED-TOMOGRAPHY; IDIOPATHIC PULMONARY-FIBROSIS; INTERSTITIAL LUNG-DISEASE; HEALTH-ASSESSMENT QUESTIONNAIRE; QUALITY-OF-LIFE; CONTROLLED-TRIAL; CT FINDINGS; WEGENERS-GRANULOMATOSIS; ANKYLOSING-SPONDYLITIS; BRONCHOALVEOLAR LAVAGE AB Few randomized controlled trials (RCT) have shown a demonstrable treatment effect in systemic sclerosis (SSc), making it difficult to evaluate outcome measures in this disease indication. Results from recent RCT, including those evaluating cyclophosphamide for SSc interstitial lung disease and endothelin receptor antagonists for pulmonary hypertension, have allowed analysis of certain organ-specific endpoints using the OMERACT filter. An earlier metaanalysis established that skin score, measures of Raynaud's, pulmonary function tests, blood pressure, pain, Health Assessment Questionnaire, and Medical Outcomes Survey Short-Form 36 are validated outcome measures in SSc. At OMERACT 8, data regarding validation of high-resolution computed tomography of the lungs, 6-minute walk test, and patient reported outcomes in SSc were presented. A Delphi exercise to develop consensus regarding a combined set of noninvasive measures for pulmonary arterial hypertension (PAH) is under way. Given the protean nature of this illness and its multiorgan system involvement, a composite responder index may be preferable. Another Delphi exercise is designed to develop consensus regarding a combined SSc response index to be validated in future RCT. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90025 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Univ Florence, I-50121 Florence, Italy. Georgetown Univ, Washington, DC 20057 USA. Univ Western Ontario, London, ON, Canada. Boston Univ, Sch Med, Boston, MA 02118 USA. Klinikum Eiber, Hamburg, Germany. Univ Michigan, Ann Arbor, MI 48109 USA. Tech Univ Dresden, D-8027 Dresden, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Furst, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 1000 Veteran Ave,Room 32-59, Los Angeles, CA 90025 USA. EM defurst@mednet.ucla.edu RI Pope, Janet/G-3342-2011 FU NIAMS NIH HHS [K24 AR2224-01A1]; NICHD NIH HHS [HD051953] NR 48 TC 52 Z9 52 U1 1 U2 8 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2007 VL 34 IS 5 BP 1194 EP 1200 PG 7 WC Rheumatology SC Rheumatology GA 164JT UT WOS:000246230700046 PM 17477486 ER PT J AU Doyle, SR Donovan, DM Kivlahan, DR AF Doyle, Suzanne R. Donovan, Dennis M. Kivlahan, Daniel R. TI The factor structure of the alcohol use disorders 14 identification test (AUDIT) SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID FIT INDEXES; DRINKING; NONNORMALITY; SENSITIVITY; EMERGENCY; VARIABLES; GOODNESS; PROJECT; SAMPLE; MODELS AB Objective: Past research assessing the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) with various exploratory and confirmatory factor analytic techniques has identified one-, two-, and three-factor solutions. Because different factor analytic procedures may result in dissimilar findings, we examined the factor structure of the AUDIT using the same factor analytic technique on two new large clinical samples and on archival data from six samples studied in previous reports. Method: Responses to the AUDIT were obtained from participants who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for alcohol dependence in two large randomized clinical trials: the COMBINE (Combining Medications and Behavioral Interventions) Study (N= 1,337; 69% men) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity; N= 1,711; 76% men). Supplementary analyses involved six correlation matrices of AUDIT data obtained from five previously published articles. Confirmatory factor analyses based on one-, two-, and three-factor models were conducted on the eight correlation matrices to assess the factor structure of the AUDIT. Results: Across samples, analyses supported a correlated, two-factor solution representing alcohol consumption and alcohol-related consequences. The three-factor solution fit the data equally well, but two factors (alcohol dependence and harmful alcohol use) were highly correlated. The one-factor solution did not provide a good fit to the data. Conclusions: These findings support a two-factor solution for the AUDIT (alcohol consumption and alcohol-related consequences). The results contradict the original three-factor design of the AUDIT and the prevalent use of the AUDIT as a one-factor screening instrument with a single cutoff score. C1 Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98105 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Exellence Subst Abuse Treatment & Educ, Seattle, WA USA. RP Doyle, SR (reprint author), Univ Washington, Inst Alcohol & Drug Abuse, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA. EM srdoyle@u.washington.edu FU NIAAA NIH HHS [U10 AA11715, U10 AA11768, U10 AA11773, U10 AA11777, U10 AA11799, U10 AA11721, U10 AA01179, U10 AA11716, U10 AA11727, U10 AA11756, U10 AA11776, U10 AA11783, U10 AA11787] NR 31 TC 27 Z9 29 U1 0 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2007 VL 68 IS 3 BP 474 EP 479 PG 6 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 199RM UT WOS:000248712900019 PM 17446988 ER PT J AU Malchau, SS Hayden, J Hornicek, F Mankin, HJ AF Malchau, Sara Sofia Hayden, James Hornicek, Francis Mankin, Henry J. TI Clear cell sarcoma of soft tissues SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE clear cell sarcoma; treatment; outcome ID MALIGNANT-MELANOMA; PARTS; SURVIVAL; APONEUROSES; EXPERIENCE; TENDONS AB Clear cell sarcoma (CCS) is a rare but highly malignant tumor of soft tissues often appearing as a small tender mass in the deep tissues of the distal extremities. We have studied 17 patients with such lesions treated since 1986 and have a high incidence of local recurrence and metastasis with a survival rate of only 47% despite surgery and for many of the patients, adjuvant therapy. The purpose of this article is to warn the readers of the dangers related to treating this seemingly benign lesion and urge them to perform wide surgery and utilize adjuvant therapy. J. Surg. Oncol. 2007;95:519-522. (C) 2006 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. EM hmankin@partners.org NR 24 TC 21 Z9 23 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAY 1 PY 2007 VL 95 IS 6 BP 519 EP 522 DI 10.1002/jso.20730 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA 163NX UT WOS:000246167800014 PM 17192915 ER PT J AU Stahl, JE Goldman, JM Rattner, DW Gazelle, GS AF Stahl, James E. Goldman, Julian M. Rattner, David W. Gazelle, G. Scott TI Adapting to a new system of surgical technologies and perioperative processes among clinicians SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE operating rooms; outcomes research; surgery; learning; adaptation; clinical trial ID OPERATING-ROOM; COMPUTER-SIMULATION; COST-EFFECTIVENESS; BLOCK TIME; CARE AB Purpose. To understand learning and adaptation to a new system of surgical technologies, and perioperative processes. Methods. Patient wait time, flow time, and surgery procedure time were recorded in the experimental ("Operating room of the future" or ORF) and control ORs over the first year of the ORF's operation. Regression methods were used to examine factors hypothesized to influence performance. Results. Flow time, wait time, and surgery procedure time for each case decreased significantly in the ORE The ORF performance demonstrated an initial overshoot followed by oscillation with 30-40 d period around the group mean. Similar behavior was observed for surgeons if they had >= 2-week hiatus from operating and had an average caseload more than 2.1 cases/week. Regression models using hypothesized learning factors predicted flow time (R-2 = 0.33) and wait time (R-2 = 0.36); adding procedure type to these models raised R-2 to 0.7 and 0.57, respectively. Conclusions. Objective observation of system performance in which a new technology is introduced can provide insights into adaptation and may have significant implications for OR scheduling, training, and cost-effectiveness evaluations. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merimac St,10th Floor, Boston, MA 02114 USA. EM James@mgh-ita.org FU NCRR NIH HHS [1 R44 RR18076-01] NR 14 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2007 VL 139 IS 1 BP 61 EP 67 DI 10.1016/j.jss.2006.08.030 PG 7 WC Surgery SC Surgery GA 158YA UT WOS:000245830300009 PM 17275033 ER PT J AU Higashi, Y Suzuki, S Sakaguchi, T Nakamura, T Baba, S Reinecker, HC Nakamura, S Konno, H AF Higashi, Yukihiro Suzuki, Shohachi Sakaguchi, Takanori Nakamura, Toshio Baba, Satoshi Reinecker, Hans-Christian Nakamura, Satoshi Konno, Hiroyuki TI Loss of claudin-1 expression correlates with malignancy of hepatocellular carcinoma SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE hepatocellular carcinoma; tight junction; claudin; adherens junction; E-cadherin; hepatectomy ID IMMUNOREACTIVE E-CADHERIN; CELL-ADHESION MOLECULES; TIGHT-JUNCTION STRANDS; TGF-BETA; COLORECTAL-CANCER; DOWN-REGULATION; UP-REGULATION; METASTASIS; PROTEINS; OCCLUDIN AB Background. The prognosis for the hepatocellular carcinoma (HCC) patient is affected by invasion and metastases. The attenuated expression of adherens junction protein epithelial-cadherin (E-cad) correlates with a more malignant potential in HCC. However, the potential of the claudin (CL) family of tight junctional proteins for HCC prognosis has remained unrecognized. Materials and methods. We immunohistochemically examined the expression of CL-1 and E-cad in resected specimens from 55 HCC cases. The percentage of CL-1-or E-cad-positive cells was counted in HCC cells and the surrounding hepatocytes and scored as 0 (0%), 1 (1-33%), 2 (34-66%), and 3 (67-100%). The expression of CL-1 or E-cad was considered "preserved" if the score in HCC was equal to or more than that in the surrounding hepatocytes, and "attenuated" if not so. Results. In nontumorous tissue, CL-1 and E-cad were observed at the lateral surface of hepatocytes and biliary epithelial cells. In well-differentiated HCCs, the expression of CL-1 and E-cad was preserved in 12 of 14 cases. In poorly differentiated HCCs, E-cad expression was preserved in 9 of 18 cases, while CL-1 expression was preserved in only 4 cases (P < 0.01 versus well-differentiated HCCs). HCCs with portal invasion showed significantly attenuated CL-1 expression than those without portal invasion (P < 0.05). The survival rate after hepatectomy for HCC with attenuated CL-1 expression was significantly lower than that for HCC with preserved CL-1 expression. Conclusions. Attenuated expression of CL-1 closely correlates with the dedifferentiation and portal invasion of HCC. Down-regulated CL-1 expression may serve as a potential marker for a poor prognosis in HCC. (c) 2007 Elsevier Inc. All rights reserved. C1 Hamamatsu Univ Sch Med, Dept Surg 2, Hamamatsu, Shizuoka 4313192, Japan. Hamamatsu Univ Sch Med, Fac Pathol, Hamamatsu, Shizuoka 4313192, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sakaguchi, T (reprint author), Hamamatsu Univ Sch Med, Dept Surg 2, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. EM saka1119@hama-med.ac.jp NR 37 TC 47 Z9 52 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2007 VL 139 IS 1 BP 68 EP 76 DI 10.1016/j.jss.2006.08.038 PG 9 WC Surgery SC Surgery GA 158YA UT WOS:000245830300010 PM 17270214 ER PT J AU Entabi, F Albadawi, H Stone, DH Sroufe, R Conrad, MF Watkins, MT AF Entabi, Fateh Albadawi, Hassan Stone, David H. Sroufe, Rameses Conrad, Mark F. Watkins, Michael T. TI Hind limb ischemia-reperfusion in the leptin receptor deficient (db/db) mouse SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 2005 CL Nashville, TN SP Soc Univ Surg DE diabetes; reperfusion injury; cytokines; inflammation ID ENDOTHELIAL GROWTH-FACTOR; SKELETAL-MUSCLE; DIABETES-MELLITUS; INJURY; HEARTS; MICE; COMPLICATIONS; TISSUE; MODEL; HYPERCHOLESTEROLEMIA AB Background. Diabetic patients have high incidence of peripheral vascular disease and limb loss after acute extremity injury. Experiments were designed to test the hypothesis that acute tissue injury in leptin receptor deficient (Db) diabetic (type2) mice would be more severe than in non-diabetic mice. Methods. Db and wild type (Wt) mice were subjected to 3 h of ischemia followed by either 4 or 24: h of reperfusion. (314 IR, 3/24 IR). Muscle analyzed for tissue viability (mitochondrial activity), cytokines (KC-murine equivalent of human IL-8, TNF alpha, IL-6), growth factor, and histological evaluation (neutrophils/uninjured muscle fibers). Tissue perfusion was detected during basal and reperfusion conditions using laser Doppler imaging. Results. Mitochondrial activity and histological evaluation for tissue injury did not differ in the Db versus Wt mice at the time intervals studied. When compared with their respective sham animals, both Db and Wt mice had similarly increased levels of KC, IL-6, and VEGF after 3/24 IR. TNF alpha levels increased in Db but not Wt mice after IR. Although absolute increases in TNFa and KC were higher in Db mice, VEGF levels were actually lower in the Db mice. Conclusion. The patterns of tissue perfusion, cytokines, and growth factors were different in Db versus Wt mice. At the acute time intervals studied, these differences did not correlate with an expected greater degree of acute muscle injury in Db mice. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Div Vasc & Endovasc Surg, Dept Surg, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Harvard Univ, Div Vasc & Endovasc Surg, Dept Surg, Massachusetts Gen Hosp,Med Sch, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 42 TC 8 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2007 VL 139 IS 1 BP 97 EP 105 DI 10.1016/j.jss.2006.08.008 PG 9 WC Surgery SC Surgery GA 158YA UT WOS:000245830300014 PM 17292407 ER PT J AU Jellinek, MS AF Jellinek, Michael S. TI Primary supervision SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Newton Wellesley Hosp, Newton, MA 02462 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jellinek, MS (reprint author), Newton Wellesley Hosp, 2014 Washington St, Newton, MA 02462 USA. EM mjellinek@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2007 VL 46 IS 5 BP 553 EP 557 DI 10.1097/CHI.0b013e3180335b39 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 161HQ UT WOS:000246005800002 PM 17450045 ER PT J AU Tsai, KY Tsao, H AF Tsai, Kenneth Y. Tsao, Hensin TI Primer on the human genome SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID IMAGING MASS-SPECTROMETRY; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; THIOPURINE METHYLTRANSFERASE ACTIVITY; MELANOMA CELL-LINES; MALIGNANT-MELANOMA; POLYMORPHIC ACETYLATION; RHEUMATOID-ARTHRITIS; BREAST-CANCER; T-CELL; MOLECULAR CLASSIFICATION AB The study of the expression patterns of many genes, or even the entire genome, is now routinely possible. Such powerful tools have enabled hypothesis-generating research at a scale never before possible. Moreover, spatially or temporally linked gene and protein expression, implying co-regulation and functional relatedness, has led to the identification of particular clusters of genes important for fundamental biologic processes, such as development and cancer. Not only is this expected to yield further mechanistic insights into disease processes, but perhaps most exciting, it will likely establish the foundation of predictive medicine, in which understanding of individual genomic signatures leads to the use of appropriately targeted therapy. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, 622 Bartlett Hall,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 115 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2007 VL 56 IS 5 BP 719 EP 735 DI 10.1016/j.jaad.2006.10.985 PG 17 WC Dermatology SC Dermatology GA 161UJ UT WOS:000246041400001 PM 17437886 ER PT J AU Skolnick, AH Alexander, KP Chen, AY Roe, MT Pollack, CV Ohman, EM Rumsfeld, JS Gibler, WB Peterson, ED Cohen, DJ AF Skolnick, Adam H. Alexander, Karen P. Chen, Anita Y. Roe, Matthew T. Pollack, Charles V., Jr. Ohman, E. Magnus Rumsfeld, John S. Gibler, W. Brian Peterson, Eric D. Cohen, David J. TI Characteristics, management, and outcomes of 5,557 patients age >= 90 years with acute coronary syndromes - Results from the CRUSADE initiative SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID INFARCTION; PHYSICIAN AB Objectives The goal of this work was to explore the treatment and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) age -90 years. Background The elderly are often excluded from clinical trials of NSTE-ACS and are underrepresented in clinical registries. Methods We used data from the CRUSADE registry to study 5,557 patients with NSTE-ACS age >= 90 years and compared their baseline characteristics, treatment patterns, and in-hospital outcomes with a cohort age 75 to 89 years (n = 46,270). Results Although both groups had much in common, compared with the younger elderly, the older elderly were less likely to be diabetic, smokers, or obese. Among patients without contraindications, the older elderly were less likely to receive glycoprotein IIb/IIIa inhibitors and statins during the first 24 h and were less likely to undergo cardiac catheterization within 48 h. The older elderly were more likely to die (12.0% vs. 7.8%) and experienced more frequent adverse events (26.8% vs. 21.3%) during the hospitalization -differences that persisted after adjustment for baseline patient and hospital characteristics. Increasing adherence to guideline-recommended therapies was associated with both increased bleeding and a graded reduction in risk-adjusted in-hospital mortality across both age groups. Conclusions In this large population of nonagenarians and centenarians with NSTE-ACS, increasing adherence to guideline-recommended therapies was associated with decreased mortality. These findings reinforce the importance of optimizing care patterns for even the oldest patients with NSTE-ACS, while examining novel approaches to reduce the risk of bleeding in this rapidly expanding patient population. C1 St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Univ Penn Hlth Syst, Penn Hosp, Philadelphia, PA USA. Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Cohen, DJ (reprint author), St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM dcohen@saint-lukes.org NR 11 TC 73 Z9 79 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 1 PY 2007 VL 49 IS 17 BP 1790 EP 1797 DI 10.1016/j.jacc.2007.01.066 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 163CH UT WOS:000246135800007 PM 17466230 ER PT J AU Teal, CR Baham, DL Gor, BJ Jones, LA AF Teal, Cayla R. Baham, Danielle L. Gor, Beverly J. Jones, Lovell A. TI Is the MEDFICTS rapid dietary fat screener valid for premenopausal African-American women? SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Dietetic-Association CY OCT, 2004 CL Anaheim, CA SP Amer Dietet Assoc ID FOOD-FREQUENCY QUESTIONNAIRE; BREAST-CANCER RISK; INTERVENTION TRIAL; RANDOMIZED-TRIAL; FIBER; RELIABILITY; HORMONE; METAANALYSIS; VEGETABLES; ADHERENCE AB Objective To assess the predictive validity of the meats, eggs, dairy, fried foods, fat in baked goods, convenience foods, fats added at the table, and snacks (MEDFICTS) questionnaire, a rapid dietary fat screening instrument, when used with African-American women. Design A case series design was utilized to assess the validity of MEDFICTS compared to the Arizona Food Frequency Questionnaire. Subjects/setting Data for this study were collected from 184 healthy premenopausal African-American women who completed both the MEDFICTS and the Arizona Food Frequency Questionnaire during screening for eligibility in a nutrition intervention study. Statistical analyses performed Analyses of sensitivity, specificity, predictive values, and receiver operating characteristic analysis were used to examine the predictive validity of MEDFICTS. Covariates of correctly and incorrectly identified groups were examined with contingency table analysis and t tests. Results MEDFICTS was a statistically significant predictor of dietary fat consumption, but underestimated fat consumption of >= 30%. MEDFICTS' sensitivity to detect those consuming >= 30% fat was 57.3%, whereas its specificity (detection of those consuming < 30% dietary fat) was 66.0%. Positive and negative predictive values were 80.6% and 38.5%, respectively. A reduction in the threshold score resulted in increased sensitivity but decreased specificity. Women identified by MEDFICTS as consuming < 30% dietary fat but who were actually consuming 30% or more reported greater consumption of fats from foods classified as mixed foods. Conclusions Study findings suggest MEDFICTS underestimates fat consumption of >= 30%. The inclusion of a category to assess mixed foods could improve the sensitivity and specificity of MEDFICTS for predicting dietary fat consumption. These results demonstrate the need for population-based validation of dietary screening instruments. C1 Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Vet Affairs Hlth Serv Res & Dev Serv Ctr Excellen, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Ctr Res Minor Hlth, Dept Hlth Dispar Res,Div Canc Prevent & Populat S, Houston, TX 77030 USA. RP Teal, CR (reprint author), Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Sect Hlth Serv Res, Dept Med, 2002 Holcombe 152, Houston, TX 77030 USA. EM cteal@bcm.tmc.edu FU NCCDPHP CDC HHS [K01# DP-000090]; NIMHD NIH HHS [P60 MD000503-02]; PHS HHS [U48 CCU619515] NR 35 TC 8 Z9 9 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 2007 VL 107 IS 5 BP 773 EP 781 DI 10.1016/j.jada.2007.02.005 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 165UD UT WOS:000246330400018 PM 17467372 ER PT J AU Shimazaki, M Martin, JL AF Shimazaki, Mark Martin, Jennifer L. TI Do herbal agents have a place in the treatment of sleep problems in long-term care? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE alternative therapies; elderly; insomnia; sleep ID VALERIAN EXTRACT; DOUBLE-BLIND; PRIMARY INSOMNIA; HIP-FRACTURES; NURSING-HOME; MELATONIN; EFFICACY; FALLS; COMPLEMENTARY; TOLERABILITY AB Sleep disruption is common in the long-term care setting. This article discusses the available literature on 2 herbal approaches to sleep problems in long-term care. The largest body of evidence exists for the use of the dietary/herbal supplements valerian and melatonin. While these agents appear to have a modest positive effect on sleep quality among older adults, most studies were small in size and included only subjective assessments of sleep quality. In addition, it is unclear whether these agents pose risks to long-term care residents because of potential drug interactions. Additional research is needed before making conclusive recommendations about the use of these interventions for sleep in the long-term care setting. C1 Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. RP Martin, JL (reprint author), VA Sepulveda GRECC, 11E,16111 Plummer St, North Hills, CA 91343 USA. EM Jennifer.martin@va.gov FU NCRR NIH HHS [P41 RR001209-200140, P41 RR001209]; NIA NIH HHS [P60 AG010415] NR 37 TC 7 Z9 7 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAY PY 2007 VL 8 IS 4 BP 248 EP 252 DI 10.1016/j.jamda.2006.11.001 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 170EF UT WOS:000246644300009 PM 17498609 ER PT J AU Al-Samarrai, NR Uman, GC Al-Samarrai, T Alessi, CA AF Al-Samarrai, Nahla R. Uman, Gwen C. Al-Samarrai, Teeb Alessi, Cathy A. TI Introducing a new incontinence management system for nursing home residents SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID URINARY-INCONTINENCE; INTERVENTION AB Objectives: To describe current practices of incontinence care in nursing homes (NHs) provided by certified nurse assistants (CNAs), and to evaluate the feasibility and acceptability of an integrated incontinence care product, the One Step Incontinence System (OSIS) in the NH setting. While the ultimate purpose of OSIS is to encourage more consistent skin cleansing and thus reduce perineal dermatitis and risk of pressure ulcers, this study reports an initial feasibility test of OSIS. Design: Controlled trial at two NH sites, with one ward at each site assigned to intervention with OSIS and one ward at each site assigned to a control condition with a box of wipes placed at the bedside (BW). Setting: Two NHs (one community and one Veterans Administration) in the Los Angeles area. Participants: 24 incontinent NH residents and 61 CNAs Intervention: OSIS integrates an adult brief and two cleansing/protective wipes into a single item byway of a waterproof pouch that is removed at the time of incontinence care. The OSIS briefs were placed on the intervention wards in the same location(s) and adjacent to regular adult briefs. Measurements: Structured observations of incontinence care episodes were performed by trained research staff at baseline on all wards, and at follow-up with either the intervention (OSIS) or control condition (BW) in place. Observations included resident location, thoroughness and duration of incontinence care, and materials used. In addition, CNAs' opinions of their preferred incontinence care materials and their experience using OSIS were obtained by self-administered survey. Results: Use of OSIS resulted in significantly greater frequency of use of cleansing wipes (97% of episodes) compared to the baseline (77% of episodes) and BW conditions (41% of episodes). In 59% of the observed episodes in the BW condition, the box of wipes was actually missing from the bedside, or completely absent from the patient's room and had to be replaced. The two wipes that were incorporated with OSIS were used for perineal skin cleansing immediately when providing incontinence care. There was a significant reduction in the percentage use of and number of cloth towels used during incontinence care with OSIS (53% of episodes, 0.8 towels) compared to baseline (67%, 1.1 towels) and BW conditions (82%, 1.2 towels; p=.002 and p=.012, respectively). CNAs were significantly less often interrupted by the need to find supplies during OSIS condition (13%) compared to baseline (23%) and BW (36%; p=.005). There were no significant differences between conditions in the thoroughness of observed cleansing. The average observed time for incontinence care from putting on gloves to fastening the clean adult brief (T1) and between uncovering the resident to fastening a clean adult brief M) decreased significantly within both groups (OSIS and BW) at follow-up (all p-values <.05), but there were no significant differences in T1 and T2 between groups at follow-up. CNAs were more likely to report that they felt that OSIS facilitated skin cleansing compared to the BW. Conclusion: We successfully implemented a trial of an innovative adult brief that encouraged skin cleansing during incontinence care. The system was easily and effectively incorporated into the nursing home, was used by CNAs whenever available (97% of the time), and was favored by CNAs. Patterns of incontinence care differed at follow-up with OSIS compared to BW, with fewer linens used, fewer wipes used, and less CNA interruption during care, which may result in greater privacy and comfort for residents. C1 Stat Plus Inc, Torrance, CA 90505 USA. Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Vital Res LLC, Los Angeles, CA USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Al-Samarrai, NR (reprint author), Stat Plus Inc, 5108 Newton St, Torrance, CA 90505 USA. EM nahla@statistics-plus.com FU NIA NIH HHS [R43 AG020867, 1R43-AG020867, R43 AG020867-01A2] NR 27 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAY PY 2007 VL 8 IS 4 BP 253 EP 261 DI 10.1016/j.jamda.2006.10.001 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 170EF UT WOS:000246644300010 PM 17498610 ER PT J AU Ebrahimzadeh, MH Dallouei, SRS AF Ebrahimzadeh, Mohamad H. Dallouei, Seyed R. Sharifi TI Chondromyxoid fibroma of the calcaneus SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID BONE AB Chondromyxoid fibroma is a rare, benign, aggressive bone tumor whose localization in the calcaneus is even rarer. We report a case of chondromyxoid fibroma in the calcaneus of a 10-year-old Iranian boy who was treated with extended curettage. After 3 years of follow-up, the patient had experienced no recurrence. C1 Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. Emdad Hosp Med Sch, Dept Orthoped Surg, Mashhad, Khorasan, Iran. RP Ebrahimzadeh, MH (reprint author), Massachusetts Gen Hosp, Dept Orthoped, 55 Fruit St,YAW 2100, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAY-JUN PY 2007 VL 97 IS 3 BP 223 EP 224 PG 2 WC Orthopedics SC Orthopedics GA 170QE UT WOS:000246678200008 PM 17507532 ER PT J AU Rohit, M Levine, A Hinkin, C Abramyan, S Saxton, E Valdes-Sueiras, M Singer, E AF Rohit, Mona Levine, Andrew Hinkin, Charles Abramyan, Shogik Saxton, Ernestine Valdes-Sueiras, Miguel Singer, Elyse TI Education correction using years in school or reading grade-level equivalent? Comparing the accuracy of two methods in diagnosing HIV-associated neurocognitive impairment SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE HIV; dementia; neuropsychology; WRAT-3; education; reading ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; BOSTON NAMING TEST; AFRICAN-AMERICAN; NORMATIVE DATA; PREMORBID INTELLIGENCE; INFECTION; LITERACY AB Neuropsychological tests generally require adjustments for years of education when determining the presence of neurocognitive impairment. However, evidence indicates that educational quality, as assessed with reading tests, may be a better reflection of educational attainment among African Americans. Thus, African Americans with poor educational quality may be incorrectly classified with neuroconitive impairment based on neuropsychological tests. We compared the accuracy of neuropsychological test scores standardized using reading grade-equivalent versus years of education in predicting neurocognitive impairment among a sample of Whites and African-American adults who were HIV+. Participants were examined by a neurologist and classified with or without HIV-associated neurocognitive disorders according to accepted criteria. Participants were also classified as impaired versus not impaired based on their neuropsychological test scores standardized by 1) self-reported education or 2) WRAT-3 reading grade-level. Cross tabulation tables were used to determine agreement of the two methods in detecting impairment. Among African-Americans, standardized scores derived from reading scores had greater specificity than those derived from years of education (84. 1% vs. 77.3). Among the Whites, correction based on years of education had both greater specificity and sensitivity. The results suggest that reading tests may be a useful alternative for determining NCI among African Americans. C1 Univ Calif Los Angeles, Natl Neurol AIDS Bank, Dept Neurol, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90025 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Dept Psychiat, Los Angeles, CA USA. Charles R Drew Univ Med & Sci, Dept Neurol, Los Angeles, CA 90059 USA. RP Levine, A (reprint author), Univ Calif Los Angeles, Natl Neurol AIDS Bank, Dept Neurol, 11645 Wilshire Blvd,Suite 770, Los Angeles, CA 90025 USA. EM ajlevine@mednet.ucla.edu FU NINDS NIH HHS [R24 NS038841-10, R24 NS038841, NS-38841] NR 38 TC 11 Z9 11 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2007 VL 13 IS 3 BP 462 EP 470 DI 10.1017/S1355617707070506 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 162WZ UT WOS:000246121500011 PM 17445295 ER PT J AU Daniels, NA Link, CL Barry, MJ McKinlay, JB AF Daniels, Nicholas A. Link, Carol L. Barry, Michael J. McKinlay, John B. TI Association between past urinary tract infections and current symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE urinary tract infection; inflammation; prostate cancer ID RISK-FACTORS; MEN; PREVALENCE; INDEX; EPIDEMIOLOGY; VALIDITY; UROLOGY; COHORT AB Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a major cause of illness, and its association with history of post urinary tract infections is unclear. We surveyed a racially, ethnically and socioeconomically diverse, community-based sample of adults aged 30-79 years in Boston, MA. This report gives estimates from the 2,301 men in the BACH survey: 700 black, 766 Hispanic and 835 white. Symptoms of chronic prostatitis-any perineal and/or ejaculatory pain and a pain score of M-were derived from the NIH Chronic Prostatitis Symptom Index and were used to identify men with symptoms suggesting CP/CPPS. The overall prevalence of symptoms suggestive of CP/CPPS is 6.3%. The number of urinary. tract infections, particularly >3, was associated with symptoms suggestive of CP/CPPS (P<0.01). There is a strong association between current symptoms of CP/CPPS and a history of urinary tract infections, particularly of multiple infections. The causality between chronic UTIs and,CP/CPPS needs to be clarified by further study. C1 Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94115 USA. New England Res Inst, Watertown, MA 02172 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Daniels, NA (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, 1701 Divisadero St,Suite 500,Box 1731, San Francisco, CA 94115 USA. EM ndaniels@medicine.ucsf.edu; jmckinlay@neriscience.com FU NIDDK NIH HHS [U01 DK056842, U01 DK56842] NR 41 TC 17 Z9 17 U1 1 U2 1 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAY PY 2007 VL 99 IS 5 BP 509 EP 516 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 167RJ UT WOS:000246468500004 PM 17534008 ER PT J AU Delori, FC Webb, RH Sliney, DH AF Delori, Francois C. Webb, Robert H. Sliney, David H. TI Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID SCANNING LASER OPHTHALMOSCOPE; PIGMENT EPITHELIAL-CELLS; LIGHT-SOURCES; OPTICAL RADIATION; IN-VIVO; HAZARDS; THRESHOLDS; DAMAGE; EYE; GUIDELINES AB After discussing the rationale and assumptions of the ANSI Z136.1-2000 Standard for protection of the human eye from laser exposure, we present the concise formulation of the exposure limits expressed as maximum permissible radiant exposure (in J/cm(2)) for light overfilling the pupil. We then translate the Standard to a form that is more practical for typical ophthalmic devices or in vision research situations, implementing the special qualifications of the Standard. The safety limits are then expressed as radiant power (watts) entering the pupil of the eye. Exposure by repetitive pulses is also addressed, as this is frequently employed in ophthalmic applications. Examples are given that will familiarize potential users with this format. (c) 2007 Optical Society of America. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. USA, Ctr Hlth Promot & Prevent Med, Aberdeen Proving Ground, MD 21010 USA. RP Delori, FC (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. EM francois.delori@schepens.harvard.edu FU NEI NIH HHS [R01 EY008511, R01 EY14106, R01 EY14165] NR 52 TC 168 Z9 172 U1 3 U2 30 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD MAY PY 2007 VL 24 IS 5 BP 1250 EP 1265 DI 10.1364/JOSAA.24.001250 PG 16 WC Optics SC Optics GA 160II UT WOS:000245933700003 PM 17429471 ER PT J AU Nguyen, BNH Azimzadeh, AM Zhang, T Wu, G Shuurman, HJ Sachs, DH Ayares, D Allan, JS Pierson, RN AF Nguyen, Bao-Ngoc H. Azimzadeh, Agnes M. Zhang, Tianshu Wu, Guosheng Shuurman, Henk-Jan Sachs, David H. Ayares, David Allan, James S. Pierson, Richard N., III TI Life-supporting function of genetically modified swine lungs in baboons SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 29-MAY 03, 2006 CL Philadelphia, PA SP Amer Assoc Thorac Surg ID TO-HUMAN MODEL; HYPERACUTE REJECTION; NATURAL ANTIBODIES; ENDOTHELIAL-CELLS; HUMAN PROTHROMBIN; HUMAN BLOOD; PIG; XENOTRANSPLANTATION; ACTIVATION; INJURY AB Objective: During ex vivo perfusion with human blood, homozygous galactosyl transferase knockout swine lungs exhibit prolonged survival (similar to 2 hours) relative to wild-type (> 15 minutes) and swine lungs expressing human decay accelerating factor (< 1 hour). In this study, the in vivo behavior of galactosyl transferase knockout lungs was evaluated. Methods: Three galactosyl transferase knockout swine left lungs were transplanted into baboons in a life-supporting model. One baboon lung allograft and two swine lung xenografts transgenic for human membrane cofactor protein (CD46) served as controls. Results: Whereas two membrane cofactor protein lungs exhibited high pulmonary vascular resistance (> 500 mm Hg . min/L) and failed to support life within 21 minutes, two of three galactosyl transferase knockout lungs supported life, for 90 and 215 minutes, and displayed low peripheral vascular resistance (48 +/- 12 mm Hg . min/L at 60 minutes), similar to the allogeneic control. Complement activation ( delta C3a < 250 ng/mL through 60 minutes) and C5b-9 deposition were minimal in both galactosyl transferase knockout and membrane cofactor protein lungs. Neutrophils, monocytes, and platelets were rapidly sequestered in galactosyl transferase knockout and human membrane cofactor protein lung recipients, unlike the allogeneic control (< 20%); and thrombin formation (delta plasma fraction 1+2 > 0.5 nmol/L) was seen in the galactosyl transferase knockout recipients. Platelet activation (beta-thromboglobulin rise > 200) and appearance of capillary congestion and vessel thrombosis confirmed coagulation activation associated with galactosyl transferase knockout lung failure. Conclusions: Galactosyl transferase knockout swine lungs are significantly protected in vivo from the physiologic consequences (increased pulmonary vascular resistance, capillary leak) associated with hyperacute lung rejection. As during ex vivo perfusion, dysregulated coagulation-thrombin elaboration, platelet activation, and intravascular thrombosis-mediates galactosyl transferase knockout lung xenograft injury. C1 Univ Maryland, Div Cardiac Surg, Baltimore, MD 21201 USA. Baltimore Vet Adm Med Ctr, Baltimore, MD 21201 USA. Immerge Biotherapeut Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Revivicor, Blacksburg, VA USA. RP Pierson, RN (reprint author), Univ Maryland, Div Cardiac Surg, 22 S Greene St N4W94, Baltimore, MD 21201 USA. EM rpierson@smail.umaryland.edu FU NHLBI NIH HHS [F32 HL079818, R01 HL67110]; NIAID NIH HHS [U01 AI 066335] NR 30 TC 28 Z9 29 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2007 VL 133 IS 5 BP 1354 EP 1363 DI 10.1016/j.jtcvs.2006.11.043 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 162BU UT WOS:000246062300032 PM 17467457 ER PT J AU Wittram, C Yoo, AJ AF Wittram, Conrad Yoo, Albert J. TI Transient interruption of contrast on CT pulmonary angiography - Proof of mechanism SO JOURNAL OF THORACIC IMAGING LA English DT Article DE computed tomography; pulmonary angiography; embolism; venae cavae; heart ID EMBOLISM AB Purpose: To test the hypothesis that a transient interruption of contrast is the result of an increase in flow of unopacified blood from the inferior vena cava (IVC) by comparing the relative IVC contribution to the right side of the heart in cases and age-matched and sex-matched controls. Materials and Methods: This retrospective study was approved by our internal review board. Of 234 consecutive patients who had both CT pulmonary angiography and a close follow-up diagnostic pulmonary angiogram, or in one case CT pulmonary angiography.. 7 cases were identified which contained a transient interruption of contrast. The study group included 2 men and 5 women. The age range was 37 to 77 years (mean 61.3 y +/- 13.3). The artifact consists of a segment of the pulmonary arteries which demonstrates poor blood enhancement between areas of increased attenuation both proximally and distally. Hounsfield units (HU) measurements were made in the areas of decreased attenuation. the areas of higher attenuation both proximally and distally, the superior vena cava, IVC, right atrium (RA), and right ventricle (RV). The relative IVC contribution was calculated by equating density in the RA and RV to a weighted average of the densities of the superior vena cava and IVC. Age-matched and sex-matched controls and a 2-tailed paired t test were used. Results: In the patients with the artifact, the average relative IVC contributions to the RA and RV are 80.1% and 79.5%, respectively. In the control patients, the values for the RA and RV are 52.8% (P = 0.02) and 55.5% (P = 0.02), respectively. Conclusions: Transient interruption of contrast of the pulmonary arteries represents a flow-related phenomenon associated with an increased IVC contribution to the right side of the heart. C1 Massachusetts Gen Hosp, Div Thorac Radiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Div Thorac Radiol, Dept Radiol, Founders Bldg 202,55 Fruit St, Boston, MA 02114 USA. EM cwittram@partners.org NR 13 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD MAY PY 2007 VL 22 IS 2 BP 125 EP 129 DI 10.1097/01.rti.0000213566.78785.26 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RS UT WOS:000246822300003 PM 17527114 ER PT J AU Ring, D Chin, K Taghinia, AH Jupiter, JB AF Ring, David Chin, Kingsley Taghinia, Amir H. Jupiter, Jesse B. TI Nonunion after functional brace treatment of diaphyseal humerus fractures SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID SHAFT FRACTURES AB Objective: To assess which fractures of the humeral diaphysis are prone to nonunion after functional bracing by analyzing patients that present for treatment of nonunion after brace treatment. Methods: Thirty-two patients treated operatively for a nonunion of the diaphyseal humerus after functional brace treatment were analyzed with respect to the location and the pattern of the original fracture. There were 21 women and 11 men with an average age of 53 years (range 23-84 years). Results: The fracture involved the proximal third of the diaphysis in 17 patients, the middle third in 14 patients, and the distal third in 1 patient. The pattern of the fracture was oblique or spiral in 27 patients with a butterfly fragment in 11 of those patients. Only four patients had a transverse fracture. Operative fixation ultimately achieved union in all 32 patients, but a second procedure was necessary for loosening of fixation or persistent nonunion in 3 older-aged patients. The functional results were good or excellent in all 32 patients. Conclusions: Compared with the epidemiology of acute diaphyseal humerus fractures, nonunions after functional bracing are more likely to follow spiral/oblique fractures that involve the mid- or proximal-third of the diaphysis. Operative treatment can gain union and improve arm function. C1 Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 9 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 2007 VL 62 IS 5 BP 1157 EP 1158 DI 10.1097/01.ta.0000222719.52619.2c PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 168OF UT WOS:000246533200019 PM 17495717 ER PT J AU Koo, L Hatton, MP Rubin, PAD AF Koo, Lily Hatton, Mark P. Rubin, Peter A. D. TI Traumatic blindness after a displaced lateral orbital wall fracture SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Hatton, MP (reprint author), 243 Charles St, Boston, MA 02114 USA. EM eye_plastics@meei.harvard.edu NR 6 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 2007 VL 62 IS 5 BP 1288 EP 1289 DI 10.1097/01.ta.0000235292.16125.fa PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 168OF UT WOS:000246533200046 PM 17495740 ER PT J AU Dahl, DM AF Dahl, Douglas M. TI Do tumor volume, tumor volume ratio, type of nerve sparing and surgical experience affect prostate specific antigen recurrence after laparoscopic radical prostatectomy? Matched pair analysis - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Dahl, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2007 VL 177 IS 5 BP 1775 EP 1775 DI 10.1016/j.juro.2007.01.180 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 158BC UT WOS:000245764900052 ER PT J AU Rau, MM Setty, BN Blake, MA Ouellette-Piazzo, K Hahn, PF Sahani, DV AF Rau, Matthew M. Setty, Bindu N. Blake, Michael A. Ouellette-Piazzo, Kathy Hahn, Peter F. Sahani, Dushyant V. TI Evaluation of renal transplant donors with 16-section multidetector CT angiography: Comparison of contrast media with low and high iodine concentrations SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ROW CT; LAPAROSCOPIC NEPHRECTOMY; ENHANCEMENT; RECONSTRUCTION; PRINCIPLES; RATIONALE; ANATOMY; KIDNEY; MDCT AB PURPOSE: To compare the degree of contrast enhancement, image quality, and accuracy of renal computed tomographic (CT) angiography performed with a 16-detector row CT unit and equal iodine doses of low- and high-iodine-concentration contrast medium in the evaluation of renal transplant donors. MATERIALS AND METHODS: Eighty donors scheduled to undergo renal CT angiography with 16-detector row CT were administered nonionic contrast media with two iodine concentrations. The first group (group A, n = 40) received a contrast medium with 300 mg of iodine per milliliter, and the second group (group B, n = 40) received a contrast medium with 370 mg of iodine per milliliter. An equal iodine dose of 550 mg per kilogram body weight was given to both groups. Contrast enhancement was quantified by measuring attenuation in the abdominal aorta and in both renal arteries. Subjective assessment of contrast enhancement, quality of reformatted images, and visualization of branch order of renal arteries were rated with a 5-point scale. The number of renal arteries and veins seen at CT was correlated with the results at surgery. RESULTS: The mean enhancement values in group B were significantly greater (P <.001) than those in group A. The mean HU (+/- standard deviation) in groups A and B were 298 +/- 76 and 344 +/- 75, respectively, in the aorta, 284 +/- 74 and 331 +/- 71 in the right renal artery, and 285 72 and 329 73 in the left renal artery. The mean enhancement, image quality, and branch orders visualized were rated better in group B than in group A (P <.01). The accuracies for correctly identifying renal arteries and veins, respectively, were 91% and 95% for group A and 96% and 96% for group B. CONCLUSION: Renal donor CT angiography with a contrast medium of 370 mg of iodine per milliliter provides greater enhancement and image quality compared with a contrast medium of 300 mg of iodine per milliliter. The diagnostic accuracies were similar. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org OI Setty, Bindu/0000-0002-2749-6822 NR 19 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2007 VL 18 IS 5 BP 603 EP 609 DI 10.1016/j.jvir.2007.02.016 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 168CT UT WOS:000246500700004 PM 17494841 ER PT J AU Mertyna, P Hines-Peralta, A Liu, ZJ Halpern, E Goldberg, W Goldberg, SN AF Mertyna, Pawel Hines-Peralta, Andrew Liu, Zheng-jun Halpern, Elkan Goldberg, Wallace Goldberg, S. Nahum TI Radiofrequency ablation: Variability in heat sensitivity in tumors and tissues SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; HEPATOCELLULAR-CARCINOMA; CANCER; CONDUCTIVITY; HYPERTHERMIA; COAGULATION; LESIONS AB PURPOSE: To characterize the thermal dosimetry (ie, heating profile) of radiofrequency ablation (RFA) in multiple ex vivo tissues and in vivo tumor models. MATERIALS AND METHODS: RFA was performed for 3-24 minutes in ex vivo bovine livers (n = 20), porcine kidneys (n = 20), and turkey muscles (n = 20) and in vivo canine venereal sarcomas (n = 8). RFA was performed by using 1 and 3-cm long tips internally cooled electrodes. In addition, RFA was performed in in vivo R3220 rat mammary adenocarcinomas (n = 36) and human renal cell carcinomas in nude mice (n = 6) by using 1-cm monopolar electrodes. Continuous temperature monitoring was performed at multiple depths to calculate thermal dosimetry, reported as the area under the curve (AUC). Cumulative equivalent minutes at 43 degrees C (CEM43) were used for the critical ablation margin. Data were compared with analysis of variance and regression analysis. RESULTS: For each tissue and/or tumor type, statistically significant temperature differences (up to 149, were observed at the ablation margin (P <.01). Temperature was dependent on the procedure duration. For 10-minute treatments, temperatures were significantly higher in the kidney compared with the R3230 tumor (72 degrees C +/- 2.2) (P <.01) and lower in R3230 tumor (41.6 degrees C +/- 1.4) (P <.05) but were similar for liver and muscle (51.6 degrees C +/- 1.6 and 54.1 +/- C +/- 1.8, respectively). Thus, a wide range of ablative temperatures were observed (41.0 degrees C +/- 0.7 to 76.7 degrees C +/- 1.9), with coagulation diameter correlating logarithmically with radiofrequency duration and AUC (R-2 = 0.85-0.95). The CEM43 demonstrated an extreme range of values (10(11)). CONCLUSION: The results of the study demonstrate a wide range of thermal sensitivity to RFA among commonly investigated tissues and tumor models, suggesting that further characterization of tissue-specific end points (ie, the duration and end temperature of ablation) is likely warranted. The AUC showed good correlation with ablation sizes, but the CEM43 proved unworkable given an extreme range of values for RFA. C1 Beth Israel Deaconess Med Ctr, Lab Minimally Invas Tumor Therapies, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. CUNY, Queens Coll, Dept Math, New York, NY 10021 USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Lab Minimally Invas Tumor Therapies, 1 Deaconess Rd,WCC308B, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu FU NIBIB NIH HHS [R01EB0004-84-01A1] NR 21 TC 42 Z9 45 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2007 VL 18 IS 5 BP 647 EP 654 DI 10.1016/j.jvir.2007.02.033 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 168CT UT WOS:000246500700010 PM 17494847 ER PT J AU Rapp, JH Wakil, L Sawhney, R Pan, XM Yenari, MA Glastonbury, C Coogan, S Wintermark, M AF Rapp, Joseph H. Wakil, Laura Sawhney, Rajiv Pan, Xian Mang Yenari, Midori A. Glastonbury, Christine Coogan, Sheila Wintermark, Max TI Subclinical embolization after carotid artery stenting: New lesions on diffusion-weighted magnetic resonance imaging occur postprocedure SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Western-Vascular-Society CY SEP 16-19, 2006 CL La Jolla, CA SP Western Vasc Soc ID CEREBRAL PROTECTION; ENDARTERECTOMY; ANGIOPLASTY; ATHEROEMBOLI; INFARCTION; ISCHEMIA; DISEASE; BRAIN; SIZE; RISK AB Objectives: The reported rate of subclinical brain injury after carotid artery stenting (CAS) seen on diffusion-weighted magnetic resonance imaging (DWI) varies from 10% to > 40%. Data from transcranial Doppler after CAS indicate that embolization may continue for several days, suggesting that that at least some lesions seen on DWI occur postprocedure. Because DWI lesions appear hour of embolization, we used DWI to prospectively study patients before CAS, 1 hour after, and 48 hours after CAS to answer this question. Methods: The study participants were 48 male patients aged 59 to 83. All patients were examined by a neurologist before and after the procedure and had DWI preprocedure and 48 hours postprocedure. In addition, 23 patients had a DWI 1 hour post-CAS. Magnetic resonance imaging exams, including axial and coronal DWI and fluid-attenuated inversion recovery images, were read by two neuroradiologists blinded to the study timing. The embolic protection device was obtained from all patients, washed, and the contents examined under a digital microscope for fragments >= 60 mu m. Results: There were two periprocedural strokes and one transient ischemic attack (TIA), but no strokes or TlAs occurred during follow-up. In the 23 patients imaged 1 hour postprocedure, new lesions were found in two (9%), and 18 (78%) had new lesions at 48 hours (P <.001). For the entire study group, the incidence of new lesions at 48 hours was 67% (36/54). The median number of DWI lesions was four (range, 1 to 17). Every protection device examined had atherosclerotic debris, with a mean of 135 +/- 73 fragments (range, 18 to 310) sized > 60 mu m and a mean of eight fragments (range, 2 to 21) sized > 500 mu m. Findings on postprocedure DWI did not correlate with the degree of stenosis, size of angioplasty balloon, or number of inflations, nor with the number or size of fragments retrieved from the protection device. Conclusions: CAS can be performed with a very low incidence of clinically evident neurologic events; however, it is associated with embolization during and after the procedure. Protection devices effectively prevent clinical and subclinical events during the procedure. Significant embolization continues for at least 48 hours postprocedure, causing lesions on DWI when there is no mechanism for cerebral protection. These data correlate with transcranial Doppler reports of continued embolization after CAS and indicate that DWI should be done as late as possible to accurately assess the rate of subclinical brain injury with CAS procedures. C1 San Francisco VA Med Ctr, Vasc Surg Serv, San Francisco, CA USA. Univ Calif San Francisco, Div Vasc Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Serv Radiol, San Francisco, CA USA. San Francisco VA Med Ctr, Serv Neurol, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Palo Alto VA Med Ctr, Vasc Surg Serv, Palo Alto, CA USA. Stanford Med Ctr, Div Vasc Surg, Stanford, CA USA. RP Rapp, JH (reprint author), San Francisco Dept Vet Affairs Med Ctr, Vasc Surg Serv, 4150 Clement St, San Francisco, CA USA. EM rappj@surgery.ucsf.edu OI GLASTONBURY, CHRISTINE/0000-0002-9611-1287; Wintermark, Max/0000-0002-6726-3951 NR 19 TC 63 Z9 67 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2007 VL 45 IS 5 BP 867 EP 872 DI 10.1016/j.jvs.2006.12.058 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 163CA UT WOS:000246135000001 PM 17376643 ER PT J AU Peterson, BG Matsumura, JS Brewster, DC Makaroun, MS AF Peterson, Brian G. Matsumura, Jon S. Brewster, David C. Makaroun, Michel S. CA Excluder Bifurcated Endoprosthesis TI Five-year report of a multicenter controlled clinical trial of open versus endovascular treatment of abdominal aortic aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID OPEN REPAIR; GORE EXCLUDER; ENDOTENSION; ENLARGEMENT; GRAFT; ENDOPROSTHESIS; TRANSMISSION; EXPERIENCE; CONVERSION; PRESSURE AB Objective: Compare long-term results of endovascular treatment and standard open repair of abdominal aortic aneurysms in a multicenter, concurrent-controlled trial. Methods: 334 subjects were treated with standard open repair (control, n = 99) or the original EXCLUDER Bifurcated Endoprosthesis (test, n = 235). Five-year clinical evaluations and corelab radiographic results are analyzed. Results: Overall and aneurysm-related survival are similar. There have been ten open conversions, most frequently for enlarging sacs without endoleak. Two patients died after conversion. Including reinterventions and complications of reinterventions as adverse events, there is significant, persistent long-term reduction in major adverse events. At 5 years, corelab reported 0% limb narrowing, 0% trunk migration, 0% component (contralateral leg, aortic extender, and iliac extender) migration, 0% fracture, endoleak in 3% (2 type II/68), and aneurysm growth (> 5 mm compared to baseline) in 38% (30/78) of the test group. There are no aneurysm ruptures in either test or control group. Conclusions: After 5 years follow-up, endovascular repair is a safer and effective treatment compared with open surgical repair for abdominal aortic aneurysms. Major adverse events are less frequent with the endograft despite the need for late reinterventions. Aneurysm expansion is observed in nearly two-fifths of patients but is not associated with endoleak or aneurysm rupture. Multicenter clinical trials are evaluating a newer version of this device designed to avoid this high rate of sac expansion. C1 Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. St Louis Univ, St Louis, MO 63103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Matsumura, JS (reprint author), Northwestern Univ, Dept Surg, Feinberg Sch Med, Suite 10-105,251 E Huron St, Chicago, IL 60611 USA. EM j-matsumura@northwestern.edu NR 31 TC 65 Z9 67 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2007 VL 45 IS 5 BP 885 EP 890 DI 10.1016/j.jvs.2007.01.044 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 163CA UT WOS:000246135000005 PM 17398057 ER PT J AU Timm, J Neukamm, M Kuntzen, T Kim, AY Chung, RT Brander, C Lauer, GM Walker, BD Allen, TM AF Timm, J. Neukamm, M. Kuntzen, T. Kim, A. Y. Chung, R. T. Brander, C. Lauer, G. M. Walker, B. D. Allen, T. M. TI Characterization of full-length hepatitis C virus genotype 4 sequences SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE full genome; genotype 4; hepatitis C; viral evolution ID ALPHA-2B PLUS RIBAVIRIN; PROTEASE INHIBITOR; PHYLOGENETIC ANALYSIS; ANTIVIRAL EFFICACY; HCV GENOTYPE-4; INFECTION; SPREAD; EGYPT; PREVALENCE; BILN-2061 AB Over 85% of the world's nearly 170 million hepatitis C virus (HCV)-infected subjects exist in regions of Africa, Southeast Asia and Middle Eastern countries where genotypes 4-6 are very common. In particular, HCV genotype 4 is highly prevalent in Egypt with more than 19% of the population infected and chronic HCV representing one of the top five leading causes of death, due in part to ineffective interferon alpha treatment against this genotype. Despite this, very little work has been carried out to characterize the sequence diversity of genotype 4, which will be critical to the development of effective vaccines and antiviral therapies against this genotype. As a result of the paucity of sequence data available for HCV genotype 4, for which only one full genome sequence is currently available, we were interested in characterizing additional genotype 4 sequences and to provide reagents for amplification of this genotype. Here we describe seven unique HCV genotype 4a full genomes, in addition to a single genotype 4d genome, and characterize their sequence diversity in relation to other more closely characterized HCV genotypes. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Div Infect Dis, Boston, MA 02114 USA. Ruhr Univ Bochum, Dept Med, D-4630 Bochum, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA USA. RP Allen, TM (reprint author), CNY 6616-149,13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [AI066345, AI07433, AI31563] NR 41 TC 27 Z9 28 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAY PY 2007 VL 14 IS 5 BP 330 EP 337 DI 10.1111/j.1365-2893.2006.00792.x PG 8 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 155YH UT WOS:000245614200006 PM 17439522 ER PT J AU Rousseau, CM Learn, GH Bhattacharya, T Nickle, DC Heckerman, D Chetty, S Brander, C Goulder, PJR Walker, BD Kiepiela, P Korber, BT Mullins, JI AF Rousseau, Christine M. Learn, Gerald H. Bhattacharya, Tamnoy Nickle, David C. Heckerman, David Chetty, Senica Brander, Christian Goulder, Philip J. R. Walker, Bruce D. Kiepiela, Photini Korber, Bette T. Mullins, James I. TI Extensive intrasubtype recombination in South African human immunodeficiency virus type I subtype C infections SO JOURNAL OF VIROLOGY LA English DT Article ID FULL-LENGTH CLONES; HIV TYPE-1; PHYLOGENETIC ANALYSIS; MAXIMUM-LIKELIHOOD; GENOME ANALYSIS; DUAL INFECTION; DRUG-USERS; SEQUENCES; SUPERINFECTION; EVOLUTION AB Recombinant human immunodeficiency virus type 1 (HIV-1) strains containing sequences from different viral genetic subtypes (intersubtype) and different lineages from within the same subtype (intrasubtype) have been observed. A consequence of recombination can be the distortion of the phylogenetic signal. Several intersubtype recombinants have been identified; however, less is known about the frequency of intrasubtype recombination. For this study, near-full-length HIV-1 subtype C genomes from 270 individuals were evaluated for the presence of intrasubtype recombination. A sliding window schema (window, 2 kb; step, 385 bp) was used to partition the aligned sequences. The Shimodaira-Hasegawa test detected significant topological incongruence in 99.6% of the comparisons of the maximum-likelihood trees generated from each sequence partition, a result that could be explained by recombination. Using RECOMBINE, we detected significant levels of recombination using five random subsets of the sequences. With a set of 23 topologically consistent sequences used as references, bootscanning followed by the interactive informative site test defined recombination breakpoints. Using two multiple-comparison correction methods, 47% of the sequences showed significant evidence of recombination in both analyses. Estimated evolutionary rates were revised from 0.5%/year (95% confidence interval [CI], 0.39 to 0.53%) with all sequences to 0.46%/Year (95% CI, 0.38 to 0.48%) with the putative recombinants removed. The timing of the subtype C epidemic origin was revised from 1961 (95% CI, 1947 to 1962) with all sequences to 1958 (95% CI, 1949 to 1960) with the putative recombinants removed. Thus, intrasubtype recombinants are common within the subtype C epidemic and these impact analyses of HIV-1 evolution. C1 Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Microsoft Res, Machine Learning & Appl Stat Grp, Redmond, WA 98052 USA. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Program, ZA-4015 Durban, South Africa. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Rousseau, CM (reprint author), Univ Washington, Dept Microbiol, 1959 NE Pacific St,Box 358070, Seattle, WA 98195 USA. EM cmr@u.washington.edu RI Bhattacharya, Tanmoy/J-8956-2013 OI Bhattacharya, Tanmoy/0000-0002-1060-652X FU NIAID NIH HHS [R37 AI047734, N01 AI 11514, P01 AI 27757, P30 AI027757, R37 AI 047734] NR 62 TC 44 Z9 47 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2007 VL 81 IS 9 BP 4492 EP 4500 DI 10.1128/JVI.02050-06 PG 9 WC Virology SC Virology GA 168DE UT WOS:000246501900013 PM 17314156 ER PT J AU Bihl, F Narayan, M Chisholm, JV Henry, LM Suscovich, TJ Brown, EE Welzel, TM Kaufmann, DE Zaman, TM Dollard, S Martin, JN Wang, F Scadden, DT Kaye, KM Brander, C AF Bihl, Florian Narayan, Murli Chisholm, John V. Henry, Leah M. Suscovich, Todd J. Brown, Elizabeth E. Welzel, Tania M. Kaufmann, Daniel E. Zaman, Tauheed M. Dollard, Sheila Martin, Jeff N. Wang, Fred Scadden, David T. Kaye, Kenneth M. Brander, Christian TI Lytic and latent antigens of the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus induce T-cell responses with similar functional properties and memory phenotypes SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; EPITOPES; IMPACT; HUMAN-HERPESVIRUS-8; IMMUNODOMINANCE; IDENTIFICATION; COINFECTION; LYMPHOCYTES; EVOLUTION AB The cellular immunity against Kaposils sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HILA-B57- and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV- and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, US Dept HHS,NIH, Rockville, MD USA. Harvard Univ, Lemuel Shattuck Hosp, Sch Med, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Ctr Regenerat Med & Technol, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. RP Brander, C (reprint author), MGH E, Partners AIDS Res Ctr, 5th Floor,5239,13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org OI Brander, Christian/0000-0002-0548-5778 FU NCI NIH HHS [N01 CP 21121]; NIAID NIH HHS [P30 AI060354, P30 AI 060534]; NIDCR NIH HHS [P01 DE 01438-01] NR 33 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2007 VL 81 IS 9 BP 4904 EP 4908 DI 10.1128/JVI.02509-06 PG 5 WC Virology SC Virology GA 168DE UT WOS:000246501900057 PM 17329344 ER PT J AU Lombard, LE Steinhauer, KM AF Lombard, Lori E. Steinhauer, Kimberly M. TI A novel treatment for hypophonic voice: Twang therapy SO JOURNAL OF VOICE LA English DT Article DE Twang; hypophonia; voice therapy; epilarynx ID VOCAL FOLD PARALYSIS AB A hypophonic voice, characterized perceptually as weak and breathy, is associated with voice disorders such as vocal fold atrophy and unilateral vocal fold paralysis. Although voice therapy programs for hypophonia typically address the vocal folds or the sound source, twang voice quality was examined in this study as an alternative technique for increasing vocal power by altering the epilarynx or the sound filter. Objective: This study investigated the effect of twang production on physiologic, acoustic, anti perceived voice handicap measures in speakers with hypophonia. Design/Methods: This prospective pilot study compared the vocal outcomes of six participants with hypophonia at pre- and posttreatment time points. Outcome measures included mean airflow rate, intensity in dB sound pressure level (SPL), maximum phonation time, and self-report of voice handicap. Results: All subjects improved in at least three of the four vocal outcome measures. Wilcoxon signed-rank test of paired differences revealed significant differences between pre- and posttherapy group means for airflow rate, SPL, and Voice Handicap Index scores. Conclusion: The twang voice quality as a manipulation of the sound filter offers a clinical complement to traditional voice therapies that primarily address the sound source. C1 Indiana Univ, Indiana, PA 15705 USA. Univ Pittsburgh, Voice Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Commun Sci & Disorders, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Lombard, LE (reprint author), Indiana Univ, 203 Davis Hall, Indiana, PA 15705 USA. EM llombard@iup.edu NR 18 TC 6 Z9 6 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAY PY 2007 VL 21 IS 3 BP 294 EP 299 DI 10.1016/j.jvoice.2005.12.006 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 171AQ UT WOS:000246707700004 PM 16527452 ER PT J AU Spiegel, B AF Spiegel, Brennan TI Hot topics in gastroenterology: Differential diagnosis of dyspepsia, GERD, and IBS SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2007 VL 16 IS 4 BP 571 EP 571 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 171DD UT WOS:000246714200039 ER PT J AU Moriarty, HJ Bunting-Perry, LK Robinson, JP Dowling-Castronovo, A AF Moriarty, Helene J. Bunting-Perry, Lisette K. Robinson, Joanne P. Dowling-Castronovo, Annemarie TI Cognitive, affective, and behavioral dimensions of the lower urinary tract symptom experience in men with Parkinson's disease SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 Univ Penn, Sch Nursing, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. SUNY New Jersey, Coll Nursing, Newark, NJ USA. EM hcincotta@msn.com; Lisette.bunting-Perry@med.va.gov; jprobins@nilgers.edu; a.dowling.castronovo@verizon.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2007 VL 34 IS 3 SU S BP S66 EP S67 PG 2 WC Nursing SC Nursing GA 171ZK UT WOS:000246773700182 ER PT J AU Robinson, JP Bunting-Perry, LK Moriarty, H Avi-Itzhak, T AF Robinson, Joanne P. Bunting-Perry, Lisette K. Moriarty, Helene Avi-Itzhak, Tamara TI An explanatory study of the lower urinary tract symptom experience and quality of life in men with Parkinson's disease SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 SUNY, Coll Nursing, Newark, NJ USA. Univ Penn, Sch Nursing, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. CUNY York Coll, Jamaica, NY 11451 USA. EM jprobins@rutgers.edu; Lisette.bunting-Perty@med.va.gov; helene.moriarty@med.va.gov; aviitzh@rci.rutgers.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2007 VL 34 IS 3 SU S BP S4 EP S4 PG 1 WC Nursing SC Nursing GA 171ZK UT WOS:000246773700005 ER PT J AU Boron, JB Turiano, NA Willis, SL Schaie, W AF Boron, Julie Blaskewicz Turiano, Nicholas A. Willis, Sherry L. Schaie, Warner TI Effects of cognitive training on change in accuracy in inductive reasoning ability SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID OLD-AGE; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; LONGITUDINAL FINDINGS; MENTAL ROTATION; PERFORMANCE; ADULTS; HYPERTENSION; INTELLIGENCE; DECLINE AB We investigated cognitive training effects on accuracy and number of items attempted in inductive reasoning performance in a sample of 335 older participants (M = 72.78 years) from the Seattle Longitudinal Study. We assessed the impact of individual characteristics, including chronic disease. The reasoning training group showed significantly greater gain in accuracy and number of attempted items than did the comparison group; gain was primarily due to enhanced accuracy. Reasoning training effects involved a complex interaction of gender, prior cognitive status, and chronic disease. Women with prior decline on reasoning but no heart disease showed the greatest accuracy increase. In addition, stable reasoning-trained women with heart disease demonstrated significant accuracy gain. Comorbidity was associated with less change in accuracy. The results support the effectiveness of cognitive training on improving the accuracy of reasoning performance. C1 [Boron, Julie Blaskewicz] Georgia Inst Technol, Sch Psychol, Atlanta, GA 30332 USA. [Turiano, Nicholas A.] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Willis, Sherry L.; Schaie, Warner] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. RP Boron, JB (reprint author), Georgia Inst Technol, Sch Psychol, 654 Cherry St, Atlanta, GA 30332 USA. EM julie.boron@psych.gatech.edu FU NIA NIH HHS [5 T32 AG00048-26, R37 AG08055, U01 AG014263, R37 AG024102] NR 40 TC 6 Z9 6 U1 2 U2 8 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 2007 VL 62 IS 3 BP P179 EP P186 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 272CH UT WOS:000253835800006 PM 17507586 ER PT J AU Brezniceanu, ML Liu, F Wei, CC Tran, S Sachetelli, S Zhang, SL Guo, DF Filep, JG Ingelfinger, JR Chan, JSD AF Brezniceanu, M.-L. Liu, F. Wei, C.-C. Tran, S. Sachetelli, S. Zhang, S.-L. Guo, D.-F. Filep, J. G. Ingelfinger, J. R. Chan, J. S. D. TI Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice SO KIDNEY INTERNATIONAL LA English DT Article DE catalase; transgenic mice; angiotensinogen; apoptosis; diabetes ID PROXIMAL TUBULAR CELLS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; GLOMERULOTUBULAR JUNCTION ABNORMALITIES; GENE-EXPRESSION; TRANSGENIC MICE; RAT-KIDNEY; ATUBULAR GLOMERULI; OXIDATIVE STRESS; EPITHELIAL-CELLS; MESANGIAL CELLS AB Increased generation of reactive oxygen species (ROS) leads to oxidative stress in diabetes. Catalase is a highly conserved heme-containing protein that reduces hydrogen peroxide to water and oxygen and is an important factor decreasing cellular injury owing to oxidative stress. Hyperglycemic conditions increase oxidative stress and angiotensinogen gene expression. Angiotensinogen conversion to angiotensin II leads to a furtherance in oxidative stress through increased generation of reactive oxygen species. In this study, we utilized mice transgenically overexpressing rat catalase in a kidney- specific manner to determine the impact on ROS, angiotensinogen and apoptotic gene expression in proximal tubule cells of diabetic animals. Proximal tubules isolated from wild- type and transgenic animals without or with streptozotocin-induced diabetes were incubated in low glucose media in the absence or presence of angiotensin II or in a high-glucose media. Our results show that the overexpression of catalase prevents the stimulation of ROS and angiotensinogen mRNA in tubules owing to elevated glucose or angiotensin II in vitro. Additionally, overexpression of catalase attenuated ROS generation, angiotensinogen and proapoptotic gene expression and apoptosis in the kidneys of diabetic mice in vivo. Our studies point to an important role of ROS in the pathophysiology of diabetic nephropathy. C1 CHU Montreal, Res Ctr, Hotel Dieu, Montreal, PQ H2W 1T8, Canada. Maison Rosemont Hosp, Res Ctr, Montreal, PQ, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02115 USA. RP Chan, JSD (reprint author), CHU Montreal, Res Ctr, Hotel Dieu, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@u-montreal.ca FU NHLBI NIH HHS [HL-48455] NR 58 TC 85 Z9 88 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2007 VL 71 IS 9 BP 912 EP 923 DI 10.1038/sj.ki.5002188 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 165JC UT WOS:000246300100013 PM 17342175 ER PT J AU Lu, QY Jin, YS Zhang, ZF Le, AD Heber, D Li, FP Dubinett, SM Rao, JY AF Lu, Qing-Yi Jin, Yu Sheng Zhang, Zuo-Feng Le, Anh D. Heber, David Li, Frederick P. Dubinett, Steven M. Rao, Jian Yu TI Green tea induces annexin-I expression in human lung adenocarcinoma A549 cells: involvement of annexin-I in actin remodeling SO LABORATORY INVESTIGATION LA English DT Article DE annexin-I; cell migration; F-actin; green tea; lung adenocacinoma; chemoprevention ID CANCER RISK; MEMBRANE INTERACTIONS; CDC42 GTPASES; CONSUMPTION; RHO; CHEMOPREVENTION; CYTOSKELETON; POPULATION; INHIBITION; MODULATION AB Green tea polyphenols exhibit multiple antitumor activities in various in vitro and in vivo tumor models, and the mechanisms of action are not clear. Previously, we found that green tea extract ( GTE) regulates actin remodeling in different cell culture systems. Actin remodeling plays an important role in cancer cell morphology, cell adhesion, motility, and invasion. Using proteomic approaches, we found GTE-induced expression of annexin-I, a multifunctional actin binding protein, in these cell lines. In this study, we aimed to further define the functional role of GTE-induced annexin-I expression in actin remodeling, cell adhesion, and motility in lung adenocarcinoma A549 cells. We found that GTE stimulates the expression of annexin-I in a dose-dependent fashion. The GTE-induced annexin-I expression appears to be at the transcription level, and the increased annexin-I expression mediates actin polymerization, resulting in enhanced cell adhesion and decreased motility. Annexin-I specific interference resulted in loss of GTE-induced actin polymerization and cell adhesion, but not motility. In fact, annexin-I specific interference itself inhibited motility even without GTE. Together, annexin-I plays an important role in GTE-induced actin remodeling, and it may serve as a potential molecular target associated with the anticancer activities of green tea. C1 Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA 90095 USA. Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Rao, JY (reprint author), Univ Calif Los Angeles, Dept Pathol & Lab Med, 10833 LeConte Ave,Box 951732, Los Angeles, CA 90095 USA. EM jrao@mednet.ucla.edu FU NCI NIH HHS [P50 CA90833] NR 41 TC 13 Z9 15 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2007 VL 87 IS 5 BP 456 EP 465 DI 10.1038/labinvest.3700534 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 157YY UT WOS:000245758700006 PM 17351649 ER PT J AU Yu, CG Zhang, XQ Huang, Q Klein, M Goyal, RK AF Yu, Chenggong Zhang, Xiaoqi Huang, Qin Klein, Michael Goyal, Raj K. TI High-fidelity DNA histograms in neoplastic progression in Barrett's esophagus SO LABORATORY INVESTIGATION LA English DT Article DE Barrett's adenocarcinoma; biomarkers for cancer progression; chromosomal instability; dysplasia; image cytometry; unstable aneuploidy ID CELL-CYCLE; IMAGE CYTOMETRY; FLOW-CYTOMETRY; CANCER-CELLS; DYSPLASIA; ADENOCARCINOMA; CARCINOMA; ABNORMALITIES; DIAGNOSIS; SECTIONS AB This study describes the high-fidelity DNA histograms in different stages of neoplastic progression to Barrett's adenocarcinoma ( BAC). High-fidelity DNA histograms were obtained with image cytometry on sections, and were classified based on DNA index values of the peaks into diploid, mild aneuploid, moderate aneuploid and severe aneuploid. Heterogeneity index ( HI) representing cells with different DNA content and the 5N exceeding cell fraction were determined. One hundred and eighty-seven cases, including 34 normal gastrointestinal mucosa ( control), 66 Barrett's-specialized intestinal metaplasia ( SIM), 22 low-grade dysplasia ( LGD), 22 high-grade dysplasia ( HGD) and 43 BAC were investigated. Controls showed sharp diploid peaks with HI values less than 13, and no 5N exceeding nuclei. SIM showed a spectrum of histograms including diploid, mild aneuploid and moderate aneuploid histograms. The frequency and severity of aneuploidy increased with worsening histological grades of dysplasia. All BAC cases were aneuploid, with moderate or severe aneuploidy. Marked elevated HI values (>20) and 5N exceeding fractions ( >5%) were found in 5%, 32%, 50% and 88% of cases with SIM, LGD, HGD and BAC, respectively. The high-fidelity DNA histograms suggest that ( 1) Barrett's SIM may already be dysplastic in nature, and all BAC may be markedly aneuploid; and ( 2) elevated cellular DNA heterogeneity and 5N fractions may be markers of progressive chromosomal changes and 'unstable aneuploidy' that identifies progressive lesions. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Dept Pathol, Boston, MA USA. VA Boston Healthcare Syst, Dept Med, Boston, MA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. VA Providence Healthcare Syst, Providence, RI USA. RP Goyal, RK (reprint author), VA Boston Healthcare Syst, Ctr Swallowing & Motil Disorders, 1400 VFW Pkwy,Bldg 3, W Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU NIDDK NIH HHS [DK62867] NR 24 TC 21 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2007 VL 87 IS 5 BP 466 EP 472 DI 10.1038/labinvest.3700531 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 157YY UT WOS:000245758700007 PM 17310216 ER PT J AU de Bakker, PIW Rosand, J AF de Bakker, Paul I. W. Rosand, Jonathan TI In search of genes for stroke SO LANCET NEUROLOGY LA English DT Editorial Material ID ISCHEMIC-STROKE; ASSOCIATION; GENETICS; SUBTYPES C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP de Bakker, PIW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM jrosand@partners.org RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 10 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2007 VL 6 IS 5 BP 383 EP 384 DI 10.1016/S1474-4422(07)70088-1 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 161XO UT WOS:000246050600004 PM 17434084 ER PT J AU Bockhorn, M Jain, RK Munn, LL AF Bockhorn, Maximilian Jain, Rakesh K. Munn, Lance L. TI Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed? SO LANCET ONCOLOGY LA English DT Article ID MATRIX METALLOPROTEINASES; GENE-EXPRESSION; CARCINOMA-CELLS; TUMOR INVASION; STROMAL CELLS; GRADIENT; GROWTH; PROGRESSION; CHEMOTAXIS; MIGRATION AB Although millions of cells are shed from a tumour every day, haematogenous metastasis is believed to be very inefficient. This inefficiency is widely assumed to be a result of the destruction of cells in the bloodstream by shear stress and the immune system and a slow rate of extravasation and proliferation in the stroma at a secondary site. Here, we propose that, whereas active intravasation of cells into the circulation is important in some tumours, others might shed cells passively into the blood or lymphatic vessels without the involvement of active cell migration. We discuss the evidence for and against this passive-shedding hypothesis and the implications for future treatments. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab Tumour Biol, Boston, MA 02114 USA. Univ Hosp Essen, Dept Gen Visceral & Transplantat Surg, Essen, Germany. RP Munn, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab Tumour Biol, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NHLBI NIH HHS [R01 HL064240, R01 HL064240-08] NR 61 TC 89 Z9 92 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2007 VL 8 IS 5 BP 444 EP 448 DI 10.1016/S1470-2045(07)70140-7 PG 5 WC Oncology SC Oncology GA 165RE UT WOS:000246322300032 PM 17466902 ER PT J AU Nichols, AC Bhattacharyya, N AF Nichols, Anthony C. Bhattacharyya, Neil TI Racial differences in stage and survival in head and neck squamous cell carcinoma SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Triological-Society Combined Section Meeting CY FEB 14-18, 2007 CL Marco Isl, FL SP Triological Soc DE head and neck cancer; laryngeal cancer; epidemiology; race ID AFRICAN-AMERICANS; LUNG-CANCER; RACE; RISK; CARE AB Objectives. The goal of this study was to characterize differences in survival between black patients and white patients with squamous cell carcinoma of the head and neck (HNSCCA). Design. Cases of oral tongue and glottic SCCA in black patients or white patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (years 1988-2002). For each primary site, TNM staging was imputed, and staging distributions were compared between races. For each black patient, a randomly selected white control was matched for age at diagnosis, sex, stage, surgical treatment, and radiation. Kaplan-Meier survival comparisons for both overall and disease-specific survival were then conducted for the matched pairs. Results. From 1,919 cases of carcinoma of the oral tongue, those of 151 black and 1,768 white patients were extracted. Black patients had a significantly elevated T stage (P =.001) and N stage (P =.002) at primary presentation. Of glottic carcinoma, 4,578 cases (625 black and 3,953 white patients) were extracted. Black patients again presented with significantly elevated T stage (P <.001) and N stage (P <.001) compared with white patients. For 43 matched pairs with tongue carcinoma, mean overall survival for black patients was 66.1 months versus 74.8 months for matched white controls (P =.502, log-rank test). Disease-specific survival was 91.1 months for black patients versus 109.6 months for white patients (P =.168). For 401 matched pairs with glottic carcinoma, mean overall survival for black patients was 96.6 months versus 114.5 months for white controls (P <.001). Similarly, the mean disease-specific survival was 149.4 months for black patients versus 167.1 months for white patients (P <.001) Conclusion: Controlling for stage and treatment, black patients demonstrate poorer overall and disease-specific survival with SCCA, implying other intrinsic or extrinsic factors influencing survival. C1 Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol, 45 Francis St ASB-2, Boston, MA 02115 USA. EM neiloy@massmed.org NR 15 TC 27 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2007 VL 117 IS 5 BP 770 EP 775 DI 10.1097/MLG.0b013e318033c800 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 163EP UT WOS:000246141900002 PM 17473666 ER PT J AU Mehta, RP WernickRobinson, M Hadlock, TA AF Mehta, Ritvik P. WernickRobinson, Mara Hadlock, Tessa A. TI Validation of the Synkinesis Assessment Questionnaire SO LARYNGOSCOPE LA English DT Article DE facial paralysis; synkinesis; quality of life; instrument validation; botulinum toxin ID FACIAL-NERVE PARALYSIS; ORAL SYNKINESIS; MOVEMENT; FACE AB Objective: To validate the Synkinesis Assessment Questionnaire (SAQ), a newly developed patient-graded instrument to evaluate facial synkinesis. Study Design: This was a prospective clinical questionnaire validation study. Methods: A total of 65 patients with facial nerve disorders were recruited from the Facial Nerve Center. In 28 patients (group I), the SAQ, a preliminary 10-item instrument, was administered at the initial visit and repeated within 3 weeks without any medical or surgical intervention. In 37 patients (group II), the SAQ was administered before botulinum toxin therapy for facial synkinesis and again 2 weeks after Botox therapy. In addition, the instrument was administered to 20 healthy subjects without facial nerve dysfunction (group III). The reliability, validity, and responsiveness of the SAQ were assessed. Results: Test-retest reliability for the SAQ was high (Spearman's rank correlation r = 0.876, P <.0001). Internal consistency of the instrument was assessed by calculating the Cronbach alpha value. This analysis supported the deletion of one item from the final SAQ. The Cronbach a for the final SAQ was 0.859. Construct validity analysis showed a statistically significant improvement in SAQ scores (P <.001) after successful administration of botulinum toxin for treatment of facial synkinesis. There was a highly statistically significant difference (P <.0001) in SAQ scores between normal subjects (group III) and patients with facial synkinesis (group II). Conclusions: The SAQ is a simple, patient-graded instrument designed to assess facial synkinesis. Instrument analysis suggests that it is a reliable and valid instrument for the assessment of facial synkinesis. The validated SAQ is the first dedicated instrument designed to assess facial synkinesis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Facial Nerve Ctr, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Facial Nerve Ctr, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 10 TC 33 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2007 VL 117 IS 5 BP 923 EP 926 DI 10.1097/MLG.0b013e3180412460 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 163EP UT WOS:000246141900033 PM 17473697 ER PT J AU Mckoy, JM Angelotta, C Bennett, CL Tallman, MS Wadleigh, M Evens, AM Kuzel, TM Trifilio, SM Raisch, DW Kell, J DeAngelo, DJ Giles, FJ AF McKoy, June M. Angelotta, Cara Bennett, Charles L. Tallman, Martin S. Wadleigh, Martha Evens, Andrew M. Kuzel, Timothy M. Trifilio, Steve M. Raisch, Dennis W. Kell, Jonathan DeAngelo, Daniel J. Giles, Francis J. TI Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): An overview from the research on adverse drug events and reports (RADAR) project SO LEUKEMIA RESEARCH LA English DT Article; Proceedings Paper CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol DE gemtuzumab ozogamicin; sinusoidal obstructive syndrome; acute myeloid leukemia; stem cell transplantation; adverse drug reactions ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; HEPATIC VENOOCCLUSIVE DISEASE; STEM-CELL TRANSPLANTATION; COMBINATION REGIMEN; CYTARABINE; MYLOTARG; CYCLOSPORINE; THERAPY; SAFETY AB Gemtuzumab ozogamicin (GO) was approved for marketing in 2000 by the United States Food and Drug Administration (FDA) for older patients with relapsed acute myeloid leukemia (AML). Four months later, 14 phase II clinical trial participants who received novel GO-containing combination chemotherapy regimens developed an unexpected hepatic toxicity termed sinusoidal obstructive syndrome (SOS) or hepatic veno-occlusive disease (VOD). Investigators associated with the Research on Adverse Drug Events and Reports (RADAR) project reviewed safety reports for GO included in reports of clinical trials and observational studies, interim reports from an FDA mandated Prospective Observational Registry, and the Food and Drug Administration's Adverse Event Reporting System. Medline searches provided incidence estimates of GO-associated SOS and comparative rates of SOS without GO. SOS is characterized by hyperbilirubinemia, painful hepatomegaly, ascites, and sudden weight gain developing at a median of 10 days following GO administration for patients who did not undergo an allogeneic SCT procedure and 13 days following an allogeneic SCT for patients who had previously received GO. Among adult AML patients who received GO in clinical trials, SOS incidence was 3% at doses <= 6 mg/m(2) if administered as monotherapy or in combination with non-hepatotoxic agents versus 28% if administered with thioguanine and 15% when administered as monotherapy at a dose of 9 mg/m(2). Observational studies identified SOS rates between 15% and 40% if an SCT is performed within 3 months of GO administration. The FDA mandated Prospective Observational Registry of patients who receive care at 60 medical centers has identified GO-associated SOS rates of 14% if an SCT is performed and 9% otherwise. Caution is advised when administering GO in routine clinical practice, particularly if administered with other hepatotoxic agents, at doses and schedules more intensive than those approved by the FDA, or within 3 months of a SCT procedure. (c) 2006 Elsevier Ltd. All rights reserved. C1 Northwestern Univ, Feinberg Sch Med, Div Hematol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Oncol, Chicago, IL 60611 USA. Northwestern Univ, Dept Med, Div Geriatr Med, Feinberg Sch Med, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. VA MidWest Ctr Hlth Serv & Policy Res, Chicago, IL USA. VA Chicago Healthcare Syst, Chicago, IL USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ New Mexico, Vet Affaris Cooperat Study Program, Clin Res Pharmaceut Coordinating Ctr, Albuquerque, NM 87131 USA. Univ Wales Hosp, Dept Hematol, Cardiff, Wales. RP Bennett, CL (reprint author), Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, 303 E Chicago,Oslon 8250, Chicago, IL 60611 USA. EM cbenne@northwestern.edu RI Bennett, Charles/C-2050-2008 NR 33 TC 89 Z9 90 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2007 VL 31 IS 5 BP 599 EP 604 DI 10.1016/j.leukres.2006.07.005 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 170OD UT WOS:000246672000004 PM 16959316 ER PT J AU Vance, GH Kim, H Hicks, GA Cherry, AM Higgins, R Hulshizer, RL Tallman, MS Fernandez, HF Dewald, GW AF Vance, Gail H. Kim, Haesook Hicks, Gary A. Cherry, Athena M. Higgins, Rodney Hulshizer, Rachael L. Tallman, Martin S. Fernandez, Hugo F. Dewald, Gordon W. TI Utility of interphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900) SO LEUKEMIA RESEARCH LA English DT Article DE FISH; acute myeloid leukemia; cytogenetics ID IN-SITU HYBRIDIZATION; ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROME; MONOSOMY-7; TRANSLOCATIONS; CHROMOSOME; PROBE AB We evaluated the efficacy of FISH to detect chromosome anomalies in the evaluation of young (< 60 years) patients with AML. Patients were enrolled in El 900, an ECOG clinical trial for AML. The protocol was designed to collect bone marrow or blood for both cytogenetic and FISH studies at study entry (diagnosis). FISH for each patient was performed and utilized eight probe sets to detect t(8;21), t(9;22), t(11;var), t(15;17), inv(16), +8, -5/5q, and -7/7q. We analyzed 237 specimens with complete cytogenetic and FISH results. Results for each specimen were classified by probe set into one of six categories. The concordance rate between cytogenetic and FISH results ranged from 98 to 100% for all probe sets and kappa analysis for concordance had a p-value of < 0.0001. The high level of agreement between cytogenetic and FISH results demonstrate the accuracy of a panel of eight FISH probe sets for the detection of significant abnormalities in AML. Data from this investigation support the use of FISH as an adjunct method to increase the yield of useful cytogenetic results in large cooperative trials and demonstrate the potential of FISH as a follow-up study of minimal residual disease in ECOG trials. (c) 2006 Elsevier Ltd. All rights reserved. C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Lab Med & Pathol, Rochester, MN USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Abbott NW Hosp, Minneapolis, MN 55407 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Miami, Miami, FL 33152 USA. RP Vance, GH (reprint author), Indiana Univ, Sch Med, 975 W Walnut St IB 264, Indianapolis, IN 46202 USA. EM ghvance@iupui.edu NR 15 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2007 VL 31 IS 5 BP 605 EP 609 DI 10.1016/j.leukres.2006.07.026 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 170OD UT WOS:000246672000005 PM 16996130 ER PT J AU Tsai, SY Posse, S Lin, YR Ko, CW Otazo, R Chung, HW Lin, FH AF Tsai, Shang-Yueh Posse, Stefan Lin, Yi-Ru Ko, Cheng-Wen Otazo, Ricardo Chung, Hsiao-Wen Lin, Fa-Hsuan TI Fast mapping of the T-2 relaxation time of cerebral metabolites using proton echo-planar spectroscopic imaging (PEPSI) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE proton echo-planar spectroscopic imaging; single-voxel spectroscopy; T-2 relaxation time; cerebral metabolites; gray/white matter difference ID HUMAN-BRAIN; CHEMICAL-SHIFT; TRANSVERSE RELAXATION; MAGNETIC-RESONANCE; MR SPECTROSCOPY; RAT-BRAIN; ISCHEMIA; T2; EDEMA; TESLA AB Metabolite T-2 is necessary for accurate quantification of the absolute concentration of metabolites using long-echo-time (TE) acquisition schemes. However, lengthy data acquisition times pose a major challenge to mapping metabolite T-2. In this study we used proton echo-planar spectroscopic imaging (PEPSI) at 3T to obtain fast T-2 maps of three major cerebral metabolites: N-acetyl-aspartate (NAA), creatine (Cre), and choline (Cho). We showed that PEPSI spectra matched T-2 values obtained using single-voxel spectroscopy (SVS). Data acquisition for 2D metabolite maps with a voxel volume of 0.95 ml (32 x 32 image matrix) can be completed in 25 min using five TEs and eight averages. A sufficient spectral signal-to-noise ratio [SNR) for T-2 estimation was validated by high Pearson's correlation coefficients between logarithmic MR signals and TEs (R-2 = 0.98, 0.97, and 0.95 for NAA, Cre, and Cho, respectively). In agreement with previous studies, we found that the T-2 values of NAA, but not Cre and Cho, were significantly different between gray matter (GM) and white matter (WM; P < 0.001). The difference between the T-2 estimates of the PEPSI and SVS scans was less than 9%. Consistent spatial distributions of T-2 were found in six healthy subjects, and disagreement among subjects was less than 10%. In summary, the PEPSI technique is a robust method to obtain fast mapping of metabolite T-2. C1 Natl Taiwan Univ, Inst Biomed Engn, Dept Elect Engn, Taipei 10764, Taiwan. Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. Natl Sun Yat Sen Univ, Dept Comp Sci & Engn, Kaohsiung 80424, Taiwan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chung, HW (reprint author), Natl Taiwan Univ, Inst Biomed Engn, Dept Elect Engn, Room 238,Bldg 2,1,Sec 4, Taipei 10764, Taiwan. EM chung@cc.ee.ntu.edu.tw RI Lin, Fa-Hsuan/G-6988-2012; Tsai, Shang-Yueh/O-2226-2013; OI Lin, Fa-Hsuan/0000-0002-9539-1731; Tsai, Shang-Yueh/0000-0002-6310-4750; Otazo, Ricardo/0000-0002-3782-4930 FU NCRR NIH HHS [P41 RR14075]; NIBIB NIH HHS [R01 EB000790-04]; NICHD NIH HHS [R01 HD040712]; NIDA NIH HHS [R01 DA14178-01]; NINDS NIH HHS [R01 NS037462] NR 34 TC 22 Z9 22 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAY PY 2007 VL 57 IS 5 BP 859 EP 865 DI 10.1002/mrm.21225 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161YJ UT WOS:000246052800007 PM 17457864 ER PT J AU Lee, J Shahram, M Schwartzman, A Pauly, JM AF Lee, Jongho Shahram, Morteza Schwartzman, Armin Pauly, John M. TI Complex data analysis in high-resolution SSFP fMRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE complex; multivariate; SSFP; phase activation; BOSS ID MAGNETIC-SUSCEPTIBILITY; BLOOD-OXYGENATION; SIGNAL BEHAVIOR; BALANCED SSFP; HUMAN BRAIN; SPIN-ECHO; 1.5 TESLA; IN-VIVO; MAGNITUDE; CONTRAST AB In transition-band steady-state free precession (SSFP) functional MRI (fMRI), functional contrast originates from a bulk frequency shift induced by a deoxygenated hemoglobin concentration change in the activated brain regions. This frequency shift causes a magnitude and/or phase-signal change depending on the off-resonance distribution of a voxel in the balanced-SSFP (bSSFP) profile. However, in early low-resolution studies, only the magnitude signal activations were shown. In this paper the task-correlated phase-signal change is presented in a high-resolution (1x1x1 mm(3)) study. To include this phase activation in a functional analysis, a new complex domain data analysis method is proposed. The results show statistically significant phase-signal changes in a large number of voxels comparable to that of the magnitude-activated voxels. The complex-data analysis method successfully includes these phase activations in the activation map and thus provides wider coverage compared to magnitude-data analysis results. C1 Stanford Univ, Dept Elect Engn, Magnet Resonance Syst Res Lab, Stanford, CA 94305 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Lee, J (reprint author), Stanford Univ, Dept Elect Engn, Magnet Resonance Syst Res Lab, Room 208,Packard Elect Engn Bldg, Stanford, CA 94305 USA. EM jonghoyi@mrsrl.stanford.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU NIBIB NIH HHS [R21EB002969] NR 34 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAY PY 2007 VL 57 IS 5 BP 905 EP 917 DI 10.1002/mrm.21195 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161YJ UT WOS:000246052800013 PM 17457883 ER PT J AU Huang, TY Liu, YJ Stemmer, A Poncelet, BP AF Huang, Teng-Yi Liu, Yi-Jui Stemmer, Alto Poncelet, Brigitte P. TI T-2 measurement of the human myocardium using a T-2-prepared transient-state TrueFISP sequence SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE myocardium; T-2 relaxation; transient-state; balanced steady-state free precession; BOLD contrast ID VASODILATOR RESPONSE; ECHO SEQUENCE; OXYGENATION; CONTRAST; MR; PERFUSION; HEART; T-ASTERISK(2); DIPYRIDAMOLE; RELAXOMETRY AB fast and motion-insensitive technique suitable for myocardial BOLD contrast imaging is presented. The method, termed TrueFISP, combines T-2 magnetization preparation with steadystate free precession (SSFP) imaging for T-2 relaxation mapping of the myocardium in healthy volunteers. The T-2 contrast-to-noise ratio (CNR) was optimized with the use of transient-state TrueFISP readout and half-Fourier readout with linear phase encoding. Single-slice myocardial T-2-weighted image was obtained within one heartbeat, and a single slice T-2 map of the myocardium was obtained in under 5-7 s. A respiratory navigator-gating method was incorporated for serial measurements and signal averaging, with the subjects breathing freely. The mean myocardial T-2 relaxation time measured in 12 healthy volunteers was 54 +/- 5.7 ms. Regional variations of T-2 values across the myocardium were 7%. Temporal variations across serial T-2 measurements in a transmural region covering similar to 0.5 cc of the left ventricular (LV) wall were 3.6% without signal averaging (number of excitations (NEX) = 1) and 1.7% with signal averaging (NEX = 10). According to our preliminary results, the T-2-TrueFISP method is expected to provide a robust and sensitive tool for clinical application of myocardial BOLD contrast imaging. C1 Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Feng Chia Univ, Dept Automat Control Engn, Taichung 40724, Taiwan. Siemens AG, Med Solut, MR Applicat Dev, Erlangen, Germany. RP Huang, TY (reprint author), Natl Taiwan Univ Sci & Technol, Dept Elect Engn, 43 Sec 4 Keelung Rd, Taipei, Taiwan. EM tyhuang@mail.ntust.edu.tw RI Teng-Yi, Huang/C-7433-2011 FU NHLBI NIH HHS [HL066489] NR 28 TC 49 Z9 49 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAY PY 2007 VL 57 IS 5 BP 960 EP 966 DI 10.1002/mrm.21208 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161YJ UT WOS:000246052800018 PM 17457877 ER PT J AU Colonques, J Ceron, J Tejedor, FJ AF Colonques, J. Ceron, J. Tejedor, F. J. TI Segregation of postembryonic neuronal and glial lineages inferred from a mosaic analysis of the Drosophila larval brain SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Drosophila; brain development; larval brain; neurogenesis; gliogenesis; neural progenitor cells; clonal analysis ID CENTRAL-NERVOUS-SYSTEM; VISUAL-SYSTEM; ASYMMETRIC DIVISION; CELL-DIVISION; PROLIFERATION PATTERN; EARLY DIFFERENTIATION; TRANSCRIPTION FACTORS; NEUROBLAST LINEAGES; MAMMALIAN HOMOLOG; SELF-RENEWAL AB Due to its intermediate complexity and its sophisticated genetic tools, the larval brain of Drosophila is a useful experimental system to study the mechanisms that control the generation of cell diversity in the CNS. In order to gain insight into the neuronal and glial lineage specificity of neural progenitor cells during postembryonic brain development, we have carried an extensive mosaic analysis throughout larval brain development. In contrast to embryonic CNS development, we have found that most postembryonic neurons and glial cells of the optic lobe and central brain originate from segregated progenitors. Our analysis also provides relevant information about the origin and proliferation patterns of several postembryonic lineages such as the superficial glia and the medial-anterior Medulla neuropile glia. Additionally, we have studied the spatio-temporal relationship between gem expression and gliogenesis. We found that gem expression is restricted to the post-mitotic cells of a few neuronal and glial lineages and it is mostly absent from postembryonic progenitors. Thus, in contrast to its major gliogenic role in the embryo, the function of gem during postembryonic brain development seems to have evolved to the specification and differentiation of certain neuronal and glial lineages. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Miguel Hernandez, Inst Neurociencias, CSIC, San Juan 03550, Alicante, Spain. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Tejedor, FJ (reprint author), Univ Miguel Hernandez, Inst Neurociencias, CSIC, Campus San Juan, San Juan 03550, Alicante, Spain. EM f.tejedor@umh.es OI Tejedor, Francisco J/0000-0003-1942-2580 NR 54 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAY PY 2007 VL 124 IS 5 BP 327 EP 340 DI 10.1016/j.mod.2007.01.004 PG 14 WC Developmental Biology SC Developmental Biology GA 164EX UT WOS:000246217400001 PM 17344035 ER PT J AU Prosser, LA Wittenberg, E AF Prosser, Lisa A. Wittenberg, Eve TI Do risk attitudes differ across domains and respondent types? SO MEDICAL DECISION MAKING LA English DT Article DE risk attitude; patients; health ID MULTIPLE-SCLEROSIS; PROSPECT-THEORY; LIFE YEARS; PREFERENCES; ADJUSTMENT; IMPAIRMENT; DISABILITY; UTILITY; CANCER; SCALE AB Objective. To evaluate differences in risk attitude across the domains of health and money for 2 types of respondents, patients and community members. Methods. Two groups of respondents, patients with multiple sclerosis (n = 56) and members of the general community (n = 57), completed a survey that collected information on risk attitudes and socioeconomic and clinical variables (e.g., disability level). Risk attitude was measured using 2 standard-gamble questions on money and 1 standard-gamble question on health outcomes. Multivariate regression was used to evaluate the relationship between risk attitude and respondent type (patient v. community), adjusting for covariates that could affect risk attitude. Results. The median certainty equivalents for money gambles were significantly different from and less than the expected value of the gamble for both types of respondents. Median certainty equivalents for the health gamble were not significantly different from the expected value for either group of respondents. For all 3 gambles, there was no difference in median certainty equivalents between the 2 types of respondents in both unadjusted and adjusted analyses. Conclusions. Risk attitude varied across domains but not by respondent type. Patients and community members were predominantly risk neutral with respect to health outcomes and risk averse with respect to money. Research on risk preferences on money outcomes may not be an appropriate proxy for risk preferences regarding health outcomes. Risk preferences may depend more on characteristics of the choice than on respondent type. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Ctr Child Hlth Care Studies, Boston, MA USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Prosser, LA (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM lprosser@hms.harvard.edu FU AHRQ HHS [K02-HS14010-01] NR 25 TC 7 Z9 7 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2007 VL 27 IS 3 BP 281 EP 287 DI 10.1177/0272989X07300602 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 173XC UT WOS:000246904800007 PM 17545498 ER PT J AU Shifren, JL Avis, NE AF Shifren, Jan L. Avis, Nancy E. TI Surgical menopause: effects on psychological well-being and sexuality SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE surgical menopause; hysterectomy; bilateral oophorectomy; psychological well-being; sexual function ID QUALITY-OF-LIFE; RANDOMIZED-TRIAL; TESTOSTERONE PATCH; HYSTERECTOMY; WOMEN; OOPHORECTOMY; OUTCOMES; DISORDER; ESTROGEN; DESIRE AB Objective: Women anticipating surgical menopause often have significant concerns regarding the effects of surgery on psychological well-being and sexuality. Results: The impact of hysterectomy, often with concurrent oophorectomy, on well-being and sexuality will vary depending on many factors. These include a woman's preoperative mental health and sexual function, the indications for surgery, and the specific procedure being performed. Whether or not estrogen therapy is an option also will affect a woman's postoperative symptoms and experience of surgical menopause. Conclusions: The majority of research on the effects of surgical menopause shows improved psychological well-being and sexual function after hysterectomy for benign disease. Women with depression or sexual problems preoperatively are at increased risk for experiencing a worsening of mood and libido postoperatively. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent ObGyn Serv, Boston, MA 02114 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. RP Shifren, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent ObGyn Serv, 55 Fruit St,Yawkey 10 A, Boston, MA 02114 USA. EM jshifren@partners.org NR 27 TC 35 Z9 39 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2007 VL 14 IS 3 BP 586 EP 591 DI 10.1097/gme.0b013e318032c505 PN 2 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 166JJ UT WOS:000246374700007 PM 17476149 ER PT J AU Aperis, G Fuchs, BB Anderson, CA Warner, JE Calderwood, SB Mylonakis, E AF Aperis, George Fuchs, Beth Burgwyn Anderson, Christine A. Warner, John E. Calderwood, Stephen B. Mylonakis, Eleftherios TI Galleria mellonella as a model host to study infection by the Francisella tularensis live vaccine strain SO MICROBES AND INFECTION LA English DT Article DE Francisella tularensis; Galleria mellonella; Tularemia; phagocytosis ID PROTEUS-MIRABILIS; TULAREMIA; LARVAE; PATHOGENESIS; HEMOLYMPH; VIRULENCE; INSECTS; SYSTEM; MICE AB We used the killing of Galleria mellonella (Lepidoptera: Pyralidae; the greater wax moth) caterpillar by the live vaccine strain (LVS) of Francisella tularensis to develop an invertebrate host system that can be used to study F. tularensis infection and the in vivo effects of antibacterial compounds on F. tularensis LVS. After injection into the insect hemocoel, F. tularensis LVS, killed caterpillars despite the association of LVS with hemocytes. The rate of killing depended on the number of bacteria injected. Antibiotic therapy with ciprofloxacin, levofloxacin or streptomycin administered before or after inoculation prolonged survival and decreased the tissue burden of F. tularensis in the hemocoel. Delayed drug treatment reduced the efficacy of antibacterials and especially streptomycin. The G. mellonella-F. tularensis LVS system may facilitate the in vivo study of F. tularensis, efficacy with antibacterial agents. (C) 2007 Elsevier Masson SAS. All rights reserved. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. New England Reg Ctr Excellence Biodef & Emerging, Boston, MA 02115 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [AI057159, K08 AI063084, AI63084, K08 AI063084-01, K08 AI063084-02, K08 AI063084-03, U54 AI057159] NR 23 TC 63 Z9 63 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2007 VL 9 IS 6 BP 729 EP 734 DI 10.1016/j.micinf.2007.02.016 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 174ZC UT WOS:000246980500006 PM 17400503 ER PT J AU Lipschutz, JH Huber, WG Dahman, MH Thomas, D AF Lipschutz, Joshua H. Huber, Wilhain G. Dahman, Marc H. Thomas, Deanna TI Practical advance in obtaining an emergency airway via cricothyroidotomy SO MILITARY MEDICINE LA English DT Article AB By the time a cricothyroidotomy is deemed necessary, the patient is in critical need of an emergency airway before anoxic damage ensues. Two things are necessary for the delivery of the requisite oxygen. First, an airway must be rapidly established. Second, the airway must be large enough to facilitate ventilation. Present methods for emergency cricothyroidotomy include needle cricothyroidotomy, which suffers from difficulties in both establishment and ventilation. We describe here a practical and widely available method for establishing a timely effective airway that has been used successfully for five patients since 1992. C1 Lutheran Gen Hosp, Dept Trauma Serv, Park Ridge, IL 60068 USA. Thomas Family Dent, Hermittage, PA 16148 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Overland Pk Reg Trauma Ctr, Overland Pk, KS 66215 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 2007 VL 172 IS 5 BP 504 EP 506 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 167XC UT WOS:000246484800012 ER PT J AU Mehra, R Tomlins, SA Shen, RL Nadeem, O Wang, L Wei, JT Pienta, KJ Ghosh, D Rubin, MA Chinnaiyan, AM Shah, RB AF Mehra, Rohit Tomlins, Scott A. Shen, Ronglai Nadeem, Owais Wang, Lei Wei, John T. Pienta, Kenneth J. Ghosh, Debashis Rubin, Mark A. Chinnaiyan, Arul M. Shah, Rajal B. TI Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer SO MODERN PATHOLOGY LA English DT Article DE localized prostate cancer; TMPRSS2; ETS; fluorescent in situ hybridization; gene aberrations ID RADICAL PROSTATECTOMY; FUSION; RECURRENCE; EXPRESSION AB Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart ( TMPRSS2, ERG, ETV4) and one fusion (TMPRSS: ETV1) fluorescence in situ hybridization ( FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2: ERG and TMPRSS2: ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2: ERG fusion, our assays allowed us to detect deletion of the 30 end of TMPRSS2 and the 50 end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P = 0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 50 and 30 partners may be involved in gene fusions in prostate cancer. C1 Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biostat, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Michigan Urol Ctr, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Bioinformat Program, Sch Med, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Shah, RB (reprint author), Univ Michigan, Dept Pathol, Sch Med, 2G332 UH,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM rajshah@umich.edu RI Wei, John/E-8967-2012; Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50CA69568, U01 CA1113913] NR 19 TC 175 Z9 186 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2007 VL 20 IS 5 BP 538 EP 544 DI 10.1038/modpathol.3800769 PG 7 WC Pathology SC Pathology GA 158YB UT WOS:000245830400005 PM 17334343 ER PT J AU Buttery, SM Yoshida, S Pellman, D AF Buttery, Shawnna M. Yoshida, Satoshi Pellman, David TI Yeast formins Bni1 and Bnr1 utilize different modes of cortical interaction during the assembly of actin cables SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CELL POLARITY; HOMOLOGY-2 DOMAIN; CAPPING PROTEIN; SECRETORY VESICLES; BINDING PROTEIN; FISSION YEAST; CYTOSKELETON; PROFILIN AB The budding yeast formins Bni1 and Bnr1 control the assembly of actin cables. These formins exhibit distinct patterns of localization and polymerize two different populations of cables: Bni1 in the bud and Bnr1 in the mother cell. We generated a functional Bni1-3GFP that improved the visualization of Bni1 in vivo at endogenous levels. Bni1 exists as speckles in the cytoplasm, some of which colocalize on actin cables. These Bni1 speckles display linear, retrograde-directed movements. Loss of polymerized actin or specifically actin cables abolished retrograde movement, and resulted in depletion of Bni1 speckles from the cytoplasm, with enhanced targeting of Bni1 to the bud tip. Mutations that impair the actin assembly activity of Bni1 abolished the movement of Bni1 speckles, even when actin cables were present. In contrast, Bnr1-GFP or 3GFP-Bnr1 did not detectably associate with actin cables and was not observed as cytoplasmic speckles. Finally, fluorescence recovery after photobleaching demonstrated that Bni1 was very dynamic, exchanging between polarized sites and the cytoplasm, whereas Bnr1 was confined to the bud neck and did not exchange with a cytoplasmic pool. In summary, our results indicate that formins can have distinct modes of cortical interaction during actin cable assembly. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu RI Yoshida, Satoshi/C-5016-2011 NR 69 TC 68 Z9 68 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2007 VL 18 IS 5 BP 1826 EP 1838 DI 10.1091/mbc.E06-09-0820 PG 13 WC Cell Biology SC Cell Biology GA 166US UT WOS:000246406700025 PM 17344480 ER PT J AU Sheth, RA Upadhyay, R Weissleder, R Mahmood, U AF Sheth, Rahul A. Upadhyay, Rabi Weissleder, Ralph Mahmood, Umar TI Real-time multichannel imaging framework for endoscopy, catheters, and fixed geometry intraoperative systems SO MOLECULAR IMAGING LA English DT Article ID BRAIN-TUMOR RESECTION; PRECLINICAL MODEL; GENE-EXPRESSION; CANCER; FEASIBILITY; VALIDATION; MARGINS; GLIOMAS; MICE AB To address the need for a clinically applicable intravital optical imaging system, we developed a new hardware and software framework. We demonstrate its utility by applying it to an endoscope-based white light and fluorescent imaging system. The capabilities include acquisition and visualization algorithms that perform registration, segmentation, and histogram-based autoexposure of two imaging channels (full-spectrum white light and near-infrared fluorescence), all in real time. Data are processed and saved as 12-bit files, matching the standards of clinical imaging. Dynamic range is further improved by the evaluation of flux as a quantitative parameter. The above features are demonstrated in a series of in vitro experiments, and the in vivo application is shown with the visualization of fluorescent-labeled vasculature of a mouse peritoneum. The approach may be applied to diverse systems, including handheld devices, fixed geometry intraoperative devices, catheter-based imaging, and multimodal systems. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Smiches 8226,185 Cambridge St, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [R24-CA92782]; NIBIB NIH HHS [R01-EB001872] NR 20 TC 12 Z9 12 U1 0 U2 3 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD MAY-JUN PY 2007 VL 6 IS 3 BP 147 EP 155 DI 10.2310/7290.2007.00012 PG 9 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 186NP UT WOS:000247785700001 PM 17532881 ER PT J AU Liu, CH Huang, SN Kim, YR Rosen, BR Liu, PK AF Liu, Christina H. Huang, Shuning Kim, Young R. Rosen, Bruce R. Liu, Philip K. TI Forebrain ischemia-reperfusion simulating cardiac arrest in mice induces edema and DNA fragmentation in the brain SO MOLECULAR IMAGING LA English DT Article ID APPARENT DIFFUSION-COEFFICIENT; FOCAL CEREBRAL-ISCHEMIA; IRON-OXIDE PARTICLES; FOS MESSENGER-RNA; DEATH IN-VIVO; C-FOS; CELL-DEATH; ANTISENSE OLIGONUCLEOTIDE; MOUSE-BRAIN; PHYSICOCHEMICAL PROPERTIES AB Brain injury affects one-third of persons who survive after heart attack, even with restoration of spontaneous circulation by cardiopulmonary resuscitation. We studied brain injury resulting from transient bilateral carotid artery occlusion (BCAO) and reperfusion by simulating heart attack and restoration of circulation, respectively, in live C57Black6 mice. This model is known to induce neuronal death in the hippocampus, striatum, and cortex. We report the appearance of edema after transient BCAO of 60 minutes and 1 day of reperfusion. Hyperintensity in diffusion-weighted magnetic resonance imaging (MRI) was detectable in the striatum, thalamus, and cortex but not in the hippocampus. To determine whether damage to the hippocampus can be detected in live animals, we infused a T-2 susceptibility magnetic resonance contrast agent (superparamagnetic iron oxide nanoparticles [SPIONs]) that was linked to single-stranded deoxyribonucleic acid (DNA) complementary in sequence to c-fos messenger ribonucleic acid (SPION-cfos); we acquired in vivo T-2*-weighted MRI 3 days later. SPION retention was measured as T-2* (milliseconds) signal reduction or R-2* value (s(-1)) elevation. We found that animals treated with 60-minute BCAO and 7-day reperfusion exhibited significantly less SPION retention in the hippocampus and cortex than sham-operated animals. These findings suggest that brain injury induced by cardiac arrest can be detected in live animals. C1 Massachusetts Gen Hosp, Dept Radiol, Transcript Imaging & NeuroRepair Lab, Charlestown, MA 02129 USA. AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Transcript Imaging & NeuroRepair Lab, 149 13th St,Room 2410, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIBIB NIH HHS [T32 EB001680]; NINDS NIH HHS [R01 NS045845, R21 NS057556, R01 NS045845-04, R21 NS057556-01A1S1, R21 NS057556-01A1, R01NS45845] NR 61 TC 14 Z9 14 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD MAY-JUN PY 2007 VL 6 IS 3 BP 156 EP 170 DI 10.2310/7290.2007.00011 PG 15 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 186NP UT WOS:000247785700002 PM 17532882 ER PT J AU Duran-Pinedo, AE Nishikawa, K Duncan, MJ AF Duran-Pinedo, Ana E. Nishikawa, Kiyoshi Duncan, Margaret J. TI The RprY response regulator of Porphyromonas gingivalis SO MOLECULAR MICROBIOLOGY LA English DT Article ID NADH-QUINONE OXIDOREDUCTASE; GENE-EXPRESSION; VIBRIO-CHOLERAE; BACTEROIDES-FRAGILIS; ESCHERICHIA-COLI; SIGNAL-TRANSDUCTION; BACILLUS-SUBTILIS; OXIDATIVE STRESS; IDENTIFICATION; PROMOTER AB Porphyromonas gingivalis is a Gram-negative oral anaerobe associated with chronic adult periodontitis. Its ecological niche is the gingival crevice, where the organism adapts to the challenges of the infectious process such as host defence and bacterial products. Bacterial responses to environmental changes are partly regulated by two-component signal transduction systems. Several intact systems were annotated in the genome of P. gingivalis, as well as an orphan regulator encoding a homologue of RprY, a response regulator from Bacteroides fragilis. With the goal of defining the environmental cues that activate RprY in P. gingivalis, we used several strategies to identify its regulon. Results from gene expression and DNA-protein binding assays identified target genes that were either involved in transport functions or associated with oxidative stress, and indicated that RprY can act as an activator and a repressor. RprY positively activated the primary sodium pump, NADH : ubiquinone oxidoreductase (NQR), and RprY protein also interacted with the promoter regions of nqrA genes from B. fragilis and Vibrio cholerae. Given that gingival bleeding and infiltration of host defence cells are symptoms of periodontal infection, iron products released from blood and reactive oxygen species from polymorphonuclear leucocytes may be potential inducers of the RprY regulon. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Aichi Gakuin Univ, Sch Dent, Dept Microbiol, Nagoya, Aichi 4648650, Japan. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. EM mduncan@forsyth.org FU NIDCR NIH HHS [R01 DE015931] NR 37 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2007 VL 64 IS 4 BP 1061 EP 1074 DI 10.1111/j.1365-2958.2007.05717.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 166RY UT WOS:000246398900017 PM 17501928 ER PT J AU Kaplan, LM Gorman, MJ AF Kaplan, Lee M. Gorman, Mark J. TI Addressing the big challenge of obesity: how to prevent regain of lost weight SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE obesity; self-regulation; weight loss; weight loss maintenance programs; weight regain C1 Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, MGH Weight Ctr, 4th Floor,50 Staniford St, Boston, MA 02114 USA. EM lmkaplan@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD MAY PY 2007 VL 4 IS 5 BP 254 EP 255 DI 10.1038/ncpgasthep0793 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 163TW UT WOS:000246187100007 PM 17426716 ER PT J AU Polkinghorn, WR Tarbell, NJ AF Polkinghorn, William R. Tarbell, Nancy J. TI Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE histopathologic; medulloblastoma; molecular; pathogenesis; risk stratification ID CENTRAL-NERVOUS-SYSTEM; PRIMITIVE NEUROECTODERMAL TUMOR; CHILDRENS CANCER GROUP; LARGE CELL/ANAPLASTIC MEDULLOBLASTOMAS; CRANIOSPINAL RADIATION-THERAPY; PROSPECTIVE RANDOMIZED TRIAL; CHROMOSOME 17P DELETIONS; PEDIATRIC-ONCOLOGY-GROUP; SONIC HEDGEHOG; CHILDHOOD MEDULLOBLASTOMA AB Medulloblastoma is the most common brain malignancy in children and tremendous advances have recently been made in understanding the pathogenesis of this tumor. The Hedgehog and Wingless signaling pathways are implicated in medulloblastoma development, and both pathways were discovered as a result of analyses of genetic syndromes associated with the tumor. Over the past 80 years, considerable progress has been made in the treatment of what was once a fatal disease. The first survival reports followed the introduction of craniospinal irradiation, and yet the success of this modality, which continues to be a central component of treatment regimens for patients older than 3 years, comes at a significant cost. The present challenge in medulloblastoma treatment is to improve upon existing survival rates and to minimize the side effects of treatment. The current tools of clinical risk assessment fail to adequately identify patients older than 3 years who require less radiation and those who require more radiation. Significant effort has been made to improve clinical risk stratification and titration of treatment by analyzing properties of the tumor cells themselves for prognostic significance. These efforts include identifying histopathologic, cytogenetic, and molecular features that may correlate with prognosis. C1 Massachusetts Gen Hosp, Pediat Radiat Oncol Unit, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tarbell, NJ (reprint author), Massachusetts Gen Hosp, Pediat Radiat Oncol Unit, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ntarbell@partners.org NR 95 TC 97 Z9 104 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAY PY 2007 VL 4 IS 5 BP 295 EP 304 DI 10.1038/ncponc0794 PG 10 WC Oncology SC Oncology GA 161FK UT WOS:000245999700009 PM 17464337 ER PT J AU Willett, CG Duda, DG di Tomaso, E Boucher, Y Czito, BG Vujaskovic, Z Vlahovic, G Bendell, J Cohen, KS Hurwitz, HI Bentley, R Lauwers, GY Poleski, M Wong, TZ Paulson, E Ludwig, KA Jain, RK AF Willett, Christopher G. Duda, Dan G. di Tomaso, Emmanuelle Boucher, Yves Czito, Brian G. Vujaskovic, Zeljko Vlahovic, Gordana Bendell, Johanna Cohen, Kenneth S. Hurwitz, Herbert I. Bentley, Rex Lauwers, Gregory Y. Poleski, Martin Wong, Terence Z. Paulson, Erik Ludwig, Kirk A. Jain, Rakesh K. TI Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Article DE bevacizumab; chemotherapy; radiation therapy; rectal carcinoma; VEGF ID COMPUTED-TOMOGRAPHY; ULTRASOUND; EXPERIENCE; CARCINOMA; ACCURACY; THERAPY; MARKERS; COLON AB Background Localized rectal cancer responds well to 5-fluorouracil and radiation-based regimens. A phase I-II trial is currently testing the efficacy of adding bevacizumab, a VEGF-specific antibody, to standard chemoradiotherapy. The case presented here is a complete pathological response seen in a patient with extensive and locally invasive carcinoma after receiving this combined treatment. Investigations Physical examination, rectal ultrasound, PET-CT scan, laboratory tests, proctoscopic examination, chest radiograph, rectal forcep biopsies with immunohistochemistry, and protein and flow cytometric analyses. Diagnosis Large, invasive, ultrasound stage T4 carcinoma of the rectum, which was positive for survivin. Management One 2-week cycle of bevacizumab alone, followed by 3 cycles of bevacizumab with continuous 5-fluorouracil infusion, and external-beam radiation therapy given 5 days per week to the pelvis, abdominoperineal resection with posterior vaginectomy, hysterectomy and bilateral salpingo-oophorectomy. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Willett, CG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3085, Durham, NC 27710 USA. EM christopher.willett@duke.edu FU NCI NIH HHS [R21- CA099237, R01-CA98706, R01 CA098706, R01 CA098706-05, P01-CA80124, R21 CA099237, P01 CA080124-08, P01 CA080124, P01 CA080124-07, R21 CA099237-02] NR 23 TC 40 Z9 40 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAY PY 2007 VL 4 IS 5 BP 316 EP 321 DI 10.1038/ncponc0813 PG 6 WC Oncology SC Oncology GA 161FK UT WOS:000245999700011 PM 17464339 ER PT J AU Rioux, JD Xavier, RJ Taylor, KD Silverberg, MS Goyette, P Huett, A Green, T Kuballa, P Barmada, MM Datta, LW Shugart, YY Griffiths, AM Targan, SR Ippoliti, AF Bernard, EJ Mei, L Nicolae, DL Regueiro, M Schumm, LP Steinhart, AH Rotter, JI Duerr, RH Cho, JH Daly, MJ Brant, SR AF Rioux, John D. Xavier, Ramnik J. Taylor, Kent D. Silverberg, Mark S. Goyette, Philippe Huett, Alan Green, Todd Kuballa, Petric Barmada, M. Michael Datta, Lisa Wu Shugart, Yin Yao Griffiths, Anne M. Targan, Stephan R. Ippoliti, Andrew F. Bernard, Edmond-Jean Mei, Ling Nicolae, Dan L. Regueiro, Miguel Schumm, L. Philip Steinhart, A. Hillary Rotter, Jerome I. Duerr, Richard H. Cho, Judy H. Daly, Mark J. Brant, Steven R. TI Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis SO NATURE GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; DENDRITIC CELLS; NADPH OXIDASE; GENE; COMPLEX; ANTIGEN; LOCALIZATION; CONCORDANCE; EXPRESSION; VARIANTS AB We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations ( combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease. C1 Univ Montreal, Montreal, PQ H1T 1C8, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA. Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. Johns Hopkins Univ, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21231 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. Univ Montreal, Montreal, PQ H2W 1V1, Canada. CHUM, Hotel Dieu, Montreal, PQ H2W 1V1, Canada. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Pittsburgh, Med Ctr, Sch Med, Dept Med,Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Yale Univ, Dept Med, Div Gastroenterol, Inflammatory Bowel Dis Ctr, New Haven, CT 06519 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Rioux, JD (reprint author), Univ Montreal, 5000 Rue Belanger, Montreal, PQ H1T 1C8, Canada. EM rioux@broad.mit.edu RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; OI Rioux, John/0000-0001-7560-8326; Duerr, Richard/0000-0001-6586-3905; Barmada, M Michael/0000-0002-3604-6460 FU NIAID NIH HHS [AI062773, R01 AI062773]; NIDDK NIH HHS [P30 DK063491-049004, DK 46763, DK43351, DK62413, DK62420, DK62422, DK62423, DK62429, DK62431, DK62432, P01 DK046763, P30 DK040561, P30 DK040561-12, P30 DK043351, P30 DK063491, P30 DK063491-019004, P30 DK063491-029004, P30 DK063491-039004, U01 DK062413, U01 DK062420, U01 DK062422, U01 DK062423, U01 DK062429, U01 DK062431, U01 DK062432, U01 DK062432-06] NR 43 TC 1063 Z9 1093 U1 10 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2007 VL 39 IS 5 BP 596 EP 604 DI 10.1038/ng2032 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 160VU UT WOS:000245971300014 PM 17435756 ER PT J AU Haiman, CA Patterson, N Freedman, ML Myers, SR Pike, MC Waliszewska, A Neubauer, J Tandon, A Schirmer, C McDonald, GJ Greenway, SC Stram, DO Le Marchand, L Kolonel, LN Frasco, M Wong, D Pooler, LC Ardlie, K Oakley-Girvan, I Whittemore, AS Cooney, KA John, EM Ingles, SA Altshuler, D Henderson, BE Reich, D AF Haiman, Christopher A. Patterson, Nick Freedman, Matthew L. Myers, Simon R. Pike, Malcolm C. Waliszewska, Alicja Neubauer, Julie Tandon, Arti Schirmer, Christine McDonald, Gavin J. Greenway, Steven C. Stram, Daniel O. Le Marchand, Loic Kolonel, Laurence N. Frasco, Melissa Wong, David Pooler, Loreall C. Ardlie, Kristin Oakley-Girvan, Ingrid Whittemore, Alice S. Cooney, Kathleen A. John, Esther M. Ingles, Sue A. Altshuler, David Henderson, Brian E. Reich, David TI Multiple regions within 8q24 independently affect risk for prostate cancer SO NATURE GENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; AFRICAN-AMERICAN MEN; VITAMIN-D-RECEPTOR; POLYMORPHISMS; LOCUS AB After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein. C1 Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, Boston, MA 02115 USA. Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. Genom Collaborat, Cambridge, MA 02139 USA. No Calif Canc Ctr, Fremont, CA 94538 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Reich, D (reprint author), Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM reich@genetics.med.harvard.edu RI Altshuler, David/A-4476-2009; Myers, Simon/A-6792-2015 OI Altshuler, David/0000-0002-7250-4107; Myers, Simon/0000-0002-2585-9626 FU NCI NIH HHS [P50 CA069568, CA67044, CA54281, R01 CA067044, R01 CA084979, R01 CA054281, R01 CA063464-09S1, R37 CA054281, R01 CA063464, R01 CA079596, CA69568, U01 CA067044, CA63464, CA84979, U01 CA063464, CA79596]; NHGRI NIH HHS [HG02758, K01 HG002758]; NICHD NIH HHS [HD00850, K12 HD000850] NR 17 TC 433 Z9 451 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2007 VL 39 IS 5 BP 638 EP 644 DI 10.1038/ng2015 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 160VU UT WOS:000245971300019 PM 17401364 ER PT J AU Kumar, MS Lu, J Mercer, KL Golub, TR Jacks, T AF Kumar, Madhu S. Lu, Jun Mercer, Kim L. Golub, Todd R. Jacks, Tyler TI Impaired microRNA processing enhances cellular transformation and tumorigenesis SO NATURE GENETICS LA English DT Article ID EMBRYONIC STEM-CELLS; LUNG-CANCER; EXPRESSION SIGNATURE; K-RAS; DICER; GENE; PROLIFERATION; BIOGENESIS; ONCOGENE AB MicroRNAs ( miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in proliferation, differentiation and apoptosis(1,2), processes commonly altered during tumorigenesis. Recent work has shown a global decrease of mature miRNA expression in human cancers(3). However, it is unclear whether this global repression of miRNAs reflects the undifferentiated state of tumors or causally contributes to the transformed phenotype. Here we show that global repression of miRNA maturation promotes cellular transformation and tumorigenesis. Cancer cells expressing short hairpin RNAs (shRNAs) targeting three different components of the miRNA processing machinery showed a substantial decrease in steady-state miRNA levels and a more pronounced transformed phenotype. In animals, miRNA processing - impaired cells formed tumors with accelerated kinetics. These tumors were more invasive than control tumors, suggesting that global miRNA loss enhances tumorigenesis. Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02139 USA. EM tjacks@mit.edu FU NCI NIH HHS [2-P01-CA42063-21, P30-CA14051] NR 29 TC 864 Z9 914 U1 4 U2 65 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2007 VL 39 IS 5 BP 673 EP 677 DI 10.1038/ng2003 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 160VU UT WOS:000245971300025 PM 17401365 ER PT J AU Ben-Neriah, Y Schmidt-Supprian, M AF Ben-Neriah, Yinon Schmidt-Supprian, Marc TI Epithelial NF-kappa B maintains host gut microflora homeostasis SO NATURE IMMUNOLOGY LA English DT Editorial Material ID INHIBITION; DISEASE; INFLAMMATION; ACTIVATION; IKK AB Epithelial NF-kappa B preserves the integrity of the gut epithelial barrier and coordinates the antimicrobial actions of the innate and adaptive immune systems. Deficiency in or hyperactivation of this transcription factor results in chronic inflammatory bowel disease. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Immunol, IL-91220 Jerusalem, Israel. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Ben-Neriah, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Immunol, IL-91220 Jerusalem, Israel. EM yinon@cc.huji.ac.il RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 NR 14 TC 23 Z9 26 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2007 VL 8 IS 5 BP 479 EP 481 DI 10.1038/ni0507-479 PG 3 WC Immunology SC Immunology GA 158YM UT WOS:000245831600011 PM 17440457 ER PT J AU Shinohara, ML Cantor, H AF Shinohara, Mari L. Cantor, Harvey TI The bridge between dendritic cells and asthma SO NATURE MEDICINE LA English DT Editorial Material ID OSTEOPONTIN EXPRESSION; INHALED ANTIGEN; INFECTION; MIGRATION AB A single molecule, osteopontin, seems to both amplify and quell the immune response in asthma-depending on the stage of the asthmatic reaction. The findings hint that, if given at the right stage, osteopontin might have value as a therapy (pages 570-578). C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shinohara, ML (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Harvey_Cantor@dfci.harvard.edu NR 15 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2007 VL 13 IS 5 BP 536 EP 538 DI 10.1038/nm0507-536 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 165JW UT WOS:000246302800016 PM 17479095 ER PT J AU Lee, SH Goswami, S Grudo, A Song, LZ Bandi, V Goodnight-White, S Green, L Hacken-Bitar, J Huh, J Bakaeen, F Coxson, HO Cogswell, S Storness-Bliss, C Corry, DB Kheradmand, F AF Lee, Seung-Hyo Goswami, Sangeeta Grudo, Ariel Song, Li-zhen Bandi, Venkata Goodnight-White, Sheila Green, Linda Hacken-Bitar, Joan Huh, Joseph Bakaeen, Faisal Coxson, Harvey O. Cogswell, Sebastian Storness-Bliss, Claudine Corry, David B. Kheradmand, Farrah TI Antielastin autoimmunity in tobacco smoking-induced emphysema SO NATURE MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; ELASTIN; AIRWAYS; HEALTH AB Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers. C1 Baylor Coll Med, Dept Med, Sect Pulm & Crit Care, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Radiol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Vancouver Gen Hosp, Dept Radiol, Vancouver, BC V6Z 1Y6, Canada. RP Kheradmand, F (reprint author), Baylor Coll Med, Dept Med, Sect Pulm & Crit Care, Houston, TX 77030 USA. EM dcorry@bcm.tmc.edu; farrahk@bcm.tmc.edu RI Lee, Seung Hyo/C-1689-2011; Lee, Seung-Hyo/B-9922-2015; Coxson, Harvey/A-9861-2017 OI Lee, Seung-Hyo/0000-0003-0010-4072; Coxson, Harvey/0000-0001-5750-9711 NR 15 TC 271 Z9 303 U1 8 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2007 VL 13 IS 5 BP 567 EP 569 DI 10.1038/nm1583 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 165JW UT WOS:000246302800023 PM 17450149 ER PT J AU Force, T Krause, DS Van Etten, RA AF Force, Thomas Krause, Daniela S. Van Etten, Richard A. TI Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition SO NATURE REVIEWS CANCER LA English DT Review ID ENDOPLASMIC-RETICULUM STRESS; CHRONIC MYELOID-LEUKEMIA; HER2-POSITIVE BREAST-CANCER; MYOCARDIAL CAPILLARY GROWTH; UNFOLDED PROTEIN RESPONSE; T-CELL PROLIFERATION; IMATINIB MESYLATE; C-ABL; CARDIAC DYSFUNCTION; OXIDATIVE STRESS AB Cancer therapy has progressed remarkably in recent years. In no area has this been more apparent than in the development of 'targeted therapies', particularly those using drugs that inhibit the activity of certain tyrosine kinases, activating mutations or amplifications of which are causal, or strongly contributory, to tumorigenesis. However, some of these therapies have been associated with toxicity to the heart. Here we summarize what is known about the cardiotoxicity of cancer drugs that target tyrosine kinases. We focus on basic mechanisms through which interruption of specific signalling pathways leads to cardiomyocyte dysfunction and/ or death, and contrast this with therapeutic responses in cancer cells. C1 Thomas Jefferson Univ, Dept Med, Translat Med & Cardiol Div, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Div Hematol Oncol, Boston, MA 02111 USA. RP Force, T (reprint author), Thomas Jefferson Univ, Dept Med, Translat Med & Cardiol Div, 1025 Walnut St, Philadelphia, PA 19107 USA. EM thomas.force@jefferson.edu OI Force, Thomas/0000-0002-0450-8659 NR 109 TC 391 Z9 407 U1 4 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2007 VL 7 IS 5 BP 332 EP 344 DI 10.1038/nrc2106 PG 13 WC Oncology SC Oncology GA 160MZ UT WOS:000245947700012 PM 17457301 ER PT J AU Weisberg, E Manley, PW Cowan-Jacob, SW Hochhaus, A Griffin, JD AF Weisberg, Ellen Manley, Paul W. Cowan-Jacob, Sandra W. Hochhaus, Andreas Griffin, James D. TI Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia SO NATURE REVIEWS CANCER LA English DT Review ID CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; INTOLERANT IM-I; ACCELERATED PHASE AP; PHILADELPHIA-CHROMOSOME; DASATINIB SPRYCEL(R); CLINICAL RESISTANCE; BLAST CRISIS; PATIENTS PTS AB Imatinib, a small-molecule ABL kinase inhibitor, is a highly effective therapy for early-phase chronic myeloid leukaemia (CML), which has constitutively active ABL kinase activity owing to the expression of the BCR-ABL fusion protein. However, there is a high relapse rate among advanced- and blast- crisis- phase patients owing to the development of mutations in the ABL kinase domain that cause drug resistance. Several second-generation ABL kinase inhibitors have been or are being developed for the treatment of imatinibresistant CML. Here, we describe the mechanism of action of imatinib in CML, the structural basis of imatinib resistance, and the potential of second- generation BCR- ABL inhibitors to circumvent resistance. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. Novartis Inst Biomed Res, CH-4056 Basel, Switzerland. Univ Heidelberg III, Med Fak Mannheim, Med Klin, D-68167 Mannheim, Germany. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 540, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu OI Hochhaus, Andreas/0000-0003-0626-0834 NR 88 TC 340 Z9 352 U1 9 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2007 VL 7 IS 5 BP 345 EP U5 DI 10.1038/nrc2126 PG 14 WC Oncology SC Oncology GA 160MZ UT WOS:000245947700013 PM 17457302 ER PT J AU Zhang, ZQ Fan, HY Goldman, JA Kingston, RE AF Zhang, Zhaoqing Fan, Hua-Ying Goldman, Joseph A. Kingston, Robert E. TI Homology-driven chromatin remodeling by human RAD54 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DNA STRAND EXCHANGE; RAD51-SSDNA NUCLEOPROTEIN FILAMENT; RECOMBINATION FACTORS RAD51; DEPENDENT ATPASE; REPAIR PROTEIN; BASE-PAIRS; COMPLEX; YEAST; RECA; RECOGNITION AB Human RAD51 and RAD54 are key players in homologous recombination, a process that requires homology recognition and strand invasion by a RAD51-single-stranded DNA (ssDNA) nucleoprotein filament and chromatin remodeling by RAD54. Here we use in vitro chromatin reconstitution systems to show that RAD51-ssDNA stimulates RAD54-dependent chromatin remodeling in a homology-dependent, polarity-independent manner. This stimulation was not seen with RAD54B or other remodelers. Chromatin remodeling by RAD54 enabled strand invasion by RAD51-ssDNA on nucleosomal templates, which was homology-and polarity-dependent. Three natural RAD54 mutants found in primary cancer cells showed specific defects in remodeling or in the RAD54-RAD51 interaction. We propose that RAD54 is recruited by RAD51-ssDNA filament to the chromatin of the intact chromosome and that it remodels that chromatin to facilitate accessibility for strand exchange. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu FU NCI NIH HHS [CA-093660, K01 CA093660]; NIGMS NIH HHS [GM48405] NR 43 TC 46 Z9 48 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2007 VL 14 IS 5 BP 397 EP 405 DI 10.1038/nsmb1223 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 163TZ UT WOS:000246187400012 PM 17417655 ER PT J AU Kock, N Kasmieh, R Weissleder, R Shah, K AF Kock, Norman Kasmieh, Randa Weissleder, Ralph Shah, Khalid TI Tumor therapy mediated by lentiviral expression of shBcl-2 and S-TRAIL SO NEOPLASIA LA English DT Article DE apoptosis; S-TRAIL; Bcl-2; gliomas; imaging ID IN-VIVO; GLIOMA-CELLS; APOPTOSIS; BCL-2; GENE; CANCER; VECTOR; DEATH; INVASIVENESS; ACTIVATION AB Tumor necrosis factor - related apoptosis-inducing ligand ( TRAIL) can selectively kill tumor cells and, in combination with other agents, could enhance tumor therapy. We explored the combined therapeutic effects of a secretable form of ( S) TRAIL-induced apoptosis and the downregulation of Bcl-2 in human gliomas. We constructed a lentiviral delivery system: 1) for the expression of short hairpin (sh) RNA to downregulate Bcl- 2 and for the expression of S-TRAIL to induce apoptosis in glioma cells; and 2) to follow delivery in vitro and the fate of tumors in real time in vivo. We demonstrate that lentiviral- mediated simultaneous downregulation of Bcl- 2 and S-TRAIL-induced apoptosis leads to an increased expression of activated caspase- 3 and caspase- 7, thus resulting in accelerated S-TRAIL-mediated apoptosis in glioma cells in vitro. Using a highly malignant human glioma model expressing EGFRvIII and firefly luciferase, we show that the combined effect of Bcl-2 downregulation and S-TRAIL-induced apoptosis results in complete eradication of gliomas compared to S-TRAIL monotherapy. These results show that simultaneous triggering of TRAIL-mediated death receptor pathway and downregulation of Bcl-2 by shRNA leads to enhanced eradication of gliomas and serves as a template in developing and monitoring combination therapies for the treatment of drug- resistant cancers. C1 Harvard Univ, Dept Neurol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, CMIR, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Shah, K (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St,5421 CMIR, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu FU NCI NIH HHS [P50 CA086355, R24 CA092782] NR 37 TC 55 Z9 63 U1 0 U2 2 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY PY 2007 VL 9 IS 5 BP 435 EP 442 DI 10.1593/neo.07223 PG 8 WC Oncology SC Oncology GA 174HN UT WOS:000246932900009 PM 17534449 ER PT J AU Reddymasu, S Gaman, A Sarosiek, I Parkman, H Hutson, A Chey, WD Katz, L Lackner, J Koch, K Semler, JR Kuo, B Mccallum, RW AF Reddymasu, S. Gaman, A. Sarosiek, I Parkman, H. Hutson, A. Chey, W. D. Katz, L. Lackner, J. Koch, K. Semler, J. R. Kuo, B. Mccallum, R. W. TI Non-digestible capsule technology to measure amplitude and frequency characteristics of gastric contractions-comparison between healthy and gastroparetic subjects SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2007 VL 19 IS 5 MA 30 BP 429 EP 429 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 165KM UT WOS:000246304400041 ER PT J AU Parkman, HP Hutson, A Katz, L Sitrin, M Kuo, B Sarosiek, I Mccallum, RW Chey, WD Hasler, W Wo, J Koch, K Lackner, J Semler, J AF Parkman, H. P. Hutson, A. Katz, L. Sitrin, M. Kuo, B. Sarosiek, I Mccallum, R. W. Chey, W. D. Hasler, W. Wo, J. Koch, K. Lackner, J. Semler, J. TI Relationship of body mass index (BMI) to gastric emptying of digestible and nondigestible solids SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 Temple Univ, Philadelphia, PA 19122 USA. Univ Buffalo, Buffalo, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Kansas, Kansas City, KS USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Kentucky, Louisville, KY USA. Univ Louisville, Sch Med, Louisville, KY 40292 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. SmartPill Corp, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2007 VL 19 IS 5 MA 33 BP 430 EP 430 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 165KM UT WOS:000246304400044 ER PT J AU Sarosiek, I Parkman, H Kuo, B Hutson, A Lackner, J Katz, L Sitrin, M Sarosiek, J Chey, WD Hasler, W Wo, J Koch, K Semler, J Mccallum, RW AF Sarosiek, I Parkman, H. Kuo, B. Hutson, A. Lackner, J. Katz, L. Sitrin, M. Sarosiek, J. Chey, W. D. Hasler, W. Wo, J. Koch, K. Semler, J. Mccallum, R. W. TI SmartPill as a unique tool for an insight into the relationship between transit times within the upper and the lower alimentary tract in health and disease. SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 Univ Kansas, Kansas City, KS USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Buffalo, Buffalo, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Kentucky, Louisville, KY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. SmartPill Corp, Buffalo, NY USA. Temple Univ, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2007 VL 19 IS 5 MA 39 BP 432 EP 432 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 165KM UT WOS:000246304400050 ER PT J AU Moulton, EA Pendse, G Morris, S Strassman, A Aiello-Lammens, M Becerra, L Borsook, D AF Moulton, Eric A. Pendse, Gautam Morris, Susie Strassman, Andrew Aiello-Lammens, Matthew Becerra, Lino Borsook, David TI Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: An fMRI study SO NEUROIMAGE LA English DT Article DE pain; sensitization; dorsolateral prefrontal cortex; amygdala; S1; brush ID POSITRON-EMISSION-TOMOGRAPHY; SPINOTHALAMIC TRACT NEURONS; ANTERIOR CINGULATE CORTEX; BRUSH-EVOKED ALLODYNIA; REGIONAL PAIN SYNDROME; NUCLEUS RAPHE MAGNUS; BRAIN-STEM; FUNCTIONAL MRI; NEUROGENIC HYPERALGESIA; INTRADERMAL INJECTION AB The aim of this study was to differentiate the processing of nociceptive information, matched for pain intensity, from capsaicin-induced hyperalgesic vs. control skin at multiple levels in the trigeminal nociceptive pathway. Using an event-related fMRI approach, 12 male subjects underwent three functional scans beginning 1 h after topical application of capsaicin to a defined location on the maxillary skin, when pain from capsaicin application had completely subsided. Brush and two levels of painful heat (low-Thermal-1 and high-Thermal-2) were applied to the site of capsaicin application and to the mirror image region on the opposite side. Temperatures for each side were set to evoke perceptually matched pain (mean temperatures [capsaicin/control]: Thermal-1= 38.4/42.8 degrees C; Thermal- 2 = 44.9/47.8 degrees C). We found differences in activation patterns following stimuli to treated and untreated sides in sensory circuits across all stimulus conditions. Across the trigeminal nociceptive pathway, Thermal-2 stimulation of hyperalgesic skin evoked greater activation in trigeminal ganglion and nucleus, thalamus, and somatosensory cortex than the control side. Thus, trigeminal nociceptive regions showed increased activation in the context of perceptually equal pain levels. Beyond these regions, contrast analyses of capsaicin vs. control skin stimulation indicated significant changes in bilateral dorsolateral prefrontal cortex and amygdala. The involvement of these emotion-related regions suggests that they may be highly sensitive to context, such as prior experience (application of capsaicin) and the specific pain mechanism (hyperalgesic vs. normal skin). (c) 2007 Elsevier Inc. All rights reserved. C1 McLean Hosp, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02478 USA. Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,MIT, Charlestown, MA 02129 USA. RP Moulton, EA (reprint author), McLean Hosp, Brain Imaging Ctr, PAIN Grp, 115 Mill St, Belmont, MA 02478 USA. EM emoulton@mclean.harvard.edu OI Aiello-Lammens, Matthew/0000-0002-6180-5959 FU NINDS NIH HHS [NS042721, R01 NS042721] NR 84 TC 32 Z9 33 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2007 VL 35 IS 4 BP 1586 EP 1600 DI 10.1016/j.neuroimage.2007.02.001 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 161TV UT WOS:000246039900020 PM 17407825 ER PT J AU Martuza, RL AF Martuza, Robert L. TI Single nucleotide polymorphism 309 affects murin-double-minute 2 protein expression but not glioma tumorigenesis - Commentary SO NEUROLOGIA MEDICO-CHIRURGICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JAPAN NEUROSURGICAL SOC PI TOKYO PA C/O AKAMON-MAE IWATA BLDG, 5-27-8 HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0470-8105 J9 NEUROL MED-CHIR JI Neurol. Med.-Chir. PD MAY PY 2007 VL 47 IS 5 BP 209 EP 209 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168BI UT WOS:000246496800007 ER PT J AU Barker, FG AF Barker, Fred G., II TI Efficacy of prophylactic antibiotics against meningitis after craniotomy: A meta-analysis SO NEUROSURGERY LA English DT Article DE antibiotic prophylaxis; meningitis; meta-analysis; nosocomial; surgical site infection; surgical wound infection ID NEGATIVE BACILLARY MENINGITIS; NEUROSURGICAL SITE INFECTIONS; CEREBROSPINAL-FLUID SHUNTS; RANDOMIZED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; RISK-FACTORS; ANTIMICROBIAL PROPHYLAXIS; BACTERIAL-MENINGITIS; WOUND-INFECTION; NOSOCOMIAL MENINGITIS AB OBJECTIVE: Although prophylactic antibiotics have been shown by randomized clinical trials (RCTs) to help prevent deep infection after craniotomies, recent reports have suggested that antibiotics are not effective in preventing postcraniotomy meningitis. METHODS: Data on meningitis as an end point from RCTs on prophylactic antibiotics for craniotomies were pooled in a random-effects meta-analysis. RESULTS: Six prospective randomized trials or trial subgroups enrolling 1729 patients or operations were identified. Antibiotics reduced postoperative infection rates in five of the six RCTs; no trial individually showed a statistically significant benefit from antibiotics. The pooled odds ratio for meningitis with antibiotic treatment in the six RCTs was 0.43 (95% confidence interval, 0.20-0.92; P = 0.03). Subgroup analyses showed no detectable difference in antibiotic efficacy if antibiotics, with or without gram-negative coverage, were used or if the trial was single or double blinded. A sensitivity analysis showed modest dependence of the results of the analysis on the specific definition of postoperative meningitis used in interpreting trial results. CONCLUSION: Prophylactic antibiotics administered before craniotomy reduce rates of postoperative meningitis by approximately one-half, a statistically and clinically significant benefit. C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Neurosurg Serv, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 98 TC 34 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2007 VL 60 IS 5 BP 887 EP 894 DI 10.1227/01.NEU.0000255425.31797.23 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 162UQ UT WOS:000246115400023 PM 17460524 ER PT J AU Choi, JK Dedeoglu, A Jenkins, BG AF Choi, Ji-Kyung Dedeoglu, Alpaslan Jenkins, Bruce G. TI Application of MRS to mouse models of neurodegenerative illness SO NMR IN BIOMEDICINE LA English DT Review DE MRS; N-acetylaspartate; neurodegenerative disease; Alzheimer's disease; Huntington's disease; Parkinson's disease; transgenic mice ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYL-ASPARTATE; AMYOTROPHIC-LATERAL-SCLEROSIS; FOCAL CEREBRAL-ISCHEMIA; PROTON NMR-SPECTROSCOPY; VIVO H-1-NMR SPECTROSCOPY; HUNTINGTONS-DISEASE MICE; BRAIN ENERGY-METABOLISM; TEMPORAL-LOBE EPILEPSY; MOLECULAR WATER PUMP AB The rapid development of transgenic mouse models of neurodegenerative diseases, in parallel with the rapidly expanding growth of MR techniques for assessing in vivo, non-invasive, neurochemistry, offers the potential to develop novel markers of disease progression and therapy. In this review we discuss the interpretation and utility of MRS for the study of these transgenic mouse and rodent models of neurodegenerative diseases such as Alzheimer's (AD), Huntington's (HD) and Parkinson's disease (PD). MRS Studies can provide a wealth of information on various facets of in vivo neurochemistry, including neuronal health, gliosis, osmoregulation, energy metabolism, neuronal-glial cycling, and molecular synthesis rates. These data provide information on the etiology, natural history and therapy of these diseases. Mouse models enable longitudinal studies with useful time frames for evaluation of neuroprotection and therapeutic interventions using many of the potential MRS markers. In addition, the ability to manipulate the genome in these models allows better mechanistic understanding of the roles of the observable neurochemicals, such as N-acetylaspartate, in the brain. The argument is made that use of MRS, combined with correlative histology and other MRI techniques, will enable objective markers with which potential therapies can be followed in a quantitative fashion. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Boston Univ, Sch Med, Bedford VA Med Ctr, Dept Neurol, Bedford, MA USA. RP Jenkins, BG (reprint author), Bldg 149,13th St, Charlestown, MA 02129 USA. EM bgj@nimr.mgh.harvard.edu OI Dedeoglu, Alpaslan/0000-0003-1156-0874 NR 169 TC 63 Z9 64 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2007 VL 20 IS 3 BP 216 EP 237 DI 10.1002/nbm.1145 PG 22 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 168XJ UT WOS:000246557000005 PM 17451183 ER PT J AU Lusk, J Winne, M DeLeskey, K AF Lusk, Janet Winne, Maria DeLeskey, Kathleen TI Nurses' perceptions of working with students in the clinical setting SO NURSE EDUCATOR LA English DT Article C1 Lawrence Mem Regis Coll, Nursing Program, Medford, MA 02155 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Winchester Hosp, Winchester, MA USA. RP Lusk, J (reprint author), Lawrence Mem Regis Coll, Nursing Program, 170 Governors Ave, Medford, MA 02155 USA. EM jlusk@lmh.edu NR 7 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-3624 J9 NURS EDUC JI Nurs. Educ. PD MAY-JUN PY 2007 VL 32 IS 3 BP 102 EP 103 DI 10.1097/01.NNE.0000270230.07156.2c PG 2 WC Nursing SC Nursing GA 169YI UT WOS:000246627600004 PM 17496501 ER PT J AU Tracy, EE AF Tracy, Erin E. TI Elective vulvoplasty - A bandage that might hurt SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Dept, Boston, MA 02114 USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Dept, Boston, MA 02114 USA. EM EETracy@partners.org NR 2 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2007 VL 109 IS 5 BP 1179 EP 1180 DI 10.1097/01.AOG.0000260394.25055.79 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171YP UT WOS:000246771600025 PM 17470601 ER PT J AU Ponte, PR Gross, AH Winer, E Connaughton, MJ Hassinger, J AF Ponte, Patricia Reid Gross, Anne H. Winer, Eric Connaughton, Mary J. Hassinger, James TI Implementing an Interdisciplinary Governance Model in a Comprehensive Cancer Center SO ONCOLOGY NURSING FORUM LA English DT Editorial Material ID PATIENT; IMPACT; TEAM; CARE C1 [Ponte, Patricia Reid] Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. [Ponte, Patricia Reid] Brigham & Womens Hosp, Oncol Nursing & Clin Serv, Boston, MA 02115 USA. [Gross, Anne H.] Dana Farber Canc Inst, Adult Ambulatory Serv, Boston, MA 02115 USA. [Winer, Eric] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. [Winer, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Connaughton, Mary J.] Connaughton Consulting, Newton, MA USA. [Hassinger, James] Hassinger & Associates Peterborough, Peterborough, NH USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2007 VL 34 IS 3 BP 611 EP 616 DI 10.1188/07.ONF.611-616 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA 378JG UT WOS:000261316400006 PM 17573318 ER PT J AU Kang, JH Willett, WC Rosner, BA Hankinson, SE Pasquale, LR AF Kang, Jae H. Willett, Walter C. Rosner, Bernard A. Hankinson, Susan E. Pasquale, Louis R. TI Prospective study of alcohol consumption and the risk of primary open-angle glaucoma SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE alcohol; primary open-angle glaucoma; prospective study ID INTRAOCULAR-PRESSURE; OCULAR HYPERTENSION; EYE; DEFINITIONS; ASSOCIATION; PREVALENCE; DISEASE AB Purpose: Alcohol intake reduces intraocular pressure, a risk factor for primary open-angle glaucoma (POAG). We investigated whether alcohol consumption is associated with a reduced risk of POAG. Methods: We followed female nurses from 1980 and male health professionals from 1986 to 2002. Eligible participants were 40+ years old, did not have POAG, and reported receiving eye examinations during follow-up. Information on alcohol consumption, potential confounders and POAG diagnoses were updated by using biennial questionnaires. We identified 856 self-reported POAG cases that were confirmed with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios (RR) of POAG. Results: Alcohol consumption <30 g/day did not influence POAG risk: compared with non-drinkers, the pooled RRs were 0.99 (95% Confidence Interval [Cl]: 0.83-1.19) for drinking <1 0 g/day, 0.96 (95% Cl: 0.76-1.22) for 10-19 g/day, and 0.95 (95% Cl: 0.68-1.33) for 20-29 g/day. Although there were suggestive inverse associations with drinking >30 g/day (RR = 0.71), this was not significant (95% Cl: 0.49-1.04), and no significant linear associations were detected. Risks of POAG did not differ by type of alcoholic beverage consumed. To evaluate the potential for detection bias, we controlled for additional factors, such as frequency of eye exams, but results were similar. Conclusion: In this large prospective study of men and women, alcohol consumption did not influence the risk of POAG. C1 Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Channing Lab, Boston, MA USA. Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA USA. RP Kang, JH (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjhk@channing.harvard.edu FU NCI NIH HHS [CA87969, CA55075]; NEI NIH HHS [EY015473, EY09611]; NHLBI NIH HHS [HL35464] NR 29 TC 25 Z9 26 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD MAY-JUN PY 2007 VL 14 IS 3 BP 141 EP 147 DI 10.1080/09286580601187963 PG 7 WC Ophthalmology SC Ophthalmology GA 186MF UT WOS:000247782100007 PM 17613849 ER PT J AU Yelin, D Boudoux, C Bounia, BE Tearney, GJ AF Yelin, D. Boudoux, C. Bounia, B. E. Tearney, G. J. TI Large area confocal microscopy SO OPTICS LETTERS LA English DT Article ID IN-VIVO; FLUORESCENCE MICROSCOPY; REFLECTANCE MICROSCOPE; MINIATURE ENDOSCOPY; LENS AB Imaging large tissue areas with microscopic resolution in vivo may offer an alternative to random excisional biopsy. We present an approach for performing confocal imaging of large tissue surface areas using spectrally encoded confocal microscopy (SECM). We demonstrate a single-optical-fiber SECM apparatus, designed for imaging luminal organs, that is capable of imaging with a transverse resolution of 2.1 mu m over a subsurface area of 16 cm(2) in less than 1 min. Due to the unique probe configuration and scanning geometery, the speed and resolution of this new imaging technology are! sufficient for comprehensively imaging large tissues areas at a microscopic scale in times that are appropriate for clinical use. (c) 2007 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yelin, D (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM gtearney@partners.org RI Boudoux, Caroline/A-6399-2012 FU NCI NIH HHS [R21CA122161-01] NR 17 TC 35 Z9 36 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAY 1 PY 2007 VL 32 IS 9 BP 1102 EP 1104 DI 10.1364/OL.32.001102 PG 3 WC Optics SC Optics GA 159JE UT WOS:000245860900031 PM 17410249 ER PT J AU Fuhr, PS Liu, L Kuyk, TK AF Fuhr, Patti S. Liu, Lei Kuyk, Thomas K. TI Relationships between feature search and mobility performance in persons with severe visual impairment SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE low vision; mobility; visual rehabilitation; visual search ID EYE-MOVEMENTS; OLDER-ADULTS; LOW-VISION; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; TARGET ECCENTRICITY; FEATURE-INTEGRATION; AGE; CONJUNCTION; TASK AB Purpose. Because visual search requires both the ability to discriminate visual features and the ability to process information in a large field of view, the association between feature search and mobility of visually impaired (VI) subjects was studied. Methods. Forty-four subjects with severe visual impairment participated in the study. Feature search performance (2 x 2 deg square target amid 1 x 1 deg square distracters) was measured for 8- to 16- and 32-item set-sizes on 10 x 10, 20 x 20, and 40 x 40 deg fields. Mobility was evaluated on indoor high-density obstacle courses under photopic and mesopic illumination. Results. In feature search, VI subjects were slower and made more errors than normal subjects, but they searched in a parallel fashion. On the mobility task, VI subjects walked slower and made more obstacle contacts than age-matched normal controls. In VI subjects, performances on feature search and mobility tasks were significantly associated, with 37.5% to 66.9 of variations in the mobility measurements being accounted for by visual search speed. Conclusions. Feature search reaction time can be a good predictor of VI patients' mobility. C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL 35233 USA. Northrop Grumman Informat Technol, Brooks City Base, TX USA. RP Fuhr, PS (reprint author), Univ Alabama, Birmingham VA Med Ctr, 700 S 19th St 124, Birmingham, AL 35233 USA. EM patti.fuhr@va.gov NR 35 TC 9 Z9 9 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD MAY PY 2007 VL 84 IS 5 BP 393 EP 400 DI 10.1097/OPX.0b013e31804f5afb PG 8 WC Ophthalmology SC Ophthalmology GA 171IE UT WOS:000246728600004 PM 17502822 ER PT J AU Song, PC Schwartz, J Blitzer, A AF Song, P. C. Schwartz, J. Blitzer, A. TI The emerging role of botulinum toxin in the treatment of temporomandibular disorders SO ORAL DISEASES LA English DT Review DE botulinum toxin; temporomandibular disorders; headache ID RANDOMIZED CLINICAL-TRIAL; TENSION-TYPE HEADACHE; ROOT GANGLIA NEURONS; TREATMENT PROGRAM; OROFACIAL PAIN; DOUBLE-BLIND; INFLAMMATION; SYMPTOMS; PREVALENCE; RAT AB The objective of this review was to discuss the emerging role of botulinum toxin in the treatment of temporomandibular disorders (TMD), to review the current literature, recent clinical trials, as well as preliminary data from our own clinical study, and to formulate an algorithm for the work-up and treatment of TMD. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Columbia Univ, Dept Clin Otolaryngol, New York, NY USA. NY Ctr Voice & Swallowing Disorders, New York, NY USA. RP Blitzer, A (reprint author), 425 W 59th St, New York, NY 10019 USA. EM ab1136@aol.com NR 49 TC 22 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD MAY PY 2007 VL 13 IS 3 BP 253 EP 260 DI 10.1111/j.1601-0825.2006.01352.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 158SI UT WOS:000245814400001 PM 17448205 ER PT J AU Emerick, KS Fabian, RL Deschler, DG AF Emerick, Kevin S. Fabian, Richard L. Deschler, Daniel G. TI Clinical presentation, management, and outcome of high-grade mucoepidermoid carcinoma of the parotid gland SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 110th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 17-20, 2006 CL Toronto, CANADA SP Amer Acad Otolaryngol Head & Neck Surg ID MAJOR SALIVARY-GLANDS; PROGNOSIS; TUMORS AB OBJECTIVE: To describe clinical features of high-grade (HG) mucoepidermoid carcinoma (MEC) of the parotid gland and assess clinical Outcomes of one surgical management approach. DESIGN/SETTING/METHODS: Retrospective case series in a tertiary care academic institution. Pathology records were reviewed from 1977 to 1997, identifying patients with parotid HG MEC. Available medical records were reviewed for data on clinical features, treatment, and Outcome. RESULTS: increased stage, increased T stage, presence of neck metastasis, and distant metastasis were all associated with poor outcome. Wide local excision and postoperative radiation (XRT) provided 82% local control. XRT alone for NO disease provided 86% regional control, while XRT and neck dissection yielded 74% control in N+ cases. CONCLUSION: High-grade MEC of the parotid gland is an aggressive disease that frequently presents at advanced stage. Parotidectomy with modified radical neck dissection and postoperative XRT provides reasonable local and regional control for patients with N+ disease. Elective selective neck dissection and radiation should be considered for T3 and T4 tumors with NO status. (C) 2007 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Emerick, KS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Kevin_Emerick@meei.harvard.edu NR 11 TC 12 Z9 13 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2007 VL 136 IS 5 BP 783 EP 787 DI 10.1016/j.otohns.2006.11.045 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 164QB UT WOS:000246247600020 PM 17478216 ER PT J AU Stern, J Heist, EK Murray, L Alabiad, C Chung, J Picard, MH Semigran, MJ Ruskin, JN Singh, JP AF Stern, Joshua Heist, E. Kevin Murray, Lorne Alabiad, Chrisfouad Chung, Jeffrey Picard, Michael H. Semigran, Marc J. Ruskin, Jeremy N. Singh, Jagmeet P. TI Elevated estimated pulmonary artery systolic pressure is associated with an adverse clinical outcome in patients receiving cardiac resynchronization therapy SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; pulmonary hypertension; heart failure; cardiac pacing ID HEART-FAILURE; DILATED CARDIOMYOPATHY; HYPERTENSION; MORBIDITY; MORTALITY; SURVIVAL AB Background: A substantial percentage of patients with heart failure remain nonresponsive to cardiac resynchronization therapy (CRT). There is a paucity of information on the impact of baseline elevated pulmonary artery pressure on clinical outcome and on left ventricular reverse remodeling (LV-RR) after CRT. We sought to investigate the impact of elevated estimated pulmonary artery systolic pressure (ePASP) on clinical outcome and LV-RR after CRT. Methods: This study retrospectively analyzed data from 68 subjects with standard indications for CRT over a 12-month period. Subjects were stratified into two groups based on the echocardiographic estimation of pulmonary artery pressure i.e., ePASP >= 50 mmHg (n = 27) and ePASP < 50 mmHg (n = 41). Long-term response was measured as a combined endpoint of heart failure hospitalizations and all cause mortality at 12 months, and compared within the two groups using the Kaplan-Meier method. Follow up echocardiograms to assess for LV-RR were available in 51 subjects (mean duration 7.1 months). LV-RR was defined as any improvement in global systolic function with reduction in left ventricular internal diameter. Results: The study population was composed of 24 women and 44 men (age, mean +/- SD; 70 +/- 11 years), with a decreased left ventricular ejection fraction ([25 +/- 9]%) and a wide QRS (171 +/- 54 ms). There were no significant differences in the clinical features between the high and low ePASP group. Subjects with ePASP >= 50 mmHg had a significantly worse clinical outcome (Hazard ratio (95% CI), 2.0 (1.2-5.5), P = 0.02). Baseline ePASP was not predictive of LV-RR (P = 0.32). Conclusion: In patients receiving CRT, although elevated estimated pulmonary artery systolic pressure (ePASP >= 50 mmHg) does not significantly impact LV reverse remodeling, it is associated with an adverse long-term outcome. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CArdiol Div,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CArdiol Div,Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 14 TC 13 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2007 VL 30 IS 5 BP 603 EP 607 DI 10.1111/j.1540-8159.2007.00719.x PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 161CI UT WOS:000245991500004 PM 17461868 ER PT J AU Kommoss, F Kommoss, S Eichhorn, J Schmidt, D AF Kommoss, F. Kommoss, S. Eichhorn, J. Schmidt, D. TI Transitional cell carcinoma of the ovary. Morphological and clinical features SO PATHOLOGE LA German DT Article DE transitional cell ovarian carcinoma; histological type; immunohistochemistry; differential diagnosis; ovarian cancer; prognosis ID UROTHELIAL DIFFERENTIATION; TUMORS; CHEMOTHERAPY; MARKERS; BLADDER; PATTERN AB Transitional cell carcinoma of the ovary (TCC-O) is a less common type of malignant surface epithelia I-stroma I tumor of the ovary, still with uncertain incidence. Histologically, TCC-O resembles urothelial carcinoma of the urinary system, and by definition does not contain a Brenner tumor component. TCC-O may not be a bona fide urothelial neoplasm, however, but rather a lesion of the Mullerian type derived from the ovarian surface epithelium. This notion is supported by the existence of mixed tumors consisting of TCC-O and other histological types of ovarian carcinoma, as well as the observation that TCC-O has a Mullerian type but not a urothelial-like immunohistochemical profile. Besides metastatic urothelial carcinoma of the urinary tract, the other types of ovarian carcinoma, as well as sex cord-stromal tumors such as adult granulosa cell tumors, have to be considered in the differential diagnosis of TCC-O. A recent analysis of a large series of advanced ovarian carcinomas treated by radical surgery and postoperative chemotherapy confirms studies that had suggested that TCC-O has a better prognosis (with current treatment) than that of the other histological types of ovarian carcinoma. Further studies applying standardized histopathological criteria are needed to clarify the true incidence and behavior of TCC-O. In addition, it is important to study the biological and molecular background of this apparently less aggressive phenotype. C1 Referenzzentrum Gynakopathol, Inst Pathol, D-68159 Mannheim, Germany. Dr Horst Schmidt Kliniken, Abt Gynakol, Wiesbaden, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kommoss, F (reprint author), Referenzzentrum Gynakopathol, Inst Pathol, A2-2, D-68159 Mannheim, Germany. EM kommoss@gyn-patho.de NR 17 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0172-8113 J9 PATHOLOGE JI Pathologe PD MAY PY 2007 VL 28 IS 3 BP 209 EP 214 DI 10.1007/s00292-007-0912-z PG 6 WC Pathology SC Pathology GA 175HK UT WOS:000247004500006 PM 17447068 ER PT J AU Franceschini, MA Thaker, S Themelis, G Krishnamoorthy, KK Bortfeld, H Diamond, SG Boas, DA Arvin, K Grant, PE AF Franceschini, Maria Angela Thaker, Sonal Themelis, George Krishnamoorthy, Kalpathy K. Bortfeld, Heather Diamond, Solomon G. Boas, David A. Arvin, Kara Grant, P. Ellen TI Assessment of infant brain development with frequency-domain near-infrared spectroscopy SO PEDIATRIC RESEARCH LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-VOLUME; ABSORPTION-SPECTRA; OPTICAL-PROPERTIES; NEWBORN-INFANTS; PRETERM INFANTS; VISUAL-CORTEX; HUMAN FETAL; OXYGENATION; FLOW AB This is the first report to demonstrate quantitative monitoring of infant brain development with frequency-domain near-infrared spectroscopy (FD-NIRS). Regionally specific increases in blood volume and oxygen consumption were measured in healthy infants during their first year. The results agree with prior PET and SPECT reports; but, unlike these methods, FD-NIRS is portable and uses nonionizing radiation. Further, new information includes the relatively constant tissue oxygenation with age and location, suggesting a tight control between local oxygen delivery and consumption in healthy infants during brain development. FD-NIRS could become the preferred clinical tool for quantitatively assessing infant brain development. C1 Massachusetts Gen Hosp, Athinuola A Martinos Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neonatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. RP Franceschini, MA (reprint author), Massachusetts Gen Hosp, Athinuola A Martinos Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM mari@nmr.mgh.harvard.edu OI Diamond, Solomon/0000-0002-7589-2942; Bortfeld, Heather/0000-0002-3545-5449 FU NICHD NIH HHS [R01 HD042908-05A1, R01 HD042908, R01-HD42908, R01 HD042908-04, R01 HD042908-03]; NINDS NIH HHS [K23 NS042758, K23 NS42758, K23 NS042758-05] NR 36 TC 68 Z9 71 U1 1 U2 6 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2007 VL 61 IS 5 BP 546 EP 551 DI 10.1203/pdr.0b013e318045be99 PN 1 PG 6 WC Pediatrics SC Pediatrics GA 161HJ UT WOS:000246005100007 PM 17413855 ER PT J AU Profit, J Zupancic, JAF Gould, JB Petersen, LA AF Profit, Jochen Zupancic, John A. F. Gould, Jeffrey B. Petersen, Laura A. TI Implementing pay-for-performance in the neonatal intensive care unit SO PEDIATRICS LA English DT Article DE pay-for-performance programs; quality improvement ID BIRTH-WEIGHT INFANTS; QUALITY-OF-CARE; MODERATELY PREMATURE-INFANTS; FINANCIAL INCENTIVES; MEDICAL-CARE; HEALTH-CARE; IMPROVEMENT; MORTALITY; RATES; EXPERIENCE AB Pay-for-performance initiatives in medicine are proliferating rapidly. Neonatal intensive care is a likely target for these efforts because of the high cost, available databases, and relative strength of evidence for at least some measures of quality. Pay-for-performance may improve patient care but requires valid measurements of quality to ensure that financial incentives truly support superior performance. Given the existing uncertainty with respect to both the effectiveness of pay-for-performance and the state of quality measurement science, experimentation with pay-for-performance initiatives should proceed with caution and in controlled settings. In this article, we describe approaches to measuring quality and implementing pay-for-performance in the NICU setting. C1 Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Texas Childrens Hosp, Sect Neonatol, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Beth Israel Deaconess Med Ctr, Harvard Neonatal Perinatal Med Program, Boston, MA 02215 USA. Calif Perinatal Qual Care Collaborat, Palo Alto, CA USA. Stanford Univ, Perinatal Epidemiol & Hlth Outcomes Res Unit, Div Neonatol, Lucile Packard Childrens Hosp,Sch Med, Palo Alto, CA 94304 USA. RP Profit, J (reprint author), Houston Ctr Qual Care & Utilizat Studies, VA HSR&D 152,200 Holcombe Blvd, Houston, TX 77030 USA. EM profit@bcm.edu OI Zupancic, John/0000-0003-1734-7193 FU NICHD NIH HHS [K23 HD056298, K23 HD056298-01] NR 50 TC 22 Z9 22 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2007 VL 119 IS 5 BP 975 EP 982 DI 10.1542/peds.2006-1565 PG 8 WC Pediatrics SC Pediatrics GA 163IM UT WOS:000246153300014 PM 17473099 ER PT J AU Berryhill, M Kveraga, K Webb, L Hughes, HC AF Berryhill, Marian Kveraga, Kestutis Webb, Lisa Hughes, Howard C. TI Multimodal access to verbal name codes SO PERCEPTION & PSYCHOPHYSICS LA English DT Review ID PRIMATE SUPERIOR COLLICULUS; SACCADIC EYE-MOVEMENTS; CROSS-MODAL INTEGRATION; VISUAL-MOTION SIGNALS; MULTISENSORY INTEGRATION; REACTION-TIME; INTERSENSORY FACILITATION; DIVIDED ATTENTION; HUMAN BRAIN; SENSORIMOTOR INTEGRATION AB Congruent information conveyed over different sensory modalities often facilitates a variety of cognitive processes, including speech perception (Sumby & Pollack, 1954). Since auditory processing is substantially faster than visual processing, auditory-visual integration can occur over a surprisingly wide temporal window (Stein, 1998). We investigated the processing architecture mediating the integration of acoustic digit names with corresponding symbolic visual forms. The digits "1" or "2" were presented in auditory, visual, or bimodal format at several stimulus onset asynchronies; (SOAs; 0, 75, 150, and 225 msec). The reaction times (RTs) for echoing unimodal auditory stimuli were approximately 100 msec faster than the RTs for naming their visual forms. Correspondingly, bimodal facilitation violated race model predictions, but only at SOA values greater than 75 msec. These results indicate that the acoustic and visual information are pooled prior to verbal response programming. However, full expression of this bimodal summation is dependent on the central coincidence of the visual and auditory inputs. These results are considered in the context of studies demonstrating multimodal activation of regions involved in speech production. C1 Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hughes, HC (reprint author), Dartmouth Coll, Dept Psychol & Brain Sci, 6207 Moore Hall, Hanover, NH 03755 USA. EM hch@dartmouth.edu NR 112 TC 9 Z9 9 U1 2 U2 5 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0031-5117 J9 PERCEPT PSYCHOPHYS JI Percept. Psychophys. PD MAY PY 2007 VL 69 IS 4 BP 628 EP 640 DI 10.3758/BF03193920 PG 13 WC Psychology; Psychology, Experimental SC Psychology GA 194SM UT WOS:000248364100016 PM 17727116 ER PT J AU Cole, JA Modell, JG Haight, BR Cosmatos, IS Stoler, JM Walker, AM AF Cole, J. Alexander Modell, Jack G. Haight, Barbara R. Cosmatos, Irene S. Stoler, Joan M. Walker, Alexander M. TI Bupropion in pregnancy and the prevalence of congenital malformations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE bupropion; antidepressants; pregnancy; first trimester; teratogen; congenital malformations; cardiovascular malformations; prevalence; odds ratio; insurance claims ID DRUG-THERAPY; FLUOXETINE; REGISTRIES; EXPOSURE; OUTCOMES; WOMEN; DEPRESSION; TRIMESTER; COMPANY; DEFECTS AB Purpose Reports from the GlaxoSmithKIine Bupropion Pregnancy Registry suggested an increase in cardiovascular defects following exposure to bupropion during pregnancy. We conducted a study of congenital malformations among infants born to women exposed to bupropion during their first trimester. Methods The study used data from UnitedHealthcare between January 1995 and September 2004. We calculated the prevalence of all congenital malformations and cardiovascular malformations associated with bupropion exposure in the estimated first trimester (1213 infants), compared with (1) other antidepressant exposure in the first trimester (4743 infants) and (2) bupropion exposure outside the first trimester (1049 infants). Malformation cases were confirmed through medical record abstraction. We calculated adjusted odds ratios (AORs) using the GEE form of logistic regression. Results For all congenital malformations, the prevalence associated with bupropion first trimester was 23.1 per 1000 infants. The AORs were 0.95 (95%CI 0.62-1.45) and 1.00 (95%CI 0.57-1.73) in comparison to other antidepressants (prevalence 23.2 per 1000) and bupropion outside the first trimester (prevalence 21.9 per 1000), respectively. For cardiovascular malformations, the prevalence associated with bupropion first trimester was 10.7 per 1000 infants. The AORs were 0.97 (95%CI 0.52-1.80) and 1.07 (95%CI 0.48-2.40) in comparison to other antidepressants (prevalence 10.8 per 1000) and bupropion outside the first trimester (prevalence 9.5 per 1000), respectively. Conclusions Results do not support a hypothesis of a teratogenic effect of first trimester bupropion exposure. The prevalence of malformations associated with bupropion exposure in the first trimester was not increased relative to the comparison groups. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 I3 Drug Safety, Epidemiol, Auburndale, MA 02466 USA. GlaxoSmithKline Inc, Neurosci Med Dev Ctr, Res Triangle Pk, NC USA. GlaxoSmithKline Inc, Worldwide Epidemiol, Philadelphia, PA USA. Massachusetts Gen Hosp, Dept Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Cole, JA (reprint author), I3 Drug Safety, Epidemiol, Riverside Ctr,Suite 3-120,275 Grove St, Auburndale, MA 02466 USA. EM alex.cole@i3drugsafety.com NR 29 TC 66 Z9 68 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAY PY 2007 VL 16 IS 5 BP 474 EP 484 DI 10.1002/pds.1296 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 168YP UT WOS:000246560200002 PM 16897811 ER PT J AU Sheng, C Hoopes, PJ Hasan, T Pogue, BW AF Sheng, Chao Hoopes, P. Jack Hasan, Tayyaba Pogue, Brian W. TI Photobleaching-based dosimetry predicts deposited dose in ALA-PpIX PDT of rodent esophagus SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDUCED PROTOPORPHYRIN-IX; INDUCED PHOTODYNAMIC THERAPY; MULTICELL TUMOR SPHEROIDS; HAIRLESS MOUSE SKIN; IN-VIVO; 5-AMINOLEVULINIC ACID; BARRETTS-ESOPHAGUS; LIGHT DOSIMETRY; FRACTIONATED ILLUMINATION; SINGLET OXYGEN AB An improved method to estimate dose to esophageal tissue was investigated in the setting of photodynamic therapy with aminolevulinic acid-induced protoporphyrin IX (PpIX) treatment. A model of treatment-induced edema in the esophagus mucosa proved to be a well controlled and useful way to test the dosimetry model, and the light from the treatment laser together with the PpIX fluorescence intensity could be quantified reliably in real time. Dosimetry calculations based upon the detected fluorescence and bleaching kinetics were used to calculate the "effective" dose to the tissue, and a correlation was shown to exist between this metric and the edema induced in the esophagus. The difference between animals with no detectable treatment effect and those with significant edema was predictable based upon the dose calculation. The underlying assumption in the interpretation of the data is that rapid photobleaching of PpIX occurs when there is ample oxygen supply, and this bleaching is not present when oxygen is limited. This leads to the prediction that integration of the light and drug dose, in intervals where appreciable photobleaching occurs, should provide a prediction of the relative dose of singlet oxygen produced. This detection system and rodent model can be used for prospective dosimetry studies that focus on optimization of esophageal PDT. C1 Harvard Med Sch, Darwin Coll, Thayer Sch Engn, Boston, MA 02115 USA. Harvard Med Sch, Dartmouth Med Sch, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Harvard Med Sch, Darwin Coll, Thayer Sch Engn, Boston, MA 02115 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P01CA84203] NR 31 TC 44 Z9 46 U1 0 U2 6 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2007 VL 83 IS 3 BP 738 EP 748 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179YU UT WOS:000247327400037 PM 17576383 ER PT J AU Hubbard, AE Hughes, JW Bespamyatnov, IO Biewer, T Cziegler, I LaBombard, B Lin, Y McDermott, R Rice, JE Rowan, WL Snipes, JA Terry, JL Wolfe, SM Wukitch, S AF Hubbard, A. E. Hughes, J. W. Bespamyatnov, I. O. Biewer, T. Cziegler, I. LaBombard, B. Lin, Y. McDermott, R. Rice, J. E. Rowan, W. L. Snipes, J. A. Terry, J. L. Wolfe, S. M. Wukitch, S. CA Alcator C-Mod Grp TI H-mode pedestal and threshold studies over an expanded operating space on Alcator C-Mod SO PHYSICS OF PLASMAS LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Division of Plasma Physics of the APS CY OCT 30-NOV 03, 2006 CL Philadelphia, PA SP APS, Div Plasma Phys ID NO MOMENTUM INPUT; POWER THRESHOLD; EDGE PLASMA; ASDEX UPGRADE; TRANSITION; TRANSPORT; CONFINEMENT; TOKAMAK; PARAMETERS; ROTATION AB This paper reports on studies of the edge transport barrier and transition threshold of the high confinement (H) mode of operation on the Alcator C-Mod tokamak [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)], over a wide range of toroidal field (2.6-7.86 T) and plasma current (0.4-1.7 MA). The H-mode power threshold and edge temperature at the transition increase with field. Barrier widths, pressure limits, and confinement are nearly independent of field at constant current, but the operational space at high B shifts toward higher temperature and lower density and collisionality. Experiments with reversed field and current show that scrape-off-layer flows in the high-field side depend primarily on configuration. In configurations with the Bx del B drift away from the active X-point, these flows lead to more countercurrent core rotation, which apparently contributes to higher H-mode thresholds. In the unfavorable case, edge temperature thresholds are higher, and slow evolution of profiles indicates a reduction in thermal transport prior to the transition in particle confinement. Pedestal temperatures in this case are also higher than in the favorable configuration. Both high-field and reversed-field results suggest that parameters at the L-H transition are influencing the evolution and parameters of the H-mode pedestal. (C) 2007 American Institute of Physics. C1 Massachusetts Gen Hosp, Plasma Sci & Fus Ctr, Cambridge, MA 02129 USA. Univ Texas, Fus Res Ctr, Austin, TX 78712 USA. Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA. RP Hubbard, AE (reprint author), Massachusetts Gen Hosp, Plasma Sci & Fus Ctr, Cambridge, MA 02129 USA. RI Bespamyatnov, Igor/C-1200-2013 NR 36 TC 18 Z9 19 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1070-664X EI 1089-7674 J9 PHYS PLASMAS JI Phys. Plasmas PD MAY PY 2007 VL 14 IS 5 AR 056109 DI 10.1063/1.2714297 PG 9 WC Physics, Fluids & Plasmas SC Physics GA 173SN UT WOS:000246892900097 ER PT J AU Ferrari, S Galletti, R Denoux, C De Lorenzo, G Ausubel, FM Dewdney, J AF Ferrari, Simone Galletti, Roberta Denoux, Carine De Lorenzo, Giulia Ausubel, Frederick M. Dewdney, Julia TI Resistance to Botrytis cinerea induced in Arabidopsis by elicitors is independent of salicylic acid, ethylene, or jasmonate signaling but requires PHYTOALEXIN DEFICIENT3 SO PLANT PHYSIOLOGY LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PLANT-DISEASE RESISTANCE; HOST-PATHOGEN INTERACTIONS; SECONDARY METABOLISM; GENE-EXPRESSION; CAMALEXIN BIOSYNTHESIS; SODIUM POLYPECTATE; DEFENSE RESPONSES; METHYL JASMONATE; ACCUMULATION AB Oligogalacturonides (OGs) released from plant cell walls by pathogen polygalacturonases induce a variety of host defense responses. Here we show that in Arabidopsis ( Arabidopsis thaliana), OGs increase resistance to the necrotrophic fungal pathogen Botrytis cinerea independently of jasmonate (JA)-, salicylic acid (SA)-, and ethylene (ET)-mediated signaling. Microarray analysis showed that about 50% of the genes regulated by OGs, including genes encoding enzymes involved in secondary metabolism, show a similar change of expression during B. cinerea infection. In particular, expression of PHYTOALEXIN DEFICIENT3 (PAD3) is strongly up-regulated by both OGs and infection independently of SA, JA, and ET. OG treatments do not enhance resistance to B. cinerea in the pad3 mutant or in underinducer after pathogen and stress1, a mutant with severely impaired PAD3 expression in response to OGs. Similarly to OGs, the bacterial flagellin peptide elicitor flg22 also enhanced resistance to B. cinerea in a PAD3-dependent manner, independently of SA, JA, and ET. This work suggests, therefore, that elicitors released from the cell wall during pathogen infection contribute to basal resistance against fungal pathogens through a signaling pathway also activated by pathogen-associated molecular pattern molecules. C1 Univ Padua, Dipartimento Territorio & Sistemi Agro Forestali, I-35020 Legnaro, Italy. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Roma La Sapienza, Dipartimento Biol Vegetale, I-00185 Rome, Italy. RP Ferrari, S (reprint author), Univ Padua, Dipartimento Territorio & Sistemi Agro Forestali, I-35020 Legnaro, Italy. EM simone.ferrari@unipd.it RI De Lorenzo, Giulia/F-5475-2013; OI De Lorenzo, Giulia/0000-0002-1707-5418; Galletti, Roberta/0000-0001-8299-7649 FU NIDDK NIH HHS [P30 DK040561-12, P30 DK040561]; NIGMS NIH HHS [GM 48707] NR 58 TC 173 Z9 184 U1 4 U2 32 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD MAY PY 2007 VL 144 IS 1 BP 367 EP 379 DI 10.1104/pp.107.095596 PG 13 WC Plant Sciences SC Plant Sciences GA 166DA UT WOS:000246356300030 PM 17384165 ER PT J AU Lu, WN Quintero-Rivera, F Fan, YL Alkuraya, FS Donovan, DJ Xi, QC Turbe-Doan, A Li, QG Campbell, CG Shanske, AL Sherr, EH Ahmad, A Peters, R Rilliet, B Parvex, P Bassuk, AG Harris, DJ Ferguson, H Kelly, C Walsh, CA Gronostajski, RM Devriendt, K Higgins, A Ligon, AH Quade, BJ Morton, CC Gusella, JF Maas, RL AF Lu, Weining Quintero-Rivera, Fabiola Fan, Yanli Alkuraya, Fowzan S. Donovan, Diana J. Xi, Qiongchao Turbe-Doan, Annick Li, Qing-Gang Campbell, Craig G. Shanske, Alan L. Sherr, Elliott H. Ahmad, Ayesha Peters, Roxana Rilliet, Benedict Parvex, Paloma Bassuk, Alexander G. Harris, David J. Ferguson, Heather Kelly, Chantal Walsh, Christopher A. Gronostajski, Richard M. Devriendt, Koenraad Higgins, Anne Ligon, Azra H. Quade, Bradley J. Morton, Cynthia C. Gusella, James F. Maas, Richard L. TI NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects SO PLOS GENETICS LA English DT Article ID CORPUS-CALLOSUM; INTERSTITIAL DELETION; URETERAL BUD; PERINATAL LETHALITY; TETHERED CORD; AXON GUIDANCE; MICE; AGENESIS; BRAIN; TRANSCRIPTION AB Complex central nervous system ( CNS) malformations frequently coexist with other developmental abnormalities, but whether the associated defects share a common genetic basis is often unclear. We describe five individuals who share phenotypically related CNS malformations and in some cases urinary tract defects, and also haploinsufficiency for the NFIA transcription factor gene due to chromosomal translocation or deletion. Two individuals have balanced translocations that disrupt NFIA. A third individual and two half-siblings in an unrelated family have interstitial microdeletions that include NFIA. All five individuals exhibit similar CNS malformations consisting of a thin, hypoplastic, or absent corpus callosum, and hydrocephalus or ventriculomegaly. The majority of these individuals also exhibit Chiari type I malformation, tethered spinal cord, and urinary tract defects that include vesicoureteral reflux. Other genes are also broken or deleted in all five individuals, and may contribute to the phenotype. However, the only common genetic defect is NFIA haploinsufficiency. In addition, previous analyses of Nfia(-/-) knockout mice indicate that Nfia deficiency also results in hydrocephalus and agenesis of the corpus callosum. Further investigation of the mouse Nfia(-/-) and Nfia(-/-) phenotypes now reveals that, at reduced penetrance, Nfia is also required in a dosage- sensitive manner for ureteral and renal development. Nfia is expressed in the developing ureter and metanephric mesenchyme, and Nfia(+/-) and Nfia(+/-) mice exhibit abnormalities of the ureteropelvic and ureterovesical junctions, as well as bifid and megaureter. Collectively, the mouse Nfia mutant phenotype and the common features among these five human cases indicate that NFIA haploinsufficiency contributes to a novel human CNS malformation syndrome that can also include ureteral and renal defects. C1 Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Med Ctr, Renal Sect, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp Western Ontario, Div Neurol, London, ON, Canada. Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Wayne State Univ, Dept Pediat, Div Genet & Metab Disorders, Detroit, MI 48202 USA. Univ Hosp Geneva, Dept Neurosurg, Geneva, Switzerland. Univ Hosp Geneva, Dept Nephrol, Geneva, Switzerland. Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. SUNY Buffalo, Dept Biochem, Buffalo, NY 14260 USA. Univ Louvain, Ctr Human Genet, Louvain, Belgium. RP Maas, RL (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM maas@genetics.med.harvard.edu RI Donovan, Diana/A-1256-2010; Alkuraya, Fowzan/A-1542-2009; OI Alkuraya, Fowzan/0000-0003-4158-341X; Lu, Weining/0000-0002-6570-3044 FU NCI NIH HHS [P30 CA006516, P30CA06516]; NIDDK NIH HHS [R01 DK063316, R01DK063316]; NIGMS NIH HHS [P01 GM061354, P01GM061354] NR 51 TC 45 Z9 45 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2007 VL 3 IS 5 BP 830 EP 843 AR e80 DI 10.1371/journal.pgen.0030080 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 183LI UT WOS:000247573900016 PM 17530927 ER PT J AU Parikh, H Carlsson, E Chutkow, WA Johansson, LE Storgaard, H Poulsen, P Saxena, R Ladd, C Schulze, PC Mazzini, MJ Jensen, CB Krook, A Bjornholm, M Tornqvist, H Zierath, JR Ridderstrale, M Altshuler, D Lee, RT Vaag, A Groop, LC Mootha, VK AF Parikh, Hemang Carlsson, Emma Chutkow, William A. Johansson, Lovisa E. Storgaard, Heidi Poulsen, Pernille Saxena, Richa Ladd, Christine Schulze, P. Christian Mazzini, Michael J. Jensen, Christine Bjorn Krook, Anna Bjornholm, Marie Tornqvist, Hans Zierath, Juleen R. Ridderstrale, Martin Altshuler, David Lee, Richard T. Vaag, Allan Groop, Leif C. Mootha, Vamsi K. TI TXNIP regulates peripheral glucose metabolism in humans SO PLOS MEDICINE LA English DT Article ID THIOREDOXIN-INTERACTING PROTEIN; DIABETES-SUSCEPTIBILITY GENES; SKELETAL-MUSCLE CELLS; INSULIN-RESISTANCE; EXPRESSION; IDENTIFICATION; ASSOCIATION; MICE; DIFFERENTIATION; HYPERGLYCEMIA AB Background Type 2 diabetes mellitus ( T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. Methods and Findings We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein ( TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. Conclusions TXNIP regulates both insulin-dependent and insulin- independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo Univ Hosp, Malmo, Sweden. Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Harvard Mit Div Hlth Sci & Technol, Broad Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Karolinska Inst, Dept Physiol & Pharmacol, Sect Integrat Physiol, Stockholm, Sweden. Karolinska Inst, Dept Mol Med & Surg Sci, Sect Integrat Physiol, Stockholm, Sweden. Novo Nordisk AS, Malov, Denmark. Univ Helsinki, Program Mol Med, Helsinki, Finland. RP Groop, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM Leif.Groop@med.lu.se; vamsi@hms.harvard.edu RI Altshuler, David/A-4476-2009; Ridderstrale, Martin/F-7678-2012; Reinius, Lovisa/C-4555-2014; Krook, Anna/K-1192-2015; OI Altshuler, David/0000-0002-7250-4107; Reinius, Lovisa/0000-0001-5029-0120; Krook, Anna/0000-0002-0891-0258; Zierath, Juleen/0000-0001-6891-7497 NR 56 TC 191 Z9 196 U1 1 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAY PY 2007 VL 4 IS 5 BP 868 EP 879 AR e158 DI 10.1371/journal.pmed.0040158 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 173RH UT WOS:000246889700016 PM 17472435 ER PT J AU Onnela, JP Saramaki, J Hyvonen, J Szabo, G Lazer, D Kaski, K Kertesz, J Barabasi, AL AF Onnela, J.-P. Saramaki, J. Hyvonen, J. Szabo, G. Lazer, D. Kaski, K. Kertesz, J. Barabasi, A.-L. TI Structure and tie strengths in mobile communication networks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE complex systems; complex networks; diffusion and spreading; phase transition; social systems ID COMMUNITY STRUCTURE; COMPLEX NETWORKS AB Electronic databases, from phone to e-mails logs, currently provide detailed records of human communication patterns, offering novel avenues to map and explore the structure of social and communication networks. Here we examine the communication patterns of millions of mobile phone users, allowing us to simultaneously study the local and the global structure of a society-wide communication network. We observe a coupling between interaction strengths and the network's local structure, with the counterintuitive consequence that social networks are robust to the removal of the strong ties but fall apart after a phase transition if the weak ties are removed. We show that this coupling significantly slows the diffusion process, resulting in dynamic trapping of information in communities and find that, when it comes to information diffusion, weak and strong ties are both simultaneously ineffective. C1 Helsinki Univ Technol, Lab Comp Engn, FI-02015 Helsinki, Finland. Univ Oxford, Clarendon Lab, Dept Phys, Oxford OX1 3PU, England. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Complex Networks Res, Notre Dame, IN 46556 USA. Harvard Univ, Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. Budapest Univ Technol & Econ, Dept Theoret Phys, H-1111 Budapest, Hungary. RP Onnela, JP (reprint author), Helsinki Univ Technol, Lab Comp Engn, POB 9203, FI-02015 Helsinki, Finland. EM jp.onnela@physics.ox.ac.uk RI Kertesz, Janos/B-3411-2012; Kaski, Kimmo/G-8067-2012; Saramaki, Jari/E-5226-2011 NR 32 TC 610 Z9 632 U1 7 U2 107 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 2007 VL 104 IS 18 BP 7332 EP 7336 DI 10.1073/pnas.0610245104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164MY UT WOS:000246239400007 PM 17456605 ER PT J AU Sukhdeo, K Mani, M Zhang, YY Dutta, J Yasui, H Rooney, MD Carrasco, DE Zheng, M He, HY Tai, YT Mitsiades, C Anderson, KC Carrasco, DR AF Sukhdeo, Kumar Mani, Mala Zhang, Yunyu Dutta, Jui Yasui, Hiroshi Rooney, Melissa D. Carrasco, Daniel E. Zheng, Mei He, Haiying Tai, Yu-Tzu Mitsiades, Constantine Anderson, Kenneth C. Carrasco, Daniel R. TI Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug therapy; Wnt signaling ID HEMATOPOIETIC STEM-CELLS; MARROW STROMAL CELLS; NF-KAPPA-B; BONE-MARROW; WNT GENE; APOPTOSIS; IDENTIFICATION; EXPRESSION; INHIBITOR; CANCER AB Multiple myeloma (MM) is an invariably fatal form of cancer characterized by clonal proliferation of malignant plasma cells in the bone marrow. The canonical Writ signaling pathway is activated in MM cells through constitutively active beta-catenin, a messenger molecule relevant to growth, survival, and migration of MM cells. The identification of a number of small molecular compounds, such as PKF115-584, which disrupt the interaction of the transcriptionally active beta-catenin/TCF protein complex, provides valuable new therapeutic tools to target an alternative pathway in MM independent of the proteasome. Here we evaluated the transcriptional, proteomic, signaling changes, and biological sequelae associated with the inhibition of Writ signaling in MM by PKF115-584. The compound blocks expression of Writ target genes and induces cytotoxicity in both patient MM cells and MM cell lines without a significant effect in normal plasma cells. In xenograft models of human MM, PKF115-584 inhibits tumor growth and prolongs survival. Taken together, these data demonstrate the efficacy of disrupting the beta-catenin/TCF transcriptional complex to exploit tumor dependence on Writ signaling as a therapeutic approach in the treatment of MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Carrasco, DR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ruben_carrasco@dfci.harvard.edu OI Sukhdeo, Kumar /0000-0001-8725-6081 FU NIGMS NIH HHS [T32 GM007250] NR 36 TC 126 Z9 128 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 2007 VL 104 IS 18 BP 7516 EP 7521 DI 10.1073/pnas.0610299104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164MY UT WOS:000246239400040 PM 17452641 ER PT J AU Calderwood, MA Venkatesan, K Xing, L Chase, MR Vazquez, A Holthaus, AM Ewence, AE Li, N Hirozane-Kishikawa, T Hill, DE Vidal, M Kieff, E Johannsen, E AF Calderwood, Michael A. Venkatesan, Kavitha Xing, Li Chase, Michael R. Vazquez, Alexel Holthaus, Amy M. Ewence, Alexandra E. Li, Ning Hirozane-Kishikawa, Tomoko Hill, David E. Vidal, Marc Kieff, Elliott Johannsen, Eric TI Epstein-Barr virus and virus human protein interaction maps SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE herpesvirus; interactome; replication; yeast two hybrid ID HERPES-SIMPLEX-VIRUS; TYPE-1 RIBONUCLEOTIDE REDUCTASE; INFECTED B-CELLS; INTERACTION NETWORK; MESSENGER-RNA; INTERACTION DATABASE; CELLULAR-PROTEIN; GENE-EXPRESSION; IDENTIFICATION; SEQUENCE AB A comprehensive mapping of interactions among Epstein-Barr virus (EBV) proteins and interactions of EBV proteins with human proteins should provide specific hypotheses and a broad perspective on EBV strategies for replication and persistence. Interactions of EBV proteins with each other and with human proteins were assessed by using a stringent high-throughput yeast two-hybrid system. Overall, 43 interactions between EBV proteins and 173 interactions between EBV and human proteins were identified. EBV-EBV and EBV-human protein interaction, or '' interactome '' maps provided a framework for hypotheses of protein function. For example, LF2, an EBV protein of unknown function interacted with the EBV immediate early R transactivator (Rta) and was found to inhibit Rta transactivation. From a broader perspective, EBV genes can be divided into two evolutionary classes, '' core '' genes, which are conserved across all herpesviruses and subfamily specific, or '' noncore '' genes. Our EBV-EBV interactome map is enriched for interactions among proteins in the same evolutionary class. Furthermore, human proteins targeted by EBV proteins were enriched for highly connected or '' hub '' proteins and for proteins with relatively short paths to all other proteins in the human interactome network. Targeting of hubs might be an efficient mechanism for EBV reorganization of cellular processes. C1 Harvard Univ, Sch Med, Channing Lab, Program Virol,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Program Virol,Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Inst Adv Studies, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Channing Lab, Program Virol,Dept Med, Boston, MA 02115 USA. EM marc.vidal@dfci.harvard.edu; ekieff@rics.bwh.harvard.edu RI Hill, David/B-6617-2011; Calderwood, Mike/B-2475-2014 OI Calderwood, Mike/0000-0001-6475-1418 FU NCI NIH HHS [R01CA85180, R01 CA047006, R01 CA085180, R01CA47006] NR 62 TC 212 Z9 221 U1 4 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 2007 VL 104 IS 18 BP 7606 EP 7611 DI 10.1073/pnas.0702332104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164MY UT WOS:000246239400055 PM 17446270 ER PT J AU Kenet, T Froemke, RC Schreiner, CE Pessah, IN Merzenich, MM AF Kenet, T. Froemke, R. C. Schreiner, C. E. Pessah, I. N. Merzenich, M. M. TI Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autism; brain development; cortical maps; environment; sensory systems ID MICROSOMAL CALCIUM-TRANSPORT; AUTISM SPECTRUM DISORDERS; SUBSTITUTED PCB CONGENERS; RYANODINE RECEPTORS; CA2+ RELEASE; 2,2',3,5',6-PENTACHLOROBIPHENYL PCB-95; DEVELOPMENTAL EXPOSURE; POSTNATAL EXPOSURE; HEARING-LOSS; NEURONS AB Noncoplanar polychlorinated biphenyls (PCBs) are widely dispersed in human environment and tissues. Here, an exemplar noncoplanar PCB was fed to rat dams during gestation and throughout three subsequent nursing weeks. Although the hearing sensitivity and brainstern auditory responses of pups were normal, exposure resulted in the abnormal development of the primary auditory cortex (A1). All was irregularly shaped and marked by internal nonresponsive zones, its topographic organization was grossly abnormal or reversed in about half of the exposed pups, the balance of neuronal inhibition to excitation for All neurons was disturbed, and the critical period plasticity that underlies normal postnatal auditory system development was significantly altered. These findings demonstrate that developmental exposure to this class of environmental contaminant alters cortical development. It is proposed that exposure to noncoplanar PCBs may contribute to common developmental disorders, especially in populations with heritable imbalances in neurotransmitter systems that regulate the ratio of inhibition and excitation in the brain. We conclude that the health implications associated with exposure to noncoplanar PCBs in human populations merit a more careful examination. C1 Univ Calif San Francisco, Keck Ctr Integrat Neurosci, San Francisco, CA 94143 USA. Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. RP Merzenich, MM (reprint author), Massachusetts Gen Hosp, CNY-6012,149 13th St, Boston, MA 02129 USA. EM merz@phy.ucsf.edu OI Schreiner, Christoph/0000-0002-4571-4328; Froemke, Robert/0000-0002-1230-6811 FU NIDCD NIH HHS [R01 DC002260-12, R01 DC002260]; NIEHS NIH HHS [P01 ES011269, P01 ES11269]; NINDS NIH HHS [R01 NS010414, NS34835, P01 NS034835] NR 72 TC 58 Z9 59 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 2007 VL 104 IS 18 BP 7646 EP 7651 DI 10.1073/pnas.0701944104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 164MY UT WOS:000246239400062 PM 17460041 ER PT J AU Levin, M AF Levin, Michael TI Gap junctional communication in morphogenesis SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE gap junctional communication; embryonic patterning; asymmetry; model; electrophoresis ID LEFT-RIGHT ASYMMETRY; NEURAL CREST CELLS; VACUOLAR H+-ATPASE; EARLY AMPHIBIAN EMBRYO; LEFT-RIGHT AXIS; MEDIATED INTERCELLULAR COMMUNICATION; PLANARIAN SCHMIDTEA-MEDITERRANEA; ENDOGENOUS ELECTRIC-FIELDS; REACTION-DIFFUSION SYSTEM; EARLY XENOPUS EMBRYO AB Gap junctions permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology. However, the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development, regeneration, and tumor progression. The molecular mechanisms by which GJC establishes local and long-range instructive morphogenetic cues are just beginning to be understood. This review summarizes the current knowledge of the involvement of GJC in the patterning of both vertebrate and invertebrate systems and discusses in detail several morphogenetic systems in which the properties of this signaling have been molecularly characterized. One model consistent with existing data in the fields of vertebrate left-right patterning and anterior-posterior polarity in flatworm regeneration postulates electrophoretically guided movement of small molecule morphogens through long-range GJC paths. The discovery of mechanisms controlling embryonic and regenerative GJC-mediated signaling, and identification of the downstream targets of GJC-permeable molecules, represent exciting next areas of research in this fascinating field. (c) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Dent Med, Forsyth Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Ctr Regenerat & Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCRR NIH HHS [C06 RR11244]; NIGMS NIH HHS [1 R01 GM06227, R01 GM067227, R01 GM067227-01A1] NR 286 TC 74 Z9 74 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD MAY-JUN PY 2007 VL 94 IS 1-2 BP 186 EP 206 DI 10.1016/j.bpiomolbio.2007.03.005 PG 21 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 180TW UT WOS:000247390000010 PM 17481700 ER PT J AU Hoshino, K Ly, HQ Frangioni, JV Hajjar, RJ AF Hoshino, Kozo Ly, Hung Q. Frangioni, John V. Hajjar, Roger J. TI In vivo tracking in cardiac stem cell-based therapy SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; CONTRAST AGENTS; PROGENITOR CELLS; TRANSGENE EXPRESSION; TOPCARE-AMI; TRANSPLANTATION; ULTRASOUND; MIGRATION; LIGHT; MAGNETODENDRIMERS C1 Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02129 USA. RP Hajjar, RJ (reprint author), Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, 149 13th St,CNY-4, Boston, MA 02129 USA. EM hajjar@cvrc.mgh.harvard.edu NR 47 TC 42 Z9 44 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 2007 VL 49 IS 6 BP 414 EP 420 DI 10.1016/j.pcad.2007.02.005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 174HO UT WOS:000246933100003 PM 17498521 ER PT J AU Fremont, AM Young, AS Chinman, M Pantoja, P Morton, S Koegel, P Sullivan, G Kanouse, D AF Fremont, Allen M. Young, Alexander S. Chinman, Matthew Pantoja, Philip Morton, Sally Koegel, Paul Sullivan, Greer Kanouse, David TI Differences in HIV care between patients with and without severe mental illness SO PSYCHIATRIC SERVICES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; MEDICAL-CARE; PSYCHIATRIC-DISORDERS; SERVICES UTILIZATION; ANCILLARY SERVICES; INFECTED ADULTS; CASE-MANAGEMENT; RISK-FACTORS; HEALTH-CARE AB Objective: This study explored how HIV care differs for infected persons with and without severe mental illness. Methods: Data were obtained through interviews with and chart review of 295 patients with severe mental illness and HIV from public mental health agencies in Los Angeles County and New York City. Data were compared with data from 1,294 HIV patients without severe mental illness from a separate national probability sample. Measures were difficulty obtaining care, whether patients recommend their HIV care provider, hospital problem score, functional health status, and disability days. Results: In Los Angeles, HIV patients with severe mental illness were more likely than those without severe mental illness to have difficulty obtaining care (p < .001); to not recommend their provider (10% versus 5%, p=. 007); and to have problematic hospital care (p=.001), poor health status (p=.001), and more disability days (p <.001). In New York City, HIV patients with severe mental illness were more likely than patients without severe mental illness to have difficulty obtaining care ( p=. 002) and not recommend their provider ( p=. 02). The relationship between severe mental illness and health status in Los Angeles and access in New York City became insignificant after adjustment for sociodemographic factors, drug use, and CD4 cell count. Further adjustment for higher case management rates among HIV patients with severe mental illness reduced disparities only in the West. Conclusions: Patients with severe mental illness experienced more problems with HIV care than patients without severe mental illness, although high case management rates for patients with severe mental illness may have offset some problems. C1 RAND Corp, Dept Hlth, Santa Monica, CA 90407 USA. Greater Los Angeles Vet Hlth Care Syst, Dept Med, Los Angeles, CA USA. Desert Pacific Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. RTI Int, Res Triangle Pk, NC USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RP Fremont, AM (reprint author), RAND Corp, Dept Hlth, 1776 Main St, Santa Monica, CA 90407 USA. EM fremont@rand.org RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU NIMH NIH HHS [P50-MH-54623, R01-MH-55936-05] NR 58 TC 10 Z9 10 U1 5 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2007 VL 58 IS 5 BP 681 EP 688 DI 10.1176/appi.ps.58.5.681 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 161JC UT WOS:000246009700015 PM 17463350 ER PT J AU Recklitis, CJ Rodriguez, P AF Recklitis, Christopher J. Rodriguez, Paola TI Screening childhood cancer survivors with the brief symptom inventory-18: Classification agreement with the symptom checklist-90-revised SO PSYCHO-ONCOLOGY LA English DT Article DE survivorship; screening; distress; BSI-18 ID BECK DEPRESSION INVENTORY; SELF-REPORT QUESTIONNAIRE; YOUNG-ADULT SURVIVORS; PSYCHOLOGICAL DISTRESS; PRIMARY-CARE; HEALTH QUESTIONNAIRE; DIAGNOSTIC-TESTS; BREAST-CANCER; SCALE; PREVALENCE AB The Brief Symptom Inventory-18 (BSI-18) is an 18-item symptom checklist used as a brief distress screening in cancer and other medical patients. This study evaluated the validity of the BSI-18 in a sample of 221 adult survivors of childhood cancers ages 18-55 (median = 26). Validity of the BSI-18 was compared to the Symptom Checklist-90-Revised (SCL-90-R). Results indicated the BSI-18 scales had acceptable internal consistency (alpha > 0.80) and were highly correlated with the corresponding SCL-90-R subscales (correlations from 0.88 to 0.94). When subjects were classified as case positive (significantly distressed) using the BSI-18 manual case-rule, classification agreement with the SCL-90-R was poor as evidenced by low sensitivity (41.78%). An alternative BSI-18 case-rule previously developed for cancer patients using the General Severity Index (GSI; GSI t-score >= 57) demonstrated better sensitivity (83.54%). ROC analysis indicated the BSI-18 had strong diagnostic utility relative to the SCL-90-R (AUC = 0.98) and several possible GSI cut-off scores were evaluated. The optimal cut-of score was a t-score >= 50 which had a sensitivity of 97.47% and a specificity of 85.21%. Results support use of the BSI-18 with adult survivors of childhood cancer but indicate an alternative case-rule must be used. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Suffolk Univ, Harvard Univ, Sch Med, Dana Farber Canc Inst,Perini Family Survivors Ctr, Boston, MA 02115 USA. RP Recklitis, CJ (reprint author), Suffolk Univ, Harvard Univ, Sch Med, Dana Farber Canc Inst,Perini Family Survivors Ctr, 44 Binney St, Boston, MA 02115 USA. EM Christopher_Recklitis@dfci.harvard.edu NR 60 TC 33 Z9 34 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAY PY 2007 VL 16 IS 5 BP 429 EP 436 DI 10.1002/pon.1069 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 172DC UT WOS:000246783300004 PM 16929465 ER PT J AU Mroczek, DK Spiro, A AF Mroczek, Daniel K. Spiro, Avron, III TI Personality change influences mortality in older men SO PSYCHOLOGICAL SCIENCE LA English DT Article ID HEALTH; RISK; NEUROTICISM; LONGEVITY; EMOTIONS; DISEASE AB Previous studies have indicated that high neuroticism is associated with early mortality. However, recent work suggests that people's level of neuroticism changes over long periods of time. We hypothesized that such changes in trait neuroticism affect mortality risk. Growth-curve parameters (levels and slopes) that quantified the trajectories of neuroticism change over 12 years were used to predict 18-year risk of mortality among 1,663 aging men. Proportional hazards models were used to estimate mortality risk from level and slope parameters, controlling for objective and subjective health, depression, and age. Although a parallel analysis of extraversion showed no significant effects, level and slope of neuroticism interacted in their effect on mortality. Men who had both a high average level of neuroticism and art increasing level of neuroticism over time had much lower survival than men without that combination. These findings suggest that it is not just the level of personality traits, but their direction of change, that is related to mortality. C1 Purdue Univ, Ctr Aging & Life Course, Dept Child Dev & Family Studies, W Lafayette, IN 47907 USA. VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Mroczek, DK (reprint author), Purdue Univ, Ctr Aging & Life Course, Dept Child Dev & Family Studies, 1200 W State St, W Lafayette, IN 47907 USA. EM dmroczek@purdue.edu FU NIA NIH HHS [P01-AG020166, P01 AG020166, R01 AG018436, R01 AG018436-07, R01-AG18436] NR 29 TC 95 Z9 95 U1 2 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD MAY PY 2007 VL 18 IS 5 BP 371 EP 376 DI 10.1111/j.1467-9280.2007.01907.x PG 6 WC Psychology, Multidisciplinary SC Psychology GA 174TW UT WOS:000246966700002 PM 17576273 ER PT J AU Elaini, AB Shetty, SK Chapman, VM Sahani, DV Boland, GW Sweeney, AT Maher, MM Slattery, JT Mueller, PR Blake, MA AF Elaini, A. Bassem Shetty, Sanjay K. Chapman, Vernon M. Sahani, Dushyant V. Boland, Giles W. Sweeney, Ann T. Maher, Michael M. Slattery, James T. Mueller, Peter R. Blake, Michael A. TI Improved detection and characterization of adrenal disease with PET-CT SO RADIOGRAPHICS LA English DT Article ID F-18-FDG PET/CT; FDG-PET; ONCOLOGY; MASSES; PHEOCHROMOCYTOMAS; TOMOGRAPHY; ADENOMA; LESIONS AB Positron emission tomography (PET)-computed tomography (CT) combines complementary modalities, thereby providing useful structural and functional information for the detection and characterization of a variety of conditions affecting the adrenal gland. The coregistered information provided by PET-CT is often superior to that provided by CT or PET owing to a variety of pitfalls inherent in the use of either modality alone. In addition, PET-CT can prove invaluable in the differentiation between benign and malignant adrenal disease. However, this combined modality also has certain limitations. Benign entities such as lipid-poor adenomas may demonstrate increased uptake at 2-[fluorine 18]fluoro-2-deoxy-D-glucose PET while being indeterminate at standard CT. Moreover, the combined information from PET-CT will not always obviate additional studies or biopsy. Nevertheless, radiologists and nuclear physicians should be familiar with the common as well as the atypical manifestations of adrenal disease at PET and CT. They should also be meticulous in the performance and interpretation of PET-CT, which is crucial for optimal diagnosis and treatment. (C) RSNA, 2007. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. St Elizabeth Hosp, Div Endocrinol, Dept Med, Boston, MA USA. RP Elaini, AB (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,32 Fruit St, Boston, MA 02114 USA. EM abelaini@partners.org NR 26 TC 30 Z9 30 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2007 VL 27 IS 3 BP 755 EP 767 DI 10.1148/rg.273055031 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 167NT UT WOS:000246459100013 PM 17495290 ER PT J AU Saokar, A Rabinowitz, CB Sahani, DV AF Saokar, Anuradha Rabinowitz, Chad B. Sahani, Dushyant V. TI Cross-sectional imaging in acute pancreatitis SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID INTRAVENOUS CONTRAST-MEDIUM; ACUTE NECROTIZING PANCREATITIS; MR CHOLANGIOPANCREATOGRAPHY; COMPUTED-TOMOGRAPHY; CLASSIFICATION-SYSTEM; DIAGNOSTIC-ACCURACY; ENHANCED CT; APACHE-II; SEVERITY; RAT AB Acute pancreatitis is a common disease with potentially serious outcomes. Multiple imaging modalities can be used to evaluate the disease process and its associated complications. Familiarity with the pathogenesis of this disease, indications for imaging, imaging protocols, staging systems, and the strengths and weaknesses of various modalities will help the radiologist optimize patient care. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 53 TC 3 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 2007 VL 45 IS 3 BP 447 EP + DI 10.1016/j.rcl.2007.04.002 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 194YT UT WOS:000248380400005 PM 17601502 ER PT J AU Kruskal, JB AF Kruskal, Jonathan B. TI Science to practice: Can optical imaging assist in characterization of the onset of angiogenesis in developing hepatic metastases in mice livers? SO RADIOLOGY LA English DT Editorial Material ID COLORECTAL-CANCER AB Optical imaging currently can be used to characterize some of the early steps in the angiogenic pathway in vivo in animals. Liu and Matsui have provided valuable information in regard to the sequential changes in the origin and nature of newly formed blood vessels during progressive stages of growth of hepatic colorectal cancer metastases. The short-term challenge is to image cellular events that precede visible vessel formation and that occur during drug-induced vascular regression. C1 Beth Israel Deaconess Med Ctr W, Dept Radiol, Boston, MA 02215 USA. RP Kruskal, JB (reprint author), Beth Israel Deaconess Med Ctr W, Dept Radiol, 1 Deaconess Rd, Boston, MA 02215 USA. EM jkruskal@bidmc.harvard.edu NR 7 TC 1 Z9 6 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2007 VL 243 IS 2 BP 307 EP 308 DI 10.1148/radiol.2432061988 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170UP UT WOS:000246691500001 PM 17456860 ER PT J AU Li, MW Biggers, JD Elmoazzen, HY Toner, M McGinnis, L Lloyd, KCK AF Li, Ming W. Biggers, John D. Elmoazzen, Heidi Y. Toner, Mehmet McGinnis, Lynda Lloyd, K. C. Kent TI Long-term storage of mouse spermatozoa after evaporative drying SO REPRODUCTION LA English DT Article ID INTRACYTOPLASMIC SPERM INJECTION; MAMMALIAN-CELLS; INTRACELLULAR TREHALOSE; FERTILIZING ABILITY; WATER SOLUTIONS; PRESERVATION; TEMPERATURE; TRANSITION; CRYOPRESERVATION; INTEGRITY AB To determine if mouse spermatozoa could be preserved long-term without using liquid nitrogen, mouse spermatozoa in trehalose-EGTA solution were partially evaporatively dried under nitrogen gas (5 min at flow rate10 I/min) and stored for 1 week and 5 months at 4, - 20, and - 80 degrees C before intracytoplasmic sperm injection. Fertilization rates were neither different with spermatozoa stored at 4, - 20, or - 80 degrees C for I week or 1, 3, and 5 months respectively, nor blastocyst formation rates with spermatozoa stored for 1 week and 1 month. However, spermatozoa stored at 4 and - 20 degrees C for 3 months resulted in fewer blastocysts (35.1 and 54.3 % respectively) when compared with spermatozoa stored at - 80 degrees C (74.4%). Blastocyst formation rates using spermatozoa stored for 5 months at -20 degrees C (57.4%) or -80 degrees C (74.5%) were not significantly different from those stored for 3 months at the same temperatures respectively, but were significantly better than those stored for 5 months at 4 degrees C (110.2 %). Blastocysts derived from spermatozoa stored for 3 and 5 months at - 20 and - 80 degrees C respectively, were then transferred to pseudopregnant mothers to develop into healthy liveborn offspring. No significant differences were found in embryo transfer rates (number of pups born/number of embryos transferred), weaning rates, or sex ratios of resultant pups, which were healthy and reproductively sound. These results demonstrate for the first time that partially evaporatively dried mouse spermatozoa in trehalose-EGTA solution can be preserved for long term at - 20 and - 80 degrees C. The possibility that the storage temperature must be less than the glass transition temperature is discussed. C1 Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA 02115 USA. RP Lloyd, KCK (reprint author), Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. EM kclloyd@ucdavis.edu FU NCRR NIH HHS [U42 RR14905, R24 RR018934] NR 36 TC 28 Z9 29 U1 1 U2 7 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD MAY PY 2007 VL 133 IS 5 BP 919 EP 929 DI 10.1530/REP-06-0096 PG 11 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 192OQ UT WOS:000248212000008 PM 17616722 ER PT J AU Steinberg, KP Kacmarek, RM AF Steinberg, Kenneth P. Kacmarek, Robert M. TI Should tidal volume be 6 mL/kg predicted body weight in virtually all patients with acute respiratory failure? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 38th Respiratory Care Journal Conference - Respiratory Controversies in the Critical Care Setting CY OCT 06-08, 2006 CL Banff, CANADA DE tidal volume; mechanical ventilation; acute lung injury; acute respiratory distress syndrome ID ACUTE LUNG INJURY; END-EXPIRATORY PRESSURE; DISTRESS-SYNDROME; MECHANICAL VENTILATION; HYPERCAPNIC ACIDOSIS; PULMONARY-EDEMA; PROTECTIVE-VENTILATION; ADULT PATIENTS; RISK-FACTOR; INFLATION AB Over the last 2 decades, it has become clear that mechanical ventilation itself can cause lung injury and affect outcome. The development of ventilator-induced lung injury is strongly associated with overdistension of lung parenchyma, and limiting lung stretch saves lives in patients with acute lung injury. The debate in this paper is whether all patients on mechanical ventilation should be managed with a tidal volume (V-T) of 6 mL/kg predicted body weight. Current data indicate that reducing lung stretch should be the standard for all patients with acute lung injury and acute respiratory distress syndrome who require ventilatory support. However, insufficient data exist to indicate that a V-T of 6 mL/kg predicted body weight should be the standard for all patients who require mechanical ventilation. Whether V-T is the correct target for therapeutic interventions is debatable. Plateau pressure may be a better target for assessing and preventing alveolar overdistension. As the data evolve, it is conceivable that the actual V-T used should be based on the individual patient's lung mechanics rather than assuming that one V-T will suit all patients. Consensus at this time is not possible, and this paper presents the arguments on both sides of the controversy. C1 Univ Washington, Div Pulm & Crit Care Med, Harborview Med Ctr, Seattle, WA 98104 USA. Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Steinberg, KP (reprint author), Univ Washington, Div Pulm & Crit Care Med, Harborview Med Ctr, 325 9th Ave,Box 359762, Seattle, WA 98104 USA. EM steinkp@u.washington.edu NR 43 TC 13 Z9 14 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2007 VL 52 IS 5 BP 556 EP 564 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 172CV UT WOS:000246782600001 PM 17484788 ER PT J AU Hess, DR Fessler, HE AF Hess, Dean R. Fessler, Henry E. TI Should noninvasive positive-pressure ventilation be used in all forms of acute respiratory failure? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 38th Respiratory Care Journal Conference - Respiratory Controversies in the Critical Care Setting CY OCT 06-08, 2006 CL Banff, CANADA DE respiratory failure; chronic obstructive pulmonary disease; pulmonary edema; weaning; meta-analysis; mechanical ventilation; noninvasive ventilation; noninvasive positive-pressure ventilation ID OBSTRUCTIVE PULMONARY-DISEASE; CONVENTIONAL MECHANICAL VENTILATION; RANDOMIZED CONTROLLED-TRIAL; ACUTE EXACERBATIONS; FACE MASK; METAANALYSIS; EXTUBATION; RISK; PREDICTORS; MORTALITY AB Noninvasive positive-pressure ventilation (NPPV) has been a major advance in the management of acute respiratory failure. Over the past decade alone, NPPV has been the subject of over 1,500 scientific papers, including 14 meta-analyses. NPPV's utility in many clinical settings has been well established, with demonstration in randomized trials of lower intubation rate, mortality, hospital stay, and advantages in other important clinical outcomes. However, it is still used in a minority of patients with acute respiratory failure. While there probably are situations in which NPPV is commonly under-utilized, there are other situations in which it is unlikely to be of benefit or likely to inflict harm. This paper debates the data for and against the more widespread application of NPPV. It will assist the clinician to identify both good and poor candidates for NPPV and thereby devote respiratory care resources where they will be most effective, and optimize patient outcomes. C1 Massachusetts Gen Hosp, Dept Resp Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Johns Hopkins Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Med, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 44 TC 7 Z9 14 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2007 VL 52 IS 5 BP 568 EP 578 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 172CV UT WOS:000246782600003 PM 17484789 ER PT J AU Fessler, HE Hess, DR AF Fessler, Henry E. Hess, Dean R. TI Does high-frequency ventilation offer benefits over conventional ventilation in adult patients with acute respiratory distress syndrome? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 38th Respiratory Care Journal Conference - Respiratory Controversies in the Critical Care Setting CY OCT 06-08, 2006 CL Banff, CANADA DE acute lung injury; acute respiratory distress syndrome; high-frequency oscillatory ventilation; high-frequency ventilation; lung-protective ventilation; mechanical ventilation ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; POSITIVE-PRESSURE VENTILATION; TIDAL VOLUME VENTILATION; END-EXPIRATORY PRESSURE; INHALED NITRIC-OXIDE; OSCILLATORY VENTILATION; MECHANICAL VENTILATION; PROTECTIVE-VENTILATION; AIRWAY PRESSURE AB High-frequency ventilation is the application of mechanical ventilation with a respiratory rate > 100 breaths/min. High-frequency oscillatory ventilation (HFOV) is the form of high-frequency ventilation most widely used in adult critical care. The principles of lung-protective ventilation have matured in parallel with the technology for HFOV. The 2 basic principles of lung-protective ventilation are the use of small tidal volume and maintenance of adequate alveolar recruitment. Research in animal models and humans demonstrate that HFOV can support gas exchange with much smaller tidal volume than can be achieved with conventional ventilation. HFOV also provides more effective lung recruitment than conventional mechanical ventilation. However, at present, evidence is lacking that survival in adults with acute respiratory distress syndrome is improved by HFOV. Although HFOV may improve P-aO2 in some patients, this improvement is often transitory. Available evidence does riot support that pulmonary inflammation is reduced with HFOV in adult acute respiratory distress syndrome. Heavy sedation and often paralysis are necessary. The promise of HFOV as a lung-protective ventilation strategy remains attractive, but additional clinical trials are needed to determine whether this approach is superior to lung-protective ventilation with conventional mechanical ventilation. C1 Johns Hopkins Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fessler, HE (reprint author), Johns Hopkins Sch Med, Div Pulm & Crit Care Med, 1830 Monument St, Baltimore, MD 21287 USA. EM hfessler@jhmi.edu FU NHLBI NIH HHS [P50 HL 073994] NR 72 TC 15 Z9 16 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2007 VL 52 IS 5 BP 595 EP 605 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 172CV UT WOS:000246782600007 PM 17484791 ER PT J AU Kacmarek, RM Kallet, RH AF Kacmarek, Robert M. Kallet, Richard H. TI Should recruitment maneuvers be used in the management of ALI and ARDS? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 38th Respiratory Care Journal Conference - Respiratory Controversies in the Critical Care Setting CY OCT 06-08, 2006 CL Banff, CANADA DE acute lung injury; acute respiratory distress syndrome; lung recruitment; positive end-expiratory pressure; fraction of inspired oxygen; ALI; ARDS ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; MECHANICAL VENTILATION; PROTECTIVE-VENTILATION; SUSTAINED INFLATION; TIDAL VOLUME; GAS-EXCHANGE; IMPEDANCE TOMOGRAPHY; ALVEOLAR RECRUITMENT AB Lung recruitment maneuvers are being used in the management of acute lung injury and acute respiratory distress syndrome, but recruitment maneuvers are controversial. The proponents argue that when properly applied to appropriately selected patients, they are effective and can be safely applied. The expectation is that the recruitment maneuver will change the course of ARDS and improve outcomes. Those opposed to recruitment maneuvers argue that no data indicate better outcomes with recruitment maneuvers and that they are potentially unsafe. Outcome data are clearly needed before recruitment maneuvers can be fully incorporated into clinical practice. If a recruitment maneuver is conducted, a decremental positive end-expiratory pressure (PEEP) trial must be done to determine the minimum PEEP that sustains the benefits of the recruitment maneuver. We explore both sides of the lung recruitment controversy. C1 Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Anesthesia, Resp Care Serv, San Francisco, CA 94143 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 78 TC 39 Z9 46 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2007 VL 52 IS 5 BP 622 EP 631 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 172CV UT WOS:000246782600011 PM 17484793 ER PT J AU Laederach, A Chan, JM Schwartzman, A Willgohs, E Altman, RB AF Laederach, Alain Chan, Joseph M. Schwartzman, Armin Willgohs, Eric Altman, Russ B. TI Coplanar and coaxial orientations of RNA bases and helices SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE RNA; structure; planar; bipolar; coaxial ID ISOSTERICITY MATRICES; MOTIFS; RECOGNITION; PAIRS AB Electrostatic interactions, base-pairing, and especially base-stacking dominate RNA three-dimensional structures. In an A-form RNA helix, base-stacking results in nearly perfect parallel orientations of all bases in the helix. Interestingly, when an RNA structure containing multiple helices is visualized at the atomic level, it is often possible to find an orientation such that only the edges of most bases are visible. This suggests that a general aspect of higher level RNA structure is a coplanar arrangement of base-normal vectors. We have analyzed all solved RNA crystal structures to determine the degree to which RNA base-normal vectors are globally coplanar. Using a statistical test based on the Watson-Girdle distribution, we determined that 330 out of 331 known RNA structures show statistically significant (p < 0.05; false discovery rate [FDR] = 0.05) coplanar normal vector orientations. Not surprisingly, 94% of the helices in RNA show bipolar arrangements of their base-normal vectors ( p < 0.05). This allows us to compute a mean axis for each helix and compare their orientations within an RNA structure. This analysis revealed that 62% (208/331) of the RNA structures exhibit statistically significant coaxial packing of helices (p < 0.05, FDR = 0.08). Further analysis reveals that the bases in hairpin loops and junctions are also generally planar. This work demonstrates coplanar base orientation and coaxial helix packing as an emergent behavior of RNA structure and may be useful as a structural modeling constraint. C1 Stanford Univ, Dept Genet, Stanford Med Ctr, Stanford, CA 94305 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Altman, RB (reprint author), Stanford Univ, Dept Genet, Stanford Med Ctr, 300 Pasteur Dr,Lane L301,Mail Code 5120, Stanford, CA 94305 USA. EM russ.altman@stanford.edu OI Laederach, Alain/0000-0002-5088-9907; Schwartzman, Armin/0000-0001-5335-1611 FU NIGMS NIH HHS [P01 GM066275, P01-GM66275, U54 GM072970] NR 24 TC 18 Z9 18 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 2007 VL 13 IS 5 BP 643 EP 650 DI 10.1261/rna.381407 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 159QX UT WOS:000245882400002 PM 17339576 ER PT J AU Yang, WH Bloch, DB AF Yang, Wei-Hong Bloch, Donald B. TI Probing the mRNA processing body using protein macroarrays and "autoantigenomics" SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE mRNA processing body; stress granule; mRNA decay; autoantigen; protein macroarray ID PRIMARY BILIARY-CIRRHOSIS; BINDING-PROTEIN; STRESS GRANULES; BODIES; SITES; YB-1; TRANSLATABILITY; AUTOANTIBODIES; DEGRADATION; EXPRESSION AB Messenger RNA processing bodies (P-bodies) are cellular structures that have a direct role in mRNA degradation. P-bodies have also been implicated in RNAi-mediated post-transcriptional gene silencing. Despite the important roles of P-bodies in cellular biology, the constituents of P-bodies and their organization have been only partially defined. Approximately 5% of patients with the autoimmune disease primary biliary cirrhosis have antibodies directed against these structures. Recent advances in protein macroarray technology permit the simultaneous screening of thousands of proteins for reactivity with autoantibodies. We used serum from patients with anti-P-body autoantibodies to screen a protein macroarray and identified 67 potential autoantigens. Immunoreactive proteins included four known P-body components and three additional primary biliary cirrhosis autoantigens. Y-box protein 1 (YB-1), a 50-kDa RNA-binding protein that was not previously known to be a P-body component, was recognized by serum from four of seven patients. YB-1 colocalized with P-body components DCP1a and Ge-1. In cells subjected to arsenite-induced oxidative stress, YB-1 localized to TIA-containing stress granules. Both YB-1 and the previously identified P-body component RAP55 translocated from P-bodies to stress granules during oxidative stress. During recovery, however, the reappearance of YB-1 in P-bodies was delayed compared with that of RAP55, suggesting that YB-1 and RAP55 may have different functions. This study demonstrates that the combination of human autoantibodies and protein macroarray technology provides a novel method for identifying and characterizing components of mRNA P-bodies. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Gen Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp E, Ctr Immunol & Inflammatory Dis, Gen Med Serv, CNY 8302,149 13th St, Charlestown, MA 02129 USA. EM bloch@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK051179] NR 36 TC 54 Z9 54 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 2007 VL 13 IS 5 BP 704 EP 712 DI 10.1261/rna.411907 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 159QX UT WOS:000245882400009 PM 17339575 ER PT J AU Bromley, E AF Bromley, Elizabeth TI Clinicians' concepts of the cognitive deficits of schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material DE neurocognition; schizophrenia; prescribing ID PERFORMANCE; DISORDER; CARE AB Several compounds to improve cognition in schizophrenia are being studied in clinical trials, but little is known about how clinicians conceptualize the cognitive deficits of schizophrenia. In a pilot study, the author asked 40 psychiatrists 3 brief questions about the clinical presentation of cognitive deficits. Descriptions of cognitive deficits show high variability. Informants describe phenomenology like follow-through, attention, and emptiness as indicative of cognitive impairment. Informants' concepts of cognitive deficits overlap substantially with positive, negative, and thought disorder symptoms. Clinicians' concepts are complex and contextualized, in contrast to the discrete skills measured by neuropsychological tests. Results suggest that appropriate prescribing of cognition-enhancing medications may be challenging. C1 Univ Calif Los Angeles, Semel Inst Hlth Serv, Res Ctr, Los Angeles, CA 90024 USA. Fdn Psychocultural Res, Palisades, CA 90272 USA. W Los Angeles Vet Affairs Med Ctr, Vet Affairs Desert Pacific Mental Illness Res Edu, Los Angeles, CA 90073 USA. RP Bromley, E (reprint author), Univ Calif Los Angeles, Semel Inst Hlth Serv, Res Ctr, 10920 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. EM ebromley@ucla.edu NR 18 TC 9 Z9 10 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2007 VL 33 IS 3 BP 648 EP 651 DI 10.1093/schbul/sbm024 PG 4 WC Psychiatry SC Psychiatry GA 178SZ UT WOS:000247241700004 PM 17420175 ER PT J AU Addington, J Cadenhead, KS Cannon, TD Cornblatt, B McGlashan, TH Perkins, DO Seidman, LJ Tsuang, M Walker, EF Woods, SW Heinssen, R AF Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming Walker, Elaine F. Woods, Scott W. Heinssen, Robert CA NAPLS Study TI North American Prodrome Longitudinal Study: A collaborative multisite approach to prodromal schizophrenia research SO SCHIZOPHRENIA BULLETIN LA English DT Article DE psychosis; prodrome; schizophrenia; consortium; early detection; prevention; NAPLS ID INTERRATER RELIABILITY; LIFE EVENTS; PREDICTIVE-VALIDITY; PSYCHOSIS; INTERVIEW; INTERVENTION; RATIONALE; ISSUES; SCALE; RISK AB This article presents the rationale, design, and preliminary findings of the North American Prodrome Longitudinal Study (NAPLS), a collaborative, multisite investigation into the earliest phase of psychotic illness. We describe how 8 independently conceived research projects were integrated methodologically, how diagnostic reliability was achieved across sites on the Structured Interview for Prodromal Syndromes, and how baseline and follow-up data were aggregated for 888 at risk and comparison subjects. Data are presented describing the demographic, academic/work, and diagnostic characteristics of 3 relevant subgroups: persons at heightened clinical risk for psychosis, help-seeking comparison subjects, and noupsychiatric controls. The NAPLS data set will be used to explore a series of questions related to prodromal psychosis, including the descriptive phenomenology of currently accepted diagnostic criteria, conversion rates over a 30-month period, predictors of psychosis onset and functional disability, and the impact of early treatment on the course of prodromal symptoms. C1 Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90024 USA. Zucker Hillside Hosp, N Shore Long Hlth Syst, Dept Psychiat Res, Recognit & Prevent Program, Glen Oaks, NY USA. Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Emory Univ, Dept Psychol, Atlanta, GA USA. RP Addington, J (reprint author), Ctr Addict & Mental Hlth, 250 Coll st, Toronto, ON M5T 1R8, Canada. EM jean_addington@camh.net FU NIMH NIH HHS [K23 MH001905, U01 MH081944, R01 MH060720] NR 24 TC 137 Z9 138 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2007 VL 33 IS 3 BP 665 EP 672 DI 10.1093/schbul/sbl075 PG 8 WC Psychiatry SC Psychiatry GA 178SZ UT WOS:000247241700009 PM 17255119 ER PT J AU Roffman, JL Weiss, AP Deckersbach, T Freudenreich, O Henderson, DC Purcell, S Wong, DH Halsted, CH Goff, DC AF Roffman, Joshua L. Weiss, Anthony P. Deckersbach, Thilo Freudenreich, Oliver Henderson, David C. Purcell, Shaun Wong, Donna H. Halsted, Charles H. Goff, Donald C. TI Effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on executive function in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat DE schizophrenia; MTHFR; executive function; negative symptoms; path analysis ID COMMON MUTATION; MEMORY PERFORMANCE; WORKING-MEMORY; FOLATE STATUS; RISK; DEFICITS; METHYLATION; SCALE AB Background: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. Methods: 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. Results: T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. Conclusions: MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates. (c) 2007 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Schizophrenia Res Program, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Univ Calif Davis, Dept Internal Med & Nutr, Davis, CA 95616 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 149 13th St,Room 2625, Charlestown, MA 02129 USA. EM jroffman@partners.org FU NIDDK NIH HHS [DK56085]; NIMH NIH HHS [MH60450, MH02025-01A3] NR 35 TC 31 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2007 VL 92 IS 1-3 BP 181 EP 188 DI 10.1016/j.schres.2007.01.003 PG 8 WC Psychiatry SC Psychiatry GA 167CZ UT WOS:000246429800022 PM 17344026 ER PT J AU Swerdlow, NR Sprock, J Light, GA Cadenhead, K Calkins, ME Dobie, DJ Freedman, R Green, MF Greenwood, TA Gur, RE Mintz, J Olincy, A Nuechterlein, KH Radant, AD Schork, NJ Seidman, LJ Siever, LJ Silverman, JM Stone, WS Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL AF Swerdlow, Neal R. Sprock, Joyce Light, Gregory A. Cadenhead, Kristin Calkins, Monica E. Dobie, Dorcas J. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Mintz, Jim Olincy, Ann Nuechterlein, Keith H. Radant, Allen D. Schork, Nicholas J. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Tsuang, Debbie W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. TI Multi-site studies of acoustic startle and prepulse inhibition in humans: Initial experience and methodological considerations based on studies by the Consortium on the Genetics of Schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE endophenotype; prepulse inhibition; schizophrenia; sex differences; startle ID TOURETTES-SYNDROME; MENSTRUAL-CYCLE; GATING DEFICITS; REFLEX; HABITUATION; RAT; STIMULATION; MODULATION; NORMALS AB Background: Startle and its inhibition by weak lead stimuli ("prepulse inhibition": PPI) are studied to understand the neurobiology of information processing in patients and community comparison subjects (CCS). PPI has a strong genetic basis in infrahumans, and there is evidence for its heritability, stability and reliability in humans. PPI has gained increasing use as an endophenotype to identify vulnerability genes for brain disorders, including schizophrenia. Genetic studies now often employ multiple, geographically dispersed test sites to accommodate the need for large and complex study samples. Here, we assessed the feasibility of using PPI in multi-site studies. Methods: Within a 7-site investigation with multiple measures, the Consortium on the Genetics of Schizophrenia conducted a methodological study of acoustic startle and PPI in CCS. Methods were manualized, videotaped and standardized across sites with intensive in-person training sessions. Equipment was acquired and programmed at the "PPI site" (UCSD), and stringent quality assurance (QA) procedures were used. Testing was completed on 196 CCS over 2.5 years, with 5 primary startle dependent measures: eyeblink startle magnitude, habituation, peak latency, latency facilitation and PPI. Results: Analyses identified significant variability across sites in some but not all primary measures, and determined factors both within the testing process and subject characteristics that influenced a number of test measures. QA procedures also identified non-standardized practices with respect to testing methods and procedural "drift", which may be particularly relevant to multi-site studies using these measures. Conclusion: With thorough oversight and QA procedures, measures of acoustic startle PPI can be acquired reliably across multiple testing sites. Nonetheless, even among sites with substantial expertise in utilizing psychophysiological measures, multi-site studies using startle and PPI as dependent measures require careful attention to methodological procedures. (c) 2007 Elsevier B.V All rights reserved. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,Massachussetts Mental Hlth Ctr,Publ, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Swerdlow, NR (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. EM nswerdlow@ucsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016 OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894 FU NIMH NIH HHS [R01 MH065571-04, K02 MH001436, K02 MH001436-07, K02 MH001436-08, K02 MH001436-09, K02 MH001436-10, R01 MH042228, R01 MH042228-17A1, R01 MH042228-18, R01 MH042228-19, R01 MH042228-20, R01 MH043518, R01 MH065554, R01 MH065558, R01 MH065562, R01 MH065571, R01 MH065571-01A1, R01 MH065571-02, R01 MH065571-03, R01 MH065578, R01 MH065588, R01 MH065707, R01 MH084071, R37 MH043518] NR 49 TC 45 Z9 48 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2007 VL 92 IS 1-3 BP 237 EP 251 DI 10.1016/j.schres.2007.01.012 PG 15 WC Psychiatry SC Psychiatry GA 167CZ UT WOS:000246429800028 PM 17346930 ER PT J AU Tregellas, JR Davalos, DB Rojas, DC Waldo, MC Gibson, L Wylie, K Du, YP Freedman, R AF Tregellas, Jason R. Davalos, Deana B. Rojas, Donald C. Waldo, Merilyne C. Gibson, Linzi Wylie, Korey Du, Yiping P. Freedman, Robert TI Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; fMRI; sensory gating; hippocampus; thalamus; prefrontal cortex ID AUDITORY EVOKED-RESPONSES; DRUG-FREE PATIENTS; NEUROPHYSIOLOGICAL EVIDENCE; BRAIN; P50; INTERNEURONS; METAANALYSIS; ACTIVATION; SYMPTOMS; DEFICITS AB Objective: Deficits in sensory gating are a common feature of schizophrenia. Failure of inhibitory gating mechanisms, shown by poor suppression of evoked responses to repeated auditory stimuli, has been previously studied using EEG methods. These methods yield information about the temporal characteristics of sensory gating deficits, but do not identify brain regions involved in the process. Hence, the neuroanatomical substrates of poor sensory gating in schizophrenia remain largely unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the functional neuroanatomy of sensory gating deficits in schizophrenia. Methods: Twelve patients with schizophrenia and 12 healthy comparison subjects were scanned at 3 Tesla while performing a sensory gating task developed for fMRI. P50 EEG evoked potential recordings from a paired-stimulus conditioning-test paradigm were obtained from the same subjects. Results: Compared to healthy comparison subjects, patients with schizophrenia exhibited greater activation in the hippocampus, thalamus, and dorsolateral prefrontal cortex (DLPFC) during the fMRI sensory gating task. No group difference was observed in the superior temporal gyrus. Schizophrenia subjects also showed decreased P50 suppression as measured with EEG. Hemodynamic response in the fMRI measure was positively correlated with test/conditioning ratios from the EEG sensory gating measure. Conclusions: Poor sensory gating in schizophrenia is associated with dysfunction of an apparent network of brain regions, including the hippocampus, thalamus and DLPFC. Greater activation of these regions is consistent with evidence for diminished inhibitory function in schizophrenia. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver VA Med Ctr, MIRECC, VISN19, Denver, CO USA. Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. RP Tregellas, JR (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Campus Box C268-71,4200 E 9th Ave, Denver, CO 80262 USA. EM Jason.Tregellas@UCHSC.edu RI Rojas, Don/F-4296-2012; Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616 FU NIMH NIH HHS [5 P50 MH068582, P50 MH044212, P50 MH044212-090001, P50 MH068582] NR 42 TC 83 Z9 87 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2007 VL 92 IS 1-3 BP 262 EP 272 DI 10.1016/j.schres.2006.12.033 PG 11 WC Psychiatry SC Psychiatry GA 167CZ UT WOS:000246429800030 PM 17336502 ER PT J AU Dighe, AS Makar, RS Lewandrowski, KB AF Dighe, Anand S. Makar, Robert S. Lewandrowski, Kent B. TI Medicolegal liability in laboratory medicine SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE laboratory medicine; critical values; medicolegal liability ID PATHOLOGISTS Q-PROBES; IDENTIFICATION ERRORS; TRANSFUSION SAFETY; BLOOD-TRANSFUSION; INFORMATION NEEDS; INSTITUTIONS; PATIENT; CARE; TECHNOLOGY; QUESTIONS AB The laboratory testing process, including the preanalytic, analytic, and postanalytic phases, is an area where errors frequently occur. These errors may impair the diagnostic process and compromise patient safety. Delay in diagnosis and failure to diagnose are common reasons for a medicolegal action. It is estimated that over 70% of medical decisions are made using laboratory data. For this reason, the laboratory is often involved either directly or indirectly in medical liability cases. The laboratory and hospital need to design systems that reduce the possibility of error and to rapidly identify and resolve the errors that do Occur. Because the pre- and postanalytic processes extend into the clinical operations of the hospital, the laboratory can play an important role in promoting patient safety by assisting clinicians with test ordering, communicating test results appropriately, and aiding in the interpretation of results. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Bigelow 510, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 31 TC 4 Z9 4 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 2007 VL 24 IS 2 BP 98 EP 107 DI 10.1016/j.semdp.2007.03.008 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 184QK UT WOS:000247656600006 PM 17633351 ER PT J AU Gobezie, R Warner, JJP AF Gobezie, Reuben Warner, Jon J. P. TI SLAP lesion: what is it...really? SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 Case Western Reserve Univ, Sch Med, Dept Orthopaed Surg, Case Shoulder & Elbow Serv, Cleveland, OH 44106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Shoulder Serv, Boston, MA USA. RP Gobezie, R (reprint author), Case Western Reserve Univ, Sch Med, Dept Orthopaed Surg, Case Shoulder & Elbow Serv, Cleveland, OH 44106 USA. EM Reuben.Gobezie@UHhospitals.org NR 1 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 2007 VL 36 IS 5 BP 379 EP 379 DI 10.1007/s00256-007-0275-9 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 149WI UT WOS:000245177200001 PM 17340163 ER PT J AU Basile, JN AF Basile, Jan N. TI Recognizing the link between CKD and CVD in the primary care setting: Accurate and early diagnosis for timely and appropriate intervention SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE chronic kidney disease; diabetes; hypertension; cardiovascular disease; proteinuria; anemia ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; DIABETIC-NEPHROPATHY; BLOOD-PRESSURE; RENAL-DISEASE; RISK-FACTOR; NONDIABETIC INDIVIDUALS; SERUM CREATININE; PROTEINURIA AB Chronic kidney disease (CKD), which is becoming increasingly prevalent in the US and worldwide, eventually progresses to end-stage renal disease (ESRD), requiring renal replacement therapy. Diabetes and hypertension, the two leading causes of CKD, are themselves reaching near epidemic proportions. Hypertension can cause both the development and progression of CKD, and CKD is a significant risk factor for the development of cardiovascular disease. Indeed, CKD patients are more likely to die of cardiovascular complications than progress to ESRD. However, data indicate that early recognition and management of CKD can have a significant positive impact on disease outcome. This creates an important interventional opportunity for the primary care physician. This report describes the major risk factors and comorbidities associated with the development and progression of CKD and offers suggestions for timely diagnosis and management of CKD in the primary care setting. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM Jan.Basile@med.va.gov NR 39 TC 7 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAY PY 2007 VL 100 IS 5 BP 499 EP 505 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 172AZ UT WOS:000246777800013 PM 17534087 ER PT J AU Levine, DA Kiefe, CI Howard, G Howard, VJ Williams, OD Allison, JJ AF Levine, Deborah A. Kiefe, Catarina I. Howard, George Howard, Virginia J. Williams, O. Dale Allison, Jeroan J. TI Reduced medication access - A marker for vulnerability in US stroke survivors SO STROKE LA English DT Article DE access to health care; secondary prevention; stroke ID CHRONICALLY ILL; ISCHEMIC-STROKE; RISK-FACTORS; CARE; HEALTH; COST; UNDERUSE; ADULTS; BENEFICIARIES; PREVALENCE AB Background and Purpose - Medication access is crucial to secondary stroke prevention. We assessed medication access and associated barriers to care across region and time in a national sample of US stroke survivors. Methods - Among all 5840 black or white stroke survivors aged >= 45 years responding to the National Health Interview Survey years 1997 to 2004, we examined inability to afford medications within the last 12 months across region ( Northeast, Midwest, West, South) and time. With logistic regression, we adjusted associations between medication inaffordability and region and time for age, sex, race, neurological disability, comorbidity, health status, insurance, income and out-of-pocket medical expenses. Results - In 2004, approximate to 76 000 US stroke survivors were unable to afford medications. Lower medication affordability was reported among stroke survivors who were <65 years old, black, female, had high comorbidity or low health status. Compared with stroke survivors able to afford medications, those unable more frequently reported lack of transportation ( 15% versus 3%; P<0.001), no health insurance ( 16% versus 3%; P<0.001), no usual place of care ( 6% versus 2%; P=0.001), income <$ 20 000 ( 66% versus 40%; P<0.001) and out-of-pocket medical expenses >=$ 2000 ( 35% versus 25%; P<0.001). From 1997 to 2004, inability to afford medications increased significantly from 8.1% to 12.7% ( P-trend=0.01) overall and increased in all US regions except the Northeast. Conclusions - We identified a vulnerable stroke survivor population with reduced medication access and increased barriers to medical care. Membership in this population has grown substantially from 1997 to 2004, potentially leading to increased recurrent stroke incidence. C1 Univ Alabama, Dept Med, Div Gen Internal Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Dept Biostat, Tuscaloosa, AL 35487 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. RP Levine, DA (reprint author), Univ Alabama, Dept Med, Div Gen Internal Med, 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA. EM dlevine@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 FU NINDS NIH HHS [NS 041588, R01 NS041588, U01 NS041588] NR 47 TC 20 Z9 21 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2007 VL 38 IS 5 BP 1557 EP 1564 DI 10.1161/STROKEAHA.106.478545 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 160DM UT WOS:000245919500024 PM 17395861 ER PT J AU Moskowitz, MA AF Moskowitz, Michael A. TI The 2006 Thomas Willis Lecture - The adventures of a translational researcher in stroke and migraine SO STROKE LA English DT Article DE migraine; research; stroke ID NITRIC-OXIDE SYNTHASE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; COA REDUCTASE INHIBITORS; FOCAL CEREBRAL-ISCHEMIA; BLOOD-FLOW; SPREADING DEPRESSION; VASCULAR HEADACHES; TRIGEMINAL GANGLIA; DRUG DEVELOPMENT; MICE LACKING C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM Moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 NR 44 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2007 VL 38 IS 5 BP 1645 EP 1651 DI 10.1161/STROKEAHA.107.483941 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 160DM UT WOS:000245919500039 PM 17413046 ER PT J AU Takeuchi, K Roehrl, MHA Sun, ZYJ Wagner, G AF Takeuchi, Koh Roehrl, Michael H. A. Sun, Zhen-Yu J. Wagner, Gerhard TI Structure of the calcineurin-NFAT complex: Defining a T cell activation switch using solution NMR and crystal coordinates SO STRUCTURE LA English DT Article ID PROTEIN-PROTEIN COMPLEXES; SELECTIVE-INHIBITION; CYCLOSPORINE-A; BETA-SHEETS; IDENTIFICATION; CYCLOPHILIN; INTERFACES; DISCOVERY; EXCHANGE; BINDING AB Calcineurin (Cn) is a serine/threonine protein phosphatase that plays pivotal roles in many physiological processes, including cell proliferation, development, and apoptosis. Most prominently, Cn targets the nuclear factors of activated T cell (NFATs), transcription factors that activate cytokine genes. Calcium-activated Cn dephosphorylates multiple residues within the regulatory domain of NFAT, triggering joint nuclear translocation. This relies crucially on the interaction between the catalytic domain of Cn (CnCat) and the conserved PxIxIT motif located in a region distinct from the dephosphorylation sites of NFAT. Here, we present the structure of the complex between the 39 kDa. CnCat and a 14 residue peptide containing a PVIVIT segment that was derived from affinity-driven peptide selection based on the conserved PxIxIT motif of NFATs. The structure of the complex was determined by using NMR assignments and structural constraints and the coordinates of the CnCat crystal structure. The NMR analysis relied on recently developed labeling and spectroscopic techniques. The VIVIT peptide is accommodated in a hydrophobic cleft formed by beta strands 11 and 14, and the loop between P strands 11 and 12, forming a short parallel beta sheet with the exposed beta strand 14 in Cn. The side chains of conserved residues in the PxIxIT sequences make extensive interactions with conserved residues in Cn, while those of nonconserved residues are solvent exposed. The architecture of the interface explains the diversity of recognition sequences compatible with NFAT function and uncovers a potential targeting site for immune-suppressive agents. The structure reveals that the orientation of the bound PxIxIT directs the phosphorylation sites in NFAT's regulatory domain toward the Cn catalytic site. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol & Lab Med, Boston, MA 02114 USA. RP Wagner, G (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM wagner@hms.harvard.edu RI Takeuchi, Koh/B-4971-2010 FU NIAID NIH HHS [AI37581, R01 AI037581-12, R01 AI037581]; NIBIB NIH HHS [P41 EB002026-32, EB 002026, P41 EB002026]; NIGMS NIH HHS [GM47467, P01 GM047467, P01 GM047467-16] NR 40 TC 32 Z9 33 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2007 VL 15 IS 5 BP 587 EP 597 DI 10.1016/j.str.2007.03.015 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 169QD UT WOS:000246605800010 PM 17502104 ER PT J AU Vera-Llonch, M Oster, G Ford, CM Lu, J Sonis, S AF Vera-Llonch, Montserrat Oster, Gerry Ford, Colleen M. Lu, John Sonis, Stephen TI Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies SO SUPPORTIVE CARE IN CANCER LA English DT Article DE oral mucositis; allogeneic; hematopoietic stem-cell transplantation; costs; outcomes ID BONE-MARROW-TRANSPLANTATION; ECONOMIC OUTCOMES; THERAPY; RECIPIENTS; REGIMENS AB Goals of the work: To assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes in patients with hematologic malignancies receiving allogeneic hematopoietic stem-cell transplantation (HSCT). Materials and methods: A retrospective chart review study of 281 allogeneic HSCT recipients with hematologic malignancies was undertaken at a single academic center. OM extent and severity were assessed across eight oropharyngeal sites using a validated scale, which was scored as follows: no erythema/ ulceration= 0; erythema only= I; ulceration, one site= II; ulceration, two sites= III; ulceration, three sites= IV and ulceration, four or more sites= V. OM assessments began on the day of conditioning and continued twice weekly within 28 days or hospital discharge. Analyses examined the relationship between the worst OM grade and selected adverse outcomes, including days with fever, days of total parenteral nutrition (TPN), days of parenteral narcotic therapy, incidence of significant ( common terminology criteria (CTC) grade 3 or 4) infection, mortality and inpatient days and charges. Main results: The mean age of the study subjects was 41 years. Of the patients, 96% (n= 269) received total body irradiation and 76% ( n= 214) experienced an OM grade of >= II (i.e., ulceration). The worst OM grade was significantly ( p < 0.05) associated with the number of days of TPN and parenteral narcotic therapy, number of days with fever, incidence of significant infection, time in hospital and total inpatient charges. Conclusions: OM is associated with worse clinical and economic outcomes in patients with hematologic malignancies undergoing allogeneic HSCT. C1 Policy Anal Inc, Brookline, MA 02445 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Oster, G (reprint author), Policy Anal Inc, 4 Davis Court, Brookline, MA 02445 USA. EM goster@pai2.com NR 14 TC 31 Z9 36 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 2007 VL 15 IS 5 BP 491 EP 496 DI 10.1007/s00520-006-0176-9 PG 6 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 153RF UT WOS:000245452000005 PM 17139495 ER PT J AU Rodriguez, JR Madanat, MG Healy, BC Thayer, SP Warshaw, AL Castillo, CFD AF Rodriguez, J. Ruben Madanat, Michael G. Healy, Brian C. Thayer, Sarah P. Warshaw, Andrew L. Castillo, Carlos Fernandez-del TI Distal pancreatectomy with splenic preservation revisited SO SURGERY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 2005 CL Nashville, TN SP Soc Univ Surg ID POSTSPLENECTOMY INFECTION; SPLEEN; RESECTION; ARTERY; VEIN; SPLENECTOMY; MANAGEMENT; MORTALITY; FISTULA; CONSERVATION AB Background. Splenic preservation (SP) during distal pancreatectomy can be accomplished by ligating the main splenic artery and vein relying on blood supply from the short gastric vessels. The purpose of this study was to examine the short-term implications of this operation, comparing it to the outcomes following distal pancreatectomy with splenectomy. Methods. The records of 259 patients who underwent distal pancreatectomy with and without SP at Massachusetts General Hospital from 1994 to 2004 were reviewed. Results. A total of 29% of patients underwent SP with this technique. These patients were more likely to be women (74% vs 56%, P = .008) and to have benign disease (93% vs 54%, P < .0001). Their operative times were shorter (2.5 vs 3.1 h, P < .0001), they had less blood loss (300 vs 500 ml, P < .0001) and a shorter duration of stay (6 days [interquartile range, 5 to 7] vs 7 days [interquartile range, 5 to 8], P = .001). SP was not a significant predictor of complications in either univariate (P = .445) or adjusted analysis (P = .543). One patient (1.4%) in the SP group was reoperated for splenic infarction and two patients (1.1%) in the splenectomy group for abscess and hemorrhage. There were 2(0.8%) postoperative deaths, both in the splenectomy group. Conclusions. Splenic preservation relying on blood supply from the short gastric vessels is reliable and safe and does not have a higher incidence of postoperative complications when compared to traditional distal pancreatectomy with splenectomy. The current series validates this approach and provides further evidence of its feasibility and safety. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC 336, Boston, MA 02114 USA. FU NIDDK NIH HHS [K08 DK071329] NR 32 TC 55 Z9 61 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2007 VL 141 IS 5 BP 619 EP 625 DI 10.1016/j.surg.2006.09.020 PG 7 WC Surgery SC Surgery GA 168US UT WOS:000246550100007 PM 17462461 ER PT J AU Sogg, S AF Sogg, Stephanie TI Alcohol misuse after bariatric surgery: epiphenomenon or "Oprah" phenomenon? SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material ID MORBIDLY OBESE; DISORDERS; PREVALENCE; ADDICTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02115 USA. RP Sogg, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02115 USA. NR 22 TC 26 Z9 26 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAY-JUN PY 2007 VL 3 IS 3 BP 366 EP 368 DI 10.1016/j.soard.2007.03.004 PG 3 WC Surgery SC Surgery GA 375EP UT WOS:000261097200002 PM 17452022 ER PT J AU Lam, PPL Binker, LIC Lugea, A Pandol, SJ Gaisano, HY AF Lam, Patrick P. L. Binker, Laura I. Cosen Lugea, Aurelia Pandol, Stephen J. Gaisano, Herbert Y. TI Alcohol redirects CCK-mediated apical exocytosis to the acinar basolateral membrane in alcoholic pancreatitis SO TRAFFIC LA English DT Article DE alcoholic pancreatitis; cholecystokinin; exocytosis; Munc18c; SNARE proteins ID REGULATED EXOCYTOSIS; ENZYME-SECRETION; CELL; CHOLECYSTOKININ; FUSION; MUNC18C; MECHANISMS; MACHINERY; PROTEINS; SYNTAXIN AB The molecular mechanism of clinical alcohol-induced pancreatitis remains vague. We had reported that experimental high-dose cholecystokinin (CCK)-induced pancreatitis is in part because of excessive aberrant basolateral exocytosis. High-dose CCK caused Munc18c on basolateral plasma membrane (BPM) to dissociate from syntaxin (Syn)-4, activating Syn-4 to complex with plasma membrane (PM)-SNAP-23 and granule-VAMP to mediate basolateral exocytosis. We now hypothesize that alcohol could render the acinar cell BPM conducive to exocytosis by a similar mechanism. Weakly stimulating postprandial doses of alcohol (20-50 mm) inhibited postprandial low-dose CCK-stimulated secretion by blocking physiologic apical exocytosis and redirecting exocytosis to less-efficient basal PM (visualized by FM1-43 fluorescence imaging) and lateral PM sites (electron microscopy). Alcohol or low-dose CCK had no effect on PM-Munc18c, but alcohol preincubation enabled low-dose CCK to displace Munc18c from BPM, leading to SNARE complex assembly in the BPM. Similarly, alcohol diet-fed rats did not exhibit morphologic defects in the pancreas nor affected PM-Munc18c behavior, but subsequent intraperitoneal injections of low-dose CCK analog cerulein caused Munc18c displacement from BPM and cytosolic degradation, which contributed to pancreatitis. We conclude that alcohol induces BPM-Munc18c to become receptive to postprandial CCK-induced displacement into the cytosol, a process which facilitates SNARE complex assembly that in turn activates restricted BPM sites to become available for aberrant exocytosis into the interstitial space, where zymogen activation would take place and cause pancreatitis. C1 Univ Toronto, Dept Med, Univ Hlth Network, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. Vet Affairs Greater Los Angeles Healthcare Syst, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Gaisano, HY (reprint author), Univ Toronto, Dept Med, Univ Hlth Network, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM herbert.gaisano@utoronto.ca FU NIAAA NIH HHS [P50 AA11999, R21 AA015579-01A1] NR 33 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-9219 J9 TRAFFIC JI Traffic PD MAY PY 2007 VL 8 IS 5 BP 605 EP 617 DI 10.1111/j.1600-0854.2007.00557.x PG 13 WC Cell Biology SC Cell Biology GA 160MK UT WOS:000245945500013 PM 17451559 ER PT J AU Murphy, MF Casbard, AC Ballard, S Shulman, IA Heddle, N Aubuchon, JP Wendel, S Thomson, A Hervig, T Downes, K Carey, PM Dzik, WH AF Murphy, Michael F. Casbard, Angela C. Ballard, Sally Shulman, Ira A. Heddle, Nancy Aubuchon, James P. Wendel, Silvano Thomson, Amanda Hervig, Tor Downes, Katharine Carey, Patricia M. Dzik, Walter H. CA BEST Res Collaborative TI Prevention of bedside errors in transfusion medicine (PROBE-TM) study: a cluster-randomized, matched-paired clinical areas trial of a simple intervention to reduce errors in the pretransfusion bedside check SO TRANSFUSION LA English DT Article ID PATIENT IDENTIFICATION; BLOOD-TRANSFUSION; SYSTEM; SAFETY AB BACKGROUND: Transfusion of the incorrect blood component is a frequent serious incident associated with transfusion and often involves misidentification of the patient and/or the unit of blood. The objective of this study was to assess the effect of a simple intervention designed to improve performance of the bedside check and to observe the durability of any effect. The intervention was a tag on blood bags reminding staff to check the patient's wristband. The tag was positioned in such a way that the transfusionist was required to remove the tag to spike the unit. STUDY DESIGN AND METHODS: The intervention was tested in a multicenter cluster-randomized controlled trial incorporating short-term and long-term follow-up periods. The primary endpoint was the proportion of patients transfused with red cell units for whom the key elements of the bedside check were all correctly completed. RESULTS: Fifteen matched-paired clinical areas at 12 participating hospitals in six countries were included in the trial. Combining data from all participating hospitals, the bedside check was correctly performed in 37 percent of transfusions during the baseline audit period. There was no evidence of a favorable effect of the intervention immediately after its introduction (pooled odds ratio, 1.09; 95% confidence interval, 0.54-2.17). There was similarly no evidence of a favorable effect after continued use of the intervention for an additional 8 weeks. CONCLUSIONS: A simple intervention in the form of a barrier warning label on blood bags reminding staff to check the patient's wristband failed to improve bedside transfusion practice. The robust study design developed for this study could be applied to investigate other interventions to improve the safety of bedside transfusion practice. C1 Natl Blood Serv, Oxford, England. MRC, Clin Trials Unit, London, England. Univ So Calif, Med Ctr, Los Angeles, CA USA. McMaster Univ, Dept Med, Hamilton, ON, Canada. Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. Hosp Sirio Libanes, Blood Bank, Sao Paulo, Brazil. Royal N Shore Hosp, Sydney, NSW, Australia. Haukeland Hosp, Bergen, Norway. Univ Hosp Cleveland, Hlth Syst, Cleveland, OH 44106 USA. Hoxworth Blood Ctr, Cincinnati, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Murphy, MF (reprint author), John Radcliffe Hosp, Natl Blood Serv, Oxford OX3 9BQ, England. EM mike.murphy@nbs.nhs.uk OI Carey, Patricia/0000-0001-8706-280X; Casbard, Angela/0000-0001-6241-3052 FU Medical Research Council [MC_U122870183] NR 15 TC 22 Z9 22 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2007 VL 47 IS 5 BP 771 EP 780 DI 10.1111/j.1537-2995.2007.01189.x PG 10 WC Hematology SC Hematology GA 161CU UT WOS:000245992700006 PM 17465940 ER PT J AU Hogan, PG Rao, A AF Hogan, Patrick G. Rao, Anjana TI Dissecting I-CRAC, a store-operated calcium current SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID PANCREATIC ACINAR-CELLS; RAT MAST-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; BOVINE CHROMAFFIN CELLS; SMOOTH-MUSCLE-CELLS; CA2+ ENTRY; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; CHANNEL FUNCTION; T-LYMPHOCYTES AB The use of Ca2+ for intracellular signalling necessitates tight local and global control of cytoplasmic Ca2+ concentration, and mechanisms for maintaining the net Ca2+ balance. It has long been recognized that intracellular Ca2+ stores exert control over Ca2+ influx at the plasma membrane through a process of store-operated Ca2+ entry (SOCE). The Ca2+ current I-CRAC is the best characterized instance of SOCE, but the elements of the pathway leading to I-CRAC have eluded biochemical definition for more than a decade. However, the recent identification of key proteins underlying I-CRAC-STIM1 and Orai1 - has led to several insights into this ER-to-plasma membrane signalling system and to the recognition that it is an ancient and conserved mechanism in multicellular organisms. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hogan, PG (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM hogan@ebr.med.harvard.edu FU NIAID NIH HHS [AI 40127]; NIGMS NIH HHS [GM 075256] NR 108 TC 78 Z9 80 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2007 VL 32 IS 5 BP 235 EP 245 DI 10.1016/j.tibs.2007.03.009 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175WH UT WOS:000247044200009 PM 17434311 ER PT J AU Michor, F AF Michor, Franziska TI Quantitative approaches to analyzing imatinib-treated chronic myeloid leukemia SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; COMPLETE CYTOGENETIC REMISSION; HEMATOPOIETIC STEM-CELLS; ABL TYROSINE KINASE; MESYLATE TREATMENT; POSITIVE CELLS; CGP 57148; PROGENITORS; INHIBITOR; PROLIFERATION AB Progress in understanding the genetic changes that drive tumorigenesis has enabled the development of molecularly targeted anticancer therapy. The first small molecule targeted to a specific protein was imatinib mesylate (Gleevec, ST1571), which is used to treat chronic myeloid leukemia (CML). A recent article presents a computational model with which to study the treatment response in CML patients and investigates the effect that imatinib exerts on leukemic stem cells. Here, I discuss insights derived from this study and their implications for imatinib therapy against CML. C1 Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Michor, F (reprint author), Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA. EM michor@fas.harvard.edu NR 20 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2007 VL 28 IS 5 BP 197 EP 199 DI 10.1016/j.tips.2007.03.003 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 171QT UT WOS:000246751200001 PM 17412430 ER PT J AU King, CR Freedland, SJ Terris, MK Kane, CJ Amling, CL Aronson, WJ Presti, JC AF King, Christopher R. Freedland, Stephen J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Aronson, William J. Presti, Joseph C., Jr. TI Impact of obesity on the utility of preoperative prostate-specific antigen velocity to predict for relapse after prostatectomy: A report from the SEARCH database SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; PSA VELOCITY; CANCER; RISK; HYPERPLASIA; RECURRENCE AB Objectives To test the validity of preoperative prostate-specific antigen velocity (PSAV) (the rate of PSA rise before diagnosis) as a predictor for relapse after radical prostatectomy, in the context of patient obesity as measured by body mass index (BMI). Methods The rates of biochemical relapse were examined among 215 patients who underwent radical prostatectomy between 1992 and 2005. Kaplan-Meier relapse rates as a function of preoperative PSAV 2 ng/mL/yr or less versus greater than 2 ng/mL/yr were compared in two groups: nonobese patients (normal to overweight, BMI less than 30 kg/m(2)) and obese patients (mild to severely obese, BMI 30 kg/m(2) or greater). Results A preoperative PSAV greater than 2 ng/mL/yr was associated with higher relapse rates after radical prostatectomy compared with a PSAV of 2 ng/mL/yr or less, with 5-year relapse-free survival rates of 60% versus 70%, respectively (P = 0.03). Prostate-specific antigen velocity was independently significant on multivariate analysis, along with biopsy Gleason score, percent positive cores, and BMI. In this study 24% of patients were obese. Prostate-specific antigen velocity greater than 2 ng/mL/yr was associated with higher relapse rates in nonobese patients (P = 0.01) but not in obese patients (P = 0.9). The two BMI groups did not differ with respect to any factors. Obese patients with slowly rising PSA (PSAV 2 ng/mL/yr or less) fared just as poorly as nonobese patients with rapidly rising PSA (PSAV greater than 2 ng/mL/yr). Obesity was independently associated with higher relapse rates. Conclusions Preoperative PSAV greater than 2 ng/mL/yr was associated with a higher risk of relapse after radical prostatectomy, but its clinical usefulness might be limited to nonobese patients. Obesity conferred higher relapse rates, regardless of other prognostic factors including preoperative PSAV. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Div Urol Oncol, Stanford, CA 94305 USA. Duke Univ, Sch Med, Div Urol Surg, Durham, NC 27706 USA. Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27706 USA. VA Med Ctr, Dept Surg, Urol Sect, Durham, NC USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. VA Med Ctr, Dept Surg, Augusta, GA 30912 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. VA Med Ctr, Dept Surg, Urol Sect, San Francisco, CA USA. Univ Alabama, Dept Urol, Birmingham, AL USA. USN, San Diego Hosp, Dept Urol, San Diego, CA 92152 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. VA Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA USA. RP King, CR (reprint author), Stanford Univ, Sch Med, Dept Radiat Oncol, Div Urol Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM crking@stanford.edu OI Terris, Martha/0000-0002-3843-7270 NR 14 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2007 VL 69 IS 5 BP 921 EP 926 DI 10.1016/j.urology.2007.01.056 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 191GK UT WOS:000248119400028 PM 17482935 ER PT J AU Spurgeon, SEF Mongoue-Tchokote, S Collins, L Priest, R Hsieh, YC Peters, LM Beer, TM Mori, M Garzotto, M AF Spurgeon, Stephen E. F. Mongoue-Tchokote, Solange Collins, Lauren Priest, Ryan Hsieh, Yi-Ching Peters, Laura M. Beer, Tornasz M. Mori, Motorni Garzotto, Mark TI Assessment of prostate-specific antigen doubling time in prediction of prostate cancer on needle biopsy SO UROLOGY LA English DT Article ID NG/ML; SERUM; RISK; MEN; FLUCTUATIONS; ERA AB Objectives Prostate-specific antigen (PSA) kinetics have failed to predict for the presence of prostate cancer in screening populations in which many patients harbor subclinical disease. We hypothesized that the prebiopsy PSA doubling time (PSADT) and PSA velocity (PSAV) could predict for cancer detection in a referral Population with a suspicion of prostate cancer. Methods Data were collected from 1699 consecutive veterans with a PSA level of 10 ng/mL or less who underwent prostate biopsy. Logistic regression analysis was performed on the following: age, race, family history, digital rectal examination findings, PSA, PSA density, PSADT, PSAV, prostate Volume, and ultrasound lesions. Model building was accomplished with 70% of the data, and validation was done using the remaining 30%. These data were also analyzed using classification and regression tree analysis. Results Using logistic regression analysis (P <0.05) on the model building set, prostate cancer was associated with age (older than 70 years), PSA level (greater than 2.9 ng/mL), PSA density (more than 0.12 ng/mL/cm(3)), digital rectal examination findings, and the presence of a lesion on ultrasonography. A PSADT of 2 to 5 years was marginally associated with prostate cancer detection (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and a PSADT of less than 2 years or longer than 5 years and PSAV were not predictive. On classification and regression tree analysis, PSADT was not selected as a predictive factor. Furthermore, neither PSADT nor PSAV was predictive of Gleason score 7 or worse cancer. Conclusions In contrast to its prognostic value after the diagnosis of prostate cancer has been established, PSA kinetics offer little to clinical decision making as predictors of cancer or high-grade cancer in men with a PSA level of 10 ng/mL or less. C1 Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Renal Transplantat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Biostat Shared Resource, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Urol Sect, Portland, OR 97201 USA. RP Garzotto, M (reprint author), Portland VA Med Ctr, Urol Sect, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM garzotto@ohsu.edu NR 15 TC 12 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2007 VL 69 IS 5 BP 931 EP 935 DI 10.1016/j.urology.2007.01.075 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 191GK UT WOS:000248119400030 PM 17482937 ER PT J AU Bleecker, E Tashkin, D Peters, S Long, A O'Connor, R Parasuraman, B Boggs, R AF Bleecker, E. Tashkin, D. Peters, S. Long, A. O'Connor, R. Parasuraman, B. Boggs, R. TI A 4-year assessment of severe and non-severe asthma in a real-world setting SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sharp Rees Stealy Med Grp, San Diego, CA USA. AstraZeneca, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2007 VL 10 IS 3 BP A111 EP A111 DI 10.1016/S1098-3015(10)68876-6 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 171DJ UT WOS:000246714800351 ER PT J AU Long, A Bleecker, E O'Connor, R Tashkin, D Peters, S Silkoff, P Parasuraman, B Boggs, R AF Long, A. Bleecker, E. O'Connor, R. Tashkin, D. Peters, S. Silkoff, P. Parasuraman, B. Boggs, R. TI A 4-year assessment of sub-acute lack of asthma control in a real-world setting SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Sharp Rees Stealy Med Grp, San Diego, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. AstraZeneca, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2007 VL 10 IS 3 BP A112 EP A112 DI 10.1016/S1098-3015(10)68878-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 171DJ UT WOS:000246714800353 ER PT J AU Weiner, JR Duh, MS Lefebvre, P Neary, MP Skarin, AT AF Weiner, J. R. Duh, M. S. Lefebvre, P. Neary, M. P. Skarin, A. T. TI Identification of patients with small cell lung cancer (SCLC) and cost assessment of intravenous (IV) chemotherapy in claims data SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Analysis Grp Inc, Boston, MA USA. Grp Analyse Ltee, Montreal, PQ, Canada. GlaxoSmithKline Inc, Collegeville, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2007 VL 10 IS 3 BP A130 EP A130 DI 10.1016/S1098-3015(10)68934-6 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 171DJ UT WOS:000246714800409 ER PT J AU Engelgau, MM Vinicor, F Simionescu, M King, GL Meininger, C Mensah, GA AF Engelgau, Michael M. Vinicor, Frank Simionescu, Maya King, George L. Meininger, Cynthia Mensah, George A. TI Summary statement IV: Obesity and diabetes: Opportunities for translation of basic research SO VASCULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT 8th International Conference on Vascular Endothelium CY JUN 25-JUL 02, 2005 CL Iraklion, GREECE DE obesity; diabetes; endothelial cells AB The worldwide epidemics of obesity and diabetes that have emerged in the 21st century are creating a major public heath problem, having struck developed countries as well as those still developing. With our present clinical tools, abilities, and understanding, we may not be prepared to respond adequately to the demands or be able to engage in effective prevention strategies. The underlying pathophysiological reasons for the increases in both obesity and diabetes may be closely related through abnormality in endothelial cells. Diverse expertise from within and outside the public health arena will be needed to explore the health implications from an "endothelium" perspective and identify those at risk for the development of chronic disease. Identification of new biological markers and better measures of current biological marker will both be critical in understanding and addressing the ongoing epidemic of chronic diseases. (c) 2006 Elsevier Inc. All rights reserved. C1 Ctr Dis Control & Prevent, Div Diabet Translat, NCCDPHP, CoCHP, Atlanta, GA 30341 USA. Inst Cellular Biol & Pathol, Bucharest, Romania. Joslin Diabet Ctr, Boston, MA 02215 USA. Texas A&M Univ, Temple, TX 76508 USA. RP Engelgau, MM (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, NCCDPHP, CoCHP, 4770 Buford Highway,Mailstop K10, Atlanta, GA 30341 USA. EM mengelgau@cdc.gov RI Simionescu, Maya /C-4794-2011; OI Mensah, George/0000-0002-0387-5326 NR 4 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1537-1891 J9 VASC PHARMACOL JI Vasc. Pharmacol. PD MAY PY 2007 VL 46 IS 5 BP 324 EP 326 DI 10.1016/j.vph.2006.10.015 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156QF UT WOS:000245663400006 PM 17275418 ER PT J AU Ogino, S Meyerhardt, JA Kawasaki, T Clark, JW Ryan, DP Kulke, MH Enzinger, PC Wolpin, BM Loda, M Fuchs, CS AF Ogino, Shuji Meyerhardt, Jeffrey A. Kawasaki, Takako Clark, Jeffrey W. Ryan, David P. Kulke, Matthew H. Enzinger, Peter C. Wolpin, Brian M. Loda, Massimo Fuchs, Charles S. TI CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma SO VIRCHOWS ARCHIV LA English DT Article DE colon cancer; CIMP; DNA methylation; epigenetics; chemotherapy ID DNA METHYLATION; BRAF MUTATION; CANCER; PHENOTYPE; TUMORS; INSTABILITY; PROMOTER; GENE; KRAS; HYPERMETHYLATION AB The CpG island methylator phenotype (CIMP) is a distinct epigenetic phenotype in colorectal carcinoma with concordant methylation in multiple promoter CpG islands. The relationship between CpG island methylation and clinical outcomes among colorectal cancer patients treated with chemotherapy has been a controversial subject. Utilizing real-time polymerase chain reaction (PCR; MethyLight technology), we quantified DNA methylation in 13 CpG island loci (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, MINT1, MINT31, IGFBP3, MGMT, and WRN) in 30 metastatic microsatellite stable colorectal carcinomas in phase I/II clinical trials of combination chemotherapy (5-fluorouracil, irinotecan, leucovorin, and gefitinib). Tumor response was assessed by CT scans performed at baseline and every 6 weeks thereafter. Overall CIMP-high status (either >= 9/13 or >= 7/13 methylated markers; identifying 3 or 5 CIMP-high tumors, respectively) and methylation in CACNA1G, IGF2, MLH1, NEUROG1, RUNX3, MINT31, and WRN were associated with worse survival (all p < 0.01). Although not statistically significant, there was a trend toward resistance to chemotherapy among tumors with CpG island methylation. In conclusion, CpG island methylation may predict poor survival in metastatic microsatellite stable colorectal carcinoma treated with chemotherapy. Additional studies are necessary to examine the role of DNA methylation in treatment efficacy. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03] NR 32 TC 73 Z9 75 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD MAY PY 2007 VL 450 IS 5 BP 529 EP 537 DI 10.1007/s00428-007-0398-3 PG 9 WC Pathology SC Pathology GA 162TW UT WOS:000246113400005 PM 17372756 ER PT J AU Farris, AB Mark, EJ Kradin, RL AF Farris, A. B., III Mark, E. J. Kradin, R. L. TI Pulmonary "inflammatory myofibroblastic" tumors: a critical examination of the diagnostic category based on quantitative immunohistochemical analysis SO VIRCHOWS ARCHIV LA English DT Article DE pulmonary inflammatory myofibroblastic tumor; pseudotumor; factor XIIIa ID DENDRITIC CELLS; PSEUDOTUMOR; HUMAN-HERPESVIRUS-8; MACROPHAGES; EXPRESSION; LUNG AB The World Health Organization classification applies the term '' pulmonary inflammatory myofibroblastic tumor '' to a histologically variegate set of pulmonary inflammatory pseudotumors. However, often these lesions bear little resemblance to tumors of myofibroblastic origin. To elucidate histogenesis, we examined 18 cases from our institution files. The cases were stained with antibodies to smooth muscle actin (SMA), Factor XIIIa, CD3, CD20, CD68, S-100, anaplastic lymphoma kinase (ALK-1), and human herpevirus-8 (HHV-8). The percentage of positive-staining cells within a defined tumor area (400,000 mu m(2)) was determined by light microscopy and morphometric analysis. Ten cases (56%) showed myofibroblastic differentiation, as judged by positive SMA staining of spindle cells. All cases showed substantial numbers of CD68+, Factor XIIIa+, and S-100+ monocytoid cells. Fifty percent were ALK-1+, and one was HHV-8+. We conclude that the term '' inflammatory myofibroblastic tumor '' is a misnomer, as nearly half of cases show no myofibroblastic differentiation. Instead, the results suggest that these lesions are composed predominantly of cells of macrophage-dendritic cell lineage. Although the multiplicity of terms previously applied to these lesions is cumbersome, retaining a descriptive phenomenological terminology may ultimately promote accurate elucidation of pathogenesis. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. EM rkradin@partners.org NR 22 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD MAY PY 2007 VL 450 IS 5 BP 585 EP 590 DI 10.1007/s00428-007-0395-6 PG 6 WC Pathology SC Pathology GA 162TW UT WOS:000246113400011 PM 17372757 ER PT J AU Northmore, DPM Oh, DJ Celenza, MA AF Northmore, D. P. M. Oh, D.-J. Celenza, M. A. TI Acuity and contrast sensitivity of the bluegill sunfish and how they change during optic nerve regeneration SO VISUAL NEUROSCIENCE LA English DT Article DE contrast sensitivity function; fish vision; fish visual acuity; optic nerve regeneration ID VISUAL-ACUITY; LEPOMIS-MACROCHIRUS; SUN-FISH; GOLDFISH; VISION; RECOVERY; LUMINANCE; FREQUENCY; OCTOPUS; TECTUM AB Spatial vision was studied in the bluegill sunfish, Lepomis macrochints (9.5-14 cm standard length) to assess the limitations imposed by the optics of the eye, the retinal receptor spacing and the retinotectal projection during regeneration. Examination of images formed by the dioptric elements of the eye showed that spatial frequencies up to 29 c/degrees could be imaged on the retina. Cone spacing was measured in the retina of fresh, intact eyes. The spacing of rows of double cones predicted 3.4 c/degrees as the cutoff spatial frequency; the spacing between rows of single an double cones predicted 6.7 c/degrees. Contrast sensitivity functions were obtained psychophysically in normals and fish with one regenerating optic nerve. Fish were trained to orient to gratings (mean luminance = 25 cd/m(2)) presented to either eye. In normals. contrast sensitivity functions were similar in shape and bandwidth to those of other species, peaking at 0.4 c/degrees with a minimum contrast threshold of 0.03 and a cutoff at about 5 c/degrees, which was within the range predicted by cone spacing. Given that the optical cutoff frequency exceeds that predicted by cone spacing, it is possible that gratings could be detected by aliasing with the bluegill's regular cone mosaic. However, tests with hi-h contrast tiratinas up to 15 c/degrees found no evidence of such detection. After crushing one optic nerve in three trained sunfish. recovery of visual avoidance, dorsal light reflex and orienting to gratings, were monitored over 315 days. At 64-69 days; postcrush, responses to gratings reappeared, and within 2-5 days contrast sensitivity at low (0.15 c/degrees) and mcchum, (1.0 c/degrees) spatial frequencies had returned to normal. At a high spatial frequency (2.93 c/degrees) recovery was Much slower, and complete only in one fish. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Chestnut Hill Coll, Philadelphia, PA USA. RP Northmore, DPM (reprint author), Univ Delaware, Dept Psychol, 220 Wolf Hall, Newark, DE 19716 USA. EM northmor@udel.edu NR 42 TC 10 Z9 11 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 2007 VL 24 IS 3 BP 319 EP 331 DI 10.1017/S0952523807070307 PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 208ZQ UT WOS:000249358300014 PM 17822574 ER PT J AU Fremont, AM Correa-de-Araujo, R Hayes, SN AF Fremont, Allen M. Correa-de-Araujo, Rosaly Hayes, Sharonne N. TI Gender disparities in managed care - It's time for action SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID QUALITY-OF-CARE; HEALTH; WOMEN C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. W Los Angeles VAMC, Los Angeles, CA USA. US Dept HHS, Off Secretary, Off Global Hlth Affairs, Rockville, MD USA. Mayo Clin, Coll Med, Womens Heart Clin, Rochester, MN USA. RP Fremont, AM (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90407 USA. EM fremont@rand.org OI Hayes, Sharonne/0000-0003-3129-362X NR 16 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2007 VL 17 IS 3 BP 116 EP 119 DI 10.1016/j.whi.2007.04.001 PG 4 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 178ZZ UT WOS:000247260400001 PM 17512754 ER PT J AU Bird, CE Fremont, AM Bierman, AS Wickstrom, S Shah, M Rector, T Horstman, T Escarce, JJ AF Bird, Chloe E. Fremont, Allen M. Bierman, Arlene S. Wickstrom, Steve Shah, Mona Rector, Thomas Horstman, Thomas Escarce, Jose J. TI Does quality of care for cardiovascular disease and diabetes differ by gender for enrollees in managed care plans? SO WOMENS HEALTH ISSUES LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; UNITED-STATES; ETHNIC-GROUPS; DISPARITIES; TRENDS; IMPACT; RACE; SEX AB Purpose. To assess gender differences in the quality of care for cardiovascular disease and diabetes for enrollees in managed care plans. Methods. We obtained data from 10 commercial and 9 Medicare plans and calculated performance on 6 Health Employer Data and Information Set (HEDIS) measures of quality of care (P-blocker use after myocardial infarction [Ml], low-density lipoprotein cholesterol [LDL-C] check after a cardiac event, and in diabetics, whether glycosylated hemoglobin [HgbA1c], LDL cholesterol, nephropathy, and eyes were checked) and a 7th HEDIS-like measure (angiotensin-converting enzyme [ACE] inhibitor use for congestive heart failure). A smaller number of plans provided HEDIS scores on 4 additional measures that require medical chart abstraction (control of LDL-C after cardiac event, blood pressure control in hypertensive patients, and HgbAlc and LDL-C control in diabetics). We used logistic regression models to adjust for age, race/ethnicity, socioeconomic status, and plan. Main Findings. Adjusting for covariates, we found significant gender differences on 5 of 11 measures among Medicare enrollees, with 4 favoring men. Similarly, among commercial enrollees, we found significant gender differences for 8 of 11 measures, with 6 favoring men. The largest disparity was for control of LDL-C among diabetics, where women were 19% less likely to achieve control among Medicare enrollees (relative risk [RR] = 0.81; 95% confidence interval [CI] 0.64-0.99) and 16% less likely among commercial enrollees (RR = 0.84; 95%Cl = 0.73-0.95). Conclusion. Gender differences in the quality of cardiovascular and diabetic care were common and sometimes substantial among enrollees in Medicare and commercial health plans. Routine monitoring of such differences is both warranted and feasible. C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ Toronto, Toronto, ON, Canada. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Ingenix, Eden Prairie, MN USA. United Healthcare, St Louis Pk, MN USA. Minneapolis Vet Adm Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Bird, CE (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM Chloe_Bird@rand.org RI Bird, Chloe/C-7107-2008; Fremont, Allen/A-7752-2009 NR 22 TC 37 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2007 VL 17 IS 3 BP 131 EP 138 DI 10.1016/j.whi.2007.03.001 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 178ZZ UT WOS:000247260400003 PM 17434752 ER PT J AU Sanders, EM LiVolsi, VA Brierley, J Shin, J Randolph, GW AF Sanders, Enoch M., Jr. LiVolsi, Virginia A. Brierley, James Shin, Jennifer Randolph, Gregory W. TI An evidence-based review of poorly differentiated thyroid cancer SO WORLD JOURNAL OF SURGERY LA English DT Review ID EXTERNAL-BEAM RADIOTHERAPY; INSULAR CARCINOMA; PROGNOSTIC-FACTORS; CLINICOPATHOLOGICAL FEATURES; FOLLICULAR CARCINOMAS; PAPILLARY CARCINOMA; RADIOACTIVE IODINE; SINGLE INSTITUTION; RADIATION-THERAPY; BIOLOGIC BEHAVIOR AB Background Poorly differentiated thyroid cancer (PDTC) presents the endocrinologist and surgeon with challenges of recognition and treatment given the lack of consensus on histopathologic definition and limited literature on surgical and nonsurgical treatment. Methods We offer an operational pathologic definition for PDTC, which should help guide future work in this area. Poorly differentiated thyroid cancer should include insular and trabecular variants but should not include solid type lesions (included by other workers) or more differentiated tumors that may have poor prognosis such as tall cell, columnar, diffuse sclerosing, and oncocytic lesions. Systematic evidence-based literature reviews focusing on two questions were carried out: (1) is PDTC associated with an intermediate prognosis relative to anaplastic and WDTC? and (2) What are the postoperative treatment options for poorly differentiated thyroid cancer? Conclusions We have found level IV evidence that PDTC is intermediate between WDTC and anaplastic cancers in terms of prognosis. It represents a disease where appropriate administration of aggressive treatment not typically necessary for routine WDTC and not effective for anaplastic disease may uniquely result in substantial benefit. Limited level IV data show conflicting results regarding I-131 treatment benefit. Given lack of morbidity and potential for benefit, we recommend that I-131 therapy be considered in all patients postoperatively. Recommendation regarding external beam radiotherapy (XRT) is based primarily on extrapolation from studies in forms of poor-prognosis WDTC where substantial data exist regarding treatment benefit. We recommend that external beam treatment be considered in all patients with PDTC with T3 tumors without distant metastasis, all patients with T4 tumors, and all patients with regional lymph node involvement. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 NR 57 TC 64 Z9 66 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAY PY 2007 VL 31 IS 5 BP 934 EP 945 DI 10.1007/s00268-007-9033-3 PG 12 WC Surgery SC Surgery GA 164LF UT WOS:000246234500008 PM 17431717 ER PT J AU Hector, RD Meikle, S Grant, L Wilkinson, RA Fishman, JA Scobie, L AF Hector, Ralph D. Meikle, Sharon Grant, Louise Wilkinson, Robert A. Fishman, Jay A. Scobie, Linda TI Pre-screening of miniature swine may reduce the risk of transmitting human tropic recombinant porcine endogenous retroviruses SO XENOTRANSPLANTATION LA English DT Article DE endogenous retrovirus; genomic locus; human tropic PERV; xenotransplantation ID HUMAN-CELLS; PIG; INFECTION AB Background: It has been reported that peripheral blood mononuclear cells from miniature swine are capable of transmitting human tropic porcine endogenous retrovirus (PERV) recombinants to both human and pig cells. It has been suggested that these recombinants are exogenous and/or driven by one or more critical loci present in the pig genome. Methods and Results: Genomic analysis of a miniature swine capable of transmitting human tropic replication competent (HTRC) recombinant PERV-A/C identified a PERV-C provirus in a region with homology to sequences located on chromosome 7. In "null" swine, incapable of in vitro transmission of PERV to human or pig cells, amplification using specific primers revealed that only two of five animals retained this locus in comparison to a total of five out of five transmitters (recombinant PERV-A/C transmission to both human and pig cells) and seven out of seven non-transmitters (replication of non-recombinant PERV in pig cells only). Conclusion: These data suggest that further analysis of these loci may provide a genetic basis for identifying pigs that are less likely to transmit human tropic PERV and would, therefore, be more suitable as source animals for human xenotransplantation. C1 Univ Glasgow, Inst Comparat Med, Div Pathol Sci, Glasgow G61 1QH, Lanark, Scotland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02115 USA. Univ Glasgow, Inst Comparat Med, Div Pathol Sci, Glasgow G12 8QQ, Lanark, Scotland. RP Scobie, L (reprint author), Univ Glasgow, Inst Comparat Med, Div Pathol Sci, Switchback Rd, Glasgow G61 1QH, Lanark, Scotland. EM l.scobie@vet.gla.ac.uk OI Hector, Ralph/0000-0002-3778-1483 FU NIAID NIH HHS [P01-AI45897, 5T32-AI07529] NR 14 TC 22 Z9 22 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2007 VL 14 IS 3 BP 222 EP 226 DI 10.1111/j.1399-3089.2007.00394.x PG 5 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 164AK UT WOS:000246204800005 PM 17489862 ER PT J AU Gusella, JF MacDonald, M AF Gusella, James F. MacDonald, Marcy TI Genetic criteria for Huntington's disease pathogenesis SO BRAIN RESEARCH BULLETIN LA English DT Editorial Material DE Huntington's disease; genetics; neurodegeneration; modifier ID KNOCK-IN MICE; AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; NEURODEGENERATIVE DISEASE; MOUSE MODEL; DNA MARKER; AGGREGATION; EXCITOTOXICITY; MECHANISMS; MODIFIERS AB Genetic analysis aims to identify the variations in DNA sequence whose functional consequences produce heritable variations in phenotype. In one of the first successes of unbiased molecular genetic analysis in human disease, the Huntington's disease (HD) gene was mapped and cloned without any prior knowledge of the nature of its protein product or of the molecular defect that underlies the characteristic phenotype of the disorder. However, while the cloning of HD and recognition of its trinucleotide repeat expansion spawned a plethora of approaches to investigating HD through its distinctive neuropathology, the: role for genetic strategies in HD research did not end there. The use of genetic analysis has remained a critical tool for defining the characteristics of the mechanism that triggers the pathogenic process, permitting the investigation of early events that occur long before traditionally recognized pathology. Delineation of these events can reveal molecular targets for development of therapies that prevent onset of HD. Most recently, an extension of genetic analysis to the identification of non-linked genetic variations that alter the course of HD pathogenesis has offered the promise of identifying modifier genes to reveal biological pathways active throughout the disease process and to provide valid targets for pharmacological intervention. Thus, unbiased genetic strategies have not only provided a crucial entree into molecular investigation of HD via a root cause that was previously unsuspected, they also represent a continuing route to accelerate the ultimate goal of developing an effective treatment for HD. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN 5830, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN 5830, 185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu FU NINDS NIH HHS [NS16367, NS32765]; NLM NIH HHS [LM008748] NR 36 TC 6 Z9 6 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR 30 PY 2007 VL 72 IS 2-3 SI SI BP 78 EP 82 DI 10.1016/j.brainresbull.2006.10.014 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 156AT UT WOS:000245621000002 PM 17352930 ER PT J AU Ilhan, SO Vural, IM Dilekoz, E Ozturk, GS Sarioglu, Y AF Ilhan, Sevil Ozger Vural, Ismail Mert Dilekoz, Ergin Ozturk, Gokce Sevim Sarioglu, Yusuf TI Enhancement effects of nicotine on neurogenic contractile responses in rabbit gastric fundus SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE nicotine; rabbit gastric fundus; nicotinic acetylcholine receptor; electrical field stimulation; nitric oxide; prostaglandins ID AMINOBUTYRIC-ACID RELEASE; ISOLATED RAT STOMACH; NITRIC-OXIDE; NORADRENALINE RELEASE; GUINEA-PIG; CHOLINERGIC NEUROTRANSMISSION; ACETYLCHOLINE-RECEPTORS; MYENTERIC PLEXUS; VAS-DEFERENS; MODULATION AB Nicotine, a nicotinic acetylcholine receptor agonist, plays a role in the modulation of neurotransmitter release following nerve stimulation in both the central and the peripheral nervous system. Nitric oxide and prostaglandins modulate the release of various neurotransmitters in different tissues. We aimed to investigate the effects of nicotine on neurogenic contractile responses via nicotinic acetylcholine receptors and, if a change occurred, to investigate the effects of N-W-nitro-L-arginine methyl ester (L-NAME) and indomethacin on this change in rabbit gastric fundus. Electrical field stimulation (EFS)-evoked contractile responses were recorded from gastric fundus strips obtained from rabbits with an isometric force displacement transducer. Nicotine was applied to preparations at varying concentrations. Then, the effects of hexamethonium, cadmium (Cd2+), indomethacin, and L-NAME were tested on the EFS-evoked contractions in the presence of nicotine. Nicotine-induced transient neurogenic contractions in a dose-dependent manner. Cd2+ and hexamethonium inhibited nicotine-induced transient neurogenic contractions, but indomethacin and L-NAME produced no effect. In conclusion, nicotine increased EFS-evoked contractile responses, possibly by facilitating neurotransmitter release from nerve terminals by a mechanism dependent on the influx of Ca2+ from voltage-gated Ca2+ channels via activation of nicotinic acetylcholine receptors in isolated rabbit gastric fundus. Endogenous nitric oxide and prostaglandins do not play a physiological role in the regulation of this neurotransmitter release. (c) 2007 Elsevier B.V. All rights reserved. C1 Gazi Univ, Fac Med, Dept Pharmacol, Sch Med, TR-06510 Ankara, Turkey. Sch Publ Hlth, Refik Saydam Hyg Ctr Presidency, Ankara, Turkey. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Vural, IM (reprint author), Gazi Univ, Fac Med, Dept Pharmacol, Sch Med, TR-06510 Ankara, Turkey. EM imvural@yahoo.com NR 37 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 30 PY 2007 VL 561 IS 1-3 BP 182 EP 188 DI 10.1016/j.ejphar.2006.12.033 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 155ED UT WOS:000245559700024 PM 17292347 ER PT J AU Parvizi, J Joseph, J Press, DZ Schmahmann, JD AF Parvizi, Josef Joseph, Jeffrey Press, Daniel Z. Schmahmann, Jeremy D. TI Pathological laughter and crying in patients with multiple system atrophy-cerebellar type SO MOVEMENT DISORDERS LA English DT Article DE olivopontocerebellar atrophy; disinhibition; emotion; behavior; pseudobulbar affect ID SPORADIC OLIVOPONTOCEREBELLAR ATROPHY; TRAUMATIC BRAIN-INJURY; PSEUDOBULBAR AFFECT; SCLEROSIS; PREVALENCE; DISORDERS; DIAGNOSIS; STROKE AB In the cerebellar type of multiple system atrophy (MSA-C), the burden of pathological changes involves the cerebellum and its associated brainstem structures in the basis pontis and the inferior olivary nucleus, and as a result, the clinical phenotype is dominated early on by the cerebellar dysfunction. We report our clinical and post mortem findings in a patient with MSA-C who exhibited pathological laughter in the absence of any congruent changes of mood. A review of the clinical notes of 27 other patients with MSA-C revealed a problem with pathological laughter, or crying, or both in 9 more patients. Our finding of about 36% occurrence suggests that the problem of dysregulation of emotional expression is more prevalent in MSA-C than the paucity of reports in the literature suggests. Our findings are consistent with the view that the cerebellum and its interconnected structures may be involved in the regulation of emotional expression. (c) 2007 Movement Disorder Society. C1 Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Parvizi, J (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM jparvizi@ucla.edu NR 30 TC 39 Z9 41 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR 30 PY 2007 VL 22 IS 6 BP 798 EP 803 DI 10.1002/mds.21348 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 163KQ UT WOS:000246159000006 PM 17290465 ER PT J AU Grady, D Barrett-Connor, E AF Grady, Deborah Barrett-Connor, Elizabeth TI Postmenopausal hormone therapy - Symptoms should be treated with lowest effective dose of hormone therapy for the shortest time possible SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; WOMEN; DEMENTIA; DISEASE C1 Univ Calif San Francisco, San Francisco, CA 94115 USA. San Francisco VA Med Ctr, San Francisco, CA 94115 USA. Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA 92093 USA. RP Grady, D (reprint author), Univ Calif San Francisco, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 9 TC 10 Z9 10 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD APR 28 PY 2007 VL 334 IS 7599 BP 860 EP 861 DI 10.1136/bmj39185.380405.BE PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 164FB UT WOS:000246217800002 PM 17463421 ER PT J AU Nahrendorf, M Sosnovik, DE Waterman, P Swirski, FK Pande, AN Aikawa, E Figueiredo, JL Pittet, MJ Weissleder, R AF Nahrendorf, Matthias Sosnovik, David E. Waterman, Peter Swirski, Filip K. Pande, Ashvin N. Aikawa, Elena Figueiredo, Jose-Luiz Pittet, Mikael J. Weissleder, Ralph TI Dual channel optical tomographic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct SO CIRCULATION RESEARCH LA English DT Article DE molecular imaging; myocardial infarction; inflammation; cathepsin; factor XIII ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; IN-VIVO; ATHEROSCLEROSIS; MICE; ACCUMULATION; TISSUE AB Inflammatory responses after myocardial infarction profoundly impact tissue repair. Yet, efficient tools to serially and noninvasively assess cellular and molecular functions in postinfarct inflammation are lacking. Here we use multichannel fluorescent molecular tomography (FMT) for spatiotemporal resolution of phagocytic and proteolytic activities mediated by macrophages and neutrophils in murine infarcts. We performed FMT imaging to compare the course of efficient and impaired healing in wild-type and FXIII-/- mice, respectively. Mice subjected to coronary ligation received simultaneous injections with Prosense-680, an activatable fluorescence sensor reporting on cathepsin activity, and CLIO-VT750, a magneto-fluorescent nanoparticle for imaging of phagocyte recruitment. On FMT, Prosense-680 infarct signal was 19-fold higher than background (P<0.05). Protease activity was higher in the infarcted lateral wall than in the remote, uninjured septum on ex vivo fluorescence reflectance imaging ( contrast to noise ratio 118 +/- 24). CLIO-VT750 FMT signal coregistered with contrast enhancement in the hypokinetic infarct on MRI. Microscopic fluorescence signal colocalized with immunoreactive staining for cathepsin, macrophages and neutrophils. Flow cytometry of digested infarcts revealed monocytes/macrophages and neutrophils as the source of the fluorescence signal. Phagocytic activity peaked on day 6, and proteolytic activity peaked on day 4 after myocardial infarction. FMT detected impaired recruitment of phagocytes and protease activity in FXIII-/- mice (P<0.05). FMT is a promising noninvasive molecular imaging approach to characterize infarct healing. Spectrally resolved imaging agents allow for simultaneous assesment of key processes of in vivo cellular functions. Specifically, we show that in vivo FMT detects impaired healing in FXIII-/- mice. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM Weissleder@helix.mgh.harvard.edu FU NCI NIH HHS [R24-CA92782]; NHLBI NIH HHS [R01-HL078641, K08 HL079984, UO1-HL080731] NR 33 TC 102 Z9 103 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 27 PY 2007 VL 100 IS 8 BP 1218 EP 1225 DI 10.1161/01.RES.0000265064.46075.31 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 161JT UT WOS:000246011900016 PM 17379832 ER PT J AU Cosen-Binker, LI Lam, PPL Binker, MG Reeve, J Pandol, S Gaisano, HY AF Cosen-Binker, Laura I. Lam, Patrick P. L. Binker, Marcelo G. Reeve, Joseph Pandol, Stephen Gaisano, Herbert Y. TI Alcohol/cholecystokinin-evoked pancreatic acinar basolateral exocytosis is mediated by protein kinase C alpha phosphorylation of Munc18c SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B ACTIVATION; ALCOHOLIC PANCREATITIS; REGULATED EXOCYTOSIS; MEMBRANE-FUSION; PLASMA-MEMBRANE; PKC-DELTA; CELLS; CHOLECYSTOKININ; MECHANISMS; MACHINERY AB The pancreatic acinus is the functional unit of the exocrine pancreas whose role is to secrete zymogens into the gut lumen for food digestion via apical exocytosis. We previously reported that supramaximal CCK induced apical blockade and redirected exocytosis to ectopic sites on the basolateral plasma membrane (BPM) of this polarized cell, leading to pancreatitis. Basolateral exocytosis was mediated by protein kinase C phosphorylation of BPM Munc18c, causing its displacement into the cytosol and activation of BPM-bound Syntaxin-4 to form aSNARE complex. To mimic the conditions of alcoholic pancreatitis, we now examined whether 20 mM alcohol followed by submaximal CCK might mimic supramaximal CCK in inducing these pathologic exocytotic events. We show that a non-secretory but clinically relevant alcohol concentration (20 mM) inhibited submaximal CCK (50 pM)-stimulated amylase secretion by blocking apical exocytosis and redirecting exocytosis to less efficient BPM, indeed mimicking supramaximal CCK (10 nM) stimulation. We further demonstrate that basolateral exocytosis caused by both stimulation protocols is mediated by PKC alpha-induced phosphorylation of Munc18c: 1) PKC alpha is activated, which binds and induces phosphorylation of PM-Munc18c at a Thr site, and these events can be inhibited by PKC alpha blockade; 2) PKC alpha inhibition blocks Munc18c displacement from the BPM; 3) PKC alpha inhibition prevents basolateral exocytosis but does not rescue apical exocytosis. We conclude that 20 mM alcohol/submaximal CCK as well supramaximal CCK stimulation can trigger pathologic basolateral exocytosis in pancreatic acinar cells via PKC alpha-mediated activation of Munc18c, which enables Syntaxin-4 to become receptive in forming a SNARE complex in the BPM; and we further postulate this to be an underlying mechanism contributing to alcoholic pancreatitis. C1 Univ Toronto, Univ Hlth Network, Dept Med, Toronto, ON M5S 1A8, Canada. Univ Toronto, Univ Hlth Network, Dept Physiol, Toronto, ON M5S 1A8, Canada. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Gaisano, HY (reprint author), Univ Toronto, Univ Hlth Network, Dept Med, Rm 7226,Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM herbert.gaisano@utoronto.ca FU NIAAA NIH HHS [R21 AA015579-01A1] NR 35 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 27 PY 2007 VL 282 IS 17 BP 13047 EP 13058 DI 10.1074/jbc.M611132200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LR UT WOS:000245942800074 PM 17324928 ER PT J AU Jin, YP Shen, LL Chong, EM Hamrah, P Zhang, Q Chen, L Dana, MR AF Jin, Yiping Shen, Linling Chong, Eva-Marie Hamrah, Pedram Zhang, Qiang Chen, Lu Dana, M. Reza TI The chemokine receptor CCR7 mediates corneal antigen-presenting cell trafficking SO MOLECULAR VISION LA English DT Article ID MATURE DENDRITIC CELLS; LYMPH-NODES; IN-VIVO; LANGERHANS CELLS; CUTTING EDGE; T-CELLS; EXPRESSION; INFLAMMATION; MATURATION; IMMATURE AB PURPOSE: Trafficking of corneal antigen-presenting cells (APC) to draining lymph nodes (LN) is critical in triggering immune responses. However, very little is known about the molecular regulation of this pathway. We investigated the expression and function of the chemokine receptor CCR7 in mediating corneal APC migration in inflammation. METHODS: Expression of CCR7 and its ligands, CCL21 and CCL19, in the normal and inflamed corneas was analyzed by RT-PCR and immunofluorescence staining. The phenotype of CCR7-expressing cells was identified by double-staining with different cell surface markers. To trace the trafficking of APC to draining LN, we injected corneal grafts with Alexa488-conjugated ovalbumin (OVA) and transplanted to syngeneic recipients. CCR7 expression on the Alexa488-conjugated OVA(+) cells in the ipsilateral draining LN was analyzed by flow cytometry. To determine the functional role of CCR7, we injected anti-CCL21 neutralizing antibody subconjunctivally after corneal transplantation and analyzed changes in numbers of OVA(+) cells in the draining LN. Each experiment was repeated at least three times. RESULTS: Both CCR7 and its ligand CCL21 were significantly upregulated in inflamed corneas as measured by RT-PCR and immunofluorescence staining. CCR7(+) cells were detected especially in the corneal periphery near LYVE-1(+) lymphatic vessels. CCR7(+) cells were universally CD11b(+)CD11c(+), and a majority were major histocompatibility complex class II positive, suggesting a monocytic dendritic cell lineage and a relative state of maturation. Forty-eight h after syngeneic transplantation with OVA-loaded grafts, CCR7 expression was detected on the OVA(+) cells in both the host corneal beds and the draining LN. Local administration of anti-CCL21 led to a significant suppression in the flow of OVA(+)CD11c(+) cells to the draining LN. CONCLUSIONS: These data suggest that in inflammation, APC expressing CCR7 on their cell surface interact with CCL21 to facilitate their migration from the cornea to draining LN via afferent lymphatics. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU NEI NIH HHS [EY-12963, R01 EY012963] NR 44 TC 50 Z9 53 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD APR 27 PY 2007 VL 13 IS 68-72 BP 626 EP 634 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 170CB UT WOS:000246638000001 PM 17515886 ER PT J AU Thai, TH Calado, DP Casola, S Ansel, KM Xiao, CC Xue, YZ Murphy, A Frendewey, D Valenzuela, D Kutok, JL Schmidt-Supprian, M Rajewsky, N Yancopoulos, G Rao, A Rajewsky, K AF Thai, To-Ha Calado, Dinis Pedro Casola, Stefano Ansel, K. Mark Xiao, Changchun Xue, Yingzi Murphy, Andrew Frendewey, David Valenzuela, David Kutok, Jeffery L. Schmidt-Supprian, Marc Rajewsky, Nikolaus Yancopoulos, George Rao, Anjana Rajewsky, Klaus TI Regulation of the germinal center response by microRNA-155 SO SCIENCE LA English DT Article ID VIRUS-INDUCED LYMPHOMAS; B-CELL PROLIFERATION; HIGH EXPRESSION; NONCODING RNA; GENE; MICE; LYMPHOTOXIN; RECEPTOR; ENCODES; BETA AB MicroRNAs are small RNA species involved in biological control at multiple levels. Using genetic deletion and transgenic approaches, we show that the evolutionarily conserved microRNA-155 (miR-155) has an important role in the mammalian immune system, specifically in regulating T helper cell differentiation and the germinal center reaction to produce an optimal T cell-dependent antibody response. miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. IFOM FIRC Inst Mol Oncol, I-20139 Milan, Italy. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Frendewey, David/0000-0003-2305-3490; Murphy, Andrew/0000-0003-4152-4081 FU NIAID NIH HHS [AI064345] NR 24 TC 873 Z9 961 U1 6 U2 49 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 27 PY 2007 VL 316 IS 5824 BP 604 EP 608 DI 10.1126/science.1141229 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 160ZC UT WOS:000245983100047 PM 17463289 ER PT J AU Abbud, M Adams, PL Alberu, J Cardella, C Chapman, J Cochat, P Cosio, F Danovitch, G Davis, C Gaston, RS Humar, A Hunsicker, LG Josephson, MA Kasiske, B Kirste, G Leichtman, A Munn, S Obrador, GT Tibell, A Wadstrom, J Zeier, M Delmonico, FL AF Abbud, Mario, Jr. Adams, Patricia L. Alberu, Josefina Cardella, Carl Chapman, Jeremy Cochat, Pierre Cosio, Fernando Danovitch, Gabriel Davis, Connie Gaston, Robert S. Humar, Atul Hunsicker, Lawrence G. Josephson, Michelle A. Kasiske, Bertram Kirste, Guinter Leichtman, Alan Munn, Stephen Obrador, Gregorio T. Tibell, Annika Wadstrom, Jonas Zeier, Martin Delmonico, Francis L. TI A report of the Lisbon conference on the care of the kidney transplant recipient SO TRANSPLANTATION LA English DT Review ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; CHRONIC ALLOGRAFT NEPHROPATHY; HEPATITIS-C-VIRUS; CLINICAL-PRACTICE GUIDELINES; CONGESTIVE-HEART-FAILURE; EARLY CYCLOSPORINE WITHDRAWAL; SOLID-ORGAN TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIAL; ACUTE CELLULAR REJECTION C1 FAMERP, Inst Urol & Nefrol, Sao Jose Do Rio Preto, SP, Brazil. FAMERP, Sch Med, Sao Jose Do Rio Preto, SP, Brazil. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. Westmead Hosp, Sydney, NSW, Australia. Hop Edouard Herriot, Lyon, France. Mayo Clin, Rochester, MN USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Washington, Seattle, WA 98195 USA. Univ Alabama, Birmingham, AL USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Chicago, Chicago, IL 60637 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Deutsch Stiftung Organ Transplantat, New Isenburg, Germany. Univ Michigan, Ann Arbor, MI 48109 USA. Auckland Dist Hlth Board, Auckland, New Zealand. Univ Panamer, Escuela Med, Mexico City, DF, Mexico. Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden. Univ Uppsala Hosp, Uppsala, Sweden. Univ Heidelberg, D-6900 Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Natl Kidney Fdn, 30 E 33rd St, New York, NY 10016 USA. EM francis_delmonico@neob.org OI Obrador, Gregorio/0000-0003-3814-7449; Abbud-Filho, Mario/0000-0002-5079-9813 NR 213 TC 48 Z9 51 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2007 VL 83 IS 8 SU S BP S1 EP S22 DI 10.1097/01.tp.0000260765.41275.e2 PG 22 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 165YJ UT WOS:000246343400001 PM 17452912 ER PT J AU Sachs, GS Nierenberg, AA Calabrese, JR Marangell, LB Wisniewski, SR Gyulai, L Friedman, ES Bowden, CL Fossey, MD Ostacher, MJ Ketter, TA Patel, J Hauser, P Rapport, D Martinez, JM Allen, MH Miklowitz, DJ Otto, MW Dennehy, EB Thase, ME AF Sachs, Gary S. Nierenberg, Andrew A. Calabrese, Joseph R. Marangell, Lauren B. Wisniewski, Stephen R. Gyulai, Laszlo Friedman, Edward S. Bowden, Charles L. Fossey, Mark D. Ostacher, Michael J. Ketter, Terence A. Patel, Jayendra Hauser, Peter Rapport, Daniel Martinez, James M. Allen, Michael H. Miklowitz, David J. Otto, Michael W. Dennehy, Ellen B. Thase, Michael E. TI Effectiveness of adjunctive antidepressant treatment for bipolar depression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; DISORDER STEP-BD; MOOD STABILIZERS; DOUBLE-BLIND; I-DISORDER; DSM-IV; VENLAFAXINE; BUPROPION; TRIAL; PREVALENCE AB BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. CONCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biopolar Clin & Res Program, Boston, MA 02114 USA. Boston Univ, Boston, MA 02215 USA. Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Cleveland, OH 44106 USA. Baylor Coll Med, Houston, TX 77030 USA. S Cent Mental Illness Res Educ & Clin Core, Houston, TX USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Oklahoma, Coll Med, Tulsa, OK USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Toledo, Coll Med, Toledo, OH 43606 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Purdue Univ, W Lafayette, IN 47907 USA. RP Sachs, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biopolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM gsachs@partners.org RI Allen, Michael/A-8776-2011; OI Wisniewski, Stephen/0000-0002-3877-9860; Ostacher, Michael/0000-0003-0353-7535 FU NIMH NIH HHS [N01MH80001] NR 31 TC 487 Z9 503 U1 7 U2 43 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2007 VL 356 IS 17 BP 1711 EP 1722 DI 10.1056/NEJMoa064135 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 160LQ UT WOS:000245942600006 PM 17392295 ER PT J AU Campbell, EG Gruen, RL Mountford, J Miller, LG Cleary, PD Blumenthal, D AF Campbell, Eric G. Gruen, Russell L. Mountford, James Miller, Lawrence G. Cleary, Paul D. Blumenthal, David TI A national survey of physician-industry relationships SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONFLICTS-OF-INTEREST; PHARMACEUTICAL-INDUSTRY; DRUG COMPANIES; DOCTORS AB BACKGROUND: Relationships between physicians and pharmaceutical, medical device, and other medically related industries have received considerable attention in recent years. We surveyed physicians to collect information about their financial associations with industry and the factors that predict those associations. METHODS: We conducted a national survey of 3167 physicians in six specialties (anesthesiology, cardiology, family practice, general surgery, internal medicine, and pediatrics) in late 2003 and early 2004. The raw response rate for this probability sample was 52%, and the weighted response rate was 58%. RESULTS: Most physicians (94%) reported some type of relationship with the pharmaceutical industry, and most of these relationships involved receiving food in the workplace (83%) or receiving drug samples (78%). More than one third of the respondents (35%) received reimbursement for costs associated with professional meetings or continuing medical education, and more than one quarter (28%) received payments for consulting, giving lectures, or enrolling patients in trials. Cardiologists were more than twice as likely as family practitioners to receive payments. Family practitioners met more frequently with industry representatives than did physicians in other specialties, and physicians in solo, two-person, or group practices met more frequently with industry representatives than did physicians practicing in hospitals and clinics. CONCLUSIONS: The results of this national survey indicate that relationships between physicians and industry are common and underscore the variation among such relationships according to specialty, practice type, and professional activities. C1 Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Melbourne, Melbourne, Vic, Australia. Royal Melbourne Hosp, Melbourne, Vic, Australia. Mediphase, Newton, MA USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Campbell, EG (reprint author), Inst Hlth Policy, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM ecampbell@partners.org NR 24 TC 214 Z9 220 U1 5 U2 17 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2007 VL 356 IS 17 BP 1742 EP 1750 DI 10.1056/NEJMsa064508 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 160LQ UT WOS:000245942600009 PM 17460228 ER PT J AU Seiden, MV O'Neill, MJ Oliva, E Patel, D Harris, NL Goodman, A AF Seiden, Michael V. O'Neill, Mary Jane Oliva, Esther Patel, Devanshi Harris, Nancy Lee Goodman, Annekathryn TI Case 13-2007: A 46-year-old woman with gynecologic and intestinal cancers - The Lynch syndrome (HNPCC) with a mutation in the MSH2 gene, endometrioid adenocarcinoma of the uterus, clear-cell adenofibromas of borderline malignancy of the ovaries, and two adenocarcinomas of the colon SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; GERMLINE MUTATIONS; SPORADIC CARCINOMAS; PROTEIN EXPRESSION; HEREDITARY; RISK; SURVIVAL; FEATURES; WOMEN C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Med Sch, Dept Med, Boston, MA USA. Harvard Med Sch, Dept Radiol, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. Gillette Ctr Womens Canc, Needham, MA USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 37 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2007 VL 356 IS 17 BP 1760 EP 1769 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 160LQ UT WOS:000245942600014 PM 17460231 ER PT J AU Kabrhel, C Thomsen, TW Setnik, GS Walls, RM AF Kabrhel, Christopher Thomsen, Todd W. Setnik, Gary S. Walls, Ron M. TI Orotracheal intubation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 26 PY 2007 VL 356 IS 17 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 160LQ UT WOS:000245942600011 ER PT J AU Danley, PD Mullen, SP Liu, F Nene, V Quackenbush, J Shaw, KL AF Danley, Patrick D. Mullen, Sean P. Liu, Fenglong Nene, Vishvanath Quackenbush, John Shaw, Kerry L. TI A cricket Gene Index: a genomic resource for studying neurobiology, speciation, and molecular evolution SO BMC GENOMICS LA English DT Article ID MITOCHONDRIAL-DNA PHYLOGENY; HAWAIIAN CRICKETS; FIELD CRICKET; GRYLLUS-BIMACULATUS; BOMBYX-MORI; SPERMLESS SPERMATOPHORES; INTERSPECIFIC GENETICS; TELEOGRYLLUS-COMMODUS; ACOUSTIC PREFERENCE; SPECIES BOUNDARIES AB Background: As the developmental costs of genomic tools decline, genomic approaches to non-model systems are becoming more feasible. Many of these systems may lack advanced genetic tools but are extremely valuable models in other biological fields. Here we report the development of expressed sequence tags ( EST's) in an orthopteroid insect, a model for the study of neurobiology, speciation, and evolution. Results: We report the sequencing of 14,502 EST's from clones derived from a nerve cord cDNA library, and the subsequent construction of a Gene Index from these sequences, from the Hawaiian trigonidiine cricket Laupala kohalensis. The Gene Index contains 8607 unique sequences comprised of 2575 tentative consensus ( TC) sequences and 6032 singletons. For each of the unique sequences, an attempt was made to assign a provisional annotation and to categorize its function using a Gene Ontology- based classification through a sequence- based comparison to known proteins. In addition, a set of unique 70 base pair oligomers that can be used for DNA microarrays was developed. All Gene Index information is posted at the DFCI Gene Indices web page. Conclusion: Orthopterans are models used to understand the neurophysiological basis of complex motor patterns such as flight and stridulation. The sequences presented in the cricket Gene Index will provide neurophysiologists with many genetic tools that have been largely absent in this field. The cricket Gene Index is one of only two gene indices to be developed in an evolutionary model system. Species within the genus Laupala have speciated recently, rapidly, and extensively. Therefore, the genes identified in the cricket Gene Index can be used to study the genomics of speciation. Furthermore, this gene index represents a significant EST resources for basal insects. As such, this resource is a valuable comparative tool for the understanding of invertebrate molecular evolution. The sequences presented here will provide much needed genomic resources for three distinct but overlapping fields of inquiry: neurobiology, speciation, and molecular evolution. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Inst Genom Res, Rockville, MD 20850 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Danley, PD (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA. EM pdanley@umd.edu; spm23@umd.edu; fliu@jimmy.harvard.edu; nene@tigr.org; johnq@jimmy.harvard.edu; kerryshaw@umd.edu OI Danley, Patrick/0000-0001-8782-5045 NR 94 TC 13 Z9 13 U1 3 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 25 PY 2007 VL 8 AR 109 DI 10.1186/1471-2164-8-109 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 173BB UT WOS:000246847400001 PM 17459168 ER PT J AU Ko, V Nanji, S Tambouret, RH Wilbur, DC AF Ko, Vincent Nanji, Shabin Tambouret, Rosemary H. Wilbur, David C. TI Testing for HPV as an objective measure for quality assurance in gynecologic cytology - Positive rates in equivocal and abnormal specimens and comparison with the ASCUS to SIL ratio SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE human papillomavirus; HPV; ASCUS; ASCUS : SIL; quality assurance ID ATYPICAL SQUAMOUS-CELLS; UNDETERMINED SIGNIFICANCE; HUMAN-PAPILLOMAVIRUS; CERVICAL CYTOLOGY; MANAGEMENT AB BACKGROUND. inappropriate use of the category of atypical squamous cells of undetermined significance ASCUS) can result in overtreatment or undertreatment of patients, which may decrease the cost effectiveness of screening. Quality assurance tools, such as the ASCUS to squamous intraepithelial lesion ratio (ASCUS:SIL) and case review, are imperfect. High-risk HPV (hrHPV) testing is an objective test for a known viral carcinogen, and hrHPV may be more useful in monitoring the quality of ASCUS interpretations. METHODS. hrHPV rates for cytologic diagnoses and patient age groups were calculated for a 2-year period. All hrHPV results for ASCUS and SIL over a 17-month period were analyzed by patient age group, over time, and by individual cytopathologist to compare hrHPV rates with the corresponding ASCUS:SIL. RESULTS. The hrHPV positive rate for SIL was > 90%, and it was 32.6% for ASCUS. Stratification by patient age showed that approximately 50% of patients younger than 30 years and older than 70 years of age were hrHPV positive, whereas other patients had a lower rate ranging from 14% to 34%. The overall ASCUS:SIL was 1.42, and the overall hrHPV positive rate was 39.9%. Over time and by individual cytopathologist, the hrHPV rate performed similarly to the ASCUS:SIL. The analysis by patient age showed a high statistical correlation (R-2 = 0.9772) between the 2 methods. CONCLUSIONS. Despite differences between these techniques, the hrHPV rate closely recapitulates the ASCUS:SIL. When used together, the 2 methods can complement each other. The desirable hrHPV-positive range appears to be 40% to 50%; however, this may vary based on the patient population. The hrHPV rate is as quick and cost effective as determining the ASCUS:SIL. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ko, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM vko@partners.org NR 14 TC 18 Z9 20 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2007 VL 111 IS 2 BP 67 EP 73 DI 10.1002/cncr.22488 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 158FQ UT WOS:000245777500001 PM 17330272 ER PT J AU Morrow, DA Scirica, BM Karwatowska-Prokopczuk, E Murphy, SA Budaj, A Varshavsky, S Wolff, AA Skene, A McCabe, CH Braunwald, E AF Morrow, David A. Scirica, Benjamin M. Karwatowska-Prokopczuk, Ewa Murphy, Sabina A. Budaj, Andrzej Varshavsky, Sergei Wolff, Andrew A. Skene, Allan McCabe, Carolyn H. Braunwald, Eugene CA MERLIN TIMI 36 Trial Investigators TI Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes - The MERLIN-TIMI 36 randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHRONIC ANGINA; AMERICAN-COLLEGE; UNSTABLE ANGINA; TASK-FORCE; MANAGEMENT; AMLODIPINE; EFFICACY; AGENT; HEART AB Context Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS). Objective To determine the efficacy and safety of ranolazine during long-term treatment of patients with non-ST-elevation ACS. Design, Setting, and Patients A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes ( MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007. Main Outcome Measures The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia. Results The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point ( cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = . 87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = . 03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = . 84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = . 91). Conclusions The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy. C1 Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. CV Therapeut, Palo Alto, CA USA. Grochowski Hosp, Dept Cardiol, Postgrad Med Sch, Warsaw, Poland. Evidence Clin & Pharmaceut Res, St Petersburg, Russia. Cytokinet, San Francisco, CA USA. Nottingham Clin Res Ltd, Nottingham, England. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 18 TC 265 Z9 279 U1 6 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2007 VL 297 IS 16 BP 1775 EP U3 DI 10.1001/jama.297.16.1775 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 160DW UT WOS:000245922100023 PM 17456819 ER PT J AU Balenci, L Saoudi, Y Grunwald, D Deloulme, JC Bouron, A Bernards, A Baudier, J AF Balenci, Laurent Saoudi, Yasmina Grunwald, Didier Deloulme, Jean Christophe Bouron, Alexandre Bernards, Andre Baudier, Jacques TI IQGAP1 regulates adult neural progenitors in vivo and vascular endothelial growth factor-triggered neural progenitor migration in vitro SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adult neurogenesis; IQGAP1; migration; neural progenitors; Rac1/Cdc42; VEGF ID STEM-CELLS; NEURITE OUTGROWTH; MAMMALIAN BRAIN; NEUROGENESIS; CDC42; VEGF; PROTEIN; PROLIFERATION; EXPRESSION; COMPONENTS AB In the germinative zone of the adult rodent brain, neural progenitors migrate into niches delimited by astrocyte processes and differentiate into neuronal precursors. In the present study, we report a modulating role for the scaffolding protein IQGAP1 in neural progenitor migration. We have identified IQGAP1 as a new marker of amplifying neural progenitor and neuronal precursor cells of the subventricular zone (SVZ) and the rostral migratory stream (RMS) in the adult mouse brain. To determine functions for IQGAP1 in neural progenitors, we compared the properties of neural progenitor cells from wild-type and Iqgap1-null mutant mice in vivo and in vitro. The in vivo studies reveal a delay in the transition of de novo neural progenitors into neuronal precursor cells in Iqgap1-null mice. In vitro, we demonstrated that IQGAP1 acts as a downstream effector in the vascular endothelial growth factor (VEGF)-dependent migratory response of neural progenitors that also impacts on their neuronal differentiation. The Rho-family GTPases cdc42/Rac1 and Lis1 are major partners of IQGAP1 in this migratory process. Finally, astrocytes of the neurogenic SVZ and RMS are shown to express VEGF. We propose that VEGF synthesized by astrocytes could be involved in the guidance of neural progenitors to neurogenic niches and that IQGAP1 is an effector of the VEGF-dependent migratory signal. C1 CEA Grenoble, Unite 873, Transduct Signal Inst Rech Technol & Sci Vivant, F-38054 Grenoble 9, France. INSERM, U873, Lab Transduct Signal, F-38054 Grenoble, France. INSERM, U836, Grp Physiopathol Cytosquelette, F-38054 Grenoble, France. Univ Grenoble 1, F-38054 Grenoble, France. CNRS, Unite Mixte Rech 5249, Lab Chim Biol Metaux, F-38054 Grenoble, France. CNRS, Unite Mixte Rech 5249, Lab Chim Biol Metaux, F-38054 Grenoble, France. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Baudier, J (reprint author), CEA Grenoble, Unite 873, Transduct Signal Inst Rech Technol & Sci Vivant, 17 Rues Martyrs, F-38054 Grenoble 9, France. EM jbaudier@cea.fr RI Baudier, Jacques/O-2183-2016 NR 33 TC 32 Z9 32 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 25 PY 2007 VL 27 IS 17 BP 4716 EP 4724 DI 10.1523/JNEUROSCI.0830-07.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 165HB UT WOS:000246293900024 PM 17460084 ER PT J AU Samaha, FF AF Samaha, Frederick F. TI New international measuring stick for defining obesity in non-Europeans SO CIRCULATION LA English DT Editorial Material DE editorials; diabetes mellitus; epidemiology; myocardial infarction; obesity ID BODY-MASS INDEX; MORTALITY; ASIANS C1 Univ Penn, Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Div Cardiovasc Med, Dept Med, Philadelphia, PA 19104 USA. RP Samaha, FF (reprint author), Univ Penn, Philadelphia VA Med Ctr, Dept Med, 8th Floor MC 111C,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM rick.samaha@va.gov NR 13 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 24 PY 2007 VL 115 IS 16 BP 2089 EP 2090 DI 10.1161/CIRCULATIONAHA.107.696260 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160DN UT WOS:000245919600002 PM 17452616 ER PT J AU Maree, AO Fitzgerald, DJ AF Maree, Andrew O. Fitzgerald, Desmond J. TI Variable platelet response to aspirin and clopidogrel in atherothrombotic disease SO CIRCULATION LA English DT Review DE aspirin; myocardial infarction; pharmacokinetics; pharmacology; platelets; thrombosis; clopidogrel ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; LOW-DOSE ASPIRIN; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ST-SEGMENT ELEVATION; HIGH-RISK PATIENTS; ADENOSINE-DIPHOSPHATE; STENT THROMBOSIS; CARDIOVASCULAR-DISEASE C1 Univ Coll Dublin, UCD Conway Inst, Dublin 4, Ireland. Harvard Univ, Sch Med, Div Cardiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fitzgerald, DJ (reprint author), Univ Coll Dublin, UCD Conway Inst, Dublin 4, Ireland. EM des.fitzgerald@ucd.ie NR 97 TC 132 Z9 141 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 24 PY 2007 VL 115 IS 16 BP 2196 EP 2207 DI 10.1161/CIRCULATIONAHA.106.675991 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160DN UT WOS:000245919600016 PM 17452618 ER PT J AU Ho, I d'Avila, A Ruskin, J Mansour, M AF Ho, Ivan d'Avila, Andre Ruskin, Jeremy Mansour, Moussa TI Percutaneous epicardial mapping and ablation of a posteroseptal accessory pathway SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray 109, Boston, MA 02114 USA. EM mmansour@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 4 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 24 PY 2007 VL 115 IS 16 BP E418 EP E421 DI 10.1161/CIRCULATIONAHA.106.673855 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 160DN UT WOS:000245919600022 PM 17452613 ER PT J AU Plouffe, BD Njoka, DN Harris, J Liao, JH Horick, NK Radisic, M Murthy, SK AF Plouffe, Brian D. Njoka, Danson N. Harris, Joscelyn Liao, Jiahui Horick, Nora K. Radisic, Milica Murthy, Shashi K. TI Peptide-mediated selective adhesion of smooth muscle and endothelial cells in microfluidic shear flow SO LANGMUIR LA English DT Article ID ELASTIN-DERIVED PEPTIDE; RECEPTOR; PROTEIN; FRACTIONATION; ENRICHMENT; CHAMBERS; AFFINITY; TISSUE; BLOOD AB Microfluidic devices have recently emerged as effective tools for cell separation compared to traditional techniques. These devices offer the advantages of small sample volumes, low cost, and high purity. Adhesion-based separation of cells from heterogeneous suspensions can be achieved by taking advantage of specific ligand-receptor interactions. The peptide sequences Arg-Glu-Asp-Val (REDV) and Val-Ala-Pro-Gly (VAPG) are known to bind preferentially to endothelial cells (ECs) and smooth muscle cells (SMCs), respectively. This article examines the roles of REDV and VAPG and fluid shear stress in achieving selective capture of ECs and SMCs in microfluidic devices. The adhesion of ECs in REDV-coated devices and SMCs in VAPG-coated devices increases significantly compared to that of the nontargeted cells with decreasing shear stress. Furthermore, the adhesion of these cells is shown to be independent of whether these cells flow through the devices as suspensions of only one cell type or as a heterogeneous suspension containing ECs, SMCs, and fibroblasts. Whereas the overall adhesion of cells in the devices is determined mainly by shear stress, the selectivity of adhesion depends on the type of peptide and on the device surface as well as on the shear stress. C1 Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. Hlth Careers Acad, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada. Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3G9, Canada. RP Murthy, SK (reprint author), Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. EM smurthy@coe.neu.edu RI Plouffe, Brian/O-2520-2015 OI Plouffe, Brian/0000-0002-1576-5714 NR 26 TC 80 Z9 83 U1 3 U2 68 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD APR 24 PY 2007 VL 23 IS 9 BP 5050 EP 5055 DI 10.1021/la0700220 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 157QX UT WOS:000245736400054 PM 17373836 ER PT J AU Kinnecom, C Lev, MH Wendell, L Smith, EE Rosand, J Frosch, MP Greenberg, SM AF Kinnecom, C. Lev, M. H. Wendell, L. Smith, E. E. Rosand, J. Frosch, M. P. Greenberg, S. M. TI Course of cerebral amyloid angiopathy - related inflammation SO NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; LOBAR INTRACEREBRAL HEMORRHAGE; APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; BETA-PEPTIDE; IMMUNIZATION; NEUROPATHOLOGY; AD AB Background: A subset of patients with cerebral amyloid angiopathy (CAA) present with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. Objective: To analyze the risk factors, diagnostic characteristics, and long-term course of this disorder. Methods: We assessed 14 consecutive patients with pathologically diagnosed CAA-related inflammation, 12 with available neuroimaging and follow-up data. Patients were evaluated for MRI appearance, APOE genotype, and clinical course over a 46.8 +/- 29.1- month follow-up. Results: Baseline MRI scans were characterized by asymmetric T2-hyperintense lesions extending to the subcortical white matter and occasionally the overlying gray matter, with signal properties suggesting vasogenic edema. Subjects could be divided into three groups based on response to immunosuppressive treatment: monophasic improvement (7/12), initial improvement followed by symptomatic relapse (3/12), and no evident response to treatment (2/12). The volume of MRI hyperintensities correlated with the severity of clinical symptoms. One patient experienced symptomatic intracerebral hemorrhage within a region of recurrent MRI hyperintensity. The APOE epsilon 4/epsilon 4 genotype was strongly associated with CAA-related inflammation, present in 76.9% (10/13) of subjects vs 5.1% (2/39) with symptomatic but noninflammatory CAA ( p < 0.0001). Conclusion: Cerebral amyloid angiopathy - related inflammation represents a clinically, pathologically, radiographically, and genetically distinct disease subtype with implications for clinical practice and ongoing immunotherapeutic approaches to Alzheimer disease. C1 Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, 55 Fruit St,CPZ 175,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NIA NIH HHS [R01 AG026484]; NINDS NIH HHS [K24 NS056207] NR 18 TC 114 Z9 123 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 24 PY 2007 VL 68 IS 17 BP 1411 EP 1416 DI 10.1212/01.wnl.0000260066.98681.2e PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 160DL UT WOS:000245919400013 PM 17452586 ER PT J AU Muehlschlegel, S Voetsch, B Singhal, AB AF Muehlschlegel, Susanne Voetsch, Barbara Singhal, Aneesh B. TI CT angiography and CT perfusion in post-CEA hyperperfusion syndrome SO NEUROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Neurocrit Care & Stroke, Boston, MA 02114 USA. RP Muehlschlegel, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Neurocrit Care & Stroke, 55 Fruit St,Blake 12, Boston, MA 02114 USA. EM smuehlschlegel@partners.org NR 1 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 24 PY 2007 VL 68 IS 17 BP 1437 EP 1437 DI 10.1212/01.wnl.0000260621.86593.39 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 160DL UT WOS:000245919400020 PM 17452594 ER PT J AU Lee, SR Guo, SZ Scannevin, RH Magliaro, BC Rhodes, KJ Wang, XY Lo, EH AF Lee, Sun-Ryung Guo, Shu-Zhen Scannevin, Robert H. Magliaro, Brian C. Rhodes, Kenneth J. Wang, Xiaoying Lo, Eng H. TI Induction of matrix metalloproteinase, cytokines and chemokines in rat cortical astrocytes exposed to plasminogen activators SO NEUROSCIENCE LETTERS LA English DT Article DE tissue-type plasminogen activator; urokinase-type plasminogen activator; matrix metal loproteinase; thrombolysis; inflammation; neurovascular unit ID FOCAL CEREBRAL-ISCHEMIA; BRAIN INJURY; STROKE; EXPRESSION; RECEPTOR; INFLAMMATION; FRACTALKINE; PROTEOLYSIS; MICE; TPA AB Plasminogen activators are used in thrombolytic stroke therapy. However, it is increasingly recognized that they have other actions besides fibrinolysis. In this study, we assess potential pro-inflammatory effects of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in rat cortical astrocytes. Both uPA and tPA induced rapid dose-dependent upregulation in MMP-2 and MMP-9, as demonstrated by zymography of conditioned media. In addition, a multiplex ELISA array demonstrated that patterned responses in chemokines and cytokines were also evoked. Exposure to tPA induced elevations in secreted MIP-2, MCP-1 and GRO/KC. Exposure to uPA induced elevations in secreted IFN-gamma, TNF-alpha, GMCSF, MIP-1 alpha, MIP-2, MIP-3 alpha, MCP-1, RANTES and fractalkine. These data suggest that plasminogen activators may trigger selected pro-inflammatory responses at the neurovascular interface. Whether these effects influence thrombolytic stroke therapy warrants further investigation. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neuroprotect Res Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Cheju Natl Univ, Dept Life Sci, Cheju 690756, South Korea. Johnson & Kohnson Pharmaceut Res & Dev, CNS Discovery Res, Spring House, PA USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Neuroprotect Res Lab, Boston, MA 02115 USA. EM lo@helix.mgh.harvard.edu FU NINDS NIH HHS [R01 NS 53560, R01 NS 56458, R01 NS 37074, P01 NS 10828, R01 NS 48422] NR 19 TC 42 Z9 45 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 24 PY 2007 VL 417 IS 1 BP 1 EP 5 DI 10.1016/j.neulet.2007.01.017 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 167ZR UT WOS:000246492000001 PM 17386975 ER PT J AU Holler, PD Yamagata, T Jiang, WY Feuerer, M Benoist, C Mathis, D AF Holler, Phillip D. Yamagata, Tetsuya Jiang, Wenyu Feuerer, Markus Benoist, Christophe Mathis, Diane TI The same genomic region conditions clonal deletion and clonal deviation to the CD8 alpha alpha and regulatory T cell lineages in NOD versus C57BL/6 mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; FoxP3; tolerance ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; NONOBESE DIABETIC MICE; CLASS-I; ANTIGEN RECEPTOR; SELF-REACTIVITY; GUT; SELECTION; COMPLEX; THYMUS; DIFFERENTIATION AB Clonal deviation is a mechanism by which immature thymocytes expressing a self -reactive T cell antigen receptor (TCR) are rescued from clonal deletion by adopting an alternative differentiation pathway resistant to apoptosis. Here, we confirm and generalize previous indications that genetic alleles in NOD mice condition ineffective clonal deviation toward the CD8 alpha alpha lineage, a peculiar population of TCR alpha beta. lymphocytes that electively colonizes the intraepithelial lymphocyte pool in the gut. Thymic selection of CD8 alpha alpha cells was very age-dependent, occurring almost exclusively in the postnatal period. Fewer CD8 alpha alpha cells were found in the thymus and intraepithelial lymphocytes of BDC2.5 TCR transgenic mice on the NOD than on the C57BL/6 (B6) background; this paucity extended to standard NOD mice, albeit to a lesser extent. CD8 alpha alpha cells resided in the BDC2.5 pancreatic infiltrate, and they were more abundant on the B6 than the NOD background, correlating with aggressivity of the lesion. A (B6(g7) x NOD)F-2 intercross in agonist-challenged BDC2.5 fetal thymic organ cultures demonstrated the existence of a major quantitative trait locus on chromosome 3, coincident with an interval associated with resistance to clonal deletion. A replicate linkage confirmed these positions and showed that the same region also controls clonal deviation toward the CD4(+)FoxP3(+) regulatory T cell lineage. That clonal deviation toward the CD8 alpha alpha and regulatory T cell pathways share genetic control further highlights the similarities between these two "rescue lineages," consistent with an immunoregulatory role for CD8 alpha alpha cells. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [R37 DK060027, DK 60027, R01 DK060027] NR 39 TC 11 Z9 13 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2007 VL 104 IS 17 BP 7187 EP 7192 DI 10.1073/pnas.0701777104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 161OK UT WOS:000246024700055 PM 17438291 ER PT J AU Harth, G Zamecnik, PC Tabatadze, D Pierson, K Horwitz, MA AF Harth, Gunter Zamecnik, Paul C. Tabatadze, David Pierson, Katherine Horwitz, Marcus A. TI Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense oligonucleotides targeting Mycobacterium tuberculosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antisense oligodeoxyribonucleotide therapy; phosphorothioate oligodeoxyribonucleotides; RNA-DNA hybrid stability; antituberculous antibiotics; species-specific targets ID GLUTAMINE-SYNTHETASE; PURIFICATION; PROTEINS; COMPLEX AB We have investigated the efficacy of modifying gene-specific antisense phosphorothioate oligodeoxyribonucleotides (PS-ODNs) by the addition of 5' and 3' hairpin extensions. As a model system, we have targeted the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase protein complex genes encoding three highly related enzymes (antigens 85 A, B, and Q. Whereas the addition of a hairpin extension at only one end of the PS-ODNs did not improve their inhibitory capacity, the addition of hairpin extensions at both ends enhanced their capacity to inhibit M. tuberculosis multiplication in comparison with unmodified PS-ODNs. A combination of three 5'-, 3'-hairpin-modified PS-ODNs (HPS-ODNs) targeting each of the three mycolyl transferase transcripts inhibited bacterial growth in broth culture by approximate to 1.75 log units (P < 0.0001) and in human THP-1 macrophages by approximate to 0.4 log units (P < 0.0001), which to our knowledge has not previously been demonstrated for any PS-ODN; reduced target gene transcription by >= 90%; caused approximate to 90% reduction in mycolyl transferase expression; and increased bacterial sensitivity to isoniazid by 8-fold. The growth-inhibitory effect of the HPS-ODNs was gene-specific. Mismatched HPS-ODNs had no growth-inhibitory capacity. This study demonstrates that 5'- and 3'-HPS-ODNs are highly efficacious against M. tuberculosis and supports the further development of antisense technology as a therapeutic modality against tuberculosis. C1 Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37 121, Dept Med,Div Infect Dis, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Zamecnik, PC (reprint author), Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37 121, Dept Med,Div Infect Dis, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM paul_zamecnik@hms.harvard.edu; mhorwitz@mednet.ucla.edu FU NIAID NIH HHS [AI 055352, R01 AI060872, R01 AI055352, AI 060872] NR 16 TC 15 Z9 16 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2007 VL 104 IS 17 BP 7199 EP 7204 DI 10.1073/pnas.0701725104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 161OK UT WOS:000246024700057 PM 17438292 ER PT J AU Scott, DR Marcus, EA Wen, Y Oh, J Sachs, G AF Scott, David R. Marcus, Elizabeth A. Wen, Yi Oh, Jane Sachs, George TI Gene expression in vivo shows that Helicobacter pylori colonizes an acidic niche on the gastric surface SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acid acclimation; gastric pH; global transcriptome; microarray ID MUCUS-BICARBONATE BARRIER; UREASE ACTIVITY; GNOTOBIOTIC PIGLETS; VIRULENCE FACTORS; PH; SECRETION; MUCOSA; ADAPTATION; PROTON; ARGINASE AB Helicobacter pylori is a gastric-dwelling pathogen responsible, with acid secretion, for peptic ulcer and a 20-fold increase in the risk of gastric cancer. Several transcriptomes have been described after short-term exposure to acidity in vitro, but there are no data identifying the effects of chronic gastric exposure on bacterial gene expression. Comparison of the in vivo to the in vitro transcriptome at pH 7.4 identified several groups of genes of known function that increased expression >2-fold, and three of these respond both to acidity in vitro and to gastric infection. Almost all known acid acclimation genes are highly up-regulated. These include ureA, ureB, and rocF and the pH-gated urea channel, urel. There is also up-regulation of two groups of motility and chemotaxis genes and for pathogenicity island genes, especially cagA, a predictor for pathogenicity. Most of these genes interact with HP0166, the response element of the pH-sensing two-component histidine kinase, HP0165/HP0166, ArsRS. Based on the pH profile of survival of urel deletion mutants in vitro and their inability to survive in gastric acidity, the habitat of the organism at the gastric surface is acidic with a pH <= 4.0. Hence, the pH of the habitat of H. pylori on the surface of the stomach largely determines the regulation of these specific groups of genes. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Ewha Womans Univ, Dongdaemun Hosp, Dept Internal Med, Seoul 110783, South Korea. RP Scott, DR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, 405 Hilgard Ave, Los Angeles, CA 90024 USA. EM dscott@ucla.edu; gsachs@ucla.edu NR 62 TC 71 Z9 78 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2007 VL 104 IS 17 BP 7235 EP 7240 DI 10.1073/pnas.0702300104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 161OK UT WOS:000246024700063 PM 17438279 ER PT J AU Hewett, JW Tannous, B Niland, BP Nery, FC Zeng, J Li, YQ Breakefield, XO AF Hewett, Jeffrey W. Tannous, Bakhos Niland, Brian P. Nery, Flavia C. Zeng, Juan Li, Yuqing Breakefield, Xandra O. TI Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE early onset dystonia; endoplasmic reticulum; luciferase; protein translation ID ENDOPLASMIC-RETICULUM STRESS; NUCLEAR-ENVELOPE; CAENORHABDITIS-ELEGANS; PC12 CELLS; FLUORESCENT PROTEIN; EXPRESSION; MEMBRANE; FIBROBLASTS; INCLUSIONS; DISEASE AB TorsinA is an AAA(+) protein located predominantly in the lumen of the endoplasmic reticulum (ER) and nuclear envelope responsible for early onset torsion dystonia (DYT1). Most cases of this dominantly inherited movement disorder are caused by deletion of a glutamic acid in the carboxyl terminal region of torsinA. We used a sensitive reporter, Gaussia luciferase (Gluc) to evaluate the role of torsinA in processing proteins through the ER. In primary fibroblasts from controls and DYT1 patients most Gluc activity (95%) was released into the media and processed through the secretory pathway, as confirmed by inhibition with brefeldinA and nococlazole. Fusion of Gluc to a fluorescent protein revealed coalignment and fractionation with ER proteins and association of Gluc with torsinA. Notably, fibroblasts from DYT1 patients were found to secrete markedly less Gluc activity as compared with control fibroblasts. This decrease in processing of Gluc in DYT1 cells appear to arise, at least in part, from a loss of torsinA activity, because mouse embryonic fibroblasts lacking torsinA also had reduced secretion as compared with control cells. These studies demonstrate the exquisite sensitivity of this reporter system for quantitation of processing through the secretory pathway and support a role for torsinA as an ER chaperone protein. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu RI Li, Yuqing/G-1596-2011 OI Li, Yuqing/0000-0003-1211-5529 FU NINDS NIH HHS [NS 037409, P01 NS037409] NR 73 TC 85 Z9 87 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 24 PY 2007 VL 104 IS 17 BP 7271 EP 7276 DI 10.1073/pnas.0701185104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 161OK UT WOS:000246024700069 PM 17428918 ER PT J AU Kurth, T Gaziano, JM Cook, NR Bubes, V Logroscino, G Diener, HC Buring, JE AF Kurth, Tobias Gaziano, J. Michael Cook, Nancy R. Bubes, Vadim Logroscino, Giancarlo Diener, Hans-Christoph Buring, Julie E. TI Migraine and risk of cardiovascular disease in men SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; PHYSICIANS HEALTH; ISCHEMIC-STROKE; BETA-CAROTENE; WOMEN; HEADACHE; AURA; TOLERABILITY; ASSOCIATIONS; PREVALENCE AB Background: The vascular component of the migraine-specific physiologic profile and the observed adverse cardiovascular risk profile in migraineurs suggest an association between migraine and cardiovascular disease (CVD). In women, migraine has been associated with increased risk of CVD, including coronary events. Compatible data in men are lacking. Methods: Prospective cohort study of 20 084 men aged 40 to 84 years participating in the Physicians' Health Study. In yearly questionnaires, men were asked for information on migraine, risk factors, and the occurrence of study end points. We classified men as having migraine if they indicated migraine during the first 5 years, after which time follow-up began. Information on aura was not available. All the men were free of CVD at the start of follow-up. During a mean of 15.7 years, we followed up participants for the occurrence of a first major CVD event (nonfatal ischemic stroke, nonfatal myocardial infarction, or death from ischemic CVD). We also evaluated the individual end points, coronary revascularization, and angina. Results: A total of 1449 men (7.2%) reported migraine, and during follow-up, 2236 major CVD events occurred. Compared with nonmigraineurs, men who reported migraine had multivariable-adjusted hazard ratios (95% confidence intervals) of 1.24 (1.06-1.46; P=.008) for major CVD, 1.12 (0.84-1.50; P=.43) for ischemic stroke, 1.42 (1.15-1.77; P<.001) for myocardial infarction, 1.05 (0.89-1.24; P=.54) for coronary revascularization, 1.15 (0.99-1.33; P=.068) for angina, and 1.07 (0.80-1.43; P=.65) for ischemic cardiovascular death. Conclusion: In this large prospective cohort of apparently healthy men, migraine was associated with increased risk of major CVD, which was driven by increased risk of myocardial infarction. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Univ Duisburg Gesamthsch, Dept Neurol, Essen, Germany. RP Kurth, T (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012; LOGROSCINO, GIANCARLO/K-5148-2016 OI Kurth, Tobias/0000-0001-7169-2620; LOGROSCINO, GIANCARLO/0000-0003-0423-3242 FU NCI NIH HHS [CA 34944, CA 40360, R01 CA097193]; NHLBI NIH HHS [HL 26490, HL 34595] NR 41 TC 140 Z9 141 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 23 PY 2007 VL 167 IS 8 BP 795 EP 801 DI 10.1001/archinte.167.8.795 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 159YF UT WOS:000245903100008 PM 17452542 ER PT J AU Volandes, AE Lehmann, LS Cook, EF Shaykevich, S Abbo, ED Gillick, MR AF Volandes, Angelo E. Lehmann, Lisa Soleymani Cook, E. Francis Shaykevich, Shimon Abbo, Elmer D. Gillick, Muriel R. TI Using video images of dementia in advance care planning SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DECISION-MAKING; PREFERENCES; DIRECTIVES AB Background: Advance care planning is a process by which patients plan for future medical care under circumstances of impaired decision-making. Central to this process is the patient's understanding and ability to imagine future health states. Methods: A before and after oral survey was used to compare the effect of a video depiction with that of a verbal description of a patient with advanced dementia for individuals selecting level of medical care at 7 primary care clinics at 2 US medical centers. The study enrolled 120 adults, half of whom were nonwhite. Results: A total of 120 subjects completed the interview. Before watching the video, 60 (50.0%) subjects preferred comfort care, 25 (20.8%) desired life-prolonging care, 22 (18.3%) chose limited care, and 13 (10.8%) were unsure of their preferences. Subject preferences changed significantly after the video: 107 (89.2%) of the subjects chose comfort care, none desired life-prolonging care, 10 (8.3%) chose limited care, and 3 (2.5%) were unsure of their preferences (P<.001). Unadjusted analysis revealed a statistically significant difference regarding preferences, based on race/ethnicity, before watching the video: 40% of African Americans and 43% of Latinos chose comfort care, compared with 58% of whites (P=.04). Differences were also noted for educational level (P=.03). After the video, differences in preferences based on race/ethnicity and educational level disappeared. Conclusions: Watching the video significantly changed preferences for care, transcending apparent differences in preferences associated with race/ethnicity and educational level. This study suggests that using video in addition to improved verbal communication may lead to more informed advance care planning by enhancing the ability of patients to imagine a hypothetical health state. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org NR 18 TC 59 Z9 59 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 23 PY 2007 VL 167 IS 8 BP 828 EP 833 DI 10.1001/archinte.167.8.828 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 159YF UT WOS:000245903100013 PM 17452547 ER PT J AU Ballantyne, JC AF Ballantyne, Jane C. TI Regulation of opioid prescribing SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID CRITICAL-ISSUES; PAIN C1 Massachusetts Gen Hosp, Pain Ctr, Div Pain Med, Boston, MA 02114 USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Pain Ctr, Div Pain Med, Boston, MA 02114 USA. EM jballantyne@partners.org NR 12 TC 5 Z9 5 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD APR 21 PY 2007 VL 334 IS 7598 BP 811 EP 812 DI 10.1136/bmj.39175.458275.BE PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 162MD UT WOS:000246090800005 PM 17446578 ER PT J AU Melrose, RJ Poulin, RM Stern, CE AF Melrose, Rebecca J. Poulin, Renee M. Stern, Chantal E. TI An fMRI investigation of the role of the basal ganglia in reasoning SO BRAIN RESEARCH LA English DT Article DE caudate; prefrontal cortex; sequencing; executive function; working m; emory; planning ID DORSOLATERAL PREFRONTAL CORTEX; PROGRESSIVE MATRICES TEST; SPATIAL WORKING-MEMORY; MEDIAL TEMPORAL-LOBE; EVENT-RELATED FMRI; LONDON TASK; NEOCORTICAL ACTIVATION; SUBSEQUENT MEMORY; HUMAN COGNITION; RHESUS-MONKEY AB Neuropsychological studies highlight the importance of the prefrontal cortex in abstract reasoning ability. The prefrontal cortex is anatomically connected to the basal ganglia through a series of parallel loops. The dorsolateral prefrontal cortex shares relatively greater connectivity with the caudate head, and it has been proposed that the caudate head may be more sensitive to executive processing. To investigate the frontostriatal circuitry underlying abstract reasoning, we designed a reasoning task in which stimuli varied sequentially across one dimension. Critically, the task required that subjects deduce and apply a sequencing rule. We also developed a match-to-sample working memory task in order to identify and contrast brain regions involved in working memory. We observed reasoning-related activation in both cortical and subcortical regions. Subcortically, the caudate was found to be bilaterally active during both the reasoning and matching tasks, and the left caudate head was more active for reasoning compared to matching. An anatomically defined region of interest analysis demonstrated activity for both reasoning and matching tasks within the body of the caudate. In contrast, the left caudate head was found to more specifically support reasoning. Cortically, we observed activity of bilateral rostrolateral prefrontal cortex, right ventrolateral prefrontal cortex, and bilateral parietal cortex during reasoning. Our results suggest that reasoning requires an interaction between cortical areas and the caudate nucleus, in which the caudate body supports both reasoning and working memory and the head of the caudate is specifically involved in the executive demands of reasoning, namely deducing and applying a sequence rule. (c) 2007 Elsevier B.V. All rights reserved. C1 Boston Univ, Cognit Neuroimaging Lab, Ctr Memory & Brain, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, MGH,MIT,HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Melrose, RJ (reprint author), Boston Univ, Cognit Neuroimaging Lab, Ctr Memory & Brain, 2 Cummington St, Boston, MA 02215 USA. EM rmelrose@bu.edu FU NCRR NIH HHS [RR14075, P41 RR14075]; NIMH NIH HHS [P50 MH071702]; NINDS NIH HHS [F31 NS052126, R01 NS040239, R01 NS40239] NR 64 TC 38 Z9 45 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 20 PY 2007 VL 1142 BP 146 EP 158 DI 10.1016/j.brainres.2007.01.060 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 158IL UT WOS:000245785000017 PM 17320049 ER PT J AU Kulkarni, RN Kahn, CR AF Kulkarni, Rohit N. Kahn, C. Ronald TI Ephs and ephrins keep pancreatic beta cells connected SO CELL LA English DT Editorial Material AB How insulin-secreting beta cells of the pancreas communicate with each other is largely unknown. In this issue of Cell, Konstantinova et al. (2007) show that the signaling proteins EphA and ephrin-A modulate insulin secretion, providing fresh insights into the functional significance of the clustering of beta cells, which occurs in islets. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Div Cell & Mol Physiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Div Obes & Hormone Act, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Div Cell & Mol Physiol, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu NR 8 TC 5 Z9 5 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 20 PY 2007 VL 129 IS 2 BP 241 EP 243 DI 10.1016/j.cell.2007.04.006 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 167TI UT WOS:000246474600010 PM 17448984 ER PT J AU Smogorzewska, A Matsuoka, S Vinciguerra, P McDonald, ER Hurov, KE Luo, J Ballif, BA Gygi, SP Hofmann, K D'Andrea, AD Elledge, SJ AF Smogorzewska, Agata Matsuoka, Shuhei Vinciguerra, Patrizia McDonald, E. Robert, III Hurov, Kristen E. Luo, Ji Ballif, Bryan A. Gygi, Steven P. Hofmann, Kay D'Andrea, Alan D. Elledge, Stephen J. TI Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair SO CELL LA English DT Article ID HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; ANEMIA PATHWAY; COMPLEX; CHROMATIN; CANCER; BRCA2; PALB2; PHOSPHORYLATION; EXPRESSION AB Fanconi anemia (FA) is a developmental and cancer-predisposition syndrome caused by mutations in genes controlling DNA interstrand crosslink repair. Several FA proteins form a ubiquitin ligase that controls monoubiquitination of the FANCD2 protein in an ATR-dependent manner. Here we describe the FA protein FANCI, identified as an ATM/ATR kinase substrate required for resistance to mitomycin C. FANCI shares sequence similarity with FANCD2, likely evolving from a common ancestral gene. The FANCI protein associates with FANCD2 and, together, as the FANCI-FANCD2 (ID) complex, localize to chromatin in response to DNA damage. Like FANCD2, FANCI is monoubiquitinated and unexpectedly, ubiquitination of each protein is important for the maintenance of ubiquitin on the other, indicating the existence of a dual ubiquitin-locking mechanism required for ID complex function. Mutation in FANCI is responsible for loss of a functional FA pathway in a patient with Fanconi anemia complementation group I. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Genet & Genom,Dept Gen, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Miltenyi Biotec GmbH, D-50829 Cologne, Germany. RP Elledge, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Genet & Genom,Dept Gen, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Smogorzewska, Agata/B-8891-2011; Hofmann, Kay/D-6714-2011 OI Hofmann, Kay/0000-0002-2289-9083 FU Howard Hughes Medical Institute; NCI NIH HHS [T32 CA009216, T32CA09216]; NHLBI NIH HHS [R37 HL052725]; NIAID NIH HHS [U19 AI067751, U19 AI067751-01, U19 AI067751-020002]; NIGMS NIH HHS [R37 GM044664, R37 GM044664-18, R37 GM044664-19]; PHS HHS [1U19A1067751] NR 38 TC 396 Z9 406 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 20 PY 2007 VL 129 IS 2 BP 289 EP 301 DI 10.1016/j.cell.2007.03.009 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 167TI UT WOS:000246474600017 PM 17412408 ER PT J AU Tsytsykova, AV Falvo, JV Schmidt-Supprian, M Courtois, G Thanos, D Goldfeld, AE AF Tsytsykova, Alla V. Falvo, James V. Schmidt-Supprian, Marc Courtois, Gilles Thanos, Dimitris Goldfeld, Anne E. TI Post-induction, stimulus-specific regulation of tumor necrosis factor mRNA expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NF-KAPPA-B; FACTOR-ALPHA GENE; BRUTONS TYROSINE KINASE; HUMAN MONOCYTIC CELLS; CREB-BINDING-PROTEIN; TOLL-LIKE RECEPTORS; ACTIVATED T-CELLS; IFN-BETA-GENE; TRANSCRIPTION FACTOR; DNA-BINDING AB The tumor necrosis factor ( TNF) gene is activated by multiple extracellular signals in a stimulus- and cell type-specific fashion. Based on the presence of kappa B-like DNA motifs in the region upstream of the TNF gene, some have proposed a direct role for NF-kappa B in lipopolysaccharide ( LPS)-induced TNF gene transcription in cells of the monocyte/macrophage lineage. However, we have previously demonstrated a general and critical role for a minimal TNF promoter region bearing only one of the kappa B-like motifs, kappa 3, which is bound by nuclear factor of activated T cell proteins in lymphocytes and fibroblasts in response to multiple stimuli and Ets proteins in LPS-stimulated macrophages. Here, in an effort to resolve these contrasting findings, we used a combination of site-directed mutagenesis of the TNF promoter, quantitative DNase I footprinting, and analysis of endogenous TNF mRNA production in response to multiple stimuli under conditions that inhibit NF-kappa B activation ( using the proteasome inhibitor lactacystin and using cells lacking either functional NF-kappa B essential modulator, which is the I kappa B kinase regulatory subunit, or the Nemo gene itself). We find that TNF mRNA production in response to ionophore is NF-kappa B-independent, but inhibition of NF-kappa B activation attenuates virus- and LPS-induced TNF mRNA levels after initial induction. We conclude that induction of TNF gene transcription by virus or LPS does not depend upon NF-kappa B binding to the proximal promoter; rather, a stimulus- specific post-induction mechanism involving NF-kappa B, yet to be characterized, is involved in the maintenance of maximal TNF mRNA levels. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Hop St Louis, INSERM, F-75015 Paris, France. Biomed Sci Res Ctr Alexander Fleming, Inst Mol Biol & Genet, Athens, Greece. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Goldfeld, AE (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM goldfeld@cbrinstitute.org RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 FU NIGMS NIH HHS [GM076685] NR 102 TC 24 Z9 24 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2007 VL 282 IS 16 BP 11629 EP 11638 DI 10.1074/jbc.M611418200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LK UT WOS:000245941900004 PM 17303559 ER PT J AU Zhu, JQ Boylan, B Luo, BH Newman, PJ Springer, TA AF Zhu, Jieqing Boylan, Brian Luo, Bing-Hao Newman, Peter J. Springer, Timothy A. TI Tests of the extension and deadbolt models of integrin activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I-LIKE DOMAIN; ALPHA(L)BETA(2) HYBRID DOMAIN; PLATELET GLYCOPROTEIN-IIIA; INSIDE-OUT ACTIVATION; LOW-AFFINITY STATE; MONOCLONAL-ANTIBODY; STRUCTURAL BASIS; LIGAND-BINDING; SUBUNIT; COMPLEX AB Despite extensive evidence that integrin conformational changes between bent and extended conformations regulate affinity for ligands, an alternative hypothesis has been proposed in which a "deadbolt" can regulate affinity for ligand in the absence of extension. Here, we tested both the deadbolt and the extension models. According to the deadbolt model, a hairpin loop in the beta 3 tail domain could act as a deadbolt to restrain the displacement of the beta 3 I domain beta 6-alpha 7 loop and maintain integrin in the low affinity state. We found that mutating or deleting the beta 3 tail domain loop has no effect on ligand binding by either alpha IIb beta 3 or alpha V beta 3 integrins. In contrast, we found that mutations that lock integrins in the bent conformation with disulfide bonds resist inside-out activation induced by cytoplasmic domain mutation. Furthermore, we demonstrated that extension is required for accessibility to fibronectin but not smaller fragments. The data demonstrate that integrin extension is required for ligand binding during integrin inside-out signaling and that the deadbolt does not regulate integrin activation. C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI 53201 USA. Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Cellular Biol, Milwaukee, WI 53226 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NHLBI NIH HHS [P01 HL044612, P01 HL048675, HL48675, HL44612] NR 44 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2007 VL 282 IS 16 BP 11914 EP 11920 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LK UT WOS:000245941900034 PM 17301049 ER PT J AU Zhao, YT Katzman, RB Delmolino, LM Bhat, I Zhang, Y Gurumurthy, CB Germaniuk-Kurowska, A Reddi, HV Solomon, A Zeng, MS Kung, A Ma, H Gao, QS Dimri, G Stanculescu, A Miele, L Wu, LZ Griffin, JD Wazer, DE Band, H Band, V AF Zhao, Yongtong Katzman, Rebecca B. Delmolino, Laurie M. Bhat, Ishfaq Zhang, Ying Gurumurthy, Channabasavaiah B. Germaniuk-Kurowska, Aleksandra Reddi, Honey V. Solomon, Aharon Zeng, Mu-Sheng Kung, Aisha Ma, Hui Gao, Qingshen Dimri, Goberdhan Stanculescu, Adina Miele, Lucio Wu, Lizi Griffin, James D. Wazer, David E. Band, Hamid Band, Vimla TI The Notch regulator MAML1 interacts with p53 and functions as a coactivator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAENORHABDITIS-ELEGANS; TUMOR-SUPPRESSOR; DNA-DAMAGE; HUMAN ADA3; TRANSCRIPTIONAL COACTIVATORS; MEDIATED TRANSACTIVATION; CELL FATE; MASTERMIND; APOPTOSIS; TUMORIGENESIS AB Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Master-mind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that binds to native p53-response elements within the promoter of the p53 target genes. Overexpression of wild-type MAML1 as well as a mutant, defective in Notch signaling, enhanced the p53-dependent gene induction in mammalian cells, whereas MAML1 knockdown reduced the p53-dependent gene expression. MAML1 increases the half-life of p53 protein and enhances its phosphorylation/acetylation upon DNA damage of cells. Finally, RNA interference-mediated knockdown of the single Caenorhabditis elegans MAML homolog, Lag-3, led to substantial abrogation of p53-mediated germ-cell apoptotic response to DNA damage and markedly reduced the expression of Ced-13 and Egl-1, downstream pro-apoptotic targets of the C. elegans p53 homolog Cep-1. Thus, we present evidence for a novel coactivator function of MAML1 for p53, independent of its function as a coactivator of Notch signaling pathway. C1 Northwestern Univ, Feinberg Sch Med, ENH Res Inst, Div Canc Biol,Dept Med, Evanston, IL 60201 USA. Northwestern Univ, Feinberg Sch Med, ENH Res Inst, Div Mol Oncol,Dept Med, Evanston, IL 60201 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60201 USA. Tufts Univ New England Med Ctr, Dept Radiat Oncol, Boston, MA 02111 USA. Loyola Univ, Med Ctr, Breast Canc Program, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Pharmacol & Expt Therapeut, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Band, V (reprint author), Northwestern Univ, Feinberg Sch Med, ENH Res Inst, Div Canc Biol,Dept Med, 1001 Univ Pl, Evanston, IL 60201 USA. EM v-band@northwestern.edu FU NCI NIH HHS [CA76118, CA81076, CA87986, CA94143, CA96844, CA99163, CA99900, R01 CA095221-01A1, R01 CA095221-02, R01 CA095221-03, R01 CA095221-04, R01 CA095221-05, R01 CA096986-01A1, R01 CA096986-02, R01 CA096986-03, R01 CA096986-04, R01 CA096986-05, R01 CA097148, T32CA70085] NR 49 TC 42 Z9 50 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2007 VL 282 IS 16 BP 11969 EP 11981 DI 10.1074/jbc.M608974200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LK UT WOS:000245941900040 PM 17317671 ER PT J AU Cowart, LA Hannun, YA AF Cowart, L. Ashley Hannun, Yusuf A. TI Selective substrate supply in the regulation of yeast de novo sphingolipid synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-STRESS RESPONSE; MEMBRANE H+-ATPASE; LONG-CHAIN BASES; SACCHAROMYCES-CEREVISIAE; SERINE PALMITOYLTRANSFERASE; PLASMA-MEMBRANE; INDUCE APOPTOSIS; FREE SPHINGOSINE; PALMITIC ACID; STEARIC-ACID AB The heat stress response of Saccharomyces cerevisiae is characterized by transient cell cycle arrest, altered gene expression, degradation of nutrient permeases, trehalose accumulation, and translation initiation of heat shock proteins. Importantly heat stress also induces de novo sphingolipid synthesis upon which many of these subprograms of the heat stress response depend. Despite extensive data addressing the roles for sphingolipids in heat stress, the mechanism( s) by which heat induces sphingolipid synthesis remains unknown. This study was undertaken to determine the events and/or factors required for heat stress-induced sphingolipid synthesis. Data presented indicate that heat does not directly alter the in vitro activity of serine palmitoyltransferase ( SPT), the enzyme responsible for initiating de novo sphingolipid synthesis. Moreover deletion of the small peptide Tsc3p, which is thought to maximize SPT activity, specifically reduced production of C-20 sphingolipid species by over 70% but did not significantly decrease overall sphingoid base production. In contrast, the fatty-acid synthase inhibitor cerulenin nearly completely blocked sphingoid base production after heat, indicating a requirement for endogenous fatty acids for heat-mediated sphingoid base synthesis. Consistent with this, genetic studies show that fatty acid import does not contribute to heat-induced de novo synthesis under normal conditions. Interestingly the absence of medium serine also ameliorated heat-induced sphingoid base production, indicating a requirement for exogenous serine for the response, and consistent with this finding, disruption of synthesis of endogenous serine did not affect heat-induced sphingolipid synthesis. Serine uptake assays indicated that heat increased serine uptake from medium by 100% during the first 10 min of heat stress. Moreover treatments that increase serine uptake in the absence of heat including acute medium acidification and glucose treatment also enhanced de novo sphingoid base synthesis equivalent to that induced by heat stress. These data agree with findings from mammalian systems that availability of substrates is a key determinant of flux through sphingolipid synthesis. Moreover data presented here indicate that SPT activity can be driven by several factors that increase serine uptake in the absence of heat. These findings may provide insights into the many systems in which de novo synthesis is increased in the absence of elevated in vitro SPT activity. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM hannun@musc.edu FU NIGMS NIH HHS [GM63265] NR 52 TC 41 Z9 41 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 20 PY 2007 VL 282 IS 16 BP 12330 EP 12340 DI 10.1074/jbc.M700685200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LK UT WOS:000245941900075 PM 17322298 ER PT J AU Tworoger, SS Eliassen, AH Sluss, P Hankinson, SE AF Tworoger, Shelley S. Eliassen, A. Heather Sluss, Patrick Hankinson, Susan E. TI A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL-PROLIFERATION; STEROID-HORMONES; GROWTH-FACTOR; WOMEN; ESTROGEN; RECEPTOR; REPRODUCIBILITY; ANTAGONISTS; EXPRESSION; CARCINOMA AB Purpose Epidemiologic studies suggest that prolactin is associated with breast cancer risk in older women. Because of limited prospective data, particularly in younger women, we examined whether prolactin concentrations were associated with breast cancer risk among women 42 to 55 years (68% premenopausal) from the Nurses' Health Study (NHS), and then conducted a pooled analysis of three studies. Patients and Methods The analysis included 377 cases of breast cancer diagnosed after blood draw and before June 2000; two controls were matched per case on age, menopausal status at blood draw and diagnosis, fasting status, and time of day and month of blood collection. These data were pooled with two previously published data sets from the NHS and NHSII cohorts (n = 1,539 cases, 2,681 controls; ages 32 to 70 years). Results Prolactin was modestly associated with an increased breast cancer risk (relative risk [RR], top v bottom quartile = 1.3; 95% CI, 0.9 to 1.9; P for trend = .12). Risk estimates did not vary by menopausal status, tumor invasiveness, or estrogen receptor (ER) status. In the pooled analysis, the overall RR was 1.3 (95% CI, 1.1 to 1.6; P for trend = .002), and did not vary by menopausal status (P for interaction = .95). The risk was strongest for women with ER+ tumors (RR = 1.6; 95% CI, 1.2 to 2.0; P for trend < .001). Correcting for within-person variability, the RR comparing the median of the top versus the bottom prolactin quartile increased from 1.3 to 1.7 for all women and from 1.5 to 2.1 for ER+ cases. Conclusion These data, in conjunction with experimental studies, indicate that prolactin likely is important in breast cancer etiology, particularly ER+ tumors, over a wide range of ages. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit Lab, Boston, MA 02114 USA. RP Tworoger, SS (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM nhsst@channing.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU NCI NIH HHS [CA49449, CA67262, P01 CA87969, P50 CA089393, R25 CA 098566-2, CA50385] NR 47 TC 110 Z9 113 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2007 VL 25 IS 12 BP 1482 EP 1488 DI 10.1200/JCO.2006.07.6356 PG 7 WC Oncology SC Oncology GA 160DO UT WOS:000245920300007 PM 17372279 ER PT J AU Giantonio, BJ Catalano, PJ Meropol, NJ O'Dwyer, PJ Mitchell, EP Alberts, SR Schwartz, MA Benson, AB AF Giantonio, Bruce J. Catalano, Paul J. Meropol, Neal J. O'Dwyer, Peter J. Mitchell, Edith P. Alberts, Steven R. Schwartz, Michael A. Benson, Al B., III TI Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED-TRIAL; PHASE-II; 1ST-LINE TREATMENT; PLUS FLUOROURACIL; CLINICAL-TRIALS; IRINOTECAN; ANTIBODY; SAFETY AB Purpose Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer. Patients and Methods Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity. Results The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting. Conclusion The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer. C1 Univ Penn, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Mt Sinai Med Ctr, Miami, FL USA. Northwestern Univ, Chicago, IL 60611 USA. RP Giantonio, BJ (reprint author), 12 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM Giantonio.bruce@jimmy.harvard.edu FU NCI NIH HHS [CA15488, CA17145, CA21115, CA23318, CA27525, CA66636] NR 26 TC 1240 Z9 1295 U1 1 U2 38 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2007 VL 25 IS 12 BP 1539 EP 1544 DI 10.1200/JCO.2006.09.6305 PG 6 WC Oncology SC Oncology GA 160DO UT WOS:000245920300015 PM 17442997 ER PT J AU Chen, W Wang, YC Abe, Y Cheney, L Udd, B Li, YP AF Chen, Wei Wang, Yucheng Abe, Yoko Cheney, Lukas Udd, Bjarne Li, Yi-Ping TI Haploinsuffciency for Znf9 in Znf9(+/-) mice is associated with multiorgan abnormalities resembling myotonic dystrophy SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ZNF9 gene; myotonic dystrophy; Znf9(+/-) mice; Znf9 haploinsufficiency; electromyography ID HYPERTROPHIC CARDIOMYOPATHY MICE; ACID-BINDING PROTEIN; EXPANDED CUG REPEAT; SKELETAL-MUSCLE; ELECTROPHYSIOLOGICAL ABNORMALITIES; MESSENGER-RNA; TYPE-2; CATARACTS; MOUSE; EXPANSIONS AB Myotonic dystrophy type 2 is caused by a (CCTG)/(CCUG)(n) repeat expansion in the first intron of the ZNF9 gene. The pathomechanism for the myotonic dystrophies is not well understood and the role of ZNF9 in myotonic dystrophy type 2 pathogenesis has not been fully clarified. We characterized Znf9(+/-) mice, in which the expression of Znf9 was significantly decreased, and found that their phenotype reflects many of the features of myotonic dystrophy, including muscle histological morphology, and myotonic discharges and heart conduction abnormalities, shown by electromyography and electrocardiogram analysis, respectively. Znf9 is normally highly expressed in heart and skeletal muscle, where skeletal muscle chloride channel 1 (Clc1) plays an important role. Clc1 expression was dramatically decreased in Znf9(+/-) mice. Znf9 transgenic mice raised Znf9 and Clcl expression and rescued the myotonic dystrophy phenotype in Znf9(+/-) mice. Our results suggest that the Znf9 haploinsufficiency contributes to the myotonic dystrophy phenotype in Znf9(+/-) mice. (c) 2007 Elsevier Ltd. All rights reserved. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Vaasa Cent Hosp, Dept Neurol, Vaasa 65130, Finland. Tampere Univ Hosp, Dept Neurol, Tampere 33520, Finland. Sch Med, Tampere 33520, Finland. Univ Helsinki, Folkhalsan Inst Genet, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM ypli@forsyth.org FU NIAMS NIH HHS [AR-44741, AR-48133] NR 36 TC 39 Z9 41 U1 0 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 20 PY 2007 VL 368 IS 1 BP 8 EP 17 DI 10.1016/j.jmb.2007.01.088 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156TJ UT WOS:000245672500002 PM 17335846 ER PT J AU Rual, JF Klitgord, N Achaz, G AF Rual, Jean-Francois Klitgord, Niels Achaz, Guillaume TI Novel insights into RNAi off-target effects using C-elegans paralogs SO BMC GENOMICS LA English DT Article ID FUNCTIONAL GENOMIC ANALYSIS; DOUBLE-STRANDED-RNA; CAENORHABDITIS-ELEGANS; INTERFERING RNAS; MAMMALIAN-CELLS; DICER; MECHANISMS; EXPRESSION; DROSOPHILA; PROTEINS AB Background: In the few years since its discovery, RNAi has turned into a very powerful tool for the study of gene function by allowing post-transcriptional gene silencing. The RNAi mechanism, which is based on the introduction of a double-stranded RNA ( dsRNA) trigger whose sequence is similar to that of the targeted messenger RNA ( mRNA), is subject to off-target cross-reaction. Results: We use a novel strategy based on phenotypic analysis of paralogs and predict that, in Caenorhabditis elegans, off-target effects occur when an mRNA sequence shares more than 95% identity over 40 nucleotides with the dsRNA. Interestingly, our results suggest that the minimum length necessary of a high-similarity stretch between a dsRNA and its target in order to observe an efficient RNAi effect varies from 30 to 50 nucleotides rather than 22 nucleotides, which is the length of siRNAs in C. elegans. Conclusion: Our predictive methods would improve the design of dsRNA and ultimately the use of RNAi as a therapeutic tool upon experimental verification. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Paris 06, UMR 7138, Paris, France. Univ Paris 06, Atelier Bioinformat, Paris, France. RP Rual, JF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. EM JRUAL@PARTNERS.ORG; niels_klitgord@dfci.harvard.edu; achaz@closun.snv.jussieu.fr RI Klitgord, Niels/B-5121-2009; OI Rual, Jean-Francois/0000-0003-4465-8819 FU NCI NIH HHS [7 R33 CA81658-02] NR 32 TC 22 Z9 23 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 19 PY 2007 VL 8 AR 106 DI 10.1186/1471-2164-8-106 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 170ZS UT WOS:000246705300001 PM 17445269 ER PT J AU Fusi, S Asaad, WF Miller, EK Wang, XJ AF Fusi, Stefano Asaad, Wael F. Miller, Earl K. Wang, Xiao-Jing TI A neural circuit model of flexible sensorimotor mapping: Learning and forgetting on multiple timescales SO NEURON LA English DT Article ID CONDITIONAL OCULOMOTOR ASSOCIATIONS; SUPPLEMENTARY EYE FIELD; PRIMATE PREFRONTAL CORTEX; SYNAPTIC PLASTICITY; NEURONAL-ACTIVITY; WORKING-MEMORY; DECISION-MAKING; SINGLE NEURONS; NETWORKS; ACQUISITION AB Volitional behavior relies on the brain's ability to remap sensory flow to motor programs whenever demanded by a changed behavioral context. To investigate the circuit basis of such flexible behavior, we have developed a biophysically based decision-making network model of spiking neurons for arbitrary sensorimotor mapping. The model quantitatively reproduces behavioral and prefrontal single-cell data from an experiment in which monkeys learn visuomotor associations that are reversed unpredictably from time to time. We show that when synaptic modifications occur on multiple timescales, the model behavior becomes flexible only when needed: slow components of learning usually dominate the decision process. However, if behavioral contexts change frequently enough, fast components of plasticity take over, and the behavior exhibits a quick forget-and-learn pattern. This model prediction is confirmed by monkey data. Therefore, our work reveals a scenario for conditional associative learning that is distinct from instant switching between sets of well-established sensorimotor associations. C1 Yale Univ, Sch Med, Dept Neurobiol, Kavli Inst Neurosci, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Picower Inst Learning & Memory, RIKEN, Neurosci Res Ctr, Cambridge, MA 02139 USA. Univ Zurich, ETH, Inst Neuroinformat, CH-8057 Zurich, Switzerland. Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Wang, XJ (reprint author), Yale Univ, Sch Med, Dept Neurobiol, Kavli Inst Neurosci, 333 Cedar St, New Haven, CT 06520 USA. EM xjwang@yale.edu RI Wang, Xiao-Jing/D-2722-2009; Asaad, Wael/I-8485-2012; Fusi, Stefano/E-9109-2011 OI Asaad, Wael/0000-0003-4406-9096; Fusi, Stefano/0000-0002-3035-6652 FU NIDA NIH HHS [DA016455, R01 DA016455, R01 DA016455-05]; NIMH NIH HHS [R01 MH062349, R01 MH062349-05]; NINDS NIH HHS [5R01NS35145-9, NS50944, R01 NS035145, R01 NS050944] NR 47 TC 86 Z9 88 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 19 PY 2007 VL 54 IS 2 BP 319 EP 333 DI 10.1016/j.neuron.2007.03.017 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 163VF UT WOS:000246190600015 PM 17442251 ER PT J AU Goes, NB Colvin, RB Harris, NL Bazari, H AF Goes, Nelson B. Colvin, Robert B. Harris, Nancy Lee Bazari, Hasan TI A 56-year-old woman with renal failure after heart-lung transplantation - Collapsing glomerulopathy, associated with severe hyaline arteriolopathy, probably caused by chronic cyclosporine toxicity (with other potential factors including hyperlipidemia and hypertension). Hypertensive arteriosclerosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; KIDNEY-TRANSPLANTATION; CHRONIC NEPHROPATHY; ALLOGRAFTS; RECIPIENTS; PROLIFERATION; INFECTION; ORGAN C1 Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Goes, NB (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. NR 31 TC 10 Z9 10 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 19 PY 2007 VL 356 IS 16 BP 1657 EP 1665 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 158AB UT WOS:000245762000010 PM 17442909 ER PT J AU Maciejewski, ML Perkins, M Li, YF Chapko, M Fortney, JC Liu, CF AF Maciejewski, Matthew L. Perkins, Mark Li, Yu-Fang Chapko, Michael Fortney, John C. Liu, Chuan-Fen TI Utilization and expenditures of veterans obtaining primary care in community clinics and VA medical centers: an observational cohort study SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID OUTPATIENT CLINICS; PERFORMANCE-MEASURES; RISK ADJUSTMENT; DISTANCE; COSTS; SERVICES; ACCESS; BIAS AB Background: To compare VA inpatient and outpatient utilization and expenditures of veterans seeking primary care in community-based outpatient clinics (CBOCs) and VA medical centers (VAMCs) in fiscal years 2000 (FY00) and 2001. Methods: The sample included 25,092 patients who obtained primary care exclusively from 108 CBOCs in FY00, 26,936 patients who obtained primary care exclusively from 72 affiliated VAMCs in FY00, and 11,450 "crossover" patients who obtained primary care in CBOCs and VAMCs in FY00. VA utilization and expenditure data were drawn from the VA's system-wide cost accounting system. Veteran demographic characteristics and a 1999 Diagnostic Cost Group risk score were obtained from VA administrative files. Outpatient utilization ( primary care, specialty care, mental health, pharmacy, radiology and laboratory) and inpatient utilization were estimated using count data models and expenditures were estimated using one-part or two-part models. The second part of two-part models was estimated using generalized linear regressions. Results: CBOC patients had a slightly more primary care visits per year than VAMC patients ( p < 0.0001), but lower primary care costs (-$71, p < 0.0001). CBOC patients had lower odds of one or more specialty, mental health, ancillary visits and hospital stays per year, and fewer numbers of visits and stays if they had any and lower specialty, mental health, ancillary and inpatient expenditures ( all, p < 0.0001). As a result, CBOC patients had lower total outpatient and overall expenditures than VAMC patients ( p < 0.0001). Conclusion: CBOCs provided veterans improved access to primary care and other services, but expenditures were contained because CBOC patients who sought health care had fewer visits and hospital stays than comparable VAMC patients. These results suggest a more complex pattern of health care utilization and expenditures by CBOC patients than has been found in prior studies. This study also illustrates that CBOCs continue to be a critical primary care and mental health access point for veterans. C1 Durham VA Med Ctr, Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC 27710 USA. Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Cent Arkansas Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Hlth Serv Res & Dev, N Little Rock, AR USA. Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC 27710 USA. EM matt@email.unc.edu; mark.perkins@med.va.gov; yli@u.washington.edu; michael.chapko@med.va.gov; FortneyJohnC@uams.edu; fliu@u.washington.edu NR 21 TC 24 Z9 24 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD APR 18 PY 2007 VL 7 AR 56 DI 10.1186/1472-6963-7-56 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 159WX UT WOS:000245899400001 PM 17442115 ER PT J AU Abraira, VE Hyun, N Tucker, AF Coling, DE Brown, MC Lu, C Hoffman, GR Goodrich, LV AF Abraira, Victoria E. Hyun, Naomi Tucker, Andrew F. Coling, Donald E. Brown, M. Christian Lu, Cindy Hoffman, Gregory R. Goodrich, Lisa V. TI Changes in Sef levels influence auditory brainstem development and function SO JOURNAL OF NEUROSCIENCE LA English DT Article DE FGF; Sef; rhombic lip; cochlear nucleus; auditory brainstem response; central auditory processing defect ID INFANTILE GAUCHERS-DISEASE; FIBROBLAST GROWTH-FACTORS; COCHLEAR NUCLEUS; RHOMBIC-LIP; CELL-POPULATIONS; MOUSE; EXPRESSION; GENE; CAT; GENERATORS AB During development of the CNS, secreted morphogens of the fibroblast growth factor (FGF) family have multiple effects on cell division, migration, and survival depending on where, when, and how much FGF signal is received. The consequences of misregulating the FGF pathway were studied in a mouse with decreased levels of the FGF antagonist Sef. To uncover effects in the nervous system, we focused on the auditory system, which is accessible to physiological analysis. We found that the mitogen-activated protein kinase pathway is active in the rhombic lip, a germinal zone that generates diverse types of neurons, including the cochlear nucleus complex of the auditory system. Sef is expressed immediately adjacent to the rhombic lip, overlapping with FGF15 and FGFR1, which is also present in the lip itself. This pattern suggests that Sef may normally function in non-rhombic lip cells and prevent them from responding to FGF ligand in the vicinity. Consistent with this idea, overexpression of Sef in chicks decreased the size of the auditory nuclei. Cochlear nucleus defects were also apparent in mice with reduced levels of Sef, with 13% exhibiting grossly dysmorphic cochlear nuclei and 26% showing decreased amounts of GFAP in the cochlear nucleus. Additional evidence for cochlear nucleus defects was obtained by electrophysiological analysis of Sef mutant mice, which have normal auditory thresholds but abnormal auditory brainstem responses. These results show both increases and decreases in Sef levels affect the assembly and function of the auditory brainstem. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. SUNY Buffalo, Ctr Hearing & Deafness, Buffalo, NY 14260 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02115 USA. RP Goodrich, LV (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM Lisa_Goodrich@hms.harvard.edu OI Coling, Donald/0000-0001-6285-5336 FU NIMH NIH HHS [R01 MH60612]; PHS HHS [NIDCD 01089] NR 61 TC 21 Z9 21 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 18 PY 2007 VL 27 IS 16 BP 4273 EP 4282 DI 10.1523/JNEUROSCI.3477-06.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 158RC UT WOS:000245810200006 PM 17442811 ER PT J AU Devor, A Tian, PF Nishimura, N Teng, IC Hillman, EMC Narayanan, SN Ulbert, I Boas, DA Kleinfeld, D Dale, AM AF Devor, Anna Tian, Peifang Nishimura, Nozomi Teng, Ivan C. Hillman, Elizabeth M. C. Narayanan, S. N. Ulbert, Istvan Boas, David A. Kleinfeld, David Dale, Anders M. TI Suppressed neuronal activity and concurrent arteriolar vasoconstriction may explain negative blood oxygenation level-dependent signal SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hemodynamic; somatosensory; two-photon; voltage-sensitive dyes; intrinsic imaging; electrode array ID VOLTAGE-SENSITIVE DYE; RAT BARREL CORTEX; SOMATOSENSORY CORTEX; HEMOGLOBIN CONCENTRATION; SPATIOTEMPORAL DYNAMICS; RECEPTIVE-FIELDS; PYRAMIDAL CELLS; NEURAL BASIS; IN-VIVO; BRAIN AB Synaptic transmission initiates a cascade of signal transduction events that couple neuronal activity to local changes in blood flow and oxygenation. Although a number of vasoactive molecules and specific cell types have been implicated, the transformation of stimulus-induced activation of neuronal circuits to hemodynamic changes is still unclear. We use somatosensory stimulation and a suite of in vivo imaging tools to study neurovascular coupling in rat primary somatosensory cortex. Our stimulus evoked a central region of net neuronal depolarization surrounded by net hyperpolarization. Hemodynamic measurements revealed that predominant depolarization corresponded to an increase in oxygenation, whereas predominant hyperpolarization corresponded to a decrease in oxygenation. On the microscopic level of single surface arterioles, the response was composed of a combination of dilatory and constrictive phases. Critically, the relative strength of vasoconstriction covaried with the relative strength of oxygenation decrease and neuronal hyperpolarization. These results suggest that a neuronal inhibition and concurrent arteriolar vasoconstriction correspond to a decrease in blood oxygenation, which would be consistent with a negative blood oxygenation level-dependent functional magnetic resonance imaging signal. C1 Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Hungarian Acad Sci, Inst Psychol, H-1068 Budapest, Hungary. RP Devor, A (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. EM adevor@ucsd.edu; dk@physics.ucsd.edu RI Hillman, Elizabeth/B-9854-2009; Ulbert, Istvan/F-2213-2010; Dale, Anders/A-5180-2010; Nishimura, Nozomi/P-8908-2015; OI Nishimura, Nozomi/0000-0003-4342-9416; Hillman, Elizabeth M. C./0000-0001-5511-1451 FU NCRR NIH HHS [R21 RR021907, R21 RR021907-03, RR021907]; NIBIB NIH HHS [EB003832, EB00790, R01 EB000790, R01 EB000790-05, R01 EB003832, R01 EB003832-03]; NINDS NIH HHS [R21 NS053684, NS-051188, NS053684, R01 NS051188, R01 NS051188-05, R21 NS053684-03] NR 54 TC 206 Z9 208 U1 1 U2 21 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 18 PY 2007 VL 27 IS 16 BP 4452 EP 4459 DI 10.1523/JNEUROSCI.0134-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 158RC UT WOS:000245810200025 PM 17442830 ER PT J AU Choi, YK Kim, JH Kim, WJ Lee, HY Park, JA Lee, SW Yoon, DK Kim, HH Chung, H Yu, YS Kim, KW AF Choi, Yoon Kyung Kim, Jeong Hun Kim, Woo Jean Lee, Hae Young Park, Jeong Ae Lee, Sae-Won Yoon, Dae-Kwan Kim, Hyun Ho Chung, Hum Yu, Young Suk Kim, Kyu-Won TI AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1 alpha SO JOURNAL OF NEUROSCIENCE LA English DT Article DE A-kinase anchor protein 12 (AKAP12); barriergenesis; blood-retinal barrier (BRB); hypoxia-inducible factor-1 alpha; retinoblastoma; retina ID ENDOTHELIAL GROWTH-FACTOR; KINASE-C SUBSTRATE; BRAIN-BARRIER; VEGF EXPRESSION; IN-VITRO; CYTOSKELETAL ARCHITECTURE; DEVELOPING MOUSE; GENE-EXPRESSION; TIGHT JUNCTIONS; HIF-ALPHA AB Many diseases of the eye such as retinoblastoma, diabetic retinopathy, and retinopathy of prematurity are associated with blood - retinal barrier (BRB) dysfunction. Identifying the factors that contribute to BRB formation during human eye development and maintenance could provide insights into such diseases. Here we show that A-kinase anchor protein 12 ( AKAP12) induces BRB formation by increasing angiopoietin-1 and decreasing vascular endothelial growth factor ( VEGF) levels in astrocytes. We reveal that AKAP12 downregulates the level of hypoxia-inducible factor-1 alpha(HIF-1 alpha) protein by enhancing the interaction of HIF-1 alpha with pVHL (von Hippel-Lindau tumor suppressor protein) and PHD2 ( prolyl hydroxylase 2). Conditioned media from AKAP12-overexpressing astrocytes induced barriergenesis by upregulating the expression of tight junction proteins in human retina microvascular endothelial cells (HRMECs). Compared with the retina during BRB maturation, AKAP12 expression in retinoblastoma patient tissue was markedly reduced whereas that of VEGF was increased. These findings suggest that AKAP12 may induce BRB formation through antiangiogenesis and barriergenesis in the developing human eye and that defects in this mechanism can lead to a loss of tight junction proteins and contribute to the development of retinal pathologies such as retinoblastoma. C1 Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul 151742, South Korea. Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul 110744, South Korea. Seoul Artif Eye Ctr, Seoul 110744, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Boston, MA 02115 USA. Anyang Univ, Coll Liberal Arts & Sci, Dept Marine Biotechnol, Inchon 417833, South Korea. RP Kim, KW (reprint author), Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul 151742, South Korea. EM qwonkim@plaza.snu.ac.kr RI Kim, Jeong Hun/J-2748-2012; Yu, Young Suk/J-5551-2012; Chung, Hum/J-5657-2012 NR 56 TC 41 Z9 46 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 18 PY 2007 VL 27 IS 16 BP 4472 EP 4481 DI 10.1523/JNEUROSCI.5368-06.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 158RC UT WOS:000245810200027 PM 17442832 ER PT J AU Ngo, TTB Peng, T Liang, XJ Akeju, O Pastorino, S Zhang, W Kotliarov, Y Zenklusen, JC Fine, HA Maric, D Wen, PY De Girolami, U Black, PM Wu, WW Shen, RF Jeffries, NO Kang, DW Park, JK AF Ngo, Teri-T B. Peng, Tien Liang, Xing-Jie Akeju, Oluwaseun Pastorino, Sandra Zhang, Wei Kotliarov, Yuri Zenklusen, Jean C. Fine, Howard A. Maric, Dragan Wen, Patrick Y. De Girolami, Umberto Black, Peter McL. Wu, Wells W. Shen, Rong-Fong Jeffries, Neal O. Kang, Dong-Won Park, John K. TI The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CHROMOSOME 1P LOSS; PHASE-III TRIAL; OLIGODENDROGLIAL TUMORS; CELL-CYCLE; ANAPLASTIC OLIGODENDROGLIOMAS; MULTISITE PHOSPHORYLATION; GRADE GLIOMAS; IN-VITRO; ARM 1P; SURVIVAL AB Background Malignant gliomas are generally resistant to all conventional therapies. Notable exceptions are anaplastic oligodendrogliomas with loss of heterozygosity on chromosome 1p (1p(+/-)). Patients with 1p(+/-) anaplastic oligodendroglioma frequently respond to procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine. Because the underlying biologic basis for this clinical finding is unclear, we evaluated differentially expressed 1p-encoded proteins in 1p(+/-) and 1p(+/+) malignant glioma cell lines and then examined whether their expression was associated with outcome of patients with anaplastic oligodendroglioma. Methods We used a comparative proteomic screen of A172 (1p(+/+)) and U251 (1p(+/+)) malignant glioma cell lines to identify differentially expressed 1p-encoded proteins, including stathmin, a microtubule-associated protein. 1 p(+/-) and 1 p(+/-) anaplastic oligodendroglioma specimens from 24 patients were assessed for stathmin expression by immunohistochemistry. The relationship between stathmin expression and clinical outcome was assessed with Kaplan-Meier analyses. RNA inhibition and cDNA transfection experiments tested effects of stathmin under- and overexpression, respectively, on the in vitro and in vivo resistance of malignant glioma cells to treatment with nitrosourea. For in vivo resistance studies, 36 mice with intracranial and 16 mice with subcutaneous xenograft tumor implants were used (one tumor per mouse). Flow cytometry was used for cell cycle analysis. Immunoblotting was used to assess protein expression. All statistical tests were two-sided. Results Decreased stathmin expression in tumors was statistically significantly associated with loss of heterozygosity in 1p (P <.001) and increased recurrence-free survival (P < 001). The median recurrence-free survival times for patients with tumors expressing low, intermediate, or high stathmin levels were 45 months (95% confidence interval [Cl] = 0 to 90 months), 17 months (95% Cl = 10.6 to 23.4 months), and 6 months (95% Cl = 1.7 to 10.3 months), respectively. Expression of stathmin was inversely associated with overall survival of nitrosourea-treated mice carrying xenograft tumors. Median survival of mice with stathmin(+/-) tumors was 95 days (95% Cl = 68.7 to 121.3 days) and that of mice with stathmin(+/+) tumors was 64 days (95% Cl = 58.2 to 69.8 days) (difference = 31 days, 95% Cl = 4.1 to 57.9 days; P <.001, log-rank test). Nitrosoureas induced mitotic arrest in malignant glioma cells, and this effect was greater in cells with decreased stathmin expression. Conclusions Loss of heterozygosity for the stathmin gene may be associated with improved outcomes of patients with 1p(+/-) anaplastic oligodendroglioma tumors. C1 NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD USA. NINDS, Flow Cytometry Facil, NIH, Bethesda, MD USA. NINDS, Off Clin Director, NIH, Bethesda, MD USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. RP Park, JK (reprint author), 35 Convent Dr,MSC 3706, Bethesda, MD 20892 USA. EM parkjk@ninds.nih.gov RI Kotliarov, Yuri/B-6938-2017 FU Intramural NIH HHS NR 49 TC 38 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 18 PY 2007 VL 99 IS 8 BP 639 EP 652 DI 10.1093/jnci/djk135 PG 14 WC Oncology SC Oncology GA 166BN UT WOS:000246352200014 PM 17440165 ER PT J AU Kitamoto, S Sukhova, GK Sun, JS Yang, M Libby, P Love, V Duramad, P Sun, CX Zhang, YD Yang, XW Peters, C Shi, GP AF Kitamoto, Shiro Sukhova, Galina K. Sun, Jiusong Yang, Min Libby, Peter Love, Victoria Duramad, Paurene Sun, Chongxiu Zhang, Yadong Yang, Xiuwei Peters, Christoph Shi, Guo-Ping TI Cathepsin L deficiency reduces diet-induced atherosclerosis in low-density lipoprotein receptor-knockout mice SO CIRCULATION LA English DT Article DE atherosclerosis; cathepsin L; collagen; elastin; metalloproteinases; receptors, LDL; remodeling ID LYSOSOMAL CYSTEINE PROTEASES; MUSCLE-CELL-MIGRATION; MATRIX METALLOPROTEINASES; MOLECULAR-CLONING; BONE-RESORPTION; CYSTATIN-C; IN-VITRO; EXPRESSION; MATRIX-METALLOPROTEINASE-9; DEGRADATION AB Background-Remodeling of the arterial extracellular matrix participates importantly in atherogenesis and plaque complication. Increased expression of the elastinolytic and collagenolytic enzyme cathepsin L ( Cat L) in human atherosclerotic lesions suggests its participation in these processes, a hypothesis tested here in mice. Methods and Results-We generated Cat L and low-density lipoprotein receptor ( LDLr) double-deficient ( LDLr-/- Cat L-/-) mice by crossbreeding Cat L-null ( Cat L-/-) and LDLr- deficient ( LDLr-/-) mice. After 12 and 26 weeks of a Western diet, LDLr(-/-)Cat L-/- mice had significantly smaller atherosclerotic lesions and lipid cores compared with littermate control LDLr-/- Cat L-/- and LDLr-/- Cat L+/+ mice. In addition, lesions from the compound mutant mice showed significantly reduced levels of collagen, medial elastin degradation, CD4(+) T cells, macrophages, and smooth muscle cells. Mechanistic studies showed that Cat L contributes to the degradation of extracellular matrix elastin and collagen by aortic smooth muscle cells. Smooth muscle cells from LDLr-/- Cat L-/- mice or those treated with a Cat L-selective inhibitor demonstrated significantly less degradation of elastin and collagen and delayed transmigration through elastin in vitro. Cat L deficiency also significantly impaired monocyte and T-lymphocyte transmigration through a collagen matrix in vitro, suggesting that blood-borne leukocyte penetration through the arterial basement membrane requires Cat L. Cysteine protease active site labeling demonstrated that Cat L deficiency did not affect the activity of other atherosclerosis-associated cathepsins in aortic smooth muscle cells and monocytes. Conclusions-Cat L directly participates in atherosclerosis by degrading elastin and collagen and regulates blood-borne leukocyte transmigration and lesion progression. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Univ Freiburg, Inst Mol Med & Zellforsch, Freiburg, Germany. RP Shi, GP (reprint author), Cardiovasc Med, NRB-7,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM gshi@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL60942, HL56985, HL67249, HL67283] NR 42 TC 67 Z9 77 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 17 PY 2007 VL 115 IS 15 BP 2065 EP 2075 DI 10.1161/CIRCULATIONAHA.107.688523 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 157SP UT WOS:000245741500014 PM 17404153 ER EF