FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gomez-Tortosa, E Newell, KL Irizarry, MC Albert, M Growdon, JH Hyman, BT AF Gomez-Tortosa, E Newell, KL Irizarry, MC Albert, M Growdon, JH Hyman, BT TI Alpha synuclein immunoreactivity in dementia with Lewy bodies. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 177 BP 553 EP 553 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700188 ER PT J AU Newell, KL Boyer, P Gomez-Tortosa, E Hobbs, W Hedley-Whyte, ET Richardson, EP Vonsattel, JP Hyman, BT AF Newell, KL Boyer, P Gomez-Tortosa, E Hobbs, W Hedley-Whyte, ET Richardson, EP Vonsattel, JP Hyman, BT TI alpha-synuclein immunoreactive neuronal cytoplasmic inclusions and axonal swellings in neuroaxonal dystrophy. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 178 BP 553 EP 553 DI 10.1097/00005072-199905000-00189 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700189 ER PT J AU Boyer, PJ McKee, AC Kowall, NW Vonsattel, JP Klein, AM Ferrante, RJ AF Boyer, PJ McKee, AC Kowall, NW Vonsattel, JP Klein, AM Ferrante, RJ TI Alpha-synuclein immunochemistry enhances diagnostic accuracy of neuropathologic examination of brains from patients with dementia. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Brown Univ, Sch Med, Providence, RI 02912 USA. Bedford VA Med Ctr, Bedford, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 182 BP 554 EP 554 DI 10.1097/00005072-199905000-00193 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700193 ER PT J AU Christie, RH Zipfel, WR Williams, RM Webb, WW Hyman, BT AF Christie, RH Zipfel, WR Williams, RM Webb, WW Hyman, BT TI In vivo multiphoton imaging of amyloid deposition in transgenic mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell Univ, Ithaca, NY 14853 USA. RI Webb, Watt/B-5905-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 204 BP 560 EP 560 DI 10.1097/00005072-199905000-00215 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700215 ER PT J AU Taylor, MD Perry, J Zlatescu, MC Stemmer-Rachamimov, AO Ang, LC Ino, Y Schwartz, M Becker, LE Louis, DN Cairncross, JG AF Taylor, MD Perry, J Zlatescu, MC Stemmer-Rachamimov, AO Ang, LC Ino, Y Schwartz, M Becker, LE Louis, DN Cairncross, JG TI The hPMS2 exon 5 mutation and malignant glioma SO JOURNAL OF NEUROSURGERY LA English DT Article DE hPMS2; oligodendroglioma; Turcot syndrome; tumor suppressor gene; glioblastoma ID FAMILIAL ADENOMATOUS POLYPOSIS; BRAIN-TUMOR SPECIMENS; TURCOT SYNDROME; MICROSATELLITE INSTABILITY; INTESTINAL POLYPOSIS; SUPPRESSOR GENE; APC GENE; OLIGODENDROGLIOMA; 19Q; GLIOBLASTOMA AB Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome Ip. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS. it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is nor commonly involved in sporadic oligodendrogliomas or glioblastomas. C1 London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. Univ Toronto, Div Neurosurg, Toronto, ON, Canada. Univ Toronto, Dept Med Neurol, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. Univ Western Ontario, Dept Oncol, London, ON, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Cairncross, JG (reprint author), London Reg Canc Ctr, Dept Med Oncol, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. FU NCI NIH HHS [CA57683, CA 69285] NR 46 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1999 VL 90 IS 5 BP 946 EP 950 DI 10.3171/jns.1999.90.5.0946 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 189YT UT WOS:000079934600019 PM 10223463 ER PT J AU Bellon, RJ Liu, AY Adler, JR Norbash, AM AF Bellon, RJ Liu, AY Adler, JR Norbash, AM TI Percutaneous transfemoral embolization of an indirect carotid-cavernous fistula with cortical venous access to the cavernous sinus SO JOURNAL OF NEUROSURGERY LA English DT Article DE carotid-cavernous fistula; endovascular therapy; transvenous embolization; Guglielmi detachable coil ID DURAL ARTERIOVENOUS-MALFORMATIONS; OPHTHALMIC VEIN APPROACH; TRANSVENOUS EMBOLIZATION AB The authors present the case of a 61-year-old man with an indirect carotid-cavernous fistula (CCF). Many now advocate a primary transvenous approach to deal with such lesions, with packing and thrombosis of the cavernous sinus leading to fistula obliteration. Transvenous access to the cavernous sinus via the inferior petrosal sinus is the usual route of access; both surgical and transfemoral superior ophthalmic vein approaches are also well described. In the case presented, the anatomy of the CCF was unfavorable for these approaches and its dominant venous egress was via a single enlarged arterialized cortical vein. The cavernous sinus was accessed with a transfemoral retrograde approach to the cortical draining vein. Successful CCF embolization was documented radiographically and clinically. To the authors' knowledge, this procedure has not been previously described in the English literature. C1 Stanford Univ, Med Ctr, Dept Neuroradiol, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. RP Bellon, RJ (reprint author), Stanford Univ, Med Ctr, Dept Neuroradiol, 200 Pasteur Dr,Room S-047, Stanford, CA 94305 USA. NR 16 TC 26 Z9 27 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1999 VL 90 IS 5 BP 959 EP 963 DI 10.3171/jns.1999.90.5.0959 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 189YT UT WOS:000079934600022 PM 10223466 ER PT J AU Khaw, BA Petrov, A Narula, J AF Khaw, BA Petrov, A Narula, J TI Complementary roles of antibody affinity and specificity for in vivo diagnostic cardiovascular targeting: How specific is antimyosin for irreversible myocardial damage? SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE antimyosin antibody; gamma imaging; affinity; specificity ID MYOSIN-SPECIFIC ANTIBODY; CARDIAC MYOSIN; MONOCLONAL-ANTIBODY; INFARCTION; LOCALIZATION; FRAGMENTS; FAB AB Background. Identification of irreversible myocyte injury with antimyosin antibody imaging depends on both antibody specificity and affinity, To characterize the role of antibody affinity, we performed studies in dogs with acute coronary occlusion followed by reperfusion using 3 monoclonal antimyosin antibodies with different affinities. Methods and Results. Dogs with experimental reperfused acute myocardial infarction were injected with 2 high-affinity radiolabeled monoclonal antimyosin Fab fragments (R11D10 and 2G42D7), 1 low-affinity antimyosin Fab (3H31E6),and a nonspecific Fab, The left lateral gamma images at 5 H were used to assess the infarct (I) to blood (B) region of interest (ROI) count density ratios by computer planimetry, All infarcts were confirmed by in vivo imaging with Tl-201 for perfusion defects as well as by postmortem histochemical staining. The mean I/B ROI (+/- standard deviation [SD]) for R11D10 (1.701 +/- 0.376) was not significantly different from that of 2G42D7 (1.501 +/- 0.267, P = NS), but both were significantly greater than that of 3H31E6 Fab (0.85 +/- 0.12, P = .0001 and .0012, respectively). The I/B ROI of 3H31E6 Fab was similar to that of nonspecific Fab (0.75 to 0.77 range). Radiolabeled R11D10 and 2G42D7 were unequivocally positive by gamma imaging in all infarcts by 5 H, No infarcts were visualized,vith 3H31E6 or nonspecific Fab, Conclusions. The low-affinity antibody, despite its specificity for cardiac myosin, cannot be used to image the infarct zone. Therefore immunoscintigraphic diagnosis of irreversible myocardial injury with radiolabeled antimyosin Fab is doubly specific because in vivo visualization required both specificity and high enough affinity of the antibody. C1 Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Ctr Cardiovasc Targeting, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Allegheny Gen Hosp, Dept Nucl Cardiol, Philadelphia, PA USA. RP Khaw, BA (reprint author), Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Ctr Cardiovasc Targeting, Mugar 205, Boston, MA 02115 USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAY-JUN PY 1999 VL 6 IS 3 BP 316 EP 323 DI 10.1016/S1071-3581(99)90044-2 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 207AA UT WOS:000080912100009 PM 10385187 ER PT J AU Meltzer, P Hillier, S Madras, BK Blundell, P Zona, T Fischman, AJ AF Meltzer, P Hillier, S Madras, BK Blundell, P Zona, T Fischman, AJ TI Preparation, RE & Tc-99m labeling and biological characterization of a highly selective DAT ligand for SPECT. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Organix Inc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 153 BP 38P EP 38P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800154 ER PT J AU Hashimoto, A Fischman, AJ Gold, HK Moroi, M Scherrer-Crosbie, M Levine, RA Yasuda, T AF Hashimoto, A Fischman, AJ Gold, HK Moroi, M Scherrer-Crosbie, M Levine, RA Yasuda, T TI "Functional" viability assessment by dual isotope F18-FDG and Tc99 m-sestamibi in acute myocardial infarction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 193 BP 48P EP 48P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800194 ER PT J AU Carter, EA Tompkins, RG Fischman, AJ AF Carter, EA Tompkins, RG Fischman, AJ TI Increased urinary excretion of Tc-99m-DTPA as an index of intestinal permeability ingestion of alcohol or acute thermal injury. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 370 BP 92P EP 92P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800371 ER PT J AU Carter, EA Yu, YM Tompkins, RG Guerrero, JL Alpert, NM Fischman, AJ AF Carter, EA Yu, YM Tompkins, RG Guerrero, JL Alpert, NM Fischman, AJ TI Measurement of canine skeletal muscle blood flow by positron emission tomography with (H2O)-O-15. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 391 BP 97P EP 97P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800392 ER PT J AU Jadvar, H Fischman, AJ AF Jadvar, H Fischman, AJ TI Clinical impact of FDG PET on the management of patients with pancreatic carcinoma: Comparison with CT and CA19-9 serology. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 421 BP 104P EP 104P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800422 ER PT J AU Choi, NC Ryu, JS Fischman, AJ Hunter, G Hamberg, L McLoud, T AF Choi, NC Ryu, JS Fischman, AJ Hunter, G Hamberg, L McLoud, T TI Correlation of quantitative F-18-FDG PET with histopathologic tumor control (rho TCP) in neoadjuvant chemo-radiotherapy (CT plus RT) for stage III non-small cell lung cancer (NSCLC). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 547 BP 136P EP 136P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800548 ER PT J AU Bonab, AA Dougherty, DD Alpert, NM Rauch, SL Fava, M Fischman, AJ AF Bonab, AA Dougherty, DD Alpert, NM Rauch, SL Fava, M Fischman, AJ TI Serotonergic and dopaminergic PET binding studies in subjects with major depression before and after treatment with an antidepressant. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 579 BP 143P EP 144P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800580 ER PT J AU Brownell, AL Nguyen, TV Chen, YCI Livni, E Jenkins, BG AF Brownell, AL Nguyen, TV Chen, YCI Livni, E Jenkins, BG TI Detection of dopamine receptor supersensitivity using pharmacological MRI (phMRI) and PET with correlation to behavioral studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 582 BP 144P EP 144P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800583 ER PT J AU Yasuda, T Zervos, GD Brag, JM Spillert, AM Fischman, AJ AF Yasuda, T Zervos, GD Brag, JM Spillert, AM Fischman, AJ TI Three dimensional location, size and intensity of ischemia: Correlation of visual assessment and automated computer analysis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Focus Imaging, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 729 BP 160P EP 160P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800646 ER PT J AU Gewirtz, H AF Gewirtz, H TI Comparison of planar versus gated SPECT Tc-99m-RBC radionuclide ventriculography for assessment of left ventricular ejection fraction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 757 BP 167P EP 167P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800674 ER PT J AU Haseley, DR Jacobson, AF Graham, MM AF Haseley, DR Jacobson, AF Graham, MM TI Comparison of LVEF and EDV obtained from sestamibi and thallium gated SPECT studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 784 BP 173P EP 173P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800701 ER PT J AU Hashimoto, A Fischman, AJ Yasuda, T AF Hashimoto, A Fischman, AJ Yasuda, T TI Left bundle branch block and pattern of myocardial perfusion abnormality. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 783 BP 173P EP 173P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800700 ER PT J AU Fischman, AJ Carter, EA Coco-Graham, WA Babich, JW AF Fischman, AJ Carter, EA Coco-Graham, WA Babich, JW TI Comparison of a Tc-99m chemotactic peptide with (18)FDG for imaging infection and sterile inflammation in rabbits. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 894 BP 199P EP 199P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800810 ER PT J AU Carter, EA Tompkins, EA Fischman, AJ AF Carter, EA Tompkins, EA Fischman, AJ TI Effects of neutrophil depletion and immunosuppression on the accumulation of a Tc-99m labeled chemotactic peptide (For-Met-Leu-Phe-Lys-HYNIC) at sites of acute bacterial infection in rats. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 895 BP 200P EP 200P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800811 ER PT J AU Jadvar, H Connolly, LP Treves, ST Fischman, AJ AF Jadvar, H Connolly, LP Treves, ST Fischman, AJ TI "Pedipet": Diagnostic role of FDG PET in the evaluation of non-CNS pediatric tumors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 908 BP 203P EP 203P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800824 ER PT J AU Connors, JM Kronauge, JF Castronovo, F Mannting, F Ulanski, JS Jones, AG Sieff, C Krijanovski, OI Antin, JH AF Connors, JM Kronauge, JF Castronovo, F Mannting, F Ulanski, JS Jones, AG Sieff, C Krijanovski, OI Antin, JH TI Human pharmacokinetics and biodistribution of In-111-DTPA-G-CSF. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Partners Canc Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1031 BP 232P EP 232P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105800946 ER PT J AU Ryu, JS Choi, NC Fischman, AJ AF Ryu, JS Choi, NC Fischman, AJ TI FDG-PET in evaluating therapeutic effect and restaging of non-small cell lung cancer after neoajuvant chemoradiotherapy: Correlation with histopathology. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1090 BP 246P EP 246P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801004 ER PT J AU Fischman, AJ Meltzer, P Hillier, S Bonab, AA Callahan, RJ Barrow, SA Madras, BK AF Fischman, AJ Meltzer, P Hillier, S Bonab, AA Callahan, RJ Barrow, SA Madras, BK TI A new 99m-technetium labeled ligand for SPECT imaging of dopamine transporter sites (O-15O5T): Preliminary evaluation in normal and MPTP treated monkeys. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Organix Inc, Woburn, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1161 BP 262P EP 262P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801075 ER PT J AU Correia, JA Burnham, CA Kaufman, D Fischman, AJ AF Correia, JA Burnham, CA Kaufman, D Fischman, AJ TI Development of a small animal PET imaging device with resolution approaching 1mm. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1258 BP 285P EP 285P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801172 ER PT J AU Bonab, AA Alpert, NM Fischman, AJ AF Bonab, AA Alpert, NM Fischman, AJ TI Comparison of methods for quantification of 5-HT2 binding. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract ID RECEPTOR C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1266 BP 287P EP 287P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801180 ER PT J AU Kimura, Y Hsu, HB Toyama, H Senda, M Fischman, AJ Alpert, NM AF Kimura, Y Hsu, HB Toyama, H Senda, M Fischman, AJ Alpert, NM TI Improved signal to noise ratio in parametric images by cluster analysis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Tokyo Med & Dent Univ, Inst Med & Dent Engn, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tokyo Metropolitan Gerentol Inst, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1269 BP 288P EP 288P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801183 ER PT J AU Choi, SW Elmaleh, DR Fischman, AJ AF Choi, SW Elmaleh, DR Fischman, AJ TI Synthesis and structure-affinity studies of piperidine-based analogs of GBR 12935: 3-aminonethyl- and 4-aminopiperidine derivatives as potential DAT-radioligands. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1341 BP 305P EP 305P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801254 ER PT J AU Choi, SW Elmaleh, DR Fischman, AJ AF Choi, SW Elmaleh, DR Fischman, AJ TI Development of novel DAT radioligands: Design, synthesis and in vitro evaluation of acyclic amine-amide analogs of GBR 12909 & 12935. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1340 BP 305P EP 305P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801253 ER PT J AU Jadvar, H AF Jadvar, H TI Nuclear imaging in microgravity. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1451 BP 322P EP 322P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801320 ER PT J AU Kurdziel, KA Gentili, A AF Kurdziel, KA Gentili, A TI Annotated directory of nuclear medicine teaching sites on the world wide web. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1999 VL 40 IS 5 SU S MA 1456 BP 323P EP 323P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 192XV UT WOS:000080105801325 ER PT J AU Yu, YM Tompkins, RG Ryan, CM Young, VR AF Yu, YM Tompkins, RG Ryan, CM Young, VR TI The metabolic basis of the increase in energy expenditure in severely burned patients SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Review ID LEUCINE KINETICS; WHOLE-BODY; INDIRECT CALORIMETRY; LACTATE PRODUCTION; ENTERAL NUTRITION; PROTEIN-SYNTHESIS; SKELETAL-MUSCLE; ATPASE ACTIVITY; YOUNG MEN; INJURY AB Background: Severe burn trauma is characterized by an elevated rate of whole-body energy expenditure. Approach: In this short review, we have attempted to assess the metabolic characteristics of and basis for the persistent increase in energy expenditure during the flow phase of the injury. We consider some aspects of normal energy metabolism, including the contribution of the major adenosine triphosphate (ATP)-consuming reactions to the standard or basal metabolic rate. Rate estimates are compiled from the literature for a number of these reactions in healthy adults and burned patients, and the values are related to the increased rates of whole-body energy expenditure with burn injury. Results: Whole-body protein synthesis, gluconeogenesis, urea production, and substrate cycles (total fatty acid and glycolytic-gluconeogenic) account for approximately 22%, 11%, 3%, 17%, and 4%, respectively, of the burn-induced increase in total energy expenditure. Conclusions: These ATP-consuming reactions, therefore, seem to explain approximately 57% of the increase in energy expenditure. The remainder of the increase may be due, in large part, to altered Na+-K+-ATPase activity and increased proton leakage across the mitochondrial membrane. C1 Massachusetts Gen Hosp, Shriners Burns Hosp & Trauma Serv, Boston, MA 02114 USA. MIT, Human Nutr Lab, Cambridge, MA 02139 USA. RP Young, VR (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR88]; NIDDK NIH HHS [DK 15856, DK42101] NR 85 TC 67 Z9 67 U1 1 U2 7 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 1999 VL 23 IS 3 BP 160 EP 168 DI 10.1177/0148607199023003160 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 193WZ UT WOS:000080161900008 PM 10338224 ER PT J AU Hendren, WH AF Hendren, WH TI From an acorn to an oak SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article ID MULLERIAN-INHIBITING SUBSTANCE; SURGICAL-MANAGEMENT; EXPERIENCE; CHILDREN; THERAPY; GROWTH; EXPRESSION; INFANCY; DISEASE; SURGERY C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hendren, WH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. NR 78 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAY PY 1999 VL 34 IS 5 SU 1 BP 46 EP 58 DI 10.1016/S0022-3468(99)90830-8 PG 13 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 199LA UT WOS:000080482000006 PM 10360488 ER PT J AU Islam, S Masiakos, P Schnitzer, JJ Doody, DP Ryan, DP AF Islam, S Masiakos, P Schnitzer, JJ Doody, DP Ryan, DP TI Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 50th Anniversary Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 16-19, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Pediat Sect Surgery DE calcium channel antagonist; recurrent pulmonary hypertension; extracorporeal membrane oxygenation ID RIGHT-VENTRICULAR HYPERTROPHY; THERAPY; VASODILATORS; NIFEDIPINE; SECONDARY AB Background/Purpose: Recurrent pulmonary hypertension in the neonatal population is an unusual event with dire consequences. Pulmonary hypertension seen in association with pulmonary hypoplasia may be refractory to conventional medical management. The effect of the calcium channel antagonist diltiazem was studied in five patients with severe pulmonary hypertension. Methods: A retrospective review of the hospital records was performed to determine the efficacy of diltiazem for refractory pulmonary hypertension. All five patients experienced and did not respond to maximal conventional therapy, which included inhaled nitric oxide, intravenous nitrates, and extracorporeal membrane oxygenation (ECMO). Right ventricular pressures were determined by transthoracic echocardiograms and were used to document improvement in the pressure gradients. Statistical analyses were performed using a paired Student's t test. A P value of less than .05 was considered significant. Results: Diltiazem significantly reduced the right ventricular systolic pressure (RVSP) from 82 +/- 8.4 mm Hg to 58.4 +/- 7 mm Hg (P = .008). Two patients died; one had a large ventricular septal defect, and the other suffered multisystem organ failure secondary to sepsis. The surviving patients were weaned off diltiazem and did not experience recurrent pulmonary hypertension. Conclusions: In cases of pulmonary hypoplasia with recurrent pulmonary hypertension, diltiazem may be considered as a thera py. A multicenter prospective trial is advocated. Copyright (C) 1999 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Pediat Surg Serv, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Pediat Surg Serv, Dept Surg, Warren 1131,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAY PY 1999 VL 34 IS 5 BP 712 EP 714 DI 10.1016/S0022-3468(99)90361-5 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 198WP UT WOS:000080447500023 PM 10359169 ER PT J AU de Groot, M Jacobson, AM Samson, JA Welch, G AF de Groot, M Jacobson, AM Samson, JA Welch, G TI Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE depression; diabetes mellitus; glycemic control ID STRUCTURED CLINICAL INTERVIEW; GLYCOSYLATED HEMOGLOBIN; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; METABOLIC CONTROL; GLUCOSE CONTROL; SUBSTANCE USE; YOUNG-ADULTS; FOLLOW-UP; RETINOPATHY AB The current study evaluated the association of glycemic control and major depression in 33 type 1 and 39 type 2 diabetes mellitus patients. Type 1 patients with a lifetime history of major depression showed significantly worse glycemic control than patients without a history of psychiatric illness (t=2.09; df-31,p<0.05). Type 2 diabetes patients with a lifetime history of major depression did not have significantly worse control than those with no history of psychiatric illness, Findings from this study indicate different relationships between lifetime major depression and glycemic control for patients with type 1 and type 2 diabetes. Treatment implications for glycemic control in type 1 and type 2 diabetes patients are discussed. (C) 1999 Elsevier Science Inc. C1 McLean Hosp, Joslin Diabet Ctr, Mental Hlth Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP de Groot, M (reprint author), McLean Hosp, Joslin Diabet Ctr, Mental Hlth Unit, Boston, MA 02215 USA. FU NIADDK NIH HHS [AM27845]; NIDDK NIH HHS [DK42315-02] NR 50 TC 66 Z9 70 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD MAY PY 1999 VL 46 IS 5 BP 425 EP 435 DI 10.1016/S0022-3999(99)00014-8 PG 11 WC Psychiatry SC Psychiatry GA 202JM UT WOS:000080648700003 PM 10404477 ER PT J AU Wilens, TE Biederman, J March, JS Wolkow, R Fine, CS Millstein, RB Faraone, SV Geller, D Spencer, TJ AF Wilens, TE Biederman, J March, JS Wolkow, R Fine, CS Millstein, RB Faraone, SV Geller, D Spencer, TJ TI Absence of cardiovascular adverse effects of sertraline in children and adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pediatric; electrocardiogram; sertraline; obsessive-compulsive disorder ID PRELIMINARY CLINICAL-EXPERIENCE; OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; DOUBLE-BLIND; MAJOR DEPRESSION; CONTROLLED TRIAL; FLUOXETINE; ANTIDEPRESSANTS; AMITRIPTYLINE; FLUVOXAMINE AB Objective: In a 12 week, placebo-controlled, parallel-design, multicenter study of sertraline for obsessive-compulsive disorder in 107 children and 80 adolescents, the authors prospectively assessed cardiovascular effects to doses of sertraline of less than or equal to 200 mg/day. Method: Vital signs (blood pressure and heart rate) and electrocardiograph parameters (ECGs) were systematically evaluated at baseline and again throughout treatment. Results: There were no clinically significant cardiovascular adverse events in any of the subjects enrolled in the study. Moreover, compared with baseline and placebo, sertraline treatment at an average dose of 167 mg did not result in any clinically meaningful changes in any ECG indices (PR, QRS, and QTc intervals), cardiac rhythm, blood pressure, or heart rate. Conclusions: These prospectively derived results support the cardiovascular safety of sertraline at doses up to 200 mg in children and adolescents. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Sch Med, Program Child & Adolescent Anxiety Disorders, Durham, NC USA. Pfizer Inc, Clin & Sci Affairs, New York, NY USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, ACC 725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20MH011175A0] NR 21 TC 20 Z9 20 U1 1 U2 1 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 1999 VL 38 IS 5 BP 573 EP 577 DI 10.1097/00004583-199905000-00019 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100019 PM 10230189 ER PT J AU Wilens, TE Spencer, TJ AF Wilens, TE Spencer, TJ TI Combining methylphenidate and clonidine: A clinically sound medication option SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID ATTENTION DEFICIT DISORDER; DOUBLE-BLIND; CHILDREN; HYPERACTIVITY; QUESTIONS; EFFICACY C1 Harvard Univ, Pediat Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Pediat Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med, ACC 725, Boston, MA 02114 USA. NR 17 TC 55 Z9 58 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 1999 VL 38 IS 5 BP 614 EP 616 DI 10.1097/00004583-199905000-00025 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 190HE UT WOS:000079956100025 PM 10230195 ER PT J AU Gonzalez, S Gonzalez, E White, WM Rajadhyaksha, M Anderson, RR AF Gonzalez, S Gonzalez, E White, WM Rajadhyaksha, M Anderson, RR TI Allergic contact dermatitis: Correlation of in vivo confocal imaging to routine histology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID IN-VIVO; SKIN; MICROSCOPY AB Background: Allergic contact dermatitis (ACD) is a common and often challenging clinical problem. In vivo near-infrared confocal reflectance microscopy (CM) is a new vital microscopy technique. Objective: CM was used to evaluate acute ACD. Methods: Patch testing by means of Finn Chambers: technique was performed in 5 subjects to induce an acute allergic skin reaction. Noninvasive CM images from normal and eczematous skin were sequentially recorded before and after removal of the Finn Chambers. Results: The epidermis and papillary dermis were clearly seen in high resolution. Retention of nuclei in stratum corneum, epidermal edema with microvesicle formation, and transepidermal migration of inflammatory cells: were observed in vivo. Isolated dendritic cells were present in the ACD sites of 2 subjects, with morphology, size, and location consistent with Langerhans cells. Dermal vasodilation was observed as well. Conclusion: CM is a useful tool to study ACD and may be able to track Langerhans cell activation. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Contact Dermatitis Unit, Boston, MA 02114 USA. Lucid Inc, Henrietta, NY USA. RP Gonzalez, S (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Blossom St,BHX-630, Boston, MA 02114 USA. NR 14 TC 101 Z9 104 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1999 VL 40 IS 5 BP 708 EP 713 DI 10.1016/S0190-9622(99)70151-9 PN 1 PG 6 WC Dermatology SC Dermatology GA 191PA UT WOS:000080029700008 PM 10321598 ER PT J AU Philbin, EF DiSalvo, TG AF Philbin, EF DiSalvo, TG TI Prediction of hospital readmission for heart failure: Development of a simple risk score based on administrative data SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ELDERLY PATIENTS; RESOURCE UTILIZATION; CARE; OUTCOMES; MANAGEMENT; QUALITY; IMPACT; VALIDATION; MORBIDITY; SURVIVAL AB OBJECTIVES The purpose of this study waste develop a convenient and inexpensive method for identifying an individual's risk for hospital readmission for congestive heart failure (CHF) using information derived exclusively from administrative data sources and available at the time of an index hospital discharge. BACKGROUND Rates of readmission are high after hospitalization for CHF. The significant determinants of rehospitalization are debated. METHODS Administrative information on all 1995 hospital discharges in New York State which were. assigned International Classification of Diseases-9-Clinical Modification codes indicative of CHF in the principal diagnosis position were obtained. The following were compared among hospital survivors who did and did not experience readmission: demographics, comorbid illness, hospital type and location, processes of care, length of stay and hospital charges. RESULTS A total of 42,731 black or white Patients were identified. The subgroup of 9,112 patients (21.3%) who were readmitted were distinguished by a greater proportion of blacks, a higher prevalence of Medicare and Medicaid insurance, more comorbid illnesses and the use of telemetry monitoring during their index hospitalization. Patients treated at rural hospitals, those discharged to skilled nursing facilities and those having echocardiograms or cardiac catheterization were less likely to be readmitted. Using multiple regression methods, a simple methodology was devised that segregated patients into low, intermediate and high risk for readmission. CONCLUSION Patient characteristics, hospital features, processes of care and clinical outcomes may be used to estimate the risk of hospital readmission for CHF. However, some of the variation in rehospitalization risk remains unexplained and may be the result of discretionary behavior by physicians and patients. (C) 1999 by the American College of Cardiology. C1 Henry Ford Hosp, Sect Heart Failure & Cardiac Transplantat, Div Cardiovasc Med, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Cardiac Unit, Heart Failure & Transplantat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Philbin, EF (reprint author), Henry Ford Hosp, Sect Heart Failure & Cardiac Transplantat, Div Cardiovasc Med, 2799 W Grand Blvd, Detroit, MI 48202 USA. NR 32 TC 124 Z9 126 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1999 VL 33 IS 6 BP 1560 EP 1566 DI 10.1016/S0735-1097(99)00059-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UH UT WOS:000081122700020 PM 10334424 ER PT J AU Woolfolk, MW Lang, WP Borgnakke, WS Taylor, GW Ronis, DL Nyquist, LV AF Woolfolk, MW Lang, WP Borgnakke, WS Taylor, GW Ronis, DL Nyquist, LV TI Determining dental checkup frequency SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID HEALTH INTERVIEW SURVEY; OLDER ADULTS; CARE; BEHAVIORS; SERVICES; ACCESS; VISITS; TRENDS AB Background, The authors assessed the dental checkup frequency of adults living in the Detroit tricounty area and identified demographic, access and subjective factors associated with visits to a dentist made not because of a dental problem. Methods. Data are from a 1994 probability based sample of adults who were interviewed and received an in-home oral examination. The authors used the variables of age, sex, education level, in-level, dental insurance status, usual place for care, objective measures of oral health, and subjective assessments of health, pain and dental anxiety to predict the frequency of dental checkups. Results, The authors found that differences in dental checkup behavior were related to demographics, access to dental care, subjective ratings of oral and general health and other self-assessments, and clinical parameters of oral health. In multiple logistic regression analysis considering all;variables simultaneously, sex, income, having a usual place for care and level of dental. care anxiety were found to be associated with having dental checkups. The authors determined the statistical significance level at P < .05. Conclusions, A total of 69.7 percent of the study population reported having had a dental check-up at least once a year in the past five years. The authors found that four factors associated with infrequent dental checkups: being male, having lower income levels, not having a usual place for care and being anxious about receiving dental care. Practice Implications. Dental health professionals should consider the correlates of dental checkup frequency identified in this study and the usefulness of proposed strategies to increase and sustain regular preventive visitation patterns in their own patient populations. C1 Univ Michigan, Sch Dent, Dept Periodont Prevent & Geriatr, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. US Dept Vet Affairs, Ann Arbor, MI USA. RP Woolfolk, MW (reprint author), Univ Michigan, Sch Dent, Dept Periodont Prevent & Geriatr, G306C,1011 N Univ Ave, Ann Arbor, MI 48109 USA. FU NIDCR NIH HHS [DE10145] NR 31 TC 31 Z9 33 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 1999 VL 130 IS 5 BP 715 EP 723 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 194PX UT WOS:000080203700022 PM 10332137 ER PT J AU Lim, A Tsuang, D Kukull, W Nochlin, D Leverenz, J McCormick, W Bowen, J Teri, L Thompson, J Peskind, ER Raskind, M Larson, EB AF Lim, A Tsuang, D Kukull, W Nochlin, D Leverenz, J McCormick, W Bowen, J Teri, L Thompson, J Peskind, ER Raskind, M Larson, EB TI Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; clinico-neuropathological; community sample; diagnosis ID HIPPOCAMPAL SCLEROSIS; DEMENTIA; DIAGNOSIS; CONSORTIUM; ESTABLISH; REGISTRY; CERAD AB OBJECTIVES: Most clinico-neuropathological correlative studies of Alzheimer's Disease (AD) are based on research cohorts that are not necessarily generalizable to patients seen in the general medical community. In this study, we examine the accuracy of the criteria used in diagnosing AD in a community-based case series of patients with memory complaints. DESIGN AND PARTICIPANTS: Clinical and neuropathological diagnoses were obtained from 134 patients evaluated for dementia who subsequently underwent autopsy. SETTING: Subjects who exhibited new symptoms of dementia and were enrolled in the University of Washington/Group Health Cooperative Alzheimer's Disease Patient Registry were eligible for this study. MEASUREMENTS: Clinico-pathological correlation was performed using NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. RESULTS: Ninety-five of the 134 cases studied met CERAD neuropathological criteria for AD. The sensitivity of NINCDS-ADRDA "probable AD" was 83 % (diagnosing AD correctly) and overall clinical diagnostic accuracy was 75%. However, there was a high rate of additional neuropathological findings. Only 34 of the 94 cases had pure AD on neuropathology, whereas the remainder frequently had coexisting vascular or Parkinson's disease lesions. CONCLUSIONS: This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria. It also shows that co-existing neuropathological findings are common in community-based A.D. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Neuropathol Lab, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Tsuang, D (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, 116MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kukull, Walter/0000-0001-8761-9014 FU NIA NIH HHS [U01AG06781, R01-AG10845] NR 32 TC 258 Z9 263 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1999 VL 47 IS 5 BP 564 EP 569 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 194NU UT WOS:000080201100011 PM 10323650 ER PT J AU Sabolic, I Herak-Kramberger, CM Breton, S Brown, D AF Sabolic, I Herak-Kramberger, CM Breton, S Brown, D TI Na/K-ATPase in intercalated cells along the rat nephron revealed by antigen retrieval SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MEDULLARY COLLECTING DUCT; RENAL CONVOLUTED TUBULES; VACUOLAR H+-ATPASE; (NA+ + K+)-ATPASE; MONOCLONAL-ANTIBODY; PLASMA-MEMBRANES; K+-ATPASE; IMMUNOCYTOCHEMICAL LOCALIZATION; IMMUNOFERRITIN DETERMINATION; KIDNEY AB The Na/K-ATPase plays a fundamental role in the physiology of various mammalian cells. In the kidney, previous immunocytochemical studies have localized this protein to the basolateral membrane in different tubule segments. However, intercalated cells (IC) of the collecting duct (CD) in rat and mouse were unlabeled with anti-Na/K-ATPase antibodies. An antigen retrieval technique has been recently described in which tissue sections are pretreated with sodium dodecyl sulfate before immunostaining. This procedure was used to reexamine the presence of Na/K-ATPase in IC along the rat nephron using monoclonal antibodies against the Na/K-ATPase alpha-subunit. Subtypes of IC along the nephron were identified by their distinctive staining with polyclonal and monoclonal antibodies to the 31-kD vacuolar H+-ATPase subunit, whereas principal cells (PC) were labeled with a polyclonal antibody to the water channel aquaporin-4 (AQP-4). In PC, the Na/K-ATPase and AQP-4 staining colocalized basolaterally. In contrast to previous reports, we found that IC of all types showed basolateral labeling with the anti-Na/K-ATPase antibody. The staining was quantified by fluorescence image analysis. It was weak to moderate in IC of cortical and outer medullary collecting ducts and most intense in IC of the initial inner medullary collecting duct. IC in the initial inner medulla showed a staining intensity that was equivalent or stronger to that in adjacent principal cells. Models of ion transport at the cellular and epithelial level in rat kidney, therefore, must take into account the potential role of a basolateral Na/K-ATPase in intercalated cell function. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Zagreb 10001, Croatia. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2,POB 291, Zagreb 10001, Croatia. FU FIC NIH HHS [1R03-TW00512-01A1]; NIDDK NIH HHS [DK42956] NR 30 TC 48 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 1999 VL 10 IS 5 BP 913 EP 922 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 189TV UT WOS:000079923000001 PM 10232676 ER PT J AU Wood, BJ Khan, MA McGovern, F Harisinghani, M Hahn, PF Mueller, PR AF Wood, BJ Khan, MA McGovern, F Harisinghani, M Hahn, PF Mueller, PR TI Imaging guided biopsy of renal masses: Indications, accuracy and impact on clinical management SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; biopsy; ultrasonography; computerized tomography ID CELL CARCINOMA; DIAGNOSIS; TUMOR AB Purpose: We evaluated the indications, accuracy and impact of image guided biopsy of focal renal masses, Materials and Methods: We retrospectively reviewed 79 image guided renal biopsies in 73 patients. indications, imaging, and histological and clinical features were analyzed. We assumed that nephrectomy, partial nephrectomy or surgical biopsy of suspicious masses would be done when no percutaneous biopsy had been performed. A change in management was defined as surgical to nonsurgical. Results: Clinical management was altered due to results in 32 of the 79 biopsies (41%) in cases managed nonoperatively, including positive and negative biopsies in those followed clinically and with imaging. Of 79 biopsies 49 (62%) were diagnosed positive for malignancy, including 15 (31%) that were not and 34 (69%) that were renal cell carcinoma. The histological diagnosis was negative on 25 biopsies (32%) and positive or negative on 74 (94%). All 5 of the 79 false-negative biopsies (6%) were due to insufficient tissue and involved highly suspicious imaging findings that required further evaluation, such as repeat biopsy or surgery. Renal cell carcinoma was identified in 4 of the 5 cases. In 12 of the 24 patients (50%) with a pre-biopsy history of nonrenal cancer biopsies were diagnostic of nonrenal cancer. No patient had major complications and in 4 small hematomas were treated with observation only. Conclusions: Image guided renal mass biopsy is safe, reliable and accurate, and it changes clinical management; in many cases by avoiding nephrectomy or other surgical options. Radiologists should promote imaging guided biopsy as a potentially useful option for managing suspicious or indeterminate renal masses. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 12 TC 133 Z9 135 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1999 VL 161 IS 5 BP 1470 EP 1474 DI 10.1016/S0022-5347(05)68929-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 185JY UT WOS:000079666900013 PM 10210375 ER PT J AU Martinez-Picado, J Savara, LV Sutton, L D'Aquila, RT AF Martinez-Picado, J Savara, LV Sutton, L D'Aquila, RT TI Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID URACIL DNA GLYCOSYLASE; DYNAMICS IN-VIVO; REVERSE-TRANSCRIPTASE; HIV-1 VARIANTS; KINETIC CHARACTERIZATION; ZIDOVUDINE RESISTANCE; CROSS-RESISTANCE; VIRAL PROTEASE; MUTATIONS; THERAPY AB The relative replicative fitness of human immunodeficiency virus type 1 (HIV-1) mutants selected by different protease inhibitors (PIs) in vivo was determined. Each mutant was compared to wild type (WT), NL4-3, in the absence of drugs by several methods, including clonal genotyping of cultures infected with two competing viral variants, kinetics of viral antigen production, and viral infectivity/virion particle ratios. A nelfinavir-selected protease D30N substitution substantially decreased replicative capacity relative to WT, while a saquinavir-selected L90M substitution moderately decreased fitness, The D30N mutant virus was also outcompeted by the L90M mutant in the absence of drugs. A major natural polymorphism of the HIV-1 protease, L63P, compensated well for the impairment of fitness caused by L90M but only slightly improved the fitness of D30N, Multiply substituted indinavir-selected mutants M46I/L63P/V82T/I84V and L10R/M46I/L63P/V82T/I84V were just as fit as WT. These results indicate that the mutations which are usually initially selected by nelfinavir and saquinavir, D30N and L90M, respectively, impair fitness. However, additional mutations may improve the replicative capacity of these and other drug-resistant mutants. Hypotheses based on the greater fitness impairment of the nelfinavir-selected D30N mutant are suggested to explain observations that prolonged responses to delayed salvage regimens, including alternate PIs, may be relatively common after nelfinavir failure. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Fundacio irsiCaixa, Badalona, Spain. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. RI Martinez-Picado, Javier/G-5507-2012 OI Martinez-Picado, Javier/0000-0002-4916-2129 FU NCI NIH HHS [CA-12464]; NIAID NIH HHS [AI-27659, R01 AI029193, U01 AI027659] NR 62 TC 321 Z9 328 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1999 VL 73 IS 5 BP 3744 EP 3752 PG 9 WC Virology SC Virology GA 185ZG UT WOS:000079701100030 PM 10196268 ER PT J AU Wilson, CC Brown, RC Korber, BT Wilkes, BM Ruhl, DJ Sakamoto, D Kunstman, K Luzuriaga, K Hanson, IC Widmayer, SM Wiznia, A Clapp, S Ammann, AJ Koup, RA Wolinsky, SM Walker, BD AF Wilson, CC Brown, RC Korber, BT Wilkes, BM Ruhl, DJ Sakamoto, D Kunstman, K Luzuriaga, K Hanson, IC Widmayer, SM Wiznia, A Clapp, S Ammann, AJ Koup, RA Wolinsky, SM Walker, BD CA Ariel Project Investigators TI Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the Ariel Project for the Prevention of Transmission of HIV from Mother to Infant SO JOURNAL OF VIROLOGY LA English DT Article ID MATERNAL VIRAL LOAD; VERTICAL TRANSMISSION; ZIDOVUDINE TREATMENT; FINE SPECIFICITY; IN-VIVO; NEUTRALIZING ANTIBODY; CHILD TRANSMISSION; PRIMARY INFECTION; GENETIC-VARIATION; IMMUNE-RESPONSES AB Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-l-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control. C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Childrens Diagnost & Treatment Ctr, Ft Lauderdale, FL 33301 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. RP Wolinsky, SM (reprint author), Northwestern Univ, Sch Med, 303 E chicago Ave, Chicago, IL 60611 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [R37AI28568, R37 AI028568]; NICHD NIH HHS [HD-31756] NR 64 TC 61 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1999 VL 73 IS 5 BP 3975 EP 3985 PG 11 WC Virology SC Virology GA 185ZG UT WOS:000079701100055 PM 10196293 ER PT J AU Putlitz, JZ Lanford, RE Carlson, RI Notvall, L De la Monte, SM Wands, JR AF Putlitz, JZ Lanford, RE Carlson, RI Notvall, L De la Monte, SM Wands, JR TI Properties of monoclonal antibodies directed against hepatitis B virus polymerase protein SO JOURNAL OF VIROLOGY LA English DT Article ID STRAND DNA-SYNTHESIS; TYPE-1 REVERSE-TRANSCRIPTASE; GENOMIC RNA ENCAPSIDATION; STEM-LOOP STRUCTURE; P-GENE-PRODUCT; MINUS-STRAND; VIRAL-DNA; IN-VITRO; INTRACELLULAR EXPRESSION; REPLICATION STRATEGY AB Hepadnavirus polymerases are multifunctional enzymes that play critical roles during the viral life cycle but have been difficult to study due to a lack of a Hell-defined panel of monoclonal antibodies (MAbs). We have used recombinant human hepatitis B virus (HBV) polymerase (Pol) expressed in and purified from baculovirus-infected insect cells to generate a panel of six: MAbs directed against HBV Pol protein. Such MAbs were subsequently characterized with respect to their isotypes and functions in analytical and preparative assays. Using these MAbs as probes together with various deletion mutants of Pol expressed in insect cells, we mapped the B-cell epitopes of Pol recognized by these MAbs to amino acids (aa) 8 to 20 and 20 to 30 in the terminal protein (TP) region of Pol, to aa 225 to 250 in the spacer region, and to sa 800 to 832 in the RNase it domain. Confocal microscopy and immunocytochemical studies using various Pol-specific MAbs revealed that the protein itself appears to be exclusively localized to the cytoplasm, Finally, MAbs specific for the TP domain, but not MAbs specific for the spacer or RNase H regions of Pol, appeared to inhibit Pol function in the in vitro priming assay, suggesting that antibody-mediated interference with TP may now be assessed in the contest of HBV replication. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78227 USA. RP Wands, JR (reprint author), Rhode Isl Hosp, Liver Res Ctr, 55 Claverick St,4th Floor, Providence, RI 02903 USA. NR 73 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1999 VL 73 IS 5 BP 4188 EP 4196 PG 9 WC Virology SC Virology GA 185ZG UT WOS:000079701100077 ER PT J AU Geissler, M Bruss, V Michalak, S Hockenjos, B Ortmann, D Offensperger, WB Wands, JR Blum, HE AF Geissler, M Bruss, V Michalak, S Hockenjos, B Ortmann, D Offensperger, WB Wands, JR Blum, HE TI Intracellular retention of hepatitis B virus surface proteins reduces interleukin-2 augmentation after genetic immunizations SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOKINE-EXPRESSING PLASMIDS; CELLULAR IMMUNE-RESPONSES; DNA-BASED IMMUNIZATION; ENVELOPE PROTEIN; CORE PROTEIN; ANTIGEN; MICE; ANTIBODY; POLYPEPTIDE; VACCINATION AB We have previously shown that hepatitis B virus (HBV) surface antigens (HBsAgs) are highly immunogenic after genetic immunization. Compared to the secreted middle HBV surface proteins (MHBs) or small HBV surface proteins (SHBs), the nonsecreted large HBV surface protein (LHBs), however, induced significantly weaker humoral and cellular immune responses that could not be augmented by genetic coimmunizations with cytokine expression plasmids, In order to understand the mechanisms underlying this phenomenon, we examined the effect of coimmunizations with an interleukin-2 (IL-2) DNA expression plasmid on the immunogenicity at the B- and T-cell level of nonsecreted wild-type LHBs, a secreted mutant LHBs, wild-type SHBs, and a nonsecreted mutant SHBs. Coimmunizations of mice with plasmids encoding wild-type SHBs or the secreted mutant LHBs and IL-2 increased anti-HBs responses, helper T-cell proliferative activity and cytotoxic T-lymphocyte killing. By contrast, coimmunizations of plasmids encoding wild-type LHBs or nonsecreted mutant SHBs and IL-2 had no significant effects on immune responses, Interestingly, mice immunized with cytokine expression plasmids 14 days after the injection of the wild-type LHRs plasmid showed augmented immune responses compared to animals simultaneously injected with both expression constructs. Anti-HBs responses in mice injected with plasmids encoding secreted forms of HBsAgs were detectable about 10 days earlier than those in mice immunized with plasmids encoding nonsecreted forms of HBsAgs. Based on these observations, we conclude that cytokines produced by DNA plasmids at the initial site of antigen presentation cannot augment LHBs specific immune responses because LHBs is not produced at high enough levels or is not accessible for uptake by antigen-presenting cells. C1 Univ Hosp Freiburg, Dept Med 2, D-79106 Freiburg, Germany. Univ Gottingen, Dept Med Microbiol, D-3400 Gottingen, Germany. Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA USA. RP Blum, HE (reprint author), Univ Hosp Freiburg, Dept Med 2, Hugstetter Str 55, D-79106 Freiburg, Germany. FU NCI NIH HHS [CA-35711, R01 CA035711, R37 CA035711]; NIAAA NIH HHS [AA-02169] NR 27 TC 25 Z9 26 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1999 VL 73 IS 5 BP 4284 EP 4292 PG 9 WC Virology SC Virology GA 185ZG UT WOS:000079701100088 PM 10196326 ER PT J AU Palsson, R Niles, JL AF Palsson, R Niles, JL TI Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding SO KIDNEY INTERNATIONAL LA English DT Article DE CVVH; continuous renal replacement therapy; heparinization; blood flow; anticoagulation; clotting ID ACUTE-RENAL-FAILURE; CONTINUOUS ARTERIOVENOUS HEMOFILTRATION; HEMODIAFILTRATION; HEMODIALYSIS; REPLACEMENT; THERAPIES AB Background. Systemic heparinization is associated with a high rate of bleeding when used to maintain patency of the extracorporeal circuit during continuous renal replacement therapy (CRRT) in critically ill patients. Regional anticoagulation can be achieved with citrate, but previously described techniques are cumbersome and associated with metabolic complications. Methods. We designed a simplified system for delivering regional citrate anticoagulation during continuous venovenous hemofiltration (CVVH). We evaluated filter life and hemorrhagic complications in the first 17 consecutive patients who received this therapy at our institution. Blood flow rate was set at 180 ml/min. Ultrafiltration rate was maintained at 2.0 liters/hr and citrate-based replacement fluid (trisodium citrate 13.3 mM, sodium chloride 100 mM, magnesium chloride 0.75 mM, dextrose 0.2%) was infused proximal to the filter to maintain the desired fluid balance. Calcium gluconate was infused through a separate line to maintain a serum-ionized calcium level of 1.0 to 1.1 mM. Results. All patients were critically ill and required mechanical ventilation and vasopressor therapy. Systemic heparin anticoagulation was judged to be contraindicated in all of the patients. A total of 85 filters were used, of which 64 were lost because of clotting, with a mean life span of 29.5 +/- 17.9 hours. The remaining 21 filters were discontinued for other reasons. Control of fluid and electrolyte balance and azotemia was excellent (mean serum creatinine after 48 to 72 hr of treatment was 2.4 +/- 1.2 mg/dl). No bleeding episodes occurred. Two patients, one with septic shock and the other with fulminant hepatic failure, developed evidence for citrate toxicity without a significant alteration in clinical status. Nine patients survived (52.9%). Conclusion. Our simplified technique of regional anticoagulation with citrate is an effective and safe form of anticoagulation for CVVH in critically ill patients with a high risk of bleeding. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Dialysis Unit, Bigelow 1052,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 119 Z9 133 U1 1 U2 5 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1999 VL 55 IS 5 BP 1991 EP 1997 DI 10.1046/j.1523-1755.1999.00444.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 188LZ UT WOS:000079849600037 PM 10231464 ER PT J AU Yang, YG Sykes, M AF Yang, YG Sykes, M TI The role of interleukin-12 in preserving the graft-versus-leukemia effect of allogeneic CD8 T cells independently of GVHD SO LEUKEMIA & LYMPHOMA LA English DT Review DE bone marrow transplantation; graft-versus-host disease; graft-versus-leukemia; interleukin-12; interferon-gamma ID BONE-MARROW TRANSPLANTATION; VS-HOST DISEASE; MAJOR HISTOCOMPATIBILITY BARRIERS; STIMULATORY FACTOR INTERLEUKIN-12; INTERFERON-GAMMA PRODUCTION; TOXIC LYMPHOCYTES-T; IFN-GAMMA; MONOCLONAL-ANTIBODIES; UNRELATED DONORS; MURINE MODEL AB Interleukin (IL)-12 is a potent immunostimulatory cytokine and inducer of Th1 cell activity and of cytotoxic T lymphocyte and natural killer cell function. This cytokine also has anti-tumor activity. Although IL-12 has been shown to be an important pathogenic cytokine in the induction of graft-versus-host disease (GVHD), injection of exogenous IL-12 to murine allogeneic bone marrow transplantation (BMT) recipients paradoxically leads to a significant delay in the onset of GVHD mortality in fully MHC plus multiple minor antigen-mismatched strain combinations, and to complete inhibition of GVHD in a single haplotype-mismatched murine BMT model. IL-12induced inhibition of GVHD is associated with reduced donor T cell activation and expansion, in part through an interferon (IFN)-gamma-mediated mechanism. Fas-mediated apoptosis of donor T cells also plays a significant role in IL-12-induced GVHD protection. Importantly, IL-12 preserves the graft-versus-leukemia (GVL) effect of allogeneic CD8 T cells against EL4, a host-type leukemia/lymphoma, while inhibiting GVHD. Like the protective effect against GVHD, the GVL effect in IL-12-treated mice is dependent on IFN-gamma. Thus, treatment with IL-12 leads to separation of GVHD-promoting and GVL effects of allogeneic BMT via an IFN-gamma-dependent mechanism. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [R01 CA64912] NR 106 TC 19 Z9 19 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAY PY 1999 VL 33 IS 5-6 BP 409 EP + PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 194LV UT WOS:000080195900001 PM 10342569 ER PT J AU Guimaraes, AR Baker, JR Jenkins, BG Lee, PL Weisskoff, RM Rosen, BR Gonzalez, RG AF Guimaraes, AR Baker, JR Jenkins, BG Lee, PL Weisskoff, RM Rosen, BR Gonzalez, RG TI Echoplanar chemical shift imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE echoplanar imaging; chemical shift imaging; N-acetyl aspartate; neurodegeneration ID PROTON MR SPECTROSCOPY; MAGNETIC-RESONANCE SPECTROSCOPY; AIDS DEMENTIA COMPLEX; HUMAN BRAIN; RAT-BRAIN; NMR AB A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degrees refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 mu l and signal-to-noise ratio similar to 7:1 in less than 13 min. Magn Reson Med 41:877-882, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH NMR Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA USA. RP Gonzalez, RG (reprint author), MGH NMR Ctr, Div Neuroradiol, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [5 R01 CA40303]; NCRR NIH HHS [RR13213]; NINDS NIH HHS [NS34626] NR 31 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 1999 VL 41 IS 5 BP 877 EP 882 DI 10.1002/(SICI)1522-2594(199905)41:5<877::AID-MRM4>3.0.CO;2-3 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CF UT WOS:000081422400004 PM 10332868 ER PT J AU Becerra, LR Breiter, HC Stojanovic, M Fishman, S Edwards, A Comite, AR Gonzalez, RG Borsook, D AF Becerra, LR Breiter, HC Stojanovic, M Fishman, S Edwards, A Comite, AR Gonzalez, RG Borsook, D TI Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fMRI; pain; heat; Peltier thermode ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN CINGULATE CORTEX; FUNCTIONAL NEUROANATOMY; PERIAQUEDUCTAL GRAY; NEUROPATHIC PAIN; HYPOTHALAMUS; RESPONSES; SKIN; NUCLEUS; MONKEY AB Brain activity was studied with functional magnetic resonance imaging (fMRI) following thermal stimulation, Two groups (n = 6/ group) of human male volunteers were given up to four noxious (46 degrees C) and four non-noxious (41 degrees C) stimuli. In the 46 degrees C experiment, positive signal changes were found in the frontal gyri, anterior and posterior cingulate gyrus, thalamus, motor cortex, somatosensory cortex (SI and SII), supplementary motor area, insula, and cerebellum. Low-level negative signal changes appeared in the amygdala and hypothalamus. Ail regions activated by 46 degrees C were also activated by 41 degrees C, However, except for SI and thalamus, significantly more activation was observed for the 46 degrees C stimulus, A significant attenuation of the signal change was observed by the third stimulus for the 46 degrees C, but not for 41 degrees C experiment. Similar findings were replicated in the second group. These fMRI findings specify differences between somatosensory and pain sensation and suggest a number of rich avenues for future research. Magn Reson Med 41:1044-1057, 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Nucl Magnet Resounance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Pain Ctr, ACC-324,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13213]; NIDA NIH HHS [DA012581]; NINDS NIH HHS [NS34626] NR 49 TC 194 Z9 200 U1 0 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 1999 VL 41 IS 5 BP 1044 EP 1057 DI 10.1002/(SICI)1522-2594(199905)41:5<1044::AID-MRM25>3.0.CO;2-M PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CF UT WOS:000081422400025 PM 10332889 ER PT J AU Weissman, JS Ayanian, JZ Chasan-Taber, S Sherwood, MJ Roth, C Epstein, AM AF Weissman, JS Ayanian, JZ Chasan-Taber, S Sherwood, MJ Roth, C Epstein, AM TI Hospital readmissions and quality of care SO MEDICAL CARE LA English DT Article DE quality of health care; congestive heart failure; pneumonia; readmissions; Medicare ID PROSPECTIVE PAYMENT SYSTEM; ELDERLY PATIENTS; POOR-QUALITY; APPROPRIATENESS; RATES; CRITERIA; PREVENTABILITY; IMPLEMENTATION; MASSACHUSETTS; ADMISSIONS AB BACKGROUND. Readmission rates are often proposed as markers for quality of care. However, a consistent link between readmissions and quality has not been established. OBJECTIVE. To test the relation of readmission to quality and the utility of readmissions as hospital quality measures. SUBJECTS. One thousand, seven hundred and fifty-eight Medicare patients hospitalized in four states between 1991 to 1992 with pneumonia or congestive heart failure (CHE). DESIGN. Case control. MEASURES. Related adverse readmissions (RARs), defined as readmissions that indicate potentially sub-optimal care during initial hospitalization, were identified from administrative data using readmission diagnoses and intervening time periods designated by physician panels. We used linear regression to estimate the association between implicit and explicit quality measures and readmission status (RARs, non-RAR readmissions, and nonread-missions), adjusting for severity. We tested whether RARs were associated with inferior care and performed simulations to determine whether RARs discriminated between hospitals on the basis of quality. RESULTS. Compared with nonreadmitted pneumonia patients, patients with RARs had lower adjusted quality measured both by explicit (0.25 standardized units, P = 0.004) and implicit methods (0.17, P = 0.047). Adjusted differences for CHF patients were 0.17 (P 0.048) and 0.20 (P = 0.017), respectively. In some analyses, patients with non-RAR readmissions also experienced lower quality. However, rates of inferior quality care did not differ significantly by readmission status, and simulations identified no meaningful relationship between RARs and hospital quality of care. CONCLUSIONS. RARs are statistically associated with lower quality of care. However, neither RARs nor other readmissions appear to be useful tools for identifying patients who experience inferior care or for comparing quality among hospitals. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Boston Biostat Inc, Framingham, MA USA. Value Hlth Sci Inc, Santa Monica, CA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [HS06331] NR 51 TC 69 Z9 71 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 1999 VL 37 IS 5 BP 490 EP 501 DI 10.1097/00005650-199905000-00008 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 195UQ UT WOS:000080270900008 PM 10335751 ER PT J AU Zhang, J Dong, H Kashket, S Duncan, MJ AF Zhang, J Dong, H Kashket, S Duncan, MJ TI IL-8 degradation by Porphyromonas gingivalis proteases SO MICROBIAL PATHOGENESIS LA English DT Article DE Porphyromonas gingivalis; epithelial cells; IL-8; proteases ID CYSTEINE PROTEINASE; EPITHELIAL-CELLS; ARG-GINGIPAIN; CYTOKINES; IDENTIFICATION; COMPONENTS; VIRULENCE; MEDIATE AB Gingival epithelial cells are the primary barrier to infection by periodontal pathogens. The production of chemotactic cytokines, including interleukin-8 (IL-8), is one mechanism the host uses in response to infection. In this study it was found that both gingival and oral epithelial cells produced IL-8, but after infection with the periodontal pathogen Porphyromonas gingivalis, accumulation of the cytokine could not be detected. Northern analysis established that infected epithelial cells still expressed IL-8 mRNA, suggesting that the cytokine was destroyed after secretion. Incubation of IL-8 with P. gingivalis cells resulted in rapid loss of the cytokine; however, in the presence of a protease inhibitor the loss was significantly retarded, indicating that IL-8 was degraded by P. gingivalis proteases. (C) 1999 Academic Press. C1 Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Dent Ctr, Nutr Sect, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Dent Ctr, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE10510] NR 20 TC 33 Z9 35 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD MAY PY 1999 VL 26 IS 5 BP 275 EP 280 DI 10.1006/mpat.1998.0277 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA 192VN UT WOS:000080100400004 PM 10222212 ER PT J AU Lichtenbeld, HC Ferarra, N Jain, RK Munn, LL AF Lichtenbeld, HC Ferarra, N Jain, RK Munn, LL TI Effect of local anti-VEGF antibody treatment on tumor microvessel permeability SO MICROVASCULAR RESEARCH LA English DT Article DE tumors; permeability; vascular endothelial growth factor (VEGF); anti-VEGF antibody; single vessel perfusion ID ENDOTHELIAL GROWTH-FACTOR; HUMAN ADENOCARCINOMA LS174T; VASCULAR-PERMEABILITY; MICROVASCULAR PERMEABILITY; SCID MICE; ANGIOGENESIS; TRANSPORT; DELIVERY; GLIOMAS AB Recent studies have shown that systemic injection of anti-VEGF antibody into tumor-bearing mice results in decreases in tumor vascular permeability, vessel diameters, and tumor regression. Using a similar animal model, we have applied anti-VEGF antibody directly to the tumor tissue growing in transparent window chambers in SCID mice. Similar to the results obtained with systemic injection, vascular permeability was greatly reduced, but the response was reached at much lower concentrations with local application. Implications of these findings on local control of tumors are discussed. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Lichtenbeld, HC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA56591, F32-CA72214-02] NR 28 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAY PY 1999 VL 57 IS 3 BP 357 EP 362 DI 10.1006/mvre.1998.2140 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 198UN UT WOS:000080442800015 PM 10329263 ER PT J AU Nielsen, GP Keel, SB Dickersin, R Selig, MK Bhan, AK Rosenberg, AE AF Nielsen, GP Keel, SB Dickersin, R Selig, MK Bhan, AK Rosenberg, AE TI Chondromyxoid fibroma: A tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation SO MODERN PATHOLOGY LA English DT Article DE chondromyxoid fibroma; myochondroblast; myofibroblast ID CARTILAGINOUS TUMORS; ULTRASTRUCTURE AB Chondromyxoid fibroma (CMF) is a rare primary benign tumor of bone that demonstrates variable histologic features and is often confused with chondrosarcoma Although the chondroid elements in CMF have been reported to be S-100 protein positive and to have chondrocytic features ultrastructurally, the immunohistochemical and ultrastructural profile of CMF, especially with respect to the peripheral nonchondroid elements, has not been extensively studied. Formalin-fixed, paraffin-embedded tissue from 10 CMFs were stained immunohistochemically with antibodies to vimentin, desmin, muscle actin, smooth muscle actin, S-100 protein, and CD34. Six tumors were also examined ultrastructurally. The chondroid areas showed variable staining for S-100 protein but did not stain for muscle actin or smooth muscle actin. The peripheral areas surrounding the chondroid areas stained diffusely for smooth muscle actin and muscle actin but did not stain for S-100 protein. CD34 highlighted the extensive vascularity that was especially prominent in the peripheral areas; no tumor cells stained for CD34. There was no staining for desmin. Ultrastructural examination showed three different cell types. Some cells showed the classic features of chondrocytes, other cells had the features of myofibroblasts, and the third cell type had the features of both chondrocytes and myofibroblasts ("myochondroblasts"). These findings support the conclusion that CMF is a tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Nielsen, GP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 12 TC 19 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 1999 VL 12 IS 5 BP 514 EP 517 PG 4 WC Pathology SC Pathology GA 197CK UT WOS:000080346900012 PM 10349990 ER PT J AU Levine, RJC Caulfield, JB Norton, P Chantler, PD Deziel, MR Slayter, HS Margossian, SS AF Levine, RJC Caulfield, JB Norton, P Chantler, PD Deziel, MR Slayter, HS Margossian, SS TI Myofibrillar protein structure and assembly during idiopathic dilated cardiomyopathy SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE myosin light chains; native thick filaments; dilated cardiomyopathy; heart failure; immunohistochemistry; mekratin ID MUSCLE THICK FILAMENTS; REGULATORY LIGHT-CHAIN; CONGESTIVE CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSIES; CONTRACTILE PROTEINS; MYOSIN; PHOSPHORYLATION; SKELETAL AB A neutral protease, mekratin, active in human hearts at end stage idiopathic dilated cardiomyopathy (IDC), mediates the breakdown of cardiac myosin LC2. Myosin purified from IDC heart tissue forms unusually short synthetic thick filaments. Therefore, determination of filament length and mekratin distribution in IDC heart muscle were initiated. Native thick filaments were prepared directly from control and IDC tissues and analyzed. Also, paraffin-embedded tissue sections were stained with a fluorescently-labeled anti-protease antibody to establish its distribution in myocardial tissues. Control sections had only very weak, background levels of fluorescence whereas IDC sections stained intensely throughout, indicating a wide ranging distribution of the protease within the myocyte cytoplasm. SDS-PAGE revealed LC2 to be present in stoichiometric amounts in control but greatly reduced in IDC heart muscle. Native thick filaments from control myocardium were structurally stable. They had a median length of 1.65 mu m with well-defined bare zones and displayed the 43 nm helical periodicity typical of the relaxed arrangement of myosin heads close to the filaments' shafts. In contrast, native IDC filaments were less stable, and had a median length of 0.9 mu m. These filaments were highly disordered: they had no surface periodicity and myosin heads were positioned away from the filaments' shafts. The shorter, less stable, aperiodic thick filaments from IDC hearts appear to result from depletion of LC2 caused by increased activity of mekratin in the IDC myocardium. C1 Allegheny Univ Hlth Sci, MCP Hahnernann Sch Med, Dept Neurobiol, Philadelphia, PA 19102 USA. Allegheny Univ Hlth Sci, MCP Hahnernann Sch Med, Dept Anat, Philadelphia, PA 19102 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ London Royal Vet Coll, London, England. Albany Med Coll, Dept Med, Albany, NY 12208 USA. Albany Med Coll, Dept Biochem & Mol Biol, Albany, NY 12208 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Margossian, SS (reprint author), Ferrahian Armenian Sch, 5300 White Oak Ave, Encino, CA 91316 USA. FU NHLBI NIH HHS [HL49597]; Wellcome Trust NR 40 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 1999 VL 195 IS 1-2 BP 1 EP 10 DI 10.1023/A:1006940513097 PG 10 WC Cell Biology SC Cell Biology GA 203LV UT WOS:000080709900001 PM 10395063 ER PT J AU Zeng, XY Chen, LH Jost, CA Maya, R Keller, D Wang, XJ Kaelin, WG Oren, M Chen, JD Lu, H AF Zeng, XY Chen, LH Jost, CA Maya, R Keller, D Wang, XJ Kaelin, WG Oren, M Chen, JD Lu, H TI MDM2 suppresses p73 function without promoting p73 degradation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID P53 TUMOR-SUPPRESSOR; ONCOPROTEIN MDM2; TRANSCRIPTIONAL ACTIVATION; SYNERGISTIC ACTIVATION; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; DNA-DAMAGE; PROTEIN; GENE; APOPTOSIS AB The newly identified p53 homolog p73 can mimic the transcriptional activation function of p53. We investigated whether p73, like p53, participates in an autoregulatory feedback loop with MDM2. p73 bound to MDM2 both in vivo and in vitro. Wild-type but not mutant MDM2, expressed in human p53 null osteosarcoma Saos-2 cells, inhibited p73- and p53-dependent transcription driven by the MDM2 promoter-derived p53RE motif as measured in transient-transfection and chloramphenicol acetyltransferase assays and also inhibited p73-induced apoptosis in p53-null human lung adenocarcinoma H1299 cells. MDM2 did not promote the degradation of p73 but instead disrupted the interaction of p73, but not of p53, with p300/CBP by competing with p73 for binding to the p300/CBP N terminus. Both p73 alpha and p73 beta stimulated the expression of the endogenous MDM2 protein. Hence, MDM2 is transcriptionally activated by p73 and, in turn, negatively regulates the function of this activator through a mechanism distinct from that used for p53 inactivation. C1 Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Louisiana State Univ, Med Ctr, Dept Microbiol, New Orleans, LA 70112 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RP Lu, H (reprint author), Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NCI NIH HHS [R01 CA 79721-01, R01 CA079721] NR 66 TC 255 Z9 259 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1999 VL 19 IS 5 BP 3257 EP 3266 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100004 PM 10207051 ER PT J AU Arnould, T Sellin, L Benzing, T Tsiokas, L Cohen, HT Kim, E Walz, G AF Arnould, T Sellin, L Benzing, T Tsiokas, L Cohen, HT Kim, E Walz, G TI Cellular activation triggered by the autosomal dominant polycystic kidney disease gene product PKD2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; CPK MOUSE; JUN; CELLS; RHO; EXPRESSION; ISOFORMS; AP-1 AB Autosomal dominant polycystic kidney disease (ADPKD) is caused by germ line mutations in at least three ADPKD genes. Two recently isolated ADPKD genes, PKD1 and PKD2, encode integral membrane proteins of unknown function. We found that PKD2 upregulated AP-1-dependent transcription in human embryonic kidney 293T cells. The PKD2-mediated AP-1 activity was dependent upon activation of the mitogen-activated protein kinases p38 and JNK1 and protein kinase C (PKC) epsilon, a calcium-independent PKC isozyme. Staurosporine, but not the calcium chelator BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N',N' -tetraacetate], inhibited PKD2-mediated signaling, consistent with the involvement of a calcium-independent PRC isozyme. Coexpression of PKD2 with the interacting C terminus of PKD1 dramatically augmented PKD2-mediated AP-1 activation. The synergistic signaling between PKD1 and PKD2 involved the activation of two distinct PKC isozymes, PKC alpha and PKC epsilon, respectively. Our findings are consistent with others that support a functional connection between PKD1 and PKD2 involving multiple signaling pathways that converge to induce AP-1 activity, a transcription factor that regulates different cellular programs such as proliferation, differentiation, and apoptosis. Activation of these signaling cascades may promote the full maturation of developing tubular epithelial cells, while inactivation of these signaling cascades may impair terminal differentiation and facilitate the development of renal tubular cysts. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Boston, MA 02215 USA. Boston Univ, Med Ctr, Dept Med, Renal Sect, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Walz, G (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, 330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK 52897, F32 DK009625]; NIMH NIH HHS [MH-01147] NR 55 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1999 VL 19 IS 5 BP 3423 EP 3434 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100019 PM 10207066 ER PT J AU Macian, F Rao, A AF Macian, F Rao, A TI Reciprocal modulatory interaction between human immunodeficiency virus type 1 Tat and transcription factor NFAT1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED T-CELLS; RNA-POLYMERASE-II; NF-KAPPA-B; LONG TERMINAL REPEAT; DNA-BINDING DOMAINS; GENE-EXPRESSION; NUCLEAR FACTOR; HIV-1 TAT; IN-VITRO; INTERLEUKIN-2 PROMOTER AB Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by interactions between both viral and host factors. These interactions are also responsible for changes in the expression of many host cell genes, including cytokines and other immune regulators, which may account for the state of immunological dysregulation that characterizes HIV-1 infection. We have investigated the role of a host cell protein, the transcription factor NFAT1, in HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this interaction, which involves the major transactivation domain of NFAT1 and the amino-terminal region of Tat, results in a reciprocal modulatory interplay between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR). Moreover, NFAT1 binds to the kappa B sites on the viral LTR and negatively regulates NF-kappa B-mediated activation of HIV-1 transcription, by competing with NF-kappa B1 for its binding sites on the HIV-1 LTR. Tat-mediated enhancement of NFAT1 transactivation may explain the upregulation of interleukin 2 and other cytokines that occurs during HIV-1 infection. We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rao, A (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471, R01 CA042471, R37 CA042471] NR 68 TC 59 Z9 61 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1999 VL 19 IS 5 BP 3645 EP 3653 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100041 PM 10207088 ER PT J AU Foretz, M Pacot, C Dugail, I Lemarchand, P Guichard, C Le Liepvre, X Berthelier-Lubrano, C Spiegelman, B Kim, JB Ferre, P Foufelle, F AF Foretz, M Pacot, C Dugail, I Lemarchand, P Guichard, C Le Liepvre, X Berthelier-Lubrano, C Spiegelman, B Kim, JB Ferre, P Foufelle, F TI ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PYRUVATE-KINASE GENE; UPSTREAM STIMULATORY FACTOR; BOUND TRANSCRIPTION FACTOR; ELEMENT-BINDING PROTEIN-1; ACID-SYNTHASE GENE; ADIPOSE-TISSUE; CHOLESTEROL-SYNTHESIS; RAT HEPATOCYTES; TRANSGENIC MICE; CULTURED-CELLS AB The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin. C1 Inst Biomed Cordeliers, INSERM, U465, F-75270 Paris 06, France. Fac Med Necker Enfants Malad, INSERM, U25, F-75730 Paris, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ferre, P (reprint author), Inst Biomed Cordeliers, INSERM, U465, 15 Rue Ecole Med, F-75270 Paris 06, France. RI Ferre, Pascal/K-1250-2013; lemarchand, patricia/C-3247-2011 NR 35 TC 363 Z9 375 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1999 VL 19 IS 5 BP 3760 EP 3768 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188AJ UT WOS:000079821100052 PM 10207099 ER PT J AU Xu, WQ Doshi, A Lei, M Eck, MJ Harrison, SC AF Xu, WQ Doshi, A Lei, M Eck, MJ Harrison, SC TI Crystal structures of c-Src reveal features of its autoinhibitory mechanism SO MOLECULAR CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; RECEPTOR TYROSINE KINASE; SIGNAL-TRANSDUCTION; CATALYTIC SUBUNIT; INSULIN-RECEPTOR; ACTIVATION; PHOSPHORYLATION; FAMILY; COMPLEX; DOMAIN AB Sro family kinases are maintained in an assembled, inactive conformation by intramolecular interactions of their SH2 and SH3 domains. Full catalytic activity requires release of these restraints as well as phosphorylation of Tyr-416 in the activation loop. In previous structures of inactive Src kinases, Tyr-416 and flanking residues are disordered. We report here four additional c-Src structures in which this segment adopts an ordered but inhibitory conformation. The ordered activation loop forms an a helix that stabilizes the inactive conformation of the kinase domain, blocks the peptide substrate-binding site, and prevents Tyr-416 phosphorylation. Disassembly of the regulatory domains, induced by SH2 or SH3 ligands, or by dephosphorylation of Tyr-527, could lead to exposure and phosphorylation of Tyr-416. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 565 Z9 578 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD MAY PY 1999 VL 3 IS 5 BP 629 EP 638 DI 10.1016/S1097-2765(00)80356-1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 201AX UT WOS:000080573400009 PM 10360179 ER PT J AU Luck, MD Carter, PH Gardella, TJ AF Luck, MD Carter, PH Gardella, TJ TI The (1-14) fragment of parathyroid hormone (PTH) activates intact and amino-terminally truncated PTH-1 receptors SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; VASOACTIVE INTESTINAL POLYPEPTIDE; PROTEIN-COUPLED RECEPTORS; BINDING DOMAINS; PTH/PTHRP RECEPTOR; EXTRACELLULAR LOOP; CHIMERIC RECEPTORS; GLUCAGON RECEPTOR; COMMON RECEPTOR; 2 RECEPTOR AB Recent mutagenesis and cross-linking studies suggest that residues in the carboxyl-terminal portion of PTH(1-34)interact with the amino-terminal extracellular domain of the receptor and thereby contribute strongly to binding energy; and that residues in the amino-terminal portion of the ligand interact with the receptor region containing the transmembrane helices and extracellular loops and thereby induce second messenger signaling. We investigated the latter component of this hypothesis using the short amino-terminal fragment PTH(1-14) and a truncated rat PTH-1 receptor (r Delta Nt) that lacks most of the amino-terminal extracellular domain. The binding of PTH(1-14) to LLC-PK1, or COS-7 cells transfected with the intact PTH-1 receptor was too weak to detect; however, PTH(1-14) dose-dependently stimulated cAMP formation in these cells over the dose range of 1-100 mu M. PTH(1-14) also stimulated cAMP formation in COS-7 cells transiently transfected with r Delta Nt, and its potency with this receptor was nearly equal to that seen with the intact receptor. In contrast, PTH(1-34) was similar to 100-fold weaker in potency with r Delta Nt than it was with the intact receptor. Alanine scanning of PTH(1-14)revealed that for both the intact and truncated receptors, the 1-9 segment of PTH forms a critical receptor activation domain. Taken together, these results demonstrate that the amino-terminal portion of PTH(1-34) interacts with the juxtamembrane regions of the PTH-1 receptor and that these interactions are sufficient for initiating signal transduction. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 54 TC 66 Z9 68 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1999 VL 13 IS 5 BP 670 EP 680 DI 10.1210/me.13.5.670 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 191RQ UT WOS:000080035700002 PM 10319318 ER PT J AU Perez, GI Tao, XJ Tilly, JL AF Perez, GI Tao, XJ Tilly, JL TI Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE apoptosis; oocyte; DNA cleavage; caspase; cell death ID PROGRAMMED CELL-DEATH; DNA FRAGMENTATION; AGED MICE; MOUSE; PROTEASES; PHOSPHATIDYLSERINE; CASPASE-3; ABSENCE; OVARY; EXPRESSION AB Accumulating evidence indicates that fragmentation of ovulated murine oocytes, resulting spontaneously or following exposure to lethal stimuli such as anticancer drugs during in-vitro culture, occurs with several hallmark features of apoptosis. However, recent work has failed to demonstrate a correlation between DNA cleavage, as assessed by DNA 3'-end-labelling, or of phosphatidylserine exposure on the outer leaflet of the plasma membrane, as measured by annexin V-staining, with fragmentation of ovulated mouse or human oocytes maintained in vitro. Consequently, these authors stated that it is 'premature to conclude that apoptosis occurs in ovulated oocytes or that such a mechanism is involved in the elimination or prevention of fertilization of oocytes with cytoplasmic or chromosomal defects'. Here, we have re-assessed DNA cleavage in normal and fragmented murine oocytes, have provided new evidence of an additional biochemical marker of apoptosis in fragmented oocytes (i.e. caspase activity), and have re-evaluated published reports regarding oocyte fragmentation, in an effort to clarify these discrepant findings. The results and discussions presented herein fully support previous conclusions reached by ourselves and others that fragmentation of ovulated oocytes is in fact an unequivocal example of apoptotic cell death. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Perez, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226]; NIEHS NIH HHS [R01-ES08430] NR 52 TC 123 Z9 125 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAY PY 1999 VL 5 IS 5 BP 414 EP 420 DI 10.1093/molehr/5.5.414 PG 7 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 193FJ UT WOS:000080125000005 PM 10338364 ER PT J AU Fournier, MV Carvalho, MD Pardee, AB AF Fournier, MV Carvalho, MD Pardee, AB TI A strategy to identify genes associated with circulating solid tumor cell survival in peripheral blood SO MOLECULAR MEDICINE LA English DT Article ID POLYMERASE-CHAIN-REACTION; DIFFERENTIAL DISPLAY; CANCER-CELLS; METASTASIS; CLONING; FAMILY; MEMBER; A1 AB Efforts in metastasis research have centered on the phenotypic and genetic differences between primary site and metastatic site tumors. However, genes that may be used as molecular markers of metastasis in circulating tumor cells remain unidentified. Genes regulating the dissemination and survival of solid tumor cells in the blood, as well as their adaptation to new environments, could be candidates for unique metastatic tumor markers. Differential display (DD) was conducted to compare the blood of tumor-free individuals with the blood of patients with lung, breast, and colon cancers. Twenty-one up-expressed genes in the tumor patient blood samples but none in the tumor-free donor blood samples were identified. Nine of these samples were isolated, amplified, and directly sequenced. A gene AB-1 homologous to a Bcl-2 family member, which might: function as an apoptosis inhibitor, was identified. The overexpression of an apoptosis inhibitor in blood from patients with metastatic tumors might be correlated with the capability of solid tumor cells to survive in peripheral blood. This is the first demonstration of the usefulness of comparing control and patient blood samples by DD to find novel potential genetic markers identifying metastasis in the blood. C1 Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Univ Fed Rio de Janeiro, Hosp Clementino Fraga Filho, Lab Control Gene Express, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Hosp Clementino Fraga Filho, Oncol Mol Lab, Rio De Janeiro, Brazil. RP Fournier, MV (reprint author), Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. OI carvalho, maria da gloria/0000-0001-5890-8095 FU NCI NIH HHS [R0-1-CA61253] NR 20 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1999 VL 5 IS 5 BP 313 EP 319 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217JB UT WOS:000081495300004 PM 10390547 ER PT J AU Wu, SV Yang, M Avedian, D Birnbaumer, M Walsh, JH AF Wu, SV Yang, M Avedian, D Birnbaumer, M Walsh, JH TI Single amino acid substitution of serine82 to asparagine in first intracellular loop of human cholecystokinin (CCK)-B receptor confers full cyclic AMP responses to CCK and gastrin SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN BETA-2-ADRENERGIC RECEPTOR; 2ND CYTOPLASMIC LOOP; A RECEPTOR; G-PROTEINS; CHROMOSOMAL LOCALIZATION; FUNCTIONAL EXPRESSION; B/GASTRIN RECEPTORS; MOLECULAR-CLONING; HUMAN BRAIN; B RECEPTOR AB To understand molecular basis of Gs coupling to cholecystokinin (CCK)-A and CCK-B receptor subtypes, we examined cAMP responses in three sets of human CCK receptor mutants expressed in human embryonic kidney (HEK)293 cells. Single or double substitutions of the four nonconserved amino acids in the first intracellular loop of the CCK-BR were made with their CCK-AR counterparts to determine which residues are critical in Gs coupling. Single substitution of Ser82 to Asn, produced maximal cAMP responses comparable with the chimeric CCK-BR containing the entire first intracellular loop of the CCK-AR. Two other single substitutions, Leu81 to Arg and Leu85 to Met, produced significant but smaller cAMP responses. Ser82 was further changed into Asp, Thr, or Ala to determine the specificity of this position in Gs coupling by the CCK-BR. Replacements of Ser to Asp or Thr showed significant cAMP increases but the stimulatory effects were smaller than Ser to Asn, whereas Ser to Ala did not enhance any cAMP response to either CCK or gastrin. Finally, CCK-AR reverse mutants were studied to compare them with their corresponding CCK-BR mutants that showed increased cAMP responses. Substitution of CCK-AR residue Arg68 to Leu resulted in a complete loss of cAMP response, whereas Asn69 to Ser or Met72 to Leu showed markedly diminished cAMP responses. These data identify that specific residues in the first intracellular loop of both CCK receptor subtypes are critical for Gs coupling. Substitution of a single residue Ser82 to Asn in the CCK-BR is sufficient to confer full cAMP responses to agonist stimulation. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis,CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Anesthesiol, Los Angeles, CA 90024 USA. RP Wu, SV (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 217, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-17294, DK-40301] NR 28 TC 19 Z9 19 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1999 VL 55 IS 5 BP 795 EP 803 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 192GM UT WOS:000080070200002 PM 10220557 ER PT J AU Finzi, D Blankson, J Siliciano, JD Margolick, JB Chadwick, K Pierson, T Smith, K Lisziewicz, J Lori, F Flexner, C Quinn, TC Chaisson, RE Rosenberg, E Walker, B Gange, S Gallant, J Siliciano, RF AF Finzi, D Blankson, J Siliciano, JD Margolick, JB Chadwick, K Pierson, T Smith, K Lisziewicz, J Lori, F Flexner, C Quinn, TC Chaisson, RE Rosenberg, E Walker, B Gange, S Gallant, J Siliciano, RF TI Latent infection of CD4(+) T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PERIPHERAL-BLOOD; LYMPH-NODES; IN-VIVO; LYMPHOCYTES; EXPRESSION; RESERVOIR; PLASMA; INDIVIDUALS AB Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. However, HIV-1 can persist in a latent form in resting CD4(+) T cells. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. The mean half-life of the latent reservoir was very long (43.9 months). If the latent reservoir consists of only 1 x 10(5) cells, eradication could take as long as 60 years. Thus, latent infection of resting CD4(+) T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Cornell Univ, Coll Med, Dept Med, New York, NY 10021 USA. Georgetown Univ, Washington, DC 20007 USA. RIGHT, Washington, DC 20007 USA. NIAID, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charleston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Charleston, MA 02129 USA. Harvard Univ, Sch Med, Charleston, MA 02129 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Siliciano, RF (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RI Quinn, Thomas/A-2494-2010; OI Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [AI43222] NR 40 TC 1167 Z9 1190 U1 5 U2 44 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 512 EP 517 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400031 PM 10229227 ER PT J AU Eto, T Takahashi, H AF Eto, T Takahashi, H TI Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon SO NATURE MEDICINE LA English DT Article ID BETA; EXPRESSION; CELLS; LIPOSOMES; LIVER; ALPHA; LINE; DNA AB Most chronic carriers of hepatitis B virus (HBV) do not respond to interferon (IFN) treatment This limitation of IFN therapy may be due in part to scant expression of IFN receptor in the liver(1,2) Because the asialoglycoprotein (ASGP) receptor is specifically expressed in the liver at high denity(3), the ASGP receptor-binding domain was generated within an N-glycosylated human IFN-beta molecule(4,5) by the removal of sialic acid to direct this cytokine to the liver. This modified IFN (asialo-IFN-beta) demonstrated greater inhibition of HBV production in ASGP receptor-positive human liver cells transfected with a replication-competent HBV construct than did conventional IFN-alpha or IFN-beta. Furthermore, the enhanced antiviral effect of asialo-IFN-beta was supported by induction of the 2'-5' oligoadenylate synthetase, an indicator of IFN activity(6), at a level significantly higher than that produced by conventional IFN-beta Moreover, mouse asialo-IFN-beta profoundry reduced viremia in vivo in HBV-transfected athymic nude mice, in contrast to conventional IFN-beta, which had no substantial effect. These experiments demonstrate that directing IFN to ASGP receptor facilitates its signaling in the liver and augments its antiviral effect, and is therefore useful in overcoming the limited antiviral effect of conventional IFNs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Takahashi, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Jackson 7,Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA57584]; NIDDK NIH HHS [NIDDK4331] NR 25 TC 36 Z9 38 U1 2 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1999 VL 5 IS 5 BP 577 EP 581 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 217KA UT WOS:000081497400041 PM 10229237 ER PT J AU Bush, AI Huang, XD Fairlie, DP AF Bush, AI Huang, XD Fairlie, DP TI The possible origin of free radicals from amyloid beta peptides in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID END-PRODUCTS; AGGREGATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol,Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Mental Hlth Res Inst, Neuropathol Lab, Parkville, Vic 3052, Australia. Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. RP Bush, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol,Genet & Aging Unit, Charlestown, MA 02129 USA. RI Fairlie, David/F-8865-2014; Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 13 TC 24 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1999 VL 20 IS 3 BP 335 EP 337 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 258DF UT WOS:000083822300011 ER PT J AU Hansen, LK Larsen, J Nielsen, FA Strother, SC Rostrup, E Savoy, R Lange, N Sidtis, J Svarer, C Paulson, OB AF Hansen, LK Larsen, J Nielsen, FA Strother, SC Rostrup, E Savoy, R Lange, N Sidtis, J Svarer, C Paulson, OB TI Generalizable patterns in neuroimaging: How many principal components? SO NEUROIMAGE LA English DT Article ID FUNCTIONAL CONNECTIVITY; LINEAR-MODELS; PET; NETWORK; FMRI AB Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets. (C) 1999 Academic Press. C1 Tech Univ Denmark, Dept Math Modeling, DK-2800 Lyngby, Denmark. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. Univ Minnesota, Vet Affairs Med Ctr, PET Imaging Serv, Minneapolis, MN 55455 USA. Univ Copenhagen, Hvidovre Hosp, Danish Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. McLean Hosp, Belmont, MA 02178 USA. Rigshosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark. RP Hansen, LK (reprint author), Tech Univ Denmark, Dept Math Modeling, Bldg 321, DK-2800 Lyngby, Denmark. RI Hansen, Lars/E-3174-2013; Nielsen, Finn/L-4697-2013; Rostrup, Egill/D-8622-2017; OI Nielsen, Finn/0000-0001-6128-3356; Strother, Stephen/0000-0002-3198-217X; Paulson, Olaf B./0000-0001-7712-8596 FU NIMH NIH HHS [P20 MH57180] NR 30 TC 104 Z9 105 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 1999 VL 9 IS 5 BP 534 EP 544 DI 10.1006/nimg.1998.0425 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 200KR UT WOS:000080539300009 PM 10329293 ER PT J AU Kimura, Y Hsu, H Toyama, H Senda, M Alpert, NM AF Kimura, Y Hsu, H Toyama, H Senda, M Alpert, NM TI Improved signal-to-noise ratio in parametric images by cluster analysis SO NEUROIMAGE LA English DT Article DE parametric image; compartment model; kinetics ID POSITRON EMISSION TOMOGRAPHY; ALGORITHMS; SYSTEM AB Parametric images are formed by analyzing the concentration history of every voxel in PET data sets. Because PET concentration data at the voxel level are rather noisy, noise propagation into the parametric image is often quite noticeable. To address this problem, a model-based clustering method has been developed to generate parametric images. The basic idea of the clustering method is to average over voxels whose concentration histories have the same shape. We applied the method to a two-parameter (K-1, k(2)) compartment model of local cerebral blood flow. The statistic R = integral tC(t) dtl integral C(t) df = integral te(-k2t) x C-a(t) dtl integral e(-k2t) x C-a(t) dt classifies curves in terms of k(2), where C(t) and C,(t) denote the tissue and blood concentration histories, respectively, and x is the convolution operator. Simulation studies of noise propagation in the clustering statistic showed that 30% voxel noise yielded a 2% standard deviation in R. Parametric images of blood flow and partition coefficient were computed for an O-15 study, with and without clustering. Cluster size affected bias, statistical precision, and computation time. With clusters of 400 voxels, the variance of the flow parameter was around 1/50 smaller with clustering, with negligible bias and a computation time of 30 s on a 64-MHz workstation for 15 x 128 x 128 images with MATLAB 5.1. (C) 1999 Academic Press. C1 Tokyo Med & Dent Univ, Inst Med & Dent Engn, Tokyo, Japan. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Tokyo Metropolitan Inst Gerontol, PET Ctr, Tokyo, Japan. RP Kimura, Y (reprint author), Tokyo Med & Dent Univ, Inst Med & Dent Engn, Tokyo, Japan. RI Kimura, Yuichi/B-3045-2008 NR 10 TC 47 Z9 47 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 1999 VL 9 IS 5 BP 554 EP 561 DI 10.1006/nimg.1999.0430 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 200KR UT WOS:000080539300011 PM 10329295 ER PT J AU Lev, MH Rosen, BR AF Lev, MH Rosen, BR TI Clinical applications of intracranial perfusion MR imaging SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID CEREBRAL BLOOD-VOLUME; POSITRON-EMISSION-TOMOGRAPHY; SUSCEPTIBILITY CONTRAST MRI; HUMAN BRAIN-TUMORS; MAGNETIC-RESONANCE; F-18 FLUORODEOXYGLUCOSE; FLUDEOXYGLUCOSE F-18; STEREOTACTIC BIOPSY; ALZHEIMERS-DISEASE; RADIATION NECROSIS C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 106 TC 104 Z9 106 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 1999 VL 9 IS 2 BP 309 EP 331 PG 23 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 204VG UT WOS:000080784800008 PM 10318717 ER PT J AU Rowley, HA Grant, PE Roberts, TPL AF Rowley, HA Grant, PE Roberts, TPL TI Diffusion MR imaging - Theory and applications SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; EXPERIMENTAL BRAIN-TUMORS; ISCHEMIC LESION VOLUMES; FOCAL CEREBRAL-ISCHEMIA; ACUTE HUMAN STROKE; MAGNETIC-RESONANCE; WEIGHTED MR; WATER DIFFUSION; WHITE-MATTER; TIME-COURSE C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 96 TC 111 Z9 116 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 1999 VL 9 IS 2 BP 343 EP 361 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 204VG UT WOS:000080784800010 PM 10318719 ER PT J AU Neumann, S Woolf, CJ AF Neumann, S Woolf, CJ TI Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury SO NEURON LA English DT Article ID ROOT GANGLION NEURONS; PERIPHERAL-NERVE AUTOGRAFTS; NEURITE GROWTH-INHIBITORS; MESSENGER-RNA EXPRESSION; PRIMARY SENSORY NEURONS; AXONAL REGENERATION; CORTICOSPINAL TRACT; GAP-43 EXPRESSION; SCHWANN-CELLS; RAT AB Regeneration is abortive following adult mammalian CNS injury. We have investigated whether increasing the intrinsic growth state of primary sensory neurons by a conditioning peripheral nerve lesion increases regrowth of their central axons. After dorsal column lesions, ail fibers stop at the injury site. Animals with a peripheral axotomy concomitant with the central lesion show axonal growth into the lesion but not into the spinal cord above the lesion. A preconditioning lesion 1 or 2 weeks prior to the dorsal column injury results in growth into the spinal cord above the lesion. In vitro, the growth capacity of DRG neurite is also increased following preconditioning lesions. The intrinsic growth state of injured neurons is, therefore, a key determinant for central regeneration. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. NR 39 TC 386 Z9 395 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1999 VL 23 IS 1 BP 83 EP 91 DI 10.1016/S0896-6273(00)80755-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 202ZA UT WOS:000080681200012 PM 10402195 ER PT J AU Vetter, DE Liberman, MC Mann, J Barhanin, J Boulter, J Brown, MC Saffiote-Kolman, J Heinemann, SF Elgoyhen, AB AF Vetter, DE Liberman, MC Mann, J Barhanin, J Boulter, J Brown, MC Saffiote-Kolman, J Heinemann, SF Elgoyhen, AB TI Role of alpha 9 nicotinic ACh receptor subunits in the development and function of cochlear efferent innervation SO NEURON LA English DT Article ID GUINEA-PIG COCHLEA; CROSSED OLIVOCOCHLEAR BUNDLE; PRODUCT OTOACOUSTIC EMISSIONS; COMPOUND ACTION-POTENTIALS; EMBRYONIC STEM-CELLS; INNER HAIR-CELLS; CONTRALATERAL SOUND; BRAIN-STEM; ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTOR AB Cochlear outer hair cells (OHCs) express alpha 9 nACh receptors and are contacted by descending, predominately cholinergic, efferent fibers originating in the CNS. Mice carrying a null mutation for the nACh alpha 9 gene were produced to investigate its role(s) in auditory processing and development of hair cell innervation. In alpha 9 knockout mice, most OHCs were innervated by one large terminal instead of multiple smaller terminals as in wild types, suggesting a role for the nACh alpha 9 subunit in development of mature synaptic connections. alpha 9 knockout mice also failed to show suppression of cochlear responses (compound action potentials, distortion product otoacoustic emissions) during efferent fiber activation, demonstrating the key role alpha 9 receptors play in mediating the only known effects of the olivocochlear system. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Beckman Res Inst, Duarte, CA 92010 USA. Inst Pharmacol Mol & Cellulare, CNRS, F-06560 Valbonne, France. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Buenos Aires, CONICET, Inst Invest Ingn Genet & Biol Mol, RA-1428 Buenos Aires, DF, Argentina. RP Vetter, DE (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NIDA NIH HHS [P50 DA005010]; NIDCD NIH HHS [DC02871, DC00188] NR 72 TC 165 Z9 169 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1999 VL 23 IS 1 BP 93 EP 103 DI 10.1016/S0896-6273(00)80756-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 202ZA UT WOS:000080681200013 PM 10402196 ER PT J AU Epstein, R Harris, A Stanley, D Kanwisher, N AF Epstein, R Harris, A Stanley, D Kanwisher, N TI The parahippocampal place area: Recognition, navigation, or encoding? SO NEURON LA English DT Article ID MEDIAL TEMPORAL-LOBE; HUMAN EXTRASTRIATE CORTEX; FUSIFORM FACE AREA; HIPPOCAMPAL-FORMATION; BRAIN ACTIVITY; MEMORY; REPRESENTATION; FAMILIARITY; EXPERIENCE; PERCEPTION AB The parahippocampal place area (PPA) has been demonstrated to respond more strongly in fMRI to scenes depicting places than to other kinds of visual stimuli. Here, we test several hypotheses about the function of the PPA. We find that PPA activity (1) is not affected by the subjects' familiarity with the place depicted, (2) does not increase when subjects experience a sense of motion through the scene, and (3) is greater when viewing novel versus repeated scenes but not novel versus repeated faces. Thus, we find no evidence that the PPA is involved in matching perceptual information to stored representations in memory, in planning routes, or in monitoring locomotion through the local or distal environment but some evidence that it is involved in encoding new perceptual information about the appearance and layout of scenes. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Epstein, R (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. RI Epstein, Russell/G-4517-2013 FU NIMH NIH HHS [MH11459]; PHS HHS [56037] NR 35 TC 452 Z9 457 U1 0 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1999 VL 23 IS 1 BP 115 EP 125 DI 10.1016/S0896-6273(00)80758-8 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 202ZA UT WOS:000080681200015 PM 10402198 ER PT J AU Chee, MWL Caplan, D Soon, CS Sriram, N Tan, EWL Thiel, T Weekes, B AF Chee, MWL Caplan, D Soon, CS Sriram, N Tan, EWL Thiel, T Weekes, B TI Processing of visually presented sentences in mandarin and English studied with fMRI SO NEURON LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; 2ND LANGUAGE; HEMISPHERIC-SPECIALIZATION; CORTICAL REPRESENTATION; PREFRONTAL CORTEX; WORD RECOGNITION; BILINGUAL BRAIN; FUNCTIONAL MRI; TEMPORAL-LOBE; PET AB Comprehension of visually presented sentences in fluent bilinguals was studied with functional magnetic resonance imaging (fMRI) using a set of conceptually similar sentences in two orthographically and phonologically distinct languages, Mandarin and English. Responses were monitored during scanning. Sentence comprehension in each language was compared to fixation in nine subjects and Tamil-like pseudo-word strings in five subjects. Spatially congruent activations in the prefrontal, temporal, and superior parietal regions and in the anterior supplementary motor area were observed for both languages and in both experiments at the individual and group levels of analysis. Proficient bilinguals exposed to both languages early in life utilize common neuroanatomical regions during the conceptual and syntactic processing of written language irrespective of their differences in surface features. C1 Singapore Gen Hosp, Cognit Neurosci Lab, Singapore 169856, Singapore. Natl Univ Singapore, Dept Social Work & Psychol, Singapore 119260, Singapore. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Univ Freiburg, Dept Radiol, D-79106 Freiburg, Germany. Univ Kent, Dept Psychol, Canterbury CT2 7LZ, Kent, England. RP Chee, MWL (reprint author), Singapore Gen Hosp, Cognit Neurosci Lab, Singapore 169856, Singapore. RI Weekes, Brendan/E-9897-2010; OI Chee, Michael/0000-0002-6087-0548 FU NIDCD NIH HHS [DC02146] NR 51 TC 141 Z9 151 U1 3 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1999 VL 23 IS 1 BP 127 EP 137 DI 10.1016/S0896-6273(00)80759-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 202ZA UT WOS:000080681200016 PM 10402199 ER PT J AU Takahashi, T Nowakowski, RS Caviness, VS AF Takahashi, T Nowakowski, RS Caviness, VS TI Cell cycle as operational unit of neocortical neuronogenesis SO NEUROSCIENTIST LA English DT Article DE cell cycle; neocortical neuronogenesis; neocortical histogenesis; mouse neocortex ID MURINE CEREBRAL WALL; AUTORADIOGRAPHIC ANALYSIS; PROLIFERATIVE EPITHELIUM; NEURONAL MIGRATION; VISUAL-CORTEX; MOUSE; SPECIFICATION; AREAS; TIME; MICE AB Neuronogenesis in the ventricular epithelium is the initial process in a succession of histogenetic events that give rise to the laminate neocortex. Herein, we review experimental findings in mouse that support the thesis that cell cycle is the operational unit of the neuronogenetic sequence, We show that the principal regulated parameters of proliferation progress uniformly as functions of cycle number and are independent of location in the proliferative epithelium. These parameters are the duration of the G(1) phase of the cell cycle and Q, the fraction of cells that leaves the cycle after mitosis, Furthermore, the specification of neuronal class and possibly also specification of a regional protomap occur coordinately with cell cycle across the expanse of the proliferative epithelium, This coordinate progression of histogenetic events with cell cycles invites the hypothesis that the mechanisms of cell cycle regulation are interdependent in proliferative cells. C1 Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 NR 45 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD MAY PY 1999 VL 5 IS 3 BP 155 EP 163 DI 10.1177/107385849900500312 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 193RP UT WOS:000080150500012 ER PT J AU Amin-Hanjani, S Schwartz, RB Sathi, S Stieg, PE AF Amin-Hanjani, S Schwartz, RB Sathi, S Stieg, PE TI Hypertensive encephalopathy as a complication of hyperdynamic therapy for vasospasm: Report of two cases SO NEUROSURGERY LA English DT Article DE hyperdynamic therapy; hypertensive encephalopathy; magnetic resonance imaging; subarachnoid hemorrhage; vasospasm ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; TISSUE PLASMINOGEN-ACTIVATOR; CEREBRAL VASOSPASM; ARTERIAL-HYPERTENSION; HYPERVOLEMIC THERAPY; MANAGEMENT; TRIAL; CT; PATHOGENESIS; NIMODIPINE AB OBJECTIVE AND IMPORTANCE: After developing subarachnoid hemorrhage, patients may deteriorate from a variety of well-known causes, including rebleeding, hydrocephalus, and vasospasm. Many patients now undergo empirical hyperdynamic vasospasm therapy with hypervolemia, induced hypertension, and nimodipine. CLINICAL PRESENTATION: We report two cases of iatrogenic hypertensive encephalopathy occurring during hyperdynamic therapy for cerebral vasospasm after subarachnoid hemorrhage. Hypertensive encephalopathy is a syndrome of rapidly evolving generalized or focal cerebral symptoms occurring in the setting of severe hypertension, which is reversible with antihypertensive therapy. INTERVENTION: The syndrome can be diagnosed in the appropriate clinical setting with computed tomographic or magnetic resonance imaging that demonstrates characteristic findings. In both cases, decreasing the blood pressure resulted in neurological improvement. CONCLUSION: In the setting of induced hypertensive/hypervolemic therapy for vasospasm, hypertensive encephalopathy should be considered as a potentially reversible cause of delayed neurological decline. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Neurosurg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Stieg, PE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Neurosurg, Boston, MA 02115 USA. NR 32 TC 24 Z9 24 U1 0 U2 0 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 1999 VL 44 IS 5 BP 1113 EP 1116 DI 10.1097/00006123-199905000-00097 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 189KN UT WOS:000079903800092 PM 10232545 ER PT J AU Weeks, J AF Weeks, J TI Outcomes assessment in the NCCN: 1998 update SO ONCOLOGY-NEW YORK LA English DT Article AB The assessment of outcomes is a major priority of the National Comprehensive Cancer Network (NCCN). To date, the NCCN's outcomes program has (1) made a systematic inventory of member institutions' existing data soul ces; (2) begun a collaborative project with the National Cancer Data Bank to compare specific surgical patterns of care in NCCN institutions with national norms; and (3) begun the creation of a prospective outcomes database within the NCCN. As the first step in the database initiative, five NCCN institutions participated in a pilot project in one disease, bi east cancer, aimed at developing and testing techniques of data collection, aggregation, and analysis. Six more sites were added to Me pilot program in 1998. As of September 1998, data on over 1,000 unique cases had been submitted to Me database, with the number of additional cases expected to triple or quadruple within the ensuing 12 months. Future plans call for (1) further expansion of the breast cancer database, both in terms of the number of institutions participating and the scope of data being collected; (2) the addition of a second disease, non-Hodgkin's lymphoma, to the database; and (3) the establishment of partnerships with other organizations for whom the database might provide useful information, such-as insurers, pharmaceutical and biotechnology firms, and regulatory and accrediting bodies. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Weeks, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 20 Z9 20 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 1999 VL 13 IS 5A SU S BP 69 EP 71 PG 3 WC Oncology SC Oncology GA 371KM UT WOS:000165178200003 PM 10370922 ER PT J AU Winer, EP Matulonis, U AF Winer, EP Matulonis, U TI The former/Munster/Seidman article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Harvard Univ, Sch Med, Breast Oncol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Winer, EP (reprint author), Harvard Univ, Sch Med, Breast Oncol Ctr, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 1999 VL 13 IS 5 BP 660 EP + PG 2 WC Oncology SC Oncology GA 392WB UT WOS:000166434600015 ER PT J AU Siafakas, CG Anatolitou, F Fusunyan, RD Walker, WA Sanderson, IR AF Siafakas, CG Anatolitou, F Fusunyan, RD Walker, WA Sanderson, IR TI Vascular endothelial growth factor (VEGF) is present in human breast milk and its receptor is present on intestinal epithelial cells SO PEDIATRIC RESEARCH LA English DT Article ID PERMEABILITY FACTOR; TUMOR-CELLS; DIFFERENTIATION; EXPRESSION; BARRIER; CACO-2 AB VEGF (vascular endothelial growth factor) is a multifunctional cytokine active on blood vessel cells. The present study measured VEGF in the aqueous phase of human milk and examined how the concentration varied with gestational age and the duration of lactation after birth, We hypothesized that VEGF-specific receptors were present on the apical surface of intestinal epithelial cells. The concentration of monomeric VEGF (containing 165 residues) measured by ELISA in the breast milk was 2 orders of magnitude greater than that measured in the serum of normal adults. The VEGF165 concentration in the first week of lactation was greater in the breast milk of mothers of full-term than in preterm babies (p < 0.05). The concentration in the breast milk of mothers of full-term infants decreased (p < 0.01) after the first week of lactation. Scatchard analysis of radioligand-receptor binding showed the presence of specific receptors for I-125-VEGF165 on the surface of Caco-2, an intestinal epithelial cell line, with a k(d) of 2.85 to 4 nM. Reverse transcriptase PCR of Caco-2 cell RNA showed mRNA for the VEGF receptor flt-1. in conclusion, VEGF is present in high concentrations in breast milk and binds to specific receptors on cells derived from intestinal epithelium. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Harvard Clin Nutr Res Ctr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Aghia Sophia Childrens Hosp, Neonatal Unit 2D, Athens 11527, Greece. Univ London Queen Mary & Westfield Coll, Dept Paediat Gastroenterol, St Bartholomews & Royal London Sch Med & Dent, London EC1A 7BE, England. RP Sanderson, IR (reprint author), St Bartholomews Hosp, Dept Paediat Gastroenterol, Suite 42,Dominion House,59 Bartholomew Close, London EC1A 7BE, England. FU NIAID NIH HHS [AI 43472]; NICHD NIH HHS [HD 12437]; NIDDK NIH HHS [DK 47753] NR 23 TC 50 Z9 51 U1 1 U2 2 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 1999 VL 45 IS 5 BP 652 EP 657 DI 10.1203/00006450-199905010-00007 PN 1 PG 6 WC Pediatrics SC Pediatrics GA 192PC UT WOS:000080086700007 PM 10231859 ER PT J AU Chang, CC Sheen, J Bligny, M Niwa, Y Lerbs-Mache, S Stern, DB AF Chang, CC Sheen, J Bligny, M Niwa, Y Lerbs-Mache, S Stern, DB TI Functional analysis of two maize cDNAs encoding T7-like RNA polymerases SO PLANT CELL LA English DT Article ID MITOCHONDRIAL GENE-EXPRESSION; GREEN-FLUORESCENT PROTEIN; YEAST MITOCHONDRIAL; ARABIDOPSIS-THALIANA; TRANSCRIPTION SYSTEM; GLUCOSE REPRESSION; NUCLEAR GENES; HIGHER-PLANTS; SIGMA-FACTOR; IN-VITRO AB We have characterized two maize cDNAs, rpoTm and rpoTp, that encode putative T7-like RNA polymerases. In vivo cellular localization experiments using transient expression of the green fluorescent protein suggest that their encoded proteins are targeted exclusively to mitochondria and plastids, respectively. An antibody raised against the C terminus of the rpoTp gene product identified mitochondrial polypeptides of similar to 100 kD. Their presence was correlated with RNA polymerase activity, and the antibody inhibited mitochondrial in vitro transcription activity. Together, these results strongly suggest that the product of rpoTm is involved in maize mitochondrial transcription. By contrast, immunoblot analysis and an antibody-linked polymerase assay indicated that rpoTp specifies a plastid RNA polymerase component. A quantitative reverse transcription-polymerase chain reaction assay was used to study the transcription of rpoTp and rpoTm in different tissues and under different environmental conditions. Although both genes were constitutively expressed, rpoTm transcripts were generally more prevalent in nonphotosynthetic tissues, whereas an increase in rpoTp transcripts paralleled chloroplast development. We suggest that these two genes encode constitutive components of the organelle transcription machinery but that their expression is nonetheless subject to modulation during plant development. C1 Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Univ Grenoble 1, Lab Genet Mol Plantes, F-38041 Grenoble 9, France. Univ Shizuoka, Sch Food & Nutrit Sci, Shizuoka 422, Japan. RP Stern, DB (reprint author), Cornell Univ, Boyce Thompson Inst Plant Res, Tower Rd, Ithaca, NY 14853 USA. FU NIGMS NIH HHS [R01GM52560] NR 66 TC 87 Z9 94 U1 2 U2 4 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD MAY PY 1999 VL 11 IS 5 BP 911 EP 926 PG 16 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 202YQ UT WOS:000080680200014 PM 10330475 ER PT J AU Vernon, JD Crane, LA Prochazka, AV Fairclough, D MacKenzie, TD AF Vernon, JD Crane, LA Prochazka, AV Fairclough, D MacKenzie, TD TI Smokers hospitalized in an urban, public hospital: Addiction, stages of change, and self-efficacy SO PREVENTIVE MEDICINE LA English DT Article DE inpatient; motivation; nicotine; smoking cessation; tobacco use disorder ID PREDICTING SMOKING CESSATION; FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; CHANGE MODELS; INTEGRATIVE MODEL; UNITED-STATES; RELAPSE; CONTEMPLATION; INTERVENTION AB Background. This study characterizes adult smokers on the medicine service of an urban, public hospital, including stage of change, self-efficacy to quit, and nicotine dependence, and explores relationships between perceived and actual smoking-related illness and these three predictive variables. Methods. Adult patients (n = 154) admitted to the Medicine service of Denver Health Medical Center in October and November 1996 were surveyed using a written questionnaire. Results. The proportion of smokers in this population was 45.7% (95% CI = 42.0%, 49.4%). Adjusted for age and sex, the proportion of smokers in this population was significantly greater than in Colorado (28.8% vs 21.8%, P < 0.001), About half (54.2%) were willing to try free nicotine patches during hospitalization. Among smokers with diseases recognized as smoking-related, 30.4% believed their reason for admission was related to smoking, compared to 20.4% among those with no smoking-related diseases (P = 0.18). Patients who believed their hospitalization was due to smoking had greater intentions (P = 0.001) and self-efficacy (P < 0.001) to quit. Conclusions. Targeting smokers who perceive that their illness is smoking-related may optimize inpatient smoking interventions. (C) 1999 American Health Foundation and Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. AMC, Ctr Canc Res, Denver, CO 80214 USA. Denver Hlth & Hosp, Denver, CO 80204 USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. RP MacKenzie, TD (reprint author), Westside Family Hlth Ctr, 1100 Fed Blvd, Denver, CO 80204 USA. NR 40 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 1999 VL 28 IS 5 BP 488 EP 495 DI 10.1006/pmed.1998.0450 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 195JM UT WOS:000080247100008 PM 10329339 ER PT J AU Krueger, GG Morgan, JR Petersen, MJ AF Krueger, GG Morgan, JR Petersen, MJ TI Biologic aspects of expression of stably integrated transgenes in cells of the skin in vitro and in vivo SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Review DE athymic mice; gene therapy; human fibroblasts; immortalized fibroblasts; nylon matrix; retroviral vectors ID GENETICALLY-MODIFIED SKIN; HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN DERMAL FIBROBLASTS; SOMATIC GENE-THERAPY; SURVIVAL IN-VIVO; HUMAN KERATINOCYTES; IMMUNODEFICIENT MICE; EPITHELIAL-CELLS; MATRIX PROTEINS; GROWTH-HORMONE AB The observation that transgenes can be stably integrated into the genome of fibroblasts using recombinant retroviruses enhanced interest in using these cells as a vector for gene therapy. This enthusiasm has lessened during the past 8 years, not because skin has lost the features that make it attractive for gene therapy, but rather because stable transgene expression in vivo has not been achieved. All investigators who have used genetically modified fibroblasts to study in vivo aspects of gene therapy have shown a decrease in transgene expression with time. This contrasts with transgene expression in similarly transduced fibroblasts in vitro, where expression is not lost or is lost very slowly. We have initiated an approach to bring further understanding to the biology of transgene expression by fibroblasts carrying stably integrated transgenes in an in vivo setting. Experiments described permit the following conclusions. Expression by and survival of genetically modified fibroblasts a) requires a persistent matrix scaffold in in vivo settings; b) is prolonged if the matrix is allowed to mature in vitro; c) is enhanced if the matrix is partially sequestered behind a coating of normal fibroblasts; and d) can be substantively prolonged in vivo by immortalizing the cells. These observations support the notion that prolonged expression of transgenes by fibroblasts can be achieved in vivo and that gene therapy utilizing fibroblasts and other cells of the skin has clinical utility. C1 Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT 84132 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Burns Hosp,Surg Serv, Boston, MA USA. RP Krueger, GG (reprint author), Univ Utah, Hlth Sci Ctr, Dept Dermatol, 50 N Med Dr, Salt Lake City, UT 84132 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [P01 HD28528] NR 48 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY-JUN PY 1999 VL 111 IS 3 BP 198 EP 205 DI 10.1046/j.1525-1381.1999.99225.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 196YT UT WOS:000080338400004 PM 10354359 ER PT J AU Engler, MM Engler, MB Goodfriend, TL Ball, DL Yu, ZG Su, P Kroetz, DL AF Engler, MM Engler, MB Goodfriend, TL Ball, DL Yu, ZG Su, P Kroetz, DL TI Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE RATS; DIETARY FISH-OIL; GAMMA-LINOLENIC ACID; BLOOD-PRESSURE; FATTY-ACIDS; MOLECULAR-CLONING; SERUM-LIPIDS; CYTOCHROME-P450; METABOLISM; EXPRESSION AB The effects of dietary docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone end corticosterone levels, adrenal aldosterone production in vitro,and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 +/- 3 vs. 33 +/- 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than In controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05), Renal cortical mRNA levels of CYP4A genes and formation of 19- and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR. C1 Univ Calif San Francisco, Dept Physiol Nursing, Lab Cardiovasc Physiol, San Francisco, CA 94143 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53705 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. RP Engler, MM (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, Lab Cardiovasc Physiol, Room N611Y,Box 0610, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL 550038]; PHS HHS [53994, 11046] NR 40 TC 34 Z9 35 U1 0 U2 6 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAY PY 1999 VL 221 IS 1 BP 32 EP 38 DI 10.1046/j.1525-1373.1999.d01-51.x PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 189KL UT WOS:000079903600004 PM 10320629 ER PT J AU Lustgarten, DL Keane, D Ruskin, J AF Lustgarten, DL Keane, D Ruskin, J TI Cryothermal ablation: Mechanism of tissue injury and current experience in the treatment of tachyarrhythmias SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID PARKINSON-WHITE SYNDROME; ATRIOVENTRICULAR NODAL REENTRY; INFERIOR WALL INFARCTION; CLOSED-HEART TECHNIQUE; LONG-TERM FOLLOW; VENTRICULAR-TACHYCARDIA; CRYOSURGICAL ABLATION; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; SURGICAL-TREATMENT C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Lustgarten, DL (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 32 Fruit St, Boston, MA 02114 USA. NR 88 TC 121 Z9 125 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 1999 VL 41 IS 6 BP 481 EP 498 DI 10.1016/S0033-0620(99)70024-1 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223PG UT WOS:000081849000006 PM 10445872 ER PT J AU Leaf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA AF Leaf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA TI Functional and electrophysiologic effects of polyunsaturated fatty acids on excitable tissues: heart and brain SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID RAT CARDIAC MYOCYTES; LONG-CHAIN; VENTRICULAR MYOCYTES; ARRHYTHMIAS; PREVENTION; CURRENTS; STIMULATION; CELLS AB It has been shown in animals and probably in humans, that n-3 polyunsaturated fatty acids (PUFAs) are antiarrhythmic. The free PUFAs stabilize the electrical activity of isolated cardiac myocytes by inhibiting sarcolemmal ion channels, so that a stronger electrical stimulus is required to elicit an action potential and the relative refractory period is markedly prolonged, This appears at present to be the probable major antiarrhythmic mechanism of the PUFAs. They similarly inhibit the Na+ and Ca2+ currents in rat hippocampal neurons which results in an increase in the electrical threshold for generalized seizures using the cortical stimulation model in rats. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Ohio State Univ, Dept Physiol, Columbus, OH 43210 USA. Leiden Univ, Med Ctr, Dept Physiol, Leiden, Netherlands. RP Leaf, A (reprint author), Massachusetts Gen Hosp E, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Billman, George/E-2758-2011 FU NIDDK NIH HHS [DK38165] NR 26 TC 16 Z9 18 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY-JUN PY 1999 VL 60 IS 5-6 BP 307 EP 312 DI 10.1016/S0952-3278(99)80004-0 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 226FF UT WOS:000082009100004 PM 10471113 ER PT J AU Laposata, M AF Laposata, M TI Fatty acid ethyl esters: current facts and speculations SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID NONOXIDATIVE ETHANOL-METABOLISM; ALCOHOL-CONSUMPTION; SYNTHASE; LIPASE AB Increasing evidence indicates that fatty acid ethyl esters (FAEE) play a role in ethanol-induced organ damage and may serve as long-term markers of ethanol intake. This report summarizes the current knowledge on the toxicity of FAEE, the enzymes associated with FAEE synthesis, FAEE as fatty acid supplements, the in vivo degradation of orally ingested FAEE and FAEE as markers of ethanol intake. A list of major unanswered questions in each of these categories is also included. C1 Harvard Univ, Clin Labs, Massachusetts Gen Hosp, Sch Med,Dept Pathol,Div Lab Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Clin Labs, Massachusetts Gen Hosp, Sch Med,Dept Pathol,Div Lab Med, 32 Fruit St, Boston, MA 02114 USA. NR 19 TC 11 Z9 11 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY-JUN PY 1999 VL 60 IS 5-6 BP 313 EP 315 DI 10.1016/S0952-3278(99)80005-2 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 226FF UT WOS:000082009100005 PM 10471114 ER PT J AU Zurier, RB Rossetti, RG Seiler, CM Laposata, M AF Zurier, RB Rossetti, RG Seiler, CM Laposata, M TI Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID GAMMA-LINOLENIC ACID; RHEUMATOID-ARTHRITIS; INDEPENDENT MECHANISM; BOTANICAL LIPIDS; SUPPRESSION; INHIBITION AB Oils enriched in certain polyunsaturated fatty acids suppress joint pain and swelling in rheumatoid arthritis patients with active synovitis. Because T lymphocyte activation is important for propagation of joint tissue injury in patients with rheumatoid arthritis, we examined the effects of fatty acids added in vitro on proliferation of human T lymphocytes stimulated with monoclonal antibodies to CD3 and CD4. Unsaturated fatty acids reduced T cell proliferation in a dose dependent manner (dihomogammalinolenic acid > gammalinolenic acid > eicosapentaenoic acid > arachidonic acid). Removal of fatty acids from cultures before cell stimulation did not change the effects, but addition of fatty acids after cell stimulation failed to reduce T cell responses. The saturated palmitic acid did not influence T cell growth. These studies indicate that small changes in cellular fatty acids can have profound effects on early events in T cell signaling and on T cell function. C1 Univ Massachusetts, Med Ctr, Div Rheumatol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Div Lab Med, Boston, MA 02214 USA. RP Zurier, RB (reprint author), Univ Massachusetts, Med Ctr, Div Rheumatol, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIAMS NIH HHS [AR38501] NR 31 TC 18 Z9 18 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY-JUN PY 1999 VL 60 IS 5-6 BP 371 EP 375 DI 10.1016/S0952-3278(99)80015-5 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 226FF UT WOS:000082009100015 PM 10471124 ER PT J AU Goodfriend, TL Egan, BM Kelley, DE AF Goodfriend, TL Egan, BM Kelley, DE TI Plasma aldosterone, plasma lipoproteins, obesity and insulin resistance in humans SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID FREE FATTY-ACIDS; HYPERTENSION; RESTRICTION; CHOLESTEROL; SECRETION AB Aldosterone production in vitro can be affected by many hormones, autacoids, ions, and lipids, but regulation in humans is incompletely understood. We measured plasma aldosterone in adult subjects with a wide range of obesity and insulin resistance, Aldosterone levels correlated with measures of Visceral obesity in one predominantly male cohort and in the women of a second cohort. in the same subjects, aldosterone correlated with insulin resistance. Aldosterone also correlated with plasma cortisol in men and women, and with DHEA-S in women. The data suggested that visceral fat stimulates adrenal steroidogenesis. We found that certain fatty acids stimulated aldosterone production in vitro by rat adrenal cells incubated with rat hepatocytes, but not adrenal cells alone. The results suggested that fatty acids from visceral adipocytes induce hepatic formation of an adrenal secretagogue. This may explain the correlation of plasma steroids with Visceral obesity. Aldosterone may contribute to vascular diseases that complicate obesity. C1 William S Middleton Mem Vet Hosp, Med Res Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Med Univ S Carolina, Dept Pharmacol, Div Clin Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Hosp, Med Res Serv, 2500 Overlook Terrace,Room C-3127, Madison, WI 53705 USA. NR 20 TC 49 Z9 49 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY-JUN PY 1999 VL 60 IS 5-6 BP 401 EP 405 DI 10.1016/S0952-3278(99)80020-9 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 226FF UT WOS:000082009100020 PM 10471129 ER PT J AU Giovannucci, E Stampfer, MJ Chan, A Krithivas, K Gann, PH Hennekens, CH Kantoff, PW AF Giovannucci, E Stampfer, MJ Chan, A Krithivas, K Gann, PH Hennekens, CH Kantoff, PW TI CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in US physicians SO PROSTATE LA English DT Article DE androgen receptor; benign prostate hyperplasia; prospective studies; CAG repeats ID CANCER RISK; TRANSACTIVATION; FINASTERIDE AB BACKGROUND. CAG repeat length in exon I of the androgen receptor (AR) gene correlates inversely with transcriptional transactivation activity of the AR. Men with shorter AR CAG repeat lengths are at higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that a shorter AR gene CAG repeat length increases the risk or developing of BPH. METHODS. Among 14,916 men of the Physicians' Health Study who had provided a blood sample in 1982, we measured AR gene CAG repeat lengths for 310 men who had surgery for; BPH up to 7.5 years of follow-up and 1,041 controls. RESULTS. Risk of surgery for BPH increased linearly with decreasing AR CAG repeat length (P (trend) = 0.03). Relative to men with a CAG repeat length greater than or equal to 25, men with a repeat length less than or equal to 19 had an odds ratio of BPH surgery of 1.76 (95% confidence interval, 1.16-2.65). CONCLUSIONS. Variability in the AR gene CAG repeat influences the development of symptomatic BPH, (C) 1999 Wiley-Liss, Inc. 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 Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA-34944]; NHLBI NIH HHS [HL-34595, HL-26490] NR 17 TC 52 Z9 54 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 1999 VL 39 IS 2 BP 130 EP 134 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 188TK UT WOS:000079864400008 PM 10221569 ER PT J AU Audrain, J Rimer, B Cella, D Stefanek, M Garber, J Pennanen, M Helzlsouer, K Vogel, V Lin, TH Lerman, C AF Audrain, J Rimer, B Cella, D Stefanek, M Garber, J Pennanen, M Helzlsouer, K Vogel, V Lin, TH Lerman, C TI The impact of a brief coping skills intervention on adherence to breast self-examination among first-degree relatives of newly diagnosed breast cancer patients SO PSYCHO-ONCOLOGY LA English DT Article ID PSYCHOLOGICAL DISTRESS; RANDOMIZED TRIAL; FAMILY HISTORY; INCREASED RISK; WOMEN AB The present investigation sought to determine (1) the impact of a single session stress management/coping intervention (problem-solving training; PST) versus a general health counseling (GHC) control condition on breast self-examination (BSE) adherence among relatives of newly diagnosed breast cancer patients, and (2) whether women with heightened perceived risk of breast cancer and/or cancer specific distress at baseline were more likely to improve their BSE adherence following PST. The participants were 510 women age 20-75 who had at least one first-degree relative with breast cancer. All of the participants completed a baseline telephone interview, an intervention (PST versus GHC), and a 3-month follow-up telephone interview. The results revealed a 36%, overall improvement in BSE adherence, with no significant between-group difference in improvement (chi(2) = 0.03, p = 0.87). The logistic regression analysis of improvement in BSE adherence revealed a statistically significant cancer-specific distress by treatment interaction (p = 0.04). Among women who received PST, those with high levels of cancer-specific distress were two times more likely to improve in BSE adherence than women low in cancer-specific distress. There was no effect of cancer-specific distress in the control condition. These results suggest that women with a family history of breast cancer who have high levels of distress may be most likely to benefit from behavioral coping skills intervention to promote adherence to breast cancer screening. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Northwestern Univ, Evanston, IL USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. RP Audrain, J (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, 2233 Wisconsin Ave NW,Suite 535, Washington, DC 20007 USA. FU NCI NIH HHS [CA63605] NR 24 TC 33 Z9 34 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD MAY-JUN PY 1999 VL 8 IS 3 BP 220 EP 229 DI 10.1002/(SICI)1099-1611(199905/06)8:3<220::AID-PON370>3.0.CO;2-C PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 208ZT UT WOS:000081023100003 PM 10390734 ER PT J AU Petrie, EC Wilkinson, CW Murray, S Jensen, C Peskind, ER Raskind, MA AF Petrie, EC Wilkinson, CW Murray, S Jensen, C Peskind, ER Raskind, MA TI Effects of Alzheimer's disease and gender on the hypothalamic-pituitary-adrenal axis response to lumbar puncture stress SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Alzheimer's; cortisol; ACTH; stress; aging; gender ID CORTICOTROPIN-RELEASING HORMONE; ADRENOCORTICAL AXIS; FEEDBACK-REGULATION; PLASMA-CORTISOL; DEMENTIA; HUMANS; ACTH; DEXAMETHASONE; SECRETION; SENSITIVITY AB Differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to lumbar puncture (LP) stress were studied in normal elderly subjects and Alzheimers disease (AD) patients of both genders. Elderly normal subjects had larger peak cortisol and ACTH responses than AD patients. These results contrast with some previous reports of increased HPA-axis responsivity associated with AD and suggest that AD-related changes in HPA responsiveness depend on the type of stressor involved and are mediated 'upstream' to the final common pathway to ACTH secretion. HPA-axis responsiveness also differed by gender, with higher peaks and prolonged elevations in elderly female subjects than in elderly males. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv 116, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Vet Affairs NW Network Mental Illness Res Educ &, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Petrie, EC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv 116, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, AG08419] NR 46 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAY PY 1999 VL 24 IS 4 BP 385 EP 395 DI 10.1016/S0306-4530(98)00088-2 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 187AC UT WOS:000079762900002 PM 10341366 ER PT J AU Wilson, SN van der Kolk, B Burbridge, J Fisler, R Kradin, R AF Wilson, SN van der Kolk, B Burbridge, J Fisler, R Kradin, R TI Phenotype of blood lymphocytes in PTSD suggests chronic immune activation SO PSYCHOSOMATICS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA AB Patients with posttraumatic stress disorder (PTSD) have a past history of extremely stressful experience and often present with somatic complaints. Peripheral blood lymphocytes (PBL) of patients with PTSD associated with a history, of childhood sexual abuse were examined for changes in immune phenotype. The ratio of CD45RO-positive to CD45RA-positive lymphocytes (CD45RO/CD45RA), an index of lymphocyte activation, was higher (P = 0.04) in the PTSD subjects than in the normal subjects. No differences were observed for the number of PBL or the representation of major T, B, or NK lymphocyte subsets. These findings suggest the presence of increased lymphocyte activation in the PBL of patients with PTSD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Trauma Ctr Human Resource Inst, Boston, MA USA. RP Wilson, SN (reprint author), 5 Longfellow Pl,Ste 213, Boston, MA 02114 USA. NR 17 TC 50 Z9 52 U1 2 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1999 VL 40 IS 3 BP 222 EP 225 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 196TD UT WOS:000080322900005 PM 10341534 ER PT J AU Falk, W AF Falk, W TI Neurobiology of primary dementia SO PSYCHOSOMATICS LA English DT Book Review C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Falk, W (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1999 VL 40 IS 3 BP 265 EP 266 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 196TD UT WOS:000080322900013 ER PT J AU Masek, BJ Sims, KB Bove, CM Korson, MS Short, P Norman, DK AF Masek, BJ Sims, KB Bove, CM Korson, MS Short, P Norman, DK TI Quality of life assessment in adults with type 1 Gaucher disease SO QUALITY OF LIFE RESEARCH LA English DT Article DE enzyme replacement therapy; Gaucher disease; quality of life ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; OF-LIFE; REPLACEMENT THERAPY AB The effect of enzyme replacement therapy on health-related quality of life in 25 adults with type 1 Gaucher disease was investigated over a 2-year period. Quality of life was assessed using the SF-36 Health Survey (SF-36). Psychological functioning was assessed using the Symptom Checklist-90R. The results indicated significant improvement in 7 of 8 SF scale scores beginning at 18 months of therapy (P < 0.05 to 0.001). The SF scale showing improvement first was Vitality (energy level and fatigue) at 6 months of therapy (P < 0.01). The SF-36 scales showing the largest improvements were Role-Physical and Social Functioning (P < 0.001). Compared to the general US adult population, the study population's health profile was significantly lower prior to starting therapy but by 24 months of therapy there were no differences between the two. No differences were found in psychological functioning compared to a US adult normative group at the start of therapy. However, within the study population there was significant improvement in mood and global functioning and fewer psychological symptoms reported at 24 months of therapy. The findings indicate that enzyme replacement therapy for type 1 Gaucher disease has a positive impact on health-related quality of life from the patient's perspective. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Div Neurogenet, Boston, MA 02114 USA. Childrens Hosp, Dept Med, Div Genet, Boston, MA USA. Amer Med Assoc, Off Biomed Sci & Clin Res, Chicago, IL 60610 USA. Massachusetts Gen Hosp, Dept Psychiat, Div Psychol, Boston, MA 02114 USA. RP Masek, BJ (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, 300 Longwood Ave, Boston, MA 02115 USA. NR 26 TC 43 Z9 43 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAY PY 1999 VL 8 IS 3 BP 263 EP 268 DI 10.1023/A:1008859420641 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 222TB UT WOS:000081799900009 PM 10472157 ER PT J AU Novelline, RA AF Novelline, RA TI Advances in emergency radiology I - Preface SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Novelline, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1999 VL 37 IS 3 BP IX EP IX PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204LT UT WOS:000080766300001 ER PT J AU Rhea, JT Rao, PM Novelline, RA AF Rhea, JT Rao, PM Novelline, RA TI Helical CT and three-dimensional CT of facial and orbital injury SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID WOODEN FOREIGN-BODY; BLOW-IN FRACTURES; LE-FORT FRACTURES; COMPUTED-TOMOGRAPHY; MAXILLOFACIAL TRAUMA; MANDIBULAR CONDYLE; MANAGEMENT; DIAGNOSIS; BODIES; EYE AB Imaging of facial trauma can be challenging because of the complex anatomy. Diagnosis and provision of useful information for presurgical planning can be simplified by considering the five regions of the face, the buttresses of the face, and the frequent types of fractures that occur. Protocols for facial CT and the costs of plain radiographs and CT are discussed. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. RP Rhea, JT (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 239,Fruit St, Boston, MA 02114 USA. NR 73 TC 40 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1999 VL 37 IS 3 BP 489 EP + DI 10.1016/S0033-8389(05)70108-1 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204LT UT WOS:000080766300003 PM 10361543 ER PT J AU Ledbetter, S Stuk, JL Kaufman, JA AF Ledbetter, S Stuk, JL Kaufman, JA TI Helical (spiral) CT in the evaluation of emergent thoracic aortic syndromes - Traumatic aortic rupture, aortic aneurysm, aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID BLUNT CHEST TRAUMA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; NATURAL-HISTORY; PROGNOSTIC IMPLICATIONS; VASCULAR COMPLICATIONS; ATYPICAL PATTERNS; DIAGNOSIS; ANGIOGRAPHY; AORTOGRAPHY; INJURY AB Catheter angiography traditionally has been the gold standard for evaluating emergent aortic syndromes. With advances in MR imaging, color Doppler ultrasound, and CT, newer, noninvasive ways of evaluating the thoracic and abdominal aorta have emerged. Each of these modalities has strengths and weaknesses, but CT plays the dominant and critical role in the evaluation of patients presenting with emergent aortic syndromes. This article focuses on the use of helical CT in the evaluation of traumatic aortic rupture, thoracic aortic aneurysm, aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. For each entity, the pathophysiology, CT technique, and characteristic CT findings are discussed. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mercy Gen Hlth Partners, Dept Radiol, Muskegon, MI USA. RP Ledbetter, S (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 86 TC 70 Z9 75 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1999 VL 37 IS 3 BP 575 EP + DI 10.1016/S0033-8389(05)70112-3 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204LT UT WOS:000080766300007 PM 10361547 ER PT J AU Novelline, RA Rhea, JT Bell, T AF Novelline, RA Rhea, JT Bell, T TI Helical CT of abdominal trauma SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID BLUNT TRAUMA; MESENTERIC INJURY; COMPUTED-TOMOGRAPHY; SPLENIC INJURY; CONTRAST MATERIAL; DIAGNOSIS; RUPTURE; BOWEL; CHILDREN; ADULTS AB CT has revolutionized the diagnostic work-up of trauma patients with suspected abdominal injuries. A wide range of intraperitoneal and retroperitoneal organ injuries can be quickly and accurately diagnosed with CT. Today, helical CT technology permits even faster examinations, with improved intravenous contrast opacification of parenchymal organs and vascular structures and reduced CT artifacts caused by patient motion, respiration, and arterial pulsation. Severely injured and potentially unstable patients, who might not have been able to tolerate the long CT examinations of the past, may be quickly evaluated today with helical CT. Accurate diagnosis requires high quality CT examinations that are performed with optimum CT protocols. This article reviews the currently recommended helical CT protocols for evaluating patients with suspected abdominal injuries, and the CT findings when injuries are present. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Novelline, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 39 TC 36 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1999 VL 37 IS 3 BP 591 EP + DI 10.1016/S0033-8389(05)70113-5 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204LT UT WOS:000080766300008 PM 10361548 ER PT J AU Melany, ML Grant, EG Farooki, S McElroy, D Kimme-Smith, C AF Melany, ML Grant, EG Farooki, S McElroy, D Kimme-Smith, C TI Effect of US contrast agents on spectral velocities: In vitro evaluation SO RADIOLOGY LA English DT Article DE blood, flow dynamics; blood vessels, stenosis or obstruction; ultrasound (US), contrast media; ultrasound (US), Doppler studies ID BLOOD-FLOW; ULTRASOUND; DOPPLER; ACCURACY; STENOSIS; PHANTOM AB PURPOSE: To evaluate the effect of ultrasonographic (US) contrast agents on measurements of peak velocity with spectral Doppler US in stenotic and nonstenotic flow states. MATERIALS AND METHODS: Nonpulsatile flow was established in a flow phantom with 0%, 50%, 75%, and 90% stenoses. SH U 508A perflenapent emulsion, and perfluorohexane emulsion were the contrast agents evaluated. Before and after administration of each contrast agent, two peak velocity measurements obtained proximal to, at the site of, and distal to the stenosis in each vessel model were averaged. The percentage difference in peak velocity after contrast agent administration was calculated for each site interrogated. The mean, SD, and coefficient of variation of the percentage difference in peak velocity were calculated. RESULTS: Percentage differences in peak velocity after contrast agent administration at different sample volume sites were not significantly different irrespective of the degree of stenosis or the contrast agent evaluated. CONCLUSION: The contrast agents evaluated do not produce a statistically significant increase in peak velocity. If this result is corroborated in clinical practice, contrast agents can be used without reevaluating existing Doppler US thresholds for stenosis. C1 Univ Calif Los Angeles, Dept Radiol Sci, Med Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. RP Melany, ML (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Med Ctr, 10833 Le Conte Ave,M-C 172115, Los Angeles, CA 90095 USA. NR 18 TC 17 Z9 18 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1999 VL 211 IS 2 BP 427 EP 431 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 189WM UT WOS:000079929200019 PM 10228524 ER PT J AU Simon, LS AF Simon, LS TI Viscosupplementation therapy with intraarticular hyaluronic acid - Fact or fantasy? SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID MULTICENTER TRIAL; OSTEOARTHRITIS; KNEE; HYLAN; HYALGAN(R) AB Pharmacologic therapy for osteoarthritis is presently only palliative and is based on the use of analgesic or anti-inflammatory agents. Simple analgesics, however, do not provide enough of an effect to satisfy the needs of many OA patients, and antiinflammatory drugs that are currently available do not have favorable risk-to-benefit ratio in typical patients with OA. A need remains, therefore, for therapies that will be analgesic, appropriately anti-inflammatory when necessary, and that may favorably alter the natural history of the disease. The development of intraarticular hyaluronic acid (HA) supplementation was thought to fulfill these criteria. This therapy has been shown to modulate pain in OA of the knee and investigators have attempted to show that it have positive effects on articular cartilage biology. This article considers these claims for HA supplementation as an important therapy for the treatment of OA. C1 Harvard Univ, Sch Med, Dept Med, Div Rheumatol & Metab Bone Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. RP Simon, LS (reprint author), Harvard Univ, Sch Med, Dept Med, Div Rheumatol & Metab Bone Dis, Boston, MA 02115 USA. NR 20 TC 25 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 1999 VL 25 IS 2 BP 345 EP + DI 10.1016/S0889-857X(05)70072-7 PG 14 WC Rheumatology SC Rheumatology GA 198EB UT WOS:000080408800008 PM 10356422 ER PT J AU Young, RH Scully, RE AF Young, RH Scully, RE TI Oxyphilic tumors of the female and male genital tracts SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE ovary; uterus; testis; oxyphilic tumors ID CORD-STROMAL TUMORS; SERTOLI-CELL TUMOR; MALIGNANT RHABDOID TUMOR; CLINICOPATHOLOGICAL ANALYSIS; ONCOCYTIC ADENOCARCINOMA; PAPILLARY CYSTADENOMAS; BORDERLINE MALIGNANCY; HEPATOID CARCINOMA; FALLOPIAN-TUBE; OVARIAN-TUMORS AB A great variety of oxyphilic tumors and tumor-like lesions occur in the female and male genital tracts, particularly in the former. The ovary is the site of a wider range of oxyphilic tumors than any other organ. Not only are its most highly specialized steroid hormone-secreting tumors and tumor-like lesions often completely or predominantly oxyphilic, but occasionally its epithelial cancers have a large component of oxyphilic cells. Several rare germ-cell tumors can also be completely or extensively oxyphilic and, being a common site of metastasis, the ovary can harbor a number of metastatic oxyphilic tumors. The lower female genital tract shares some of the problems in differential diagnosis with the ovary, and can be involved by a variety of mesenchymal oxyphilic tumors as well, In the male genital tract, the testis may be the site of a number of the same oxyphilic tumor types encountered in the ovary, but much less frequently, partly because the testis is an uncommon site of metastatic spread. Copyright (C) 1999 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St,Warren 215, Boston, MA 02114 USA. NR 77 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 1999 VL 16 IS 2 BP 146 EP 161 PG 16 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 225PK UT WOS:000081969800009 PM 10452580 ER PT J AU Langdale, LA Wilson, L Jurkovich, GJ Liggitt, HD AF Langdale, LA Wilson, L Jurkovich, GJ Liggitt, HD TI Effects of immunomodulation with interferon-gamma on hepatic ischemia-reperfusion injury SO SHOCK LA English DT Article ID RECEPTOR-BETA CHAIN; IFN-GAMMA; NEUTROPHILS CONTRIBUTE; ENDOTHELIAL-CELLS; HUMAN MONOCYTES; EXPRESSION; ADHESION; RELEASE; ENDOTOXEMIA; MACROPHAGE AB The development of an inflammatory response after injury depends on the participation of a variety of cell populations and endogenous mediators. Interferon-gamma (IFN-gamma) is a potent cellular immunomodulating cytokine that contributes to acute and chronic inflammation. In this study, the effects of immunomodulation on ischemia-reperfusion injury were examined using increasing doses of recombinant, rabbit-specific IFN-gamma in an in situ model of hepatic ischemia-reperfusion. Pretreatment with low dose IFN-gamma augmented injury as measured by histology, aminotransferase concentrations, and myeloperoxidase activity. By contrast, high dose IFN-gamma pretreatment, equivalent to IFN-gamma supplements used in clinical trials, resulted in a lack of neutrophil infiltration and minimal progression of late phase, neutrophil-mediated reperfusion injury. These results suggest that immunomodulating mediators such as IFN-gamma may play a regulating role in the evolution of ischemia-reperfusion, contributing to the development and resolution of acute hepatic injury. C1 Univ Washington, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. RP Langdale, LA (reprint author), VA Puget Sound Hlth Care, Dept Surg, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 33 TC 11 Z9 12 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9,, AUGUSTA, GA 30901 USA SN 1073-2322 J9 SHOCK JI Shock PD MAY PY 1999 VL 11 IS 5 BP 356 EP 361 DI 10.1097/00024382-199905000-00009 PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 195VQ UT WOS:000080273200009 PM 10353542 ER PT J AU Yao, L Gentili, A Cracchiolo, A AF Yao, L Gentili, A Cracchiolo, A TI MR imaging findings in spring ligament insufficiency SO SKELETAL RADIOLOGY LA English DT Article DE MRI, foot, injury; ligament, spring; pes planus; posterior tibial tendonopathy ID POSTERIOR TIBIAL TENDON; ANATOMY AB Objective. Spring ligament insufficiency is associated with chronic posterior tibial tendon dysfunction, and may constitute an indication for surgical repair or reconstruction. This study examines the accuracy of MRI for the diagnosis of insufficiency of the spring ligament. Design and patients. Two experienced musculoskeletal radiologists independently scored the MRI findings in 13 cases of surgically proven spring ligament insufficiency and in 18 control subjects, using a standardized scoring system. Results. Insufficiency of the spring ligament was associated with increased signal heterogeneity on short TE spin echo images, and an increase in the thickness of the medial portion of the ligament. The sensitivity of MRT for the diagnosis of spring ligament insufficiency was 54-77%, while the specificity was 100%. MRI assessment of the plantar portion of the spring ligament was unreliable (kappa=0.33), but the assessment of global ligament integrity was substantially reproducible (kappa=0.76). Conclusion. The medial portion of the spring ligament can be reliably assessed on routine MRI, The findings of spring ligament insufficiency on MRI are only moderately sensitive but highly specific. C1 Georgetown Univ, Med Ctr, Dept Radiol, MRI, Washington, DC 20007 USA. Univ Calif Los Angeles, Dept Radiol Sci, W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Orthoped Surg, Los Angeles, CA 90024 USA. RP Yao, L (reprint author), Georgetown Univ, Med Ctr, Dept Radiol, MRI, 2nd Floor,CCC Bldg,3800 Reservoir Rd NW, Washington, DC 20007 USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 9 TC 36 Z9 39 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 1999 VL 28 IS 5 BP 245 EP 250 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 212RC UT WOS:000081229200001 PM 10424329 ER PT J AU Ehara, S Rosenthal, DI Aoki, J Fukuda, K Sugimoto, H Mizutani, H Okada, K Hatori, M Abe, M AF Ehara, S Rosenthal, DI Aoki, J Fukuda, K Sugimoto, H Mizutani, H Okada, K Hatori, M Abe, M TI Peritumoral edema in osteoid osteoma on magnetic resonance imaging SO SKELETAL RADIOLOGY LA English DT Article DE magnetic resonance imaging; osteoid osteoma; periosteal reaction; bone marrow edema ID CT AB Objective. To determine whether there is a relationship between the peritumoral edema caused by osteoid osteoma seen on magnetic resonance (MR) imaging and the patient's age, duration of symptoms, or location of the lesion. Design and patients. All histologically proven osteoid osteomas seen in our institutions during a 5-year period in patients with known age, gender, duration of symptoms, and available radiological and MR imaging examinations were included in this study. The extent of the edema in the bone marrow and extraosseous soft tissue around the nidus of osteoid osteoma on T2-weighted MR imaging were graded from 1 (nonexistent) to 4 (extensive) by two masked observers. The relationships between the patient's age, duration of symptoms, and location of lesions were evaluated by Pearson's correlation coefficient and analysis of variance. Results. Twenty-seven cases met the inclusion criteria. The observer agreement on grading was good. Patients of 15 years of age or younger had significantly higher grades than patients older than 15 years. There was a moderate negative linear correlation between the patient's age and peritumoral edema. No significant relationship was identified between edema and the duration of symptoms or the location of lesions. Conclusion. Osteoid osteomas in younger patients tend to be associated with more extensive peritumoral edema. C1 Iwate Univ, Sch Med, Dept Radiol, Morioka, Iwate 0208505, Japan. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Shunshu Univ, Sch Med, Dept Radiol, Matsumoto, Nagano 390, Japan. Jikei Univ, Sch Med, Dept Radiol, Tokyo 105, Japan. Jichi Med Sch, Dept Radiol, Minami Kawachi, Tochigi 32904, Japan. Nagoya City Univ, Sch Med, Dept Radiol, Nagoya, Aichi 467, Japan. Akita Univ, Sch Med, Dept Orthopaed Surg, Akita 010, Japan. Tohoku Univ, Sch Med, Dept Orthopaed Surg, Sendai, Miyagi 98077, Japan. Iwate Med Univ, Sch Med, Dept Orthoped Surg, Morioka, Iwate 020, Japan. RP Ehara, S (reprint author), Iwate Univ, Sch Med, Dept Radiol, Morioka, Iwate 0208505, Japan. NR 13 TC 33 Z9 37 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 1999 VL 28 IS 5 BP 265 EP 270 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 212RC UT WOS:000081229200004 PM 10424332 ER PT J AU Singer, RJ Clough, J Johnson, M Atkinson, JB Copeland, M AF Singer, RJ Clough, J Johnson, M Atkinson, JB Copeland, M TI Pigmented schwannoma of the ventral spinal cord SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID INTRAMEDULLARY MELANOTIC SCHWANNOMA AB Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man, Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors. C1 Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Neuropathol, Nashville, TN USA. RP Singer, RJ (reprint author), Massachusetts Gen Hosp, Brain Aneurysm AVM Ctr, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 4 Z9 4 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAY PY 1999 VL 92 IS 5 BP 532 EP 534 DI 10.1097/00007611-199905000-00019 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 197FJ UT WOS:000080354100019 PM 10342906 ER PT J AU Ojemann, RG Samii, M Cordula, M AF Ojemann, RG Samii, M Cordula, M TI Suboccipital resection of a medial acoustic neuroma with hearing preservation - Commentary SO SURGICAL NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Ojemann, RG (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD MAY PY 1999 VL 51 IS 5 BP 552 EP 553 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 193QG UT WOS:000080147200032 ER PT J AU Sanchez, AC Ilag, LL Yang, D Brar, DS Ausubel, F Khush, GS Yano, M Saskai, T Li, Z Huang, N AF Sanchez, AC Ilag, LL Yang, D Brar, DS Ausubel, F Khush, GS Yano, M Saskai, T Li, Z Huang, N TI Genetic and physical mapping of xa13, a recessive bacterial blight resistance gene in rice SO THEORETICAL AND APPLIED GENETICS LA English DT Article DE genetic map; physical map; map-based gene cloning; disease resistance; rice; DNA markers ID ASYMMETRIC INTERLACED PCR; RFLP MARKERS; MAP; POPULATION; SEQUENCES; FRAGMENTS; CLONING; GENOME; CLONES; RAPD AB The recessive gene, xal3, confers resistance to Philippine race 6 (PXO99) of the bacterial blight pathogen Xanthomonas oryzae pv oryzae. Fine genetic mapping and physical mapping were conducted as initial steps in an effort to isolate the gene. Using nine selected DNA markers and two F-2 populations of 132 and 230 plants, xal3 was fine-mapped to a genomic region < 4 cM on the long arm of rice chromosome 8, flanked by two RFLP markers, RG136 and R2027. Four DNA markers. RG136, R2027, S14003, and G1149, in the target region were used to identify bacterial artificial chromosome (BAC) clones potentially harboring the xal3 locus from a rice BAC library. A total of 11 BACs were identified. forming four separate contigs including a single-clone contig, 29I3, associated with the RG136 STS marker, the S14003 contig consisting of four clones (44F8, 41O2, 12A16, and 12F20). the G1149 contig with two clones, 23D11 and 21H18, and the R2027 contig consisting of four overlapping clones, 42C23, 30B5, 6B7 and 21H14. Genetic mapping indicated that the xa13 locus was contained in the R2027 contig, Chromosomal walking on the R2027 contig resulted in two more clones, 33C7 and 14L3. DNA fingerprinting showed that the six clones of the R2027 contig were overlapping. Clone 44F8 hybridized with a single fragment from the clone 14L3, integrating the R2027 and S14003 contigs into a single contig consisting of ten BAC clones with a total size of approximately 330 kb, The physical presence of the xa13 locus in the contig was determined by mapping the ends of the BAC inserts generated by TAIL-PCR. In an F2 Population of 230 plants, the BAG-end markers 42C23R and 6B7F flanked the xa13 locus, The probes 21H14F and 21H14R derived from BAC clone 21H14 were found to Rank xa13 at a distance of 0.5 cM on either side, using a second F2 population of 132 plants. Thus, genetic mapping indicated that the contig and the 96-kb clone, 21H14, contained the xa13 locus. C1 Int Rice Res Inst, Plant Breeding Genet & Biochem Div, Manila 1099, Philippines. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Natl Inst Agrobiol Resources, Rice Genome Program, Ibaraki, Osaka 305, Japan. RP Li, Z (reprint author), Int Rice Res Inst, Plant Breeding Genet & Biochem Div, POB 933, Manila 1099, Philippines. RI Khush, Gurdev Singh/C-5109-2009 NR 28 TC 23 Z9 32 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0040-5752 J9 THEOR APPL GENET JI Theor. Appl. Genet. PD MAY PY 1999 VL 98 IS 6-7 BP 1022 EP 1028 DI 10.1007/s001220051163 PG 7 WC Agronomy; Plant Sciences; Genetics & Heredity; Horticulture SC Agriculture; Plant Sciences; Genetics & Heredity GA 200HR UT WOS:000080534000021 ER PT J AU Sugawara, M Sugawara, Y Wen, K AF Sugawara, M Sugawara, Y Wen, K TI Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles SO THYROID LA English DT Article ID TRANSCRIPTION FACTORS; FRTL-5 CELLS; RAT; THYROTROPIN; DNA; IODINATION; METABOLISM; INVITRO; INVIVO; DRUGS AB Methimazole (MMI) and propylthiouracil (PTU) are common antithyroid drugs for treating hyperthyroidism because the 2 drugs inhibit thyroid peroxidase (TPO)-catalyzed thyroid hormone formation. We studied whether the 2 drugs actually inhibit cellular TPO activity in cultured porcine follicles. Porcine follicles were cultured in the presence of 1 mU/mL thyrotropin (TSH) for 7 days. Then follicles were exposed to MMI or PTU in the presence of 0.1 mu M Kl for 2 days. TPO activity was measured in the 100,000 x g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 mu M and 10 mu M) or PTU (10 mu M and 100 mu M) for 2 days caused a significant increase in cellular TPO activity; 100 mu M MMI inhibited cellular TPO activity. The presence of cyclic adenosine monophosphate (cAMP)-generating system (forskolin) in TSH-free medium increased MMI-mediated TPO activity. Cyclohexamide inhibited MMI-mediated TPO activation, indicating that new protein synthesis is required for increased TPO activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in TPO mRNA by PTU or MMI. In conclusion, MMI and PTU at therapeutic concentrations can increase TPO mRNA and cellular TPO activity, although the 2 drugs inhibit the TPO-H2O2-mediated catalytic reaction. C1 W Los Angeles Vet Affairs Med Ctr, Res & Med Ctr, Div Endocrinol & Metab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. RP Sugawara, M (reprint author), W Los Angeles Vet Affairs Med Ctr, Res & Med Ctr, Div Endocrinol & Metab, 111M,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 27 TC 10 Z9 14 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 1999 VL 9 IS 5 BP 513 EP 518 DI 10.1089/thy.1999.9.513 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200AA UT WOS:000080515200015 PM 10365684 ER PT J AU Szpirer, C Szpirer, J Van Vooren, P Tissir, F Simon, JS Koike, G Jacob, HJ Lander, ES Helou, K Klinga-Levan, K Levan, G AF Szpirer, C Szpirer, J Van Vooren, P Tissir, F Simon, JS Koike, G Jacob, HJ Lander, ES Helou, K Klinga-Levan, K Levan, G TI Gene-based anchoring of the rat genetic linkage and cytogenetic maps SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 12th International Workshop on Alloantigenic Systems in the Rat CY JUL 08-10, 1998 CL HALIFAX, CANADA SP Roche Pharmaceut, Novartis Pharma Canada Inc, SangStat Med Corp, Wyeth Ayerst, Fujisawa Canada Inc C1 Free Univ Brussels, Dept Biol Mol, B-1640 Rhode St Genese, Belgium. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Univ Gothenburg, CMB Genet, Gothenburg, Sweden. RP Szpirer, C (reprint author), Free Univ Brussels, Dept Biol Mol, Rue Chevaux 67, B-1640 Rhode St Genese, Belgium. FU NHLBI NIH HHS [5RO1 HL55726, HL08968] NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD MAY PY 1999 VL 31 IS 3 BP 1541 EP 1543 DI 10.1016/S0041-1345(99)00030-5 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 195CR UT WOS:000080232000030 PM 10330994 ER PT J AU Van Etten, RA AF Van Etten, RA TI Cycling, stressed-out and nervous: cellular functions of c-Abl SO TRENDS IN CELL BIOLOGY LA English DT Review ID TYROSINE KINASE-ACTIVITY; DNA-DAMAGE; TRANSFORMING ABILITY; SIGNAL-TRANSDUCTION; IONIZING-RADIATION; GENOTOXIC STRESS; BINDING-PROTEIN; DROSOPHILA-ABL; GENE-PRODUCT; SH3 REGION AB c-Abl, the product of the cellular homologue of the transforming gene of Abelson murine leukaemia virus, has been a protein in search of a purpose for over two decades. Because c-Abl is implicated in the pathogenesis of several human leukaemias, understanding the functions of Abl is an important goal. Recently, biochemical and genetic approaches have converged to shed new light on the mechanism of regulation of c-Abl kinase activity and the multiple roles of c-Abl in cellular physiology. This review summarizes our current understanding of the many facets of c-Abl biology, emphasizing recent studies on Drosophila and mammalian Abl. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. FU NCI NIH HHS [CA74625, CA77691] NR 62 TC 224 Z9 227 U1 1 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAY PY 1999 VL 9 IS 5 BP 179 EP 186 DI 10.1016/S0962-8924(99)01549-4 PG 8 WC Cell Biology SC Cell Biology GA 221ZV UT WOS:000081758500004 PM 10322452 ER PT J AU Maznev, AA McAuliffe, DJ Doukas, AG Nelson, KA AF Maznev, AA McAuliffe, DJ Doukas, AG Nelson, KA TI Wide-band acoustic spectroscopy of biological material based on a laser-induced grating technique SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE laser ultrasound; ultrasound attenuation; sound velocity; thermal grating spectroscopy ID EMPIRICAL ULTRASONIC PROPERTIES; MAMMALIAN-TISSUES; ATTENUATION; COMPILATION; GENERATION; DIFFUSION; PROBE AB A laser-induced transient grating technique enables fast noncontact acoustic measurements on transparent biological materials in a frequency range from tens of megahertz to 1 GHz, We have applied this method to the characterization of bovine vitreous and found high-frequency acoustic attenuation values to be close to those of water, with a quadratic dependence on frequency, in contrast to low-frequency data. The potential of the technique for studying other biological materials, such as human stratum corneum, is demonstrated. (C) 1999 World Federation for Ultrasound in Medicine & Biology. C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. RP Maznev, AA (reprint author), MIT, Dept Chem, Room NW14-1213, Cambridge, MA 02139 USA. NR 21 TC 3 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAY PY 1999 VL 25 IS 4 BP 601 EP 607 DI 10.1016/S0301-5629(98)00191-4 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 194VK UT WOS:000080191900014 PM 10386736 ER PT J AU George, DJ Kantoff, PW AF George, DJ Kantoff, PW TI Prognostic indicators in hormone refractory prostate cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PREDICT PATHOLOGICAL STAGE; PHASE-II; ACID-PHOSPHATASE; EUROPEAN-ORGANIZATION; ORAL ESTRAMUSTINE; ANTIGEN FAILURE; CLINICAL-TRIAL; BONE-SCAN; END-POINT; THERAPY AB Prognostic factors in hormone refractory prostate cancer currently are of limited use to clinicians. Although studies have identified several factors that predict for poor survival in patients, most are either retrospective, or nonrandomized. Therefore, large prospective, randomized trials are needed to validate the significance of these factors. In addition, these indicators' are largely descriptive of the patients' condition or the extent of disease. As more treatment options are developed for these patients, functionally relevant and prognostic molecular markers are needed to direct their care. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 1230 Dana Bldg,44 Binney St, Boston, MA 02115 USA. NR 53 TC 15 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD MAY PY 1999 VL 26 IS 2 BP 303 EP + DI 10.1016/S0094-0143(05)70070-7 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 196VH UT WOS:000080328100006 PM 10361553 ER PT J AU Yip, I Heber, D Aronson, W AF Yip, I Heber, D Aronson, W TI Nutrition and prostate cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID UNITED-STATES; KINASE-ACTIVITY; FATTY-ACIDS; CELL-LINES; VITAMIN-D; TYROSINE PHOSPHORYLATION; INDUCED APOPTOSIS; BETA-CAROTENE; NIH-3T3 CELLS; NUDE-MICE AB Scientific evidence suggests that differences in the diet may, in large part, account for the variability of prostate cancer rates around the world. Epidemiologic studies and animal experiments have yielded compelling results to warrant clinical intervention studies on nutrition from scientists who work on the prevention and treatment of prostate cancer. This article reviews the most recent evidence as to possible mechanisms of action of various dietary constituents, and explores evidence of various nutritional strategies for the prevention of prostate cancer progression. C1 Univ Calif Los Angeles, Ctr Human Nutr, Div Clin Nutr, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Yip, I (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, Div Clin Nutr, Sch Med, 900 Vet Ave,Warren Hall,Rm 12-217, Los Angeles, CA 90095 USA. NR 94 TC 34 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD MAY PY 1999 VL 26 IS 2 BP 403 EP + DI 10.1016/S0094-0143(05)70079-3 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 196VH UT WOS:000080328100015 PM 10361562 ER PT J AU Barry, MJ AF Barry, MJ TI Impact of a shared decision-making program on patients with benign prostatic hyperplasia - Comment SO UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Practices Evaulat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaulat Ctr, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1999 VL 53 IS 5 BP 920 EP 920 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 189HD UT WOS:000079898200011 ER PT J AU Collins, MM Stafford, RS O'Leary, MP Barry, MJ AF Collins, MM Stafford, RS O'Leary, MP Barry, MJ TI Distinguishing chronic prostatitis and benign prostatic hyperplasia symptoms: Results of national survey of physician visits SO UROLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Urological-Association CY MAY 30-JUN 04, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Urol Assoc AB Objectives. The morbidity of chronic prostatitis results from a constellation of genitourinary symptoms. A recent study classified 21 of these symptoms into three categories: pain, voiding complaints, and sexual dysfunction. Pain symptoms predominated among patients with prostatitis. Using data from a nationwide survey of physician visits, we examined the most common symptoms reported by men at chronic prostatitis visits and contrasted the results with visits for benign prostatic hyperplasia (BPH). Methods. We analyzed 81,034 visits by men (18 years and older) to office-based physicians of all specialties in the National Ambulatory Medical Care Surveys of 1990 to 1996, using sampling weights to make national estimates. U.S. physicians selected by random stratified sampling completed visit forms that included patients' reasons for visits and physicians' diagnoses. Results. In 1990 to 1996, there were 765 visits (national estimate 1.5 million visits/yr; 95% confidence interval = 0.9 to 2.1) with a diagnosis of chronic prostatitis. Among chronic prostatitis visits, 20% were for pain, 19% for urinary symptoms, and 1% for sexual dysfunction. Among 2271 BPH visits, 2% were for pain, 33% for voiding complaints, and 1% for sexual dysfunction. The most common reason coded for chronic prostatitis visits was painful urination (14% of chronic prostatitis visits, but only 1.7% of BPH visits). Conclusions. Pain was slightly more common than voiding complaints, but much more common than sexual dysfunction among chronic prostatitis visits. The most common reason for chronic prostatitis visits was painful urination, which was uncommon among patients with BPH. Pain distinguished chronic prostatitis from BPH better than any other urinary symptom. UROLOGY 53: 921-925, 1999. (C) 1999, Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Med Serv, Div Gen Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Med Serv, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. FU AHRQ HHS [HS09538, HS 08397]; NIDDK NIH HHS [DK53736] NR 15 TC 26 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1999 VL 53 IS 5 BP 921 EP 925 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 189HD UT WOS:000079898200012 PM 10223484 ER PT J AU Bent, S AF Bent, S TI Adulterants in herbal products: dangerous and deceitful - Comment SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material ID CONTROLLED TRIAL; CHINESE C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. RP Bent, S (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD MAY PY 1999 VL 170 IS 5 BP 259 EP 260 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 203DV UT WOS:000080693100007 PM 18751139 ER PT J AU Warrens, AN Simon, AR Theodore, PR Sykes, M AF Warrens, AN Simon, AR Theodore, PR Sykes, M TI Human-porcine receptor-ligand compatibility within the immune system: relevance for xenotransplantation SO XENOTRANSPLANTATION LA English DT Review DE adhesion molecules; co-stimulation transplantation; selectins; integrins; major histocompatibility complex; tolerance; xenotransplantation ID HUMAN T-CELLS; ENDOTHELIAL-CELLS; E-SELECTIN; ADHESION MOLECULES; POTENTIAL ROLE; EXPRESSION; RECOGNITION; ANTIBODIES; CLONING; VCAM AB Immune responses to xenografts are likely to be highly dependent on the efficiency of molecular interactions between the donor and the recipient species. This brief review summarizes what is currently known about the compatibilities across the human-porcine species barrier of the molecular interactions that are important in the immune response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL54038] NR 20 TC 26 Z9 26 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1999 VL 6 IS 2 BP 75 EP 78 DI 10.1034/j.1399-3089.1999.00020.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 220CR UT WOS:000081647400001 PM 10431783 ER PT J AU Oriol, R Candelier, JJ Taniguchi, S Balanzino, L Peters, L Niekrasz, M Hammer, C Cooper, DKC AF Oriol, R Candelier, JJ Taniguchi, S Balanzino, L Peters, L Niekrasz, M Hammer, C Cooper, DKC TI Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research SO XENOTRANSPLANTATION LA English DT Article DE alpha Gal; animal models; carbohydrate epitope; glycotope; domestic animals; histochemistry; lectin; tissue expression; wild animals; xanotransplantation ID ALPHA-GALACTOSYL EPITOPES; ANTI-GAL ANTIBODY; HUMAN NATURAL ANTIBODIES; ORGAN XENOTRANSPLANTATION; TRANSGENIC MICE; LEWIS ANTIGENS; PIG-TISSUES; EXPRESSION; ABH; TRANSPLANTATION AB We investigated the main glycotopes expressed on the tissues of 44 animal species, including primates, nonprimate mammals, marsupials. birds. and a reptile. Paraffin-embedded tissue sections of kidney, heart, liver, pancreas, lung, brain and intestine of 24 domestic animal species were stained with seven fluorescent-labeled lectins. Testis sections of 20 African wild animal species were tested with the same lectins. Overall, three main immunofluorescence patterns were found in the vascular compartment. First, humans and Old World monkeys express genetically polymorphic ABH antigens and do not express alpha Gal. Second, New World monkeys, other mammals, and marsupials do not express ABH antigens, but have large amounts of a genetically monomorphic alpha Gal. Third. birds and reptiles do not express either ABH or alpha Gal, but have monomorphic beta Gal, probably different from the lactosamine precursor of ABH and alpha Gal. Epithelial cells producing exocrine secretions also expressed carbohydrate epitopes. The fluorescence patterns of the cells of the exocrine compartment are similar, but not identical, to those expressed in the vascular compartment. All the animals tested have some ABH and beta Gal in exocrine tissues, but New World monkeys and lower mammals are the only ones expressing alpha Gal in exocrine tissues. C1 INSERM, U504, F-94807 Villejuif, France. Baptist Med Ctr, Oklahoma Transplantat Inst, Oklahoma City, OK 73112 USA. Vet Adm Med Ctr, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Div Anim Resources, Oklahoma City, OK USA. Univ Munich, Inst Surg Res, D-8000 Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Oriol, R (reprint author), INSERM, U504, 16 Av Paul Vaillant Couturier, F-94807 Villejuif, France. NR 54 TC 21 Z9 21 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1999 VL 6 IS 2 BP 79 EP 89 DI 10.1034/j.1399-3089.1999.00008.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 220CR UT WOS:000081647400002 PM 10431784 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1998, part 4 SO XENOTRANSPLANTATION LA English DT Article ID XENOTRANSPLANTATION; CELLS; MICE; RETROVIRUS; DEFICIENT; REJECTION; ZOONOSIS C1 Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, GRB 504, Boston, MA 02114 USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1999 VL 6 IS 2 BP 155 EP 156 DI 10.1034/j.1399-3089.1999.00021.x PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 220CR UT WOS:000081647400011 PM 10431793 ER PT J AU Shi, CW Patel, A Zhang, D Wang, H Carmeliet, P Reed, GL Lee, ME Haber, E Sibinga, NES AF Shi, CW Patel, A Zhang, D Wang, H Carmeliet, P Reed, GL Lee, ME Haber, E Sibinga, NES TI Plasminogen is not required for neointima formation in a mouse model of vein graft stenosis SO CIRCULATION RESEARCH LA English DT Article DE bypass surgery; coronary disease; intimal hyperplasia; arteriosclerosis; gene knockout ID CORONARY-BYPASS SURGERY; SAPHENOUS-VEIN; DEFICIENT MICE; TRANSPLANT ARTERIOSCLEROSIS; INTIMAL HYPERPLASIA; C-MYB; ATHEROSCLEROSIS; DISEASE; ARTERY; ANGIOPLASTY AB Recent studies of mice that lack plasminogen have identified a critical role for this zymogen in arterial remodeling. To permit the use of these (and other) genetically modified mice in the analysis of venous injury, we developed a model in which a patch cut from the external jugular vein of a mouse is grafted to repair a surgically created defect in its carotid artery. In wild-type mice, the venous graft showed initial endothelial denudation and formation of a neointima that progressively and reproducibly expanded in a manner analogous to human vein graft disease, albeit at an accelerated pace. This neointima occupied 37+/-4.6% of the vessel lumen at day 7 and 66+/-5.7% at day 20. The proliferative index of neointimal cells assessed by proliferating cell nuclear antigen staining was 50.6+/-3.6% at day 7 and 15.2+/-2.0% at day 20. CD45-positive leukocytes and a-actin-positive smooth muscle cells accounted for 9.5+/-1.0% and 9.9+/-1.1% of intimal area at day 7, respectively, with the latter increasing to 40.9+/-2.6% at day 20. Collagen accounted for 6.8+/-0.7% of intimal area at day 7 and 20.7+/-1.8% at day 20. Surprisingly, even though arterial neointima formation due to electrostatic and immune-mediated injury is impaired in plasminogen -/- mice, in our study vein graft neointima formation in these mice was not significantly different from that in controls (70.9+/-6.4 versus 65.6+/-4.4% luminal occlusion, P=NS). Thus, plasmin proteolysis, although critical in extracellular matrix degradation and cellular migration after arterial injury, does not appear to be so important in vein graft neointima formation, perhaps because of the relative lack of structural barriers to cellular migration in the normal vein wall. This novel model of vein graft injury should be useful for further studies of differences in the response to injury of arterial and venous tissues. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Flanders Interuniv Inst Biotechnol, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Sibinga, NES (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL03274, HL57314]; NIGMS NIH HHS [GM53249] NR 44 TC 24 Z9 25 U1 0 U2 1 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 30 PY 1999 VL 84 IS 8 BP 883 EP 890 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 190BX UT WOS:000079942600003 PM 10222334 ER PT J AU Marino, M Zheng, G McCluskey, RT AF Marino, M Zheng, G McCluskey, RT TI Megalin (gp330) is an endocytic receptor for thyroglobulin on cultured Fisher rat thyroid cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; HEPARAN-SULFATE PROTEOGLYCANS; HEYMANN NEPHRITIS; LDL RECEPTOR; MEDIATES ENDOCYTOSIS; POTENTIAL ROLE; GENE FAMILY; PROTEIN; BINDING; INTERNALIZATION AB We recently reported that megalin (gp330), an endocytic receptor found on the apical surface of thyroid cells, binds thyroglobulin (Tg) with high affinity in solid phase assays. Megalin-bound Tg was releasable by heparin, Here we show that Fisher rat thyroid (FRTL-5) cells, a differentiated rat thyroid cell line, can bind and endocytose Tg via megalin, We first demonstrated that FRTL-5 cells express megalin in a thyroid-stimulating hormone-dependent manner. Evidence of Tg binding to megalin on FRTL-5 cells and on an immortalized rat renal proximal tubule cell line (IRPT cells), was obtained by incubating the cells with I-125-Tg, followed by chemical cross-linking and immunoprecipitation of I-125-Tg with antibodies against megalin, To investigate cell binding further, we developed an assay in which cells were incubated with unlabeled Tg at 4 degrees C, followed by incubation with heparin, which released almost all of the cell-bound Tg into the medium. In solid phase experiments designed to illuminate the mechanism of heparin release, we demonstrated that Tg is a heparin-binding protein, as are several megalin ligands, The amount of Tg released by heparin from FRTL-5 and IRPT cells, measured by enzyme-linked immunosorbent assay (ELISA), was markedly reduced by two megalin competitors, receptor-associated protein (RAP) and 1H2 (monoclonal antibody against megalin), indicating that much of the Tg released by heparin had been bound to megalin (similar to 60-80%). The amount inhibited by RAP was considered to represent specific binding to megalin, which was saturable and of high affinity (K(d)similar to 11.2 nM), Tg endocytosis by FRTL-5 and IRPT cells was demonstrated in experiments in which cells were incubated with unlabeled Tg at 37 degrees C, followed by heparin to remove cell-bound Tg, The amount of Tg internalized (measured by ELISA in the cell lysates) was reduced by RAP and 1H2, indicating that Tg endocytosis is partially mediated by megalin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, Charlestown, MA 02129 USA. RP McCluskey, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 46301] NR 44 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 1999 VL 274 IS 18 BP 12898 EP 12904 DI 10.1074/jbc.274.18.12898 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 192BC UT WOS:000080056800099 PM 10212279 ER PT J AU Brandstetter, H Whittington, DA Lippard, SJ Frederick, CA AF Brandstetter, H Whittington, DA Lippard, SJ Frederick, CA TI Better understanding of the soluble methane monooxygenase protein B structure through mutation and analysis SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA. MIT, Dept Chem, Dana Farber Canc Inst, Cambridge, MA 02139 USA. RI Brandstetter, Hans/E-6754-2011 OI Brandstetter, Hans/0000-0002-6089-3045 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR 30 PY 1999 VL 74 IS 1-4 BP 337 EP 337 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 211JP UT WOS:000081157700628 ER PT J AU Artavanis-Tsakonas, S Rand, MD Lake, RJ AF Artavanis-Tsakonas, S Rand, MD Lake, RJ TI Notch signaling: Cell fate control and signal integration in development SO SCIENCE LA English DT Review ID DORSAL/VENTRAL COMPARTMENT BOUNDARY; SENSORY ORGAN LINEAGE; SPLIT COMPLEX GENES; DOMAINS IN-VIVO; ACTIVATED NOTCH; NEUROBLAST SEGREGATION; CAENORHABDITIS-ELEGANS; TRANSCRIPTIONAL ACTIVATION; DROSOPHILA-NEUROGENESIS; INTRACELLULAR DOMAIN AB Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development. Signals exchanged between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus, Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cell Biol,Canc Ctr, Charlestown, MA 02129 USA. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cell Biol,Canc Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NINDS NIH HHS [NS26084] NR 109 TC 3648 Z9 3832 U1 29 U2 250 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 30 PY 1999 VL 284 IS 5415 BP 770 EP 776 DI 10.1126/science.284.5415.770 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 192AW UT WOS:000080056200036 PM 10221902 ER PT J AU Vernick, DM Keel, SB Scully, RE Mark, EJ McNeely, WF Ebeling, SH Rabinov, JD Staecker, H Durand, ML AF Vernick, DM Keel, SB Scully, RE Mark, EJ McNeely, WF Ebeling, SH Rabinov, JD Staecker, H Durand, ML TI A 20-year-old woman with chronic otitis media - Tuberculous otitis media. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MIDDLE-EAR; MASTOIDITIS; SERIES C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vernick, DM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 22 TC 6 Z9 7 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 29 PY 1999 VL 340 IS 17 BP 1349 EP 1354 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 191BQ UT WOS:000080001700008 ER PT J AU Bradley, SR Standaert, DG Rhodes, KJ Rees, HD Testa, CM Levey, AI Conn, PJ AF Bradley, SR Standaert, DG Rhodes, KJ Rees, HD Testa, CM Levey, AI Conn, PJ TI Immunohistochemical localization of subtype 4a metabotropic glutamate receptors in the rat and mouse basal ganglia SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE globus pallidus; corticostriatal pathway; presynaptic heteroreceptor; electron microscopy; confocal microscopy ID MEDIATED SYNAPTIC POTENTIALS; PYRAMIDAL CELLS; ACTIVATION; HIPPOCAMPUS; EXPRESSION; INTERNEURONS; STRIATUM; SYNAPSES; PROTEINS; NEURONS AB Recent studies suggest that metabotropic glutamate receptors (mGluRs) may play a significant role in regulating basal ganglia functions. In this study, we investigated the localization of mGluR4a protein in the mouse and rat basal ganglia. Polyclonal antibodies that specifically react with the metabotropic glutamate receptor subtype mGluR4a were produced and characterized by Western blot analysis. These antibodies recognized a native protein in wild-type mouse brain with a molecular weight similar to the molecular weight of the band from a mGluR4a-transfected cell line. The immunoreactivity was absent in brains of knockout mice deficient in mGluR4. mGluR4a immunoreactivity was most intense in the molecular layer of the cerebellum. We also found a striking mGluR4a immunoreactivity in globus pallidus, and moderate staining in substantia nigra pars reticulata and entopeduncular nucleus. Moderate to low mGluR4a immunoreactivity was present in striatum and other brain regions, including hippocampus, neocortex, and thalamus. Double labeling with mGluR4a antibodies and antibodies to either a dendritic marker or a marker of presynaptic terminals suggest a localization of mGluR4a on presynaptic terminals. Immunocytochemistry at electron microscopy level confirmed these results, revealing that in the globus pallidus, mGluR4a is mainly localized in presynaptic sites in axonal elements. Finally, quinolinic acid lesion of striatal projection neurons decreased mGluR4a immunoreactivity in globus pallidus, suggesting a localization of mGluR4a on striatopallidal terminals. These data support the hypothesis that mGluR4a serves as a presynaptic heteroreceptor in the globus pallidus, where it may play an important role in regulating g-amino-n-butyric acid (GABA) release from striatopallidal terminals. (C) 1999 Wiley-Liss, Inc. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Wyeth Ayerst Res, CNS Disorders, Princeton, NJ 08543 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Conn, PJ (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Rollins Res Bldg, Atlanta, GA 30322 USA. RI Conn, Peter/D-7848-2012; Levey, Allan/F-2104-2011; OI Levey, Allan/0000-0002-3153-502X; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS28405, NS31373, NS34361] NR 38 TC 117 Z9 120 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 28 PY 1999 VL 407 IS 1 BP 33 EP 46 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 182EB UT WOS:000079484600003 PM 10213186 ER PT J AU Fujishima, H Mejia, ROS Bingham, CO Lam, BK Sapirstein, A Bonventre, JV Austen, KF Arm, JP AF Fujishima, H Mejia, ROS Bingham, CO Lam, BK Sapirstein, A Bonventre, JV Austen, KF Arm, JP TI Cytosolic phospholipase A(2) is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-1; P388D(1) MACROPHAGES; SIGNAL-TRANSDUCTION; D-2 GENERATION; ACTIVATION; GENE; TRANSLOCATION; LEUKOTRIENES; INFLAMMATION; EXPRESSION AB We have used mice in which the gene for cytosolic phospholipase A(2) (cPLA(2)) has been disrupted to demonstrate the absolute requirement for cPLA(2) in both the immediate and the delayed phases of eicosanoid generation by bone marrow-derived mast cells. For the immediate phase, quantitative analysis of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA(2) prevented the provision of arachidonic acid substrate for biosynthesis of proximal intermediates. By analogy, we conclude that arachidonic acid substrate was also not available to prostaglandin endoperoxide synthase 1 in the immediate phase of prostaglandin (PG) D-2 generation. These defects occurred with two distinct stimuli, stem cell factor and IgE/antigen, which were, however, sufficient for signal transduction defined by exocytosis of beta-hexosaminidase, Whereas cPLA(2) is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD(2) generation is more complex and involves the activation dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD(2). C1 Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Partners Asthma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anesthesia Serv, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci, Boston, MA 02115 USA. RP Arm, JP (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Smith Res Bldg,Room 638B,1 Jimmy Fund Way, Boston, MA 02115 USA. FU HSRD VA [TPP 97-001]; NHLBI NIH HHS [HL36110, P01 HL036110]; NIAID NIH HHS [AI22531, AI31599, P01 AI031599, U19 AI031599]; NIDDK NIH HHS [P01 DK038452, R01 DK039773, R37 DK039773]; NINDS NIH HHS [F32 NS010828, P01 NS010828, P50 NS010828] NR 33 TC 144 Z9 147 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 27 PY 1999 VL 96 IS 9 BP 4803 EP 4807 DI 10.1073/pnas.96.9.4803 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200016 PM 10220374 ER PT J AU Mao, XH Fujiwara, Y Orkin, SH AF Mao, XH Fujiwara, Y Orkin, SH TI Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SITE-SPECIFIC RECOMBINATION; EMBRYONIC STEM-CELLS; TRANSGENIC MICE; MOUSE EMBRYOS; GERM-LINE; GENE; DELETION; GALACTOSIDASE; MUTAGENESIS; EXPRESSION AB Effective use of conditional Cre recombinase-loxP gene modification requires Cre-expressing mouse strains with defined patterns of expression. To assess the in vivo functionality of Cre expressing mice, we have engineered an improved reporter strain for monitoring Cre-mediated excisions. The beta-galactosidase-neomycin phosphotransferase fusion gene (beta geo)-trapped ROSA26 locus was modified by gene targeting such that beta geo is expressed only after Cre-mediated excision of loxP-flanked DNA sequences. beta geo from the excised ROSA26 allele is expressed ubiquitously in embryos and adult mice. By mating the reporter strain with Cre-expressing transgenic mice, we have shown that the loxP-flanked ROSA26 allele is accessible to Cre during early embryogenesis, as well as in a specific hematopoietic lineage (T lymphocytes). This improved reporter strain should facilitate monitoring in vivo Cre-mediated excision events in a variety of experimental contexts. C1 Harvard Univ, Sch Med, Dept Pediat, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dept Pediat, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. NR 27 TC 235 Z9 242 U1 1 U2 4 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 27 PY 1999 VL 96 IS 9 BP 5037 EP 5042 DI 10.1073/pnas.96.9.5037 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200056 PM 10220414 ER PT J AU Klein, C Brin, MF Kramer, P Sena-Esteves, M de Leon, D Doheny, D Bressman, S Fahn, S Breakefield, XO Ozelius, LJ AF Klein, C Brin, MF Kramer, P Sena-Esteves, M de Leon, D Doheny, D Bressman, S Fahn, S Breakefield, XO Ozelius, LJ TI Association of a missense change in the D2 dopamine receptor with myoclonus dystonia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PARKINSONS-DISEASE; GENE DYT1; MUTATION; BINDING; ALCOHOLISM; LINKAGE; SCHIZOPHRENIA; INHERITANCE; RESIDUES; FAMILIES AB Hereditary autosomal dominant myoclonus dystonia (MD) is a movement disorder characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Although various large families with MD have been described, no positive linkage has been found to a chromosomal location. We report a family with eight members with MD. Linkage analysis identified a 23-centimorgan region on chromosome 11q23 that cosegregates with the disease state (maximum multipoint logarithm of odds score = 2.96 at D11S897). This region contains an excellent candidate gene for involvement in the etiology of MD, the D2 dopamine receptor (DRD2) gene. Neurotransmission mediated by DRD2 is known to have a key role in the control of movement and also has been implicated in reward and reinforcement mechanisms and psychiatric disorders. Sequencing of the coding region of DRD2 indicated that all affected and obligate carriers were heterozygous for a Val154Ile change in exon 3 of the protein, which is highly conserved across species. This change was found neither in other unaffected members of the pedigree nor in 250 control chromosomes. Our finding provides evidence for the involvement of DRD2 in a disorder of the central nervous system and should lead to further insight into the function of the dopaminergic system in dystonia and other movement and mood disorders. C1 Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Mt Sinai Hosp, Movement Disorders Ctr, Dept Neurol, New York, NY 10029 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Columbia Presbyterian Med Ctr, Dept Neurol, Dystonia Clin Res Ctr, New York, NY 10032 USA. RP Ozelius, LJ (reprint author), Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. FU NINDS NIH HHS [NS28384, R01 NS028384] NR 40 TC 92 Z9 95 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 27 PY 1999 VL 96 IS 9 BP 5173 EP 5176 DI 10.1073/pnas.96.9.5173 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 193HQ UT WOS:000080130200080 PM 10220438 ER PT J AU Yamada, K Ierino, FL Gianello, PR Shimizu, A Colvin, RB Sachs, DH AF Yamada, K Ierino, FL Gianello, PR Shimizu, A Colvin, RB Sachs, DH TI Role of the thymus in transplantation tolerance in miniature swine - III. Surgical manipulation of the thymus interferes with stable induction of tolerance to class I-mismatched renal allografts SO TRANSPLANTATION LA English DT Article ID DONOR-SPECIFIC UNRESPONSIVENESS; INTRATHYMIC INJECTION; CARDIAC ALLOGRAFTS; MECHANISMS; CHIMERISM; ANTIGEN; SKIN; ALLOPEPTIDES; CYCLOSPORINE; INOCULATION AB Background Previous studies have demonstrated that long-term tolerance of class I mismatched renal allografts in miniature swine is induced by a short course of cyclosporine (CyA), and that a total thymectomy 21 days before transplantation abrogates the induction of stable tolerance. We have now examined the effects of surgical manipulation of the thymus, with or without a reduction in the thymic volume, on the induction of tolerance. Materials and Methods. Miniature swine receiving a transplant of a class I-mismatched renal allograft and 12 days of CyA underwent either (1) a partial thymectomy 21 days before kidney transplantation (day -21), (2) serial thymic biopsies (to evaluate the effect of surgical trauma and reduction in volume of the thymus) or serial incisions of the thymus thymus (to evaluate the effect of surgical trauma without changes in thymic volume), (3) a sham thymectomy on day -21, or serial sham thymic surgery on the same POD as the thymic biopsies and incisions (control animals), Results. Control animals had a stable plasma creatinine, had donor-specific unresponsiveness in cell-mediated lympholysis (CML) assays, had absence of rejection in kidney biopsy specimens, and did not develop anti-donor class I immunoglobulin (Ig)G alloantibodies. Animals undergoing a partial thymectomy on day -21 or serial thymic biopsies showed severe renal dysfunction, histological evidence of rejection in kidney biopsy specimens and anti-donor reactivity in CML assays; all but one animal developed anti-donor class I IgG alloantibodies. Serial incisions of the thymus induced an increase in plasma creatinine and histological rejection in 1 of 3 animals and anti-donor cytotoxic T cells in vitro in all 3 animals, Conclusions. A partial thymectomy or serial thymic biopsies markedly interfere with the induction of tolerance to renal allografts, Serial thymic incisions also interfere with the induction of tolerance, but to a lesser degree, These studies may have implications for tolerance-inducing protocols that involve thymic manipulation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, MGH E,Bldg 149-9019, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 34 TC 27 Z9 29 U1 0 U2 1 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 1999 VL 67 IS 8 BP 1112 EP 1119 DI 10.1097/00007890-199904270-00005 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 192WH UT WOS:000080102300005 PM 10232560 ER PT J AU Ierino, FL Gojo, S Banerjee, PT Giovino, M Xu, YX Gere, J Kaynor, C Awwad, M Monroy, R Rembert, J Hatch, T Foley, A Kozlowski, T Yamada, K Neethling, FA Fishman, J Bailin, M Spitzer, TR Cooper, DKC Cosimi, AB LeGuern, C Sachs, DH AF Ierino, FL Gojo, S Banerjee, PT Giovino, M Xu, YX Gere, J Kaynor, C Awwad, M Monroy, R Rembert, J Hatch, T Foley, A Kozlowski, T Yamada, K Neethling, FA Fishman, J Bailin, M Spitzer, TR Cooper, DKC Cosimi, AB LeGuern, C Sachs, DH TI Transfer of swine major histocompatibility complex class II genes into autologous bone marrow cells of baboons for the induction of tolerance across xenogeneic barriers SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; HEMATOPOIETIC STEM-CELLS; IN-VIVO; RETROVIRAL TRANSDUCTION; HYPERACUTE REJECTION; NATURAL ANTIBODIES; NONHUMAN-PRIMATES; MIXED CHIMERISM; EXPRESSION; THERAPY AB Background The present study examined the potential role of gene therapy in the induction of tolerance to anti-porcine major histocompatibility complex (SLA) class II-mediated responses after porcine renal or skin xenografts, Methods. Baboons were treated with a non-myeloablative or a myeloablative preparative regimen before bone marrow transplantation with autologous bone marrow cells retrovirally transduced to express both SLA class II DR and neomycin phosphotransferase (Neo(R)) genes, or the Neo(R) gene alone. Four months or more after bone marrow transplantation, the immunological response to a porcine kidney or skin xenograft was examined. Both the renal and skin xenografts were SLA DR-matched to the transgene, and recipients were conditioned by combinations of complement inhibitors, adsorption of natural antibodies, immunosuppressive therapy, and splenectomy, Results. Although the long-term presence of the SLA transgene was detected in the peripheral blood and/or bone marrow cells of all baboons, the transcription of the transgene was transient. Autopsy tissues were available from one animal and demonstrated expression of the SLA DR transgene in lymphohematopoietic tissues, After kidney and skin transplantation, xenografts were rejected after 8-22 days. Long-term follow-up of control animals demonstrated that high levels of induced IgG antibodies to new non-alpha Gal epitopes developed after organ rejection. In contrast, induced non-alpha Gal IgG antibody responses were minimal in the SLA DR-transduced baboons. Conclusions. Transfer and expression of xenogeneic class II DR transgenes can be achieved in baboons. This therapy may prevent late T cell-dependent responses to porcine xenografts, which include induced non-alpha Gal IgG antibody responses. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Bone Marrow Transplant, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Biotransplant Inc, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 50 TC 35 Z9 38 U1 0 U2 1 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 1999 VL 67 IS 8 BP 1119 EP 1128 DI 10.1097/00007890-199904270-00006 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 192WH UT WOS:000080102300006 PM 10232561 ER PT J AU Saint, S Lipsky, BA AF Saint, S Lipsky, BA TI Preventing catheter-related bacteriuria - Should we? Can we? How? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID URINARY-TRACT INFECTIONS; NURSING-HOME PATIENTS; DAILY MEATAL CARE; URETHRAL CATHETERIZATION; ANTIBIOTIC-PROPHYLAXIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; ANTIMICROBIAL PROPHYLAXIS; INFRAVESICAL OBSTRUCTION; TRANSURETHRAL RESECTION; PERIODIC INSTILLATIONS AB Up to 25% of hospitalized patients undergo urinary catheterization, and about 5% develop bacteriuria each day of catheterization, Catheter-related bacteriuria is associated with increased morbidity and mortality. We performed an evidence-based synthesis of the literature on preventing catheter-associated urinary tract infections (UTIs) to develop recommendations for clinicians. Catheterization should be avoided when not required and when needed, should be terminated as soon as possible. Use of suprapubic and condom catheters may be associated with a lower risk of UTI than use of urethral catheters, Aseptic catheter insertion and a properly maintained closed drainage system are crucial to reducing the risk of bacteriuria, Instillation of antimicrobial agents into the bladder or urinary drainage bag and rigorous meatal cleansing seem to be of little benefit. Use of urinary catheters coated with silver alloy may reduce the risk of UTI, Systemic antimicrobial drug therapy seems to prevent UTIs, but primarily for patients catheterized for 3 to 14 days. Antibiotic drug prophylaxis is especially valuable in patients undergoing transurethral resection of the prostate or renal transplantation. Using these methods, urinary catheter-associated UTI can often be prevented for weeks, but not longer terms. C1 Univ Michigan, Med Ctr, Taubman Ctr 3116, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA USA. RP Saint, S (reprint author), Univ Michigan, Med Ctr, Taubman Ctr 3116, Dept Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 103 TC 149 Z9 153 U1 0 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 26 PY 1999 VL 159 IS 8 BP 800 EP 808 DI 10.1001/archinte.159.8.800 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 189CX UT WOS:000079887500003 PM 10219925 ER PT J AU Ramirez, JJ Finklestein, SP Keller, J Abrams, W George, MN Parakh, T AF Ramirez, JJ Finklestein, SP Keller, J Abrams, W George, MN Parakh, T TI Basic fibroblast growth factor enhances axonal sprouting after cortical injury in rats SO NEUROREPORT LA English DT Article DE entorhinal cortex; hippocampus; neuroplasticity; neurotrophic factor ID ENTORHINAL CORTEX LESIONS; MESSENGER-RNA EXPRESSION; DENTATE GYRUS; DEAFFERENTED HIPPOCAMPUS; ADULT-RATS; TRANSECTION; AFFERENTS; ORIGIN; BRAIN; CELLS AB THE trophic factors responsible for initiating and guiding the outgrowth of axons hare proven to be elusive throughout most of this century. Entorhinal cortex injury, which denervates the hippocampal formation of rats, induces axonal sprouting by several surviving hippocampal afferents and results in a significant elevation of growth factors, one of which is basic fibroblast growth factor (bFGF). The possibility that bFGF may regulate lesion-induced hippocampal sprouting was examined by making i.v. bFGF infusions into rats with unilateral entorhinal lesions. Basic FGF treatment significantly increased sprouting by the cholinergic septodentate pathway. Thus, the increase in bFGF following central nervous system injury may signal its role in the regulation of injury-related axonal remodeling of a. cholinergic pathway. (C) 1999 Lippincott Williams & Wilkins. C1 Davidson Coll, Dept Psychol, Lab Behav Neurosci, Davidson, NC 28036 USA. Massachusetts Gen Hosp, Dept Neurol, CNS, Growth Factor Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ramirez, JJ (reprint author), Davidson Coll, Dept Psychol, Lab Behav Neurosci, POB 1719, Davidson, NC 28036 USA. FU NINDS NIH HHS [NS31740] NR 25 TC 42 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 26 PY 1999 VL 10 IS 6 BP 1201 EP 1204 DI 10.1097/00001756-199904260-00008 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 199NH UT WOS:000080488200009 PM 10363924 ER PT J AU Leuchter, AF Uijtdehaage, SHJ Cook, IA O'Hara, R Mandelkern, M AF Leuchter, AF Uijtdehaage, SHJ Cook, IA O'Hara, R Mandelkern, M TI Relationship between brain electrical activity and cortical perfusion in normal subjects SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE cerebral perfusion; quantitative electroencephalogram (QEEG); positron emission tomography (PET); cordance; normal subjects ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; CENTRAL NERVOUS-SYSTEM; QUANTITATIVE EEG; ALZHEIMERS-DISEASE; OXYGEN-METABOLISM; ENERGY-METABOLISM; INFARCTION; ELECTROENCEPHALOGRAPHY; FREQUENCY AB Cerebral glucose uptake and perfusion are accepted as tightly coupled measures of energy utilization in both normal and diseased brain. The coupling of brain electrical activity to perfusion has been demonstrated, however, only in the presence of chronic brain disease. Very few studies have examined the relationship between cerebral electrical activity and energy utilization in normal brain tissue. To clarify this relationship, we performed 33 (H2O)-O-15-positron emission tomography (PET) scans in six normal subjects both at rest and during a simple motor task, and acquired surface-recorded quantitative electroencephalogram (QEEG) data simultaneously with isotope injection. We examined the associations between cerebral perfusion directly underlying each recording electrode and three QEEG measures (absolute power, relative power, and cordance). All EEG measures had moderately strong; coupling with perfusion at most frequency bands, although the directions of the associations differed from those previously reported in subjects with stroke or dementia. Of the three QEEG measures examined, cordance had the strongest relationship with perfusion (multiple R-2 = 0.58). Cordance and PET were equally effective in detecting lateralized activation associated with the motor task, while EEG power did not detect this activation. Electrodes in the concordant state had a significantly higher mean perfusion than those in the discordant state. These results indicate that normal brain electrical activity has a moderately strong association with cerebral perfusion. Cordance may be the most useful QEEG measure for monitoring cerebral perfusion in subjects without chronic brain disease. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Quantitat EEG Lab, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Medicat Dev Res Unit, Los Angeles, CA 90073 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. W Los Angeles Vet Affairs Med Ctr, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Leuchter, AF (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Quantitat EEG Lab, 760 Westwood Plaza, Los Angeles, CA 90024 USA. OI Uijtdehaage, Sebastian/0000-0001-8598-4683 FU NIDA NIH HHS [1YO1 DA50038]; NIMH NIH HHS [1KO2 MH01165, 1RO1 MH40705] NR 47 TC 101 Z9 107 U1 0 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 26 PY 1999 VL 90 IS 2 BP 125 EP 140 DI 10.1016/S0925-4927(99)00006-2 PG 16 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 202AY UT WOS:000080631000005 PM 10482384 ER PT J AU Livingston, DM AF Livingston, DM TI Hot papers - Cancer genetics - Association of BRCA1 with Rad51 in mitotic and meiotic cells by R. Scully, J.J. Chen, A. Plug, Y.H. Xiao, D. Weaver, J. Feunteun, T. Ashley, D.M. Livingston - Comments SO SCIENTIST LA English DT Editorial Material ID FAMILIAL BREAST; LINKAGE C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD APR 26 PY 1999 VL 13 IS 9 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 189MZ UT WOS:000079910300015 ER PT J AU Shores, MM White, SS Veith, RC Szot, P AF Shores, MM White, SS Veith, RC Szot, P TI Tyrosine hydroxylase mRNA is increased in old age and norepinephrine uptake transporter mRNA is decreased in middle age in locus coeruleus of Brown-Norway rats SO BRAIN RESEARCH LA English DT Article DE aging; norepinephrine transporter; tyrosine hydroxylase; locus coeruleus; Brown-Norway rat ID MESSENGER-RNA; NORADRENERGIC NEURONS; CERULEUS NEURONS; RELEASE; BRAIN; NORADRENALINE; HYPOTHALAMUS; NEUROTRANSMITTER; RESTORATION; PROJECTIONS AB In normal aging, cell loss occurs in the locus coeruleus (LC), the major noradrenergic nucleus in the brain. This study examined changes in the LC of aged rats by measuring mRNA expression for tyrosine hydroxylase (TH) and the norepinephrine uptake transporter (NET). TH and NET mRNA expression were measured by in situ hybridization in young, middle-aged and aged rats. It appears that in middle age, the transporter system responds initially to LC cell loss by decreasing NET mRNA expression. Then, with further aging and cell loss, TH mRNA expression increases which may potentially increase NE synthesis in the remaining neurons. These findings suggest that multiple regulatory components are used to maintain stable noradrenergic synaptic levels despite neuronal loss. Published by Elsevier Science B.V. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Shores, MM (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way 182B, Seattle, WA 98195 USA. NR 31 TC 29 Z9 30 U1 0 U2 0 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 24 PY 1999 VL 826 IS 1 BP 143 EP 147 DI 10.1016/S0006-8993(99)01200-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 191VH UT WOS:000080041900017 PM 10216207 ER PT J AU Broder, K Reinhardt, E Ahern, JA Lifton, R Tamborlane, W Pober, B AF Broder, K Reinhardt, E Ahern, JA Lifton, R Tamborlane, W Pober, B TI Elevated ambulatory blood pressure in 20 subjects with Williams syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Williams syndrome; ambulatory blood pressure monitoring; hypertension ID ESSENTIAL-HYPERTENSION; SYSTEMIC HYPERTENSION; BEUREN-SYNDROME; ANOMALIES; HYPERCALCEMIA; SECONDARY; CHILDREN; ELASTIN AB Previous studies report conflicting frequencies of hypertension in cohorts of patients with Williams syndrome (WS), We studied blood pressure (BP) in WS using 24-hour ambulatory BP monitoring, This technique reliably measures day- and nighttime BP in a subject's natural environment and provides better prognostic information on long-term risks of hypertension than casual BP determinations, Twenty WS subjects evaluated through a multidisciplinary WS clinic and 35 age and gender-matched controls were studied, We found that WS subjects had significantly higher ambulatory BP than controls. After controlling for age, sex, and weight, the diagnosis of WS added approximately 10 mmHg to mean daytime and nighttime BPs, Hypertension, as defined by elevated mean daytime BP, was present in 40% of WS subjects versus 14% of controls (P < 0.05); among the children studied this difference was even more dramatic with 46% of WS children versus 6% of control children classified as hypertensive (P = 0.01), We also demonstrated normal diurnal BP variation but no evidence of a "white coat" effect or increased BP variability. Interestingly, parental reporting of a history of infantile hypercalcemia was strongly associated with the presence of hypertension (P = 0,008). Our data demonstrate that both children and adults with WS have higher mean BP and higher frequency of hypertension than healthy controls, Thus, elevated BP readings in the office setting should not be dismissed but require more thorough assessment. Am. J, Med. Genet. 83:356-360, 1999. (C) 1999 Wiley-Liss, Inc. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Emory Univ, Dept Polit Sci, Atlanta, GA 30322 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Internal Med, New Haven, CT 06510 USA. RP Pober, B (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06510 USA. FU NCRR NIH HHS [RR06022] NR 33 TC 34 Z9 35 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 23 PY 1999 VL 83 IS 5 BP 356 EP 360 DI 10.1002/(SICI)1096-8628(19990423)83:5<356::AID-AJMG2>3.0.CO;2-X PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 184DY UT WOS:000079596100002 PM 10232742 ER PT J AU Lin, AE Neri, G Hughes-Benzie, R Weksberg, R AF Lin, AE Neri, G Hughes-Benzie, R Weksberg, R TI Cardiac anomalies in the Simpson-Golabi-Behmel syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE multiple congenital anomaly MR syndrome; arrhythmias; Wiedemann-Beckwith syndrome; cardiomyopathy; cardiovascular malformation; congenital heart defect; macrosomia; overgrowth syndrome; Simpson-Golabi-Behmel syndrome ID WIEDEMANN-BECKWITH SYNDROME; ELEVATED MATERNAL SERUM; OVERGROWTH SYNDROME; AFFECTED MALES; ROSEN SYNDROME; FAMILIES; DYSPLASIA; GENE AB Diverse cardiac abnormalities have been reported in patients with the Simpson-Golabi-Behmel syndrome (SGBS), and it is suspected that they are related to the apparently high incidence of early death. To clarify the incidence and significance of the various cardiac abnormalities, we reviewed 101 SGBS patients (89 from the literature, 12 new). All were male, except for one clearly affected female patient with translocation X;1 [Punnett, 1994: Am J Med Genet 50: 391-393]. Ninety-six of 99 (97%) patients had the classic phenotype of macrosomia and typical "coarse" face. Thirty-six patients (36%) had a cardiac abnormality, of whom 26 (26%) had a cardiovascular malformation (CVM). After excluding 24 patients with insufficient clinical data, these percentages among the 77 informative cases were 47% and 34%, respectively. When grouped according to a mechanistic classification, most cases (20/26, or 77%) were class II CVMs (attributed to altered embryonic intracardiac flow). Other cardiac abnormalities included cardiomyopathy (n = 4) and electrocardiogram (ECG) conduction or rhythm abnormalities (n = 12); three of the affected patients (25%) also had a CVM. Among 92 informative cases, there were 29 (32%) deaths, a figure that excludes seven elective terminations. Among the 25 patients younger than 3 years, death was associated with a cardiac abnormality in six (23%). GPC3 mutation analysis using Southern blot testing and polymerase chain reaction amplification was performed for 37 of 101 (37%) patients. A mutation was detected in 26 of the 37 patients tested (70%), 12 of whom (46%) had a cardiac abnormality. We conclude that cardiac abnormalities of any type are common in SGBS (almost one-half of informative cases), with CVMs seen in one-third of cases. The heterogeneous ECG abnormalities in this survey must be viewed with caution, since they may represent a genuine component of the syndrome or reporting bias. Determining the true prevalence and natural history of cardiac abnormalities in SGBS will require a larger number of patients and more consistent prospective cardiac evaluations. There are sufficient data to recommend a baseline echocardiogram and ECG in SGBS patients. Data are insufficient to define a cardiac phenotype/molecular correlation. Am. J. Med. Genet. 83:378-381, 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Univ Cattolica Sacro Cuore, Fac Med & Chirurg A Gemelli, Ist Genet Med, Rome, Italy. Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Hosp Sick Children, Div Clin Genet, Toronto, ON M5G 1X8, Canada. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. NR 38 TC 34 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 23 PY 1999 VL 83 IS 5 BP 378 EP 381 DI 10.1002/(SICI)1096-8628(19990423)83:5<378::AID-AJMG7>3.0.CO;2-A PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 184DY UT WOS:000079596100007 PM 10232747 ER PT J AU Czerwiec, E Kalume, DE Begley, GS Hambe, B Roepstorff, P Furie, BC Furie, B Stenflo, J AF Czerwiec, E Kalume, DE Begley, GS Hambe, B Roepstorff, P Furie, BC Furie, B Stenflo, J TI Isolation, sequence analysis and cloning of novel Gla-containing peptides from the venom of the marine snail C-textile. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Marine Biol Lab, Woods Hole, MA 02543 USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Odense Univ, Odense, Denmark. Univ Lund, Malmo, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1395 EP A1395 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400428 ER PT J AU Kwong, PD Wyatt, R Sodroski, J Hendrickson, WA AF Kwong, PD Wyatt, R Sodroski, J Hendrickson, WA TI Evading the immune system: Insights from the crystal structure of the HIV gp120 envelope glycoprotein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Columbia Univ, Dept Biochem & Mol Biol, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1590 EP A1590 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401539 ER PT J AU Lu, H Zeng, X Chen, L Jost, CA Maya, R Keller, D Wang, X Kaelin, WG Oren, M Chen, J AF Lu, H Zeng, X Chen, L Jost, CA Maya, R Keller, D Wang, X Kaelin, WG Oren, M Chen, J TI MDM2 suppresses p73 function without promoting p73 degradation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Louisiana State Univ, Med Ctr, Dept Microbiol, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1538 EP A1538 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033401245 ER PT J AU Montgomery, RB Guzman, J Stahl, WL AF Montgomery, RB Guzman, J Stahl, WL TI Constitutive epidermal growth factor receptor kinase activity induces paclitaxel resistance and alters beta-tubulin isotype expression. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98108 USA. VA Puget Sound HCS, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1481 EP A1481 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400914 ER PT J AU Rudolph, L Chin, L Artandi, S Lee, HW Greenberg, R Gottlieb, G Singer, R Greider, C DePinho, R AF Rudolph, L Chin, L Artandi, S Lee, HW Greenberg, R Gottlieb, G Singer, R Greider, C DePinho, R TI Telomeres, tumorigenesis and aging in the telomerase-deficient mouse. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1330 EP A1330 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400056 ER PT J AU Shioda, T Li, H Yahata, T Andriole, S Isselbacher, KJ AF Shioda, T Li, H Yahata, T Andriole, S Isselbacher, KJ TI A novel family of non-DNA-binding transcriptional activators requiring the CBP/p300 co-activators for their activities. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Tumor Biol, Ctr Canc, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400277 ER PT J AU Szostak, JW AF Szostak, JW TI Directed protein evolution and functional genomics using RNA-protein fusions SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 23 PY 1999 VL 13 IS 7 SU S BP A1337 EP A1337 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QX UT WOS:000082033400098 ER PT J AU Mannick, JB Hausladen, A Liu, LM Hess, DT Zeng, M Miao, QX Kane, LS Gow, AJ Stamler, JS AF Mannick, JB Hausladen, A Liu, LM Hess, DT Zeng, M Miao, QX Kane, LS Gow, AJ Stamler, JS TI Fas-induced caspase denitrosylation SO SCIENCE LA English DT Article ID PROGRAMMED CELL-DEATH; NITRIC-OXIDE; S-NITROSYLATION; INHIBITS APOPTOSIS; ACTIVATION; SUPPRESSION; MECHANISMS; P21(RAS); RECEPTOR; NEURONS AB Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell Lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Resp Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Durham, NC 27710 USA. RP Mannick, JB (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Gow, Andrew/N-8566-2013 OI Gow, Andrew/0000-0003-0876-5158 FU NHLBI NIH HHS [HL59130, HL52529]; NIGMS NIH HHS [GM57601-01] NR 35 TC 593 Z9 614 U1 1 U2 11 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 23 PY 1999 VL 284 IS 5414 BP 651 EP 654 DI 10.1126/science.284.5414.651 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190FH UT WOS:000079951100047 PM 10213689 ER PT J AU Kamura, T Koepp, DM Conrad, MN Skowyra, D Moreland, RJ Iliopoulos, O Lane, WS Kaelin, WG Elledge, SJ Conaway, RC Harper, JW Conway, JW AF Kamura, T Koepp, DM Conrad, MN Skowyra, D Moreland, RJ Iliopoulos, O Lane, WS Kaelin, WG Elledge, SJ Conaway, RC Harper, JW Conway, JW TI Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase SO SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CELL-CYCLE EXIT; F-BOX; SACCHAROMYCES-CEREVISIAE; PROTEIN; GENE; IDENTIFICATION; PATHWAY; CDC53; PROTEOLYSIS AB The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G(1) to S cell cycle transition. These findings provide a further Link between VHL and the cellular ubiquitination machinery. C1 Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA. Baylor Coll Med, Verna & Marrs McLean Dept Biochem, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Harvard Microchem Facil, Cambridge, MA 02138 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. RP Conway, JW (reprint author), Oklahoma Med Res Fdn, Howard Hughes Med Inst, 825 NE 13th St, Oklahoma City, OK 73104 USA. OI Conaway, Joan/0000-0002-2786-0663 FU NIA NIH HHS [AG-11085]; NIGMS NIH HHS [GM41628] NR 31 TC 555 Z9 568 U1 1 U2 15 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 23 PY 1999 VL 284 IS 5414 BP 657 EP 661 DI 10.1126/science.284.5414.657 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190FH UT WOS:000079951100049 PM 10213691 ER PT J AU Berrueta, L Tirnauer, JS Schuyler, SC Pellman, D Bierer, BE AF Berrueta, L Tirnauer, JS Schuyler, SC Pellman, D Bierer, BE TI The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain SO CURRENT BIOLOGY LA English DT Article ID BINDING PROTEIN; MICROTUBULES; P150(GLUED); REVEALS; YEAST; ACTIN AB Human EB1 is a highly conserved protein that binds to the carboxyl terminus of the human adenomatous polyposis coli (APC) tumor suppressor protein [1], a domain of APC that is commonly deleted in colorectal neoplasia [2]. EB1 belongs to a family of microtubule-associated proteins that includes Schizosaccharomyces pombe Mal3 [3] and Saccharomyces cerevisiae Bim1p [4], Bim1p appears to regulate the timing of cytokinesis as demonstrated by a genetic interaction with Act5, a component of the yeast dynactin complex [5], Whereas the predominant function of the dynactin complex in yeast appears to be in positioning the mitotic spindle [6], in animal cells, dynactin has been shown to function in diverse processes, including organelle transport, formation of the mitotic spindle, and perhaps cytokinesis [7-10], Here, we demonstrate that human EB1 can be coprecipitated with p150(Glued), a member of the dynactin protein complex. EB1 was also found associated with the intermediate chain of cytoplasmic dynein (CDIC) and with dynamitin (p50), another component of the dynactin complex, but not with dynein heavy chain, in a complex that sedimented at approximately 5S in a sucrose density gradient. The association of EB1 with members of the dynactin complex was independent of APC and was preserved in the absence of an intact microtubule cytoskeleton, The molecular interaction of EB1 with members of the dynactin complex and with CDIC may be important for microtubule-based processes. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, 10 Ctr Dr, Bethesda, MD 20892 USA. OI Berrueta, Lisbeth/0000-0002-5674-6448 NR 17 TC 119 Z9 121 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 22 PY 1999 VL 9 IS 8 BP 425 EP 428 DI 10.1016/S0960-9822(99)80190-0 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190BR UT WOS:000079942100019 PM 10226031 ER PT J AU Amano, B Nishiyama, T Burgeson, RE AF Amano, B Nishiyama, T Burgeson, RE TI A specific and sensitive ELISA for laminin 5 SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE laminin 5; keratinocytes; ELISA; extracellular matrix ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; GENE LAMC2; KERATINOCYTES; EXPRESSION; KALININ; ADHESION; GAMMA-2; CLONING; LAMB3; COMPONENTS AB A sandwich ELISA for laminin 5 was developed by using two monoclonal antibodies specific for human laminin 5, basement membrane (BM)165 and 6F12, which were raised against the laminin alpha 3 chain and the laminin beta 3 chain, respectively. Laminin 5 was purified from squamous carcinoma cell (SCC) 25-conditioned medium, using 6F12-conjugated Sepharose. This preparation was used as the standard for the ELISA. This sandwich ELISA was sensitive enough to detect reproducibly as little as 125 pg of laminin 5. This assay could detect laminin 5 produced by human keratinocytes but not other laminins produced by human fibroblasts. A portion of the laminin 5 that was secreted by the keratinocytes was deposited around the cells, and the rest was released into the medium. To measure total synthesized laminin 5, the intracellular and deposited laminin 5 was solubilized by treatment with a mixture of several kinds of detergents that did not interfere with the sandwich ELISA, and the laminin in both the culture medium and the solubilized cell layer was quantified. The amount of laminin 5 synthesis by keratinocytes depended on the cell number, the duration of culture, and the extracellular matrix proteins on which keratinocytes were plated. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Shiseido Life Sci Res Ctr, Skin Biol Res Labs, Kanazawa Ku, Yokohama, Kanagawa 2368643, Japan. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Amano, B (reprint author), Shiseido Life Sci Res Ctr, Skin Biol Res Labs, Kanazawa Ku, 2-12-1 Fukuura, Yokohama, Kanagawa 2368643, Japan. RI Nishiyama, Toshio/C-5434-2013 NR 25 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 22 PY 1999 VL 224 IS 1-2 BP 161 EP 169 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 195AQ UT WOS:000080227300017 ER PT J AU Yang, A Schweitzer, R Sun, DQ Kaghad, M Walker, N Bronson, RT Tabin, C Sharpe, A Caput, D Crum, C McKeon, F AF Yang, A Schweitzer, R Sun, DQ Kaghad, M Walker, N Bronson, RT Tabin, C Sharpe, A Caput, D Crum, C McKeon, F TI p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development SO NATURE LA English DT Article ID VERTEBRATE LIMB; P53 HOMOLOG; MICE; DIFFERENTIATION; KERATINOCYTE; INVOLVEMENT; EXPRESSION; INITIATION; INDUCTION; CELLS AB The p63 gene, a homologue of the tumour-suppressor p53 (refs 1-5), is highly expressed in the basal or progenitor layers of many epithelial tissues(1). Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for Limb development The embryonic epidermis of p63(-/-) mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Sanofi Biorech, F-31676 Labege, France. Tufts Univ, Sch Vet Med, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. RP McKeon, F (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NR 30 TC 1478 Z9 1531 U1 2 U2 57 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 1999 VL 398 IS 6729 BP 714 EP 718 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 189RP UT WOS:000079920100052 PM 10227294 ER PT J AU Gerszten, RE Garcia-Zepeda, EA Lim, YC Yoshida, M Ding, HA Gimbrone, MA Luster, AD Luscinskas, FW Rosenzweig, A AF Gerszten, RE Garcia-Zepeda, EA Lim, YC Yoshida, M Ding, HA Gimbrone, MA Luster, AD Luscinskas, FW Rosenzweig, A TI MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions SO NATURE LA English DT Article ID LEUKOCYTE ADHESION; CHEMOATTRACTANT PROTEIN-1; CHEMOTACTIC CYTOKINES; APOLIPOPROTEIN-E; CC CHEMOKINES; IN-VITRO; CELLS; ATHEROSCLEROSIS; MICE; ALPHA-4-BETA-1 AB Monocytes contribute to the development of atherosclerotic lesions in mouse models(1-3), The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma(4,5), and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in vascular lesions(6,7). Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear how it could recruit monocytes(6,8). Here we investigate the ability of chemokines to control the interaction of monocytes under now conditions with vascular endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-I and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte-endothelial interactions under now conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to vascular endothelium reveals an unexpected role for this chemokine in monocyte recruitment. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Tokyo Med & Dent Univ, Med Res Inst, Tokyo, Japan. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 29 TC 796 Z9 834 U1 5 U2 40 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 1999 VL 398 IS 6729 BP 718 EP 723 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 189RP UT WOS:000079920100053 PM 10227295 ER PT J AU Holloway, RG Vickrey, BG Keran, CM Lesser, E Iverson, D Larson, W Swarztrauber, K AF Holloway, RG Vickrey, BG Keran, CM Lesser, E Iverson, D Larson, W Swarztrauber, K TI US neurologists in the 1990s - Trends in practice characteristics SO NEUROLOGY LA English DT Article ID CARE; MANAGEMENT; REFORM AB Background: The American Academy of Neurology (AAN) conducts periodic surveys of its members to profile and monitor changes in the characteristics of US neurologists and their practices. Objective: To assess neurologists' characteristics, geographic distribution, practice arrangements, professional activities, practice volume, procedures performed, sources of revenue, involvement with managed care and capitation, and other selected topics. Methods: The AAN Member Census survey was sent to US neurologists in the fall of 1996 (response rate = 89%), and the Practice Profile survey was sent to a random sample of 1,986 US neurologists in the summer of 1997 (response rate = 55%) who had completed a Member Census survey. The results of the Practice Profile survey were compared with those of two prior surveys conducted in 1991 to 1992 and 1993 to 1994. Results: The mean age of US neurologists is 48 years, 18% are women, 93% are US citizens, and 24% are international medical graduates. The proportion of neurologists in solo practices, group practices, and medical schools/universities has not changed. The weekly hours worked has remained stable (58 hours), but the time spent in administrative activities has increased (p < 0.001). The average number of patient visits per week to neurologists appears to have increased (p < 0.001), as has the proportion of neurologists performing procedures (p < 0.05). The majority of neurologists have contracts with managed care organizations (82%), and a minority (32%) have capitated payment arrangements. Medicare continues to be the largest source of clinical revenue. Nearly 50% of all respondents have experience in developing clinical practice guidelines or critical pathways, and >20% of respondents employed physician extenders to assist in their practices. Conclusion: Neurologists are spending more time in administrative activities, are performing or interpreting more procedures, and are seeing more patients. Neurologists' involvement with capitation is comparable with that in a nationally representative sample of physicians, and they are exploring innovative ways, such as developing practice guidelines and using physician extenders, to improve the quality and efficiency of providing neurologic care. C1 Univ Rochester, Dept Neurol & Community & Prevent Med, Rochester, NY 14642 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Amer Acad Neurol, St Paul, MN USA. Fdn Med Partners, Nashua, NH USA. Humboldt Neurol Med Grp, Eureka, CA USA. Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. Univ Los Angeles, Ctr Study Hlth Care Provider Behav, W Los Angeles Vet Adm, Los Angeles, CA USA. Univ Los Angeles, Dept Neurol, Los Angeles, CA USA. RP Holloway, RG (reprint author), Univ Rochester, Dept Neurol, 1351 Mt Hope Profess Bldg,Suite 220, Rochester, NY 14642 USA. NR 25 TC 10 Z9 11 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 22 PY 1999 VL 52 IS 7 BP 1353 EP 1361 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 189KG UT WOS:000079903200009 PM 10227617 ER PT J AU Hayward, LJ Sandoval, GM Cannon, SC AF Hayward, LJ Sandoval, GM Cannon, SC TI Defective slow inactivation of sodium channels contributes to familial periodic paralysis SO NEUROLOGY LA English DT Article ID PARAMYOTONIA-CONGENITA; MYOTONIA; MUTANT; MUTATIONS; AXONS AB Objective: To evaluate the effects of missense mutations within the skeletal muscle sodium (Na) channel on slow inactivation (SI) in periodic paralysis and related myotonic disorders. Background: Na channel mutations in hyperkalemic periodic paralysis and the nondystrophic myotonias interfere with the normally rapid inactivation of muscle Na currents following an action potential. This defect causes persistent inward Na currents that produce muscle depolarization, myotonia, or onset of weakness. Distinct from fast inactivation is the process called SI, which limits availability of Na channels on a time scale of seconds to minutes, thereby influencing muscle excitability. Methods: Human Na channel cDNAs containing mutations associated with paralytic and nonparalytic phenotypes were transiently expressed in human embryonic kidney cells for whole-cell Na current recording. Extent of SI over a range of conditioning voltages (-120 to +20 mV) was defined as the fraction of Na current that failed to recover within 20 ms at -100 mV. The time course of entry to SI at -30 mV was measured using a conditioning pulse duration of 20 ms to 60 seconds. Recovery from SI at -100 mV was assessed over 20 ms to 10 seconds. Results: The two most common hyperkalemic periodic paralysis (HyperPP) mutations responsible for episodic attacks of weakness or paralysis, T704M and M1592V, showed clearly impaired SI, as we and others have observed previously for the rat homologs of these mutations. In addition, a new paralysis-associated mutant, I693T, with cold-induced weakness, exhibited a comparable defect in SI. However, SI remained intact for both the HyperPP/paramyotonia congenita (PMC) mutant, A1156T, and the nonparalytic potassium-aggravated myotonia (PAM) mutant, V1589M. Conclusions: SI is defective in a subset of mutant Na channels associated with episodic weakness (HyperPP or PMC) but remains intact for mutants studied so far that cause myotonia without weakness (PAM). C1 Massachusetts Gen Hosp, EDR 413A, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, EDR 413A, Dept Neurol, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR42703]; NINDS NIH HHS [5K08NS01990-02] NR 21 TC 84 Z9 89 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 22 PY 1999 VL 52 IS 7 BP 1447 EP 1453 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 189KG UT WOS:000079903200025 PM 10227633 ER PT J AU Cudkowicz, ME Sexton, PM Ellis, T Hayden, DL Gwilt, PR Whalen, J Brown, RH AF Cudkowicz, ME Sexton, PM Ellis, T Hayden, DL Gwilt, PR Whalen, J Brown, RH TI The pharmacokinetics and pharmacodynamics of Procysteine in amyotrophic lateral sclerosis SO NEUROLOGY LA English DT Article ID GLUTATHIONE LEVELS; BRAIN AB In 13 subjects with ALS, we studied the safety and pharmacokinetic properties of Procysteine, a cysteine prodrug that increases levels of intracellular glutathione. We found that oral administration of Procysteine was safe. Procysteine enters CSF after both IV and oral dosing and accumulates to significant levels in CSF. We also observed that CSF levels of glutathione fall dramatically with aging. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA USA. Harvard Univ, Sch Med, MGH, Gen Clin Res Ctr, Boston, MA USA. Univ Nebraska, Ctr Med, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE 68198 USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, Dept Neurol, 82 Blossom St,Rm ACC 836, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR 01066]; NIA NIH HHS [1P01AG12992]; NINDS NIH HHS [K08 NS 01896] NR 10 TC 21 Z9 21 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 22 PY 1999 VL 52 IS 7 BP 1492 EP 1494 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 189KG UT WOS:000079903200034 PM 10227642 ER PT J AU Yee, AS Simon, JH Anderson, CA Sze, CI Filley, CM AF Yee, AS Simon, JH Anderson, CA Sze, CI Filley, CM TI Diffusion-weighted MRI of right-hemisphere dysfunction in Creutzfeldt-Jakob disease SO NEUROLOGY LA English DT Article C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Yee, AS (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Box 182,4200 E 9th Ave, Denver, CO 80262 USA. NR 7 TC 32 Z9 32 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 22 PY 1999 VL 52 IS 7 BP 1514 EP 1515 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 189KG UT WOS:000079903200043 PM 10227651 ER PT J AU Callus, BA Mathey-Prevot, B AF Callus, BA Mathey-Prevot, B TI Rapid selection of tetracycline-controlled inducible cell lines using a green fluorescent-transactivator fusion protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CONTROLLED GENE-EXPRESSION; EFFICACY AB We describe a modification of the tetracycline-controlled expression system that facilitates the rapid identification of tetracycline-sensitive clones. The TetR/VP16 transactivator protein was tagged with the green fluorescent protein (GFP) at its N-terminus, This results in a functional transactivator which allows cells expressing high levels of the modified transactivator to be selected by fluorescent-activated cell sorting. After expansion, single cell clones that maintain a high level of GFP fluorescence can be tested for their ability to transactivate a luciferase gene under control of the Tet operator, leading to the rapid identification of clones with strong inducibility. (C) 1999 Academic Press. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Callus, BA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [P50 DK49216] NR 12 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 21 PY 1999 VL 257 IS 3 BP 874 EP 878 DI 10.1006/bbrc.1999.0558 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189UV UT WOS:000079925300041 PM 10208877 ER PT J AU Russell, PS AF Russell, PS TI Understanding resource use in liver transplantation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Russell, PS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Room 510,White Bldg, Boston, MA 02114 USA. EM psrussell@partners.org NR 9 TC 5 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 1999 VL 281 IS 15 BP 1431 EP 1432 DI 10.1001/jama.281.15.1431 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 185ZF UT WOS:000079701000034 PM 10217060 ER PT J AU Wang, TJ Ausiello, JC Stafford, RS AF Wang, TJ Ausiello, JC Stafford, RS TI Trends in antihypertensive drug advertising, 1985-1996 SO CIRCULATION LA English DT Article DE hypertension; practice patterns; drug therapy; advertising ID UNITED-STATES; NEPHROPATHY; THERAPIES; HEALTH AB Background-Over the past decade, calcium channel blockers (CCBs) and ACE inhibitors have been used increasingly in the treatment of hypertension. In contrast, beta-blocker and diuretic use has decreased. It has been suggested that pharmaceutical marketing has influenced these prescribing patterns. No objective analysis of advertising for antihypertensive therapies exists, however. Methods and Results-We reviewed the January, April, July, and October issues of the New England Journal of Medicine from 1985 to 1996 (210 issues). The intensity of drug promotion was measured as the proportion of advertising pages used to promote a given medication. Statistical analyses used the chi(2) test for trend. Advertising for CCBs increased from 4.6% of advertising pages in 1985 to 26.9% in 1996, while advertising for beta-blockers (12.4% in 1985 to 0% in 1996) and diuretics (4.2% to 0%) decreased (all P<0.0001). A nonsignificant increase was observed in advertising for ACE inhibitors (3.5% to 4.3%, P=0.17). Although the total number of drug advertising pages per issue decreased from 60 pages in 1985 to 42 pages in 1996 (P<0.001), the number of pages devoted to calcium channel blocker advertisements nearly quadrupled. Conclusions-Increasing promotion of CCBs has mirrored trends in physician prescribing. An association between advertising and prescribing patterns could explain why CCBs have supplanted better-substantiated therapies for hypertension. C1 Harvard Univ, Inst Hlth Policy, Massachusetts Gen Hosp, Sch Med,Med Serv,Gen Med Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Stafford, RS (reprint author), Harvard Univ, Inst Hlth Policy, Massachusetts Gen Hosp, Sch Med,Med Serv,Gen Med Div, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [HS-90198] NR 18 TC 57 Z9 58 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 APR 20 PY 1999 VL 99 IS 15 BP 2055 EP 2057 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 186LQ UT WOS:000079731500018 PM 10209012 ER PT J AU Force, T Rosenzweig, A Choukroun, G Hajjar, R AF Force, T Rosenzweig, A Choukroun, G Hajjar, R TI Calcineurin inhibitors and cardiac hypertrophy SO LANCET LA English DT Editorial Material ID ACTIVATED PROTEIN-KINASES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. RP Force, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02129 USA. OI Force, Thomas/0000-0002-0450-8659 NR 17 TC 17 Z9 17 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 17 PY 1999 VL 353 IS 9161 BP 1290 EP 1292 DI 10.1016/S0140-6736(99)90016-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 195XU UT WOS:000080278100006 PM 10218524 ER PT J AU Rohatgi, R Ma, L Miki, H Lopez, M Kirchhausen, T Takenawa, T Kirschner, MW AF Rohatgi, R Ma, L Miki, H Lopez, M Kirchhausen, T Takenawa, T Kirschner, MW TI The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly SO CELL LA English DT Article ID ALDRICH-SYNDROME PROTEIN; DEPOLYMERIZING PROTEIN; LISTERIA-MONOCYTOGENES; BINDING; RAC; CYTOSKELETON; MOTILITY; RHO; PHOSPHORYLATION; REORGANIZATION AB Although small GTP-binding proteins of the Rho family have been implicated in signaling to the actin cytoskeleton, the exact nature of the linkage has remained obscure. We describe a novel mechanism that links one Rho family member, Cdc42, to actin polymerization. N-WASP, a ubiquitously expressed Cdc42-interacting protein, is required for Cdc42-stimulated actin polymerization in Xenopus egg extracts. The C terminus of N-WASP binds to the Arp2/3 complex and dramatically stimulates its ability to nucleate actin polymerization. Although full-length N-WASP is less effective, its activity can be greatly enhanced by Cdc42 and phosphatidylinositol (4,5) bisphosphate. Therefore, N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Biochem, Tokyo 108, Japan. RP Kirschner, MW (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RI Ma, Le/A-3733-2013; OI Ma, Le/0000-0003-2769-9416 FU NHLBI NIH HHS [5PO1 HL 59561-02]; NIGMS NIH HHS [GM26875] NR 37 TC 880 Z9 890 U1 2 U2 35 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 16 PY 1999 VL 97 IS 2 BP 221 EP 231 DI 10.1016/S0092-8674(00)80732-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 187GY UT WOS:000079779800011 PM 10219243 ER PT J AU Mutus, B Redmond, RW Akhter, S AF Mutus, B Redmond, RW Akhter, S TI Evidence for peroxynitrite formation during S-nitrosoglutathione photolysis in air saturated solutions SO FEBS LETTERS LA English DT Article DE S-nitrosoglutathione; peroxynitrite; photolysis; nitric oxide ID NITRIC-OXIDE; PHOTOCHEMICAL RELEASE; SUPEROXIDE; MECHANISM; NITRATION; HYDROXYLATION AB Flash photolysis of S-nitrosoglutathione (GSNO) in aerated solutions at pH 10 gave rise to an absorption with a maximum around 310-320 nm, This peal is spectrally similar to that display ed by ONOO-. The decay kinetics of this absorption mas compared to that of authentic ONOO-, generated independently. An excellent correlation was obtained. Further proof of ONOO- generation aas provided by HPLC studies showing the production of 3-nitrotyrosine on irradiation of GSNO in the presence of tyrosine at pH 7.4, In addition, the nitration yield nas increased similar to 5-fold in the presence of bicarbonate and totally eliminated,vith DMPO, indicating the requirement of a radical intermediate for peroxynitrite production during S-nitrosothiol photolysis. (C) 1999 Federation of European Biochemical Societies. C1 Univ Windsor, Sch Phys Sci, Windsor, ON N9B 3P4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02165 USA. RP Mutus, B (reprint author), Univ Windsor, Sch Phys Sci, Windsor, ON N9B 3P4, Canada. NR 16 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 16 PY 1999 VL 449 IS 1 BP 79 EP 82 DI 10.1016/S0014-5793(99)00311-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 189NF UT WOS:000079910900018 PM 10225433 ER PT J AU Zucker, SD Goessling, W Hoppin, AG AF Zucker, SD Goessling, W Hoppin, AG TI Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ORGANIC ANION UPTAKE; PERFUSED-RAT-LIVER; PLASMA-MEMBRANE; UDP-GLUCURONOSYLTRANSFERASE; BINDING-PROTEIN; HEPATIC-UPTAKE; SERUM-ALBUMIN; FATTY-ACIDS; PHOSPHOLIPID-BILAYERS; FLIP-FLOP AB The liver is responsible for the clearance and metabolism of unconjugated bilirubin, the hydrophobic end-product of heme catabolism. Although several putative bilirubin transporters have been described, it has been alternatively proposed that bilirubin enters the hepatocyte by passive diffusion through the plasma membrane. In order to elucidate the mechanism of bilirubin uptake, we measured the rate of bilirubin transmembrane diffusion (flip-flop) using stopped-flow fluorescence techniques. Unconjugated bilirubin rapidly diffuses through model phosphatidylcholine vesicles, with a first-order rate constant of 5.3 s(-1) (t(1/2) = 130 ms). The flip-flop rate is independent of membrane cholesterol content, phospholipid acyl saturation, and lipid packing, consistent with thermodynamic analyses demonstrating minimal steric constraint to bilirubin transmembrane diffusion. The coincident decrease in pH of the entrapped vesicle volume supports a mechanism whereby the bilirubin molecule crosses the lipid bilayer as the uncharged diacid. Transport of bilirubin by native rat hepatocyte membranes exhibits kinetics comparable with that in model vesicles, suggesting that unconjugated bilirubin crosses cellular membranes by passive diffusion through the hydrophobic lipid core. In contrast, there is no demonstrable flip-flop of bilirubin diglucuronide or bilirubin ditaurate in phospholipid vesicles, yet these compounds rapidly traverse isolated rat hepatocyte membranes, confirming the presence of a facilitated uptake system(s) for hydrophilic bilirubin conjugates. C1 Univ Cincinnati, Med Ctr, Div Digest Dis, Cincinnati, OH 45267 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pediat Gastroenterol, Boston, MA 02114 USA. RP Zucker, SD (reprint author), Univ Cincinnati, Med Ctr, Div Digest Dis, 231 Bethesda Ave,ML 0595, Cincinnati, OH 45267 USA. FU NIDDK NIH HHS [DK-51679] NR 54 TC 85 Z9 87 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 1999 VL 274 IS 16 BP 10852 EP 10862 DI 10.1074/jbc.274.16.10852 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900030 PM 10196162 ER PT J AU Choundhury, GG Kim, YS Simon, M Wozney, J Harris, S Ghosh-Choundhury, N Abboud, HE AF Choundhury, GG Kim, YS Simon, M Wozney, J Harris, S Ghosh-Choundhury, N Abboud, HE TI Bone morphogenetic protein 2 inhibits platelet-derived growth factor-induced c-fos gene transcription and DNA synthesis in mesangial cells - Involvement of mitogen-activated protein kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASES; FAMILY MEDIATOR SMAD1; TGF-BETA; SIGNALING PATHWAYS; EYE DEVELOPMENT; MAP KINASE; BMP; DIFFERENTIATION; KIDNEY; NUCLEUS AB Bone morphogenetic proteins (BMPs) play an important role in nephrogenesis. The biologic effect and mechanism of action of these proteins in the adult kidney has not yet been studied. We investigated the effect of BMP2, a member of these growth and differentiation factors, on mitogenic signal transduction pathways induced by platelet-derived growth factor (PDGF) in glomerular mesangial cells. PDGF is a growth and survival factor for these cells in vitro and in vivo. Incubation of mesangial cells with increasing concentrations of BMP2 inhibited PDGF-induced DNA synthesis in a dose-dependent manner with maximum inhibition at 250 ng/ml. Immune complex tyrosine kinase assay of PDGF receptor beta immunoprecipitates from lysates of mesangial cells treated with PDGF showed no inhibitory effect of BMP2 on PDGF receptor tyrosine phosphorylation, This indicates that the inhibition of DNA synthesis is likely due to postreceptor events. However, BMP2 significantly inhibited PDGF-stimulated mitogen-activated protein kinase (MAPK) activity that phosphorylates the Elk-1 transcription factor, a component of the ternary complex factor. Using a fusion protein-based reporter assay, we also show that BMP2 blocks PDGF-induced Elk-1-mediated transcription. Furthermore, we demonstrate that BMP2 inhibits PDGF-induced transcription of c-fos gene, a natural target of Elk-1 that normally forms a ternary complex that activates the serum response element of the c-fos gene. These data provide the first evidence that in mesangial cells, BMP2 signaling cross-talks with MAPK-based transcriptional events to inhibit PDGF-induced DNA synthesis. One target for this inhibition is the early response gene c-fos. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Inst Genet, Cambridge, MA 01810 USA. RP Choundhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR44728]; NIDDK NIH HHS [DK 50190, DK43988] NR 52 TC 50 Z9 51 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 1999 VL 274 IS 16 BP 10897 EP 10902 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900035 PM 10196167 ER PT J AU van den Brink, MRM Kapeller, R Pratt, JC Chang, JH Burakoff, SJ AF van den Brink, MRM Kapeller, R Pratt, JC Chang, JH Burakoff, SJ TI The extracellular signal-regulated kinase pathway is required for activation-induced cell death of T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAS-LIGAND EXPRESSION; NIH 3T3 CELLS; PROTEIN-KINASE; INDUCED APOPTOSIS; ANTIGEN RECEPTOR; TYROSINE KINASE; HYBRIDOMAS; LYMPHOCYTES; INHIBITOR; DIFFERENTIATION AB T cells can undergo activation-induced cell death (AICD) upon stimulation of the T cell receptor-CD3 complex. We found that the extracellular signal-regulated kinase (ERK) pathway is activated during AICD, Transient transfection of a dominant interfering mutant of mitogen-activated/extracellular signal-regulated receptor protein kinase kinase (MEK1) demonstrated that down-regulation of the ERK pathway inhibited Fast expression during AICD, whereas activation of the ERK pathway with a constitutively active MEK1 resulted in increased expression of Fast. We also found that pretreatment with the specific MEK1 inhibitor PD98059 prevented the induction of Fast expression during AICD and inhibited AICD. However, PD98059 had no effect on other apoptotic stimuli. We found only very weak ERK activity during Fas-mediated apoptosis (induced by Fas cross-linking). Furthermore, preincubation with the MEK1 inhibitor did not inhibit Fas-mediated apoptosis, Finally, we also demonstrated that pretreatment with the MEK1 inhibitor could delay and decrease the expression of the orphan nuclear steroid receptor Nur77, which has been shown to be essential for AICD. In conclusion, this study demonstrates that the ERK pathway is required for AICD of T cells and appears to regulate the induction of Nur77 and Fast expression during AICD. C1 Dana Farber Canc Inst, Div Pediat Oncol, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. RP van den Brink, MRM (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA09382, 5PO1 CA39542] NR 41 TC 83 Z9 83 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 1999 VL 274 IS 16 BP 11178 EP 11185 DI 10.1074/jbc.274.16.11178 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186VV UT WOS:000079751900071 PM 10196203 ER PT J AU Deutsch, JC Butler, JA Marsh, AM Ross, CA Norris, JM AF Deutsch, JC Butler, JA Marsh, AM Ross, CA Norris, JM TI Rapid mass spectrometric analysis for ascorbate and related organic acids in small volumes of plasma for use in pediatric subjects SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE ascorbic acid; vitamins ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COULOMETRIC ELECTROCHEMICAL DETECTION; DEHYDROASCORBIC ACID; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; VITAMIN-C AB A gas chromatographic-mass spectrometric isotope dilution method was developed for analysis of ascorbate on 10 mu l samples of plasma. This assay was reproducible (standard deviation of less than 4%) and gave values for plasma ascorbate content within 8% of our previously published gas chromatographic-mass spectrometric method. Non-specific sample preparation allowed other analytes to be determined on the same sample by adjusting data acquisition parameters and adding the appropriate internal standard. Analysis on 28 subjects fell within the expected range for plasma ascorbate 68+/-29 mu m (11.9+/-5.0 mu g/ml) and established a normal range for plasma threonate of 28.1+/-2.4 mu m (3.8+/-0.4 mu g/ml). (C) 1999 Elsevier Science B.V. All rights reserved. C1 Denver Vet Affairs Hosp, Div Hematol, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. Denver Vet Affairs Hosp, Div Gastroenterol, Dept Med, Denver, CO 80220 USA. Denver Vet Affairs Hosp, Dept Prevent Med & Biometr, Denver, CO 80220 USA. RP Deutsch, JC (reprint author), Denver Vet Affairs Hosp, Div Hematol, Dept Med, 4200 E 9th Ave,Campus Box B-170, Denver, CO 80220 USA. FU NIDDK NIH HHS [R01DK49654] NR 18 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 16 PY 1999 VL 726 IS 1-2 BP 79 EP 84 DI 10.1016/S0378-4347(99)00030-4 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 191XC UT WOS:000080046100009 PM 10348173 ER PT J AU Radhakrishnan, I Perez-Alvarado, GC Parker, D Dyson, HJ Montminy, MR Wright, PE AF Radhakrishnan, I Perez-Alvarado, GC Parker, D Dyson, HJ Montminy, MR Wright, PE TI Structural analyses of CREB-CBP transcriptional activator-coactivator complexes by NMR spectroscopy: Implications for mapping the boundaries of structural domains SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CREB; CBP; NMR spectroscopy; protein-protein interactions; domain mapping ID CHEMICAL-SHIFT; SECONDARY STRUCTURE; DNA-BINDING; INTERFACES; PROTEINS; MODEL AB A number of signal-dependent and development-specific transcription factors recruit CREB binding protein (CBP) for their transactivation function. The KIX domain of CBP is a common docking site for many of these transcription factors. We recently determined the solution structure of the KIX domain complexed to one of its targets, the Ser133-phosphorylated kinase inducible transactivation domain (pKID) of the cyclic AMP response element binding protein. The NMR studies have now been extended to a slightly longer KIX construct that, unlike the original KIX construct, is readily amenable to structural analysis in both the free and pKID-bound forms. This addition of six residues (KRRSRL) to the C terminus of the original construct elongates the C-terminal alpha 3 helix of KIX by about eight residues. On the basis of the NMR structure of the original KIX construct, residues in the extended helix are predicted to be solvent exposed and thus are not expected to contribute to the hydrophobic core of the domain. Their role appears to be in the stabilization of the a3 helix through favorable electrostatic interactions with the helix dipole, which in turn confers stability on the core of the KIX domain. These results have important implications for the identification of novel protein domain boundaries. Chemical shift perturbation mapping firmly establishes a similar mode of pKID binding to the longer KIX construct and rules out any additional intermolecular interactions between residues in the C-terminal extension and pKID. (C) 1999 Academic Press C1 Scripps Res Inst, Skaggs Inst Chem Biol, Dept Mol Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Cell Biol, Joslin Diabet Ctr,Div Res, Boston, MA 02215 USA. RP Wright, PE (reprint author), Scripps Res Inst, Skaggs Inst Chem Biol, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Wright, Peter/0000-0002-1368-0223; Dyson, Helen Jane/0000-0001-6855-3398 NR 23 TC 54 Z9 56 U1 0 U2 8 PU ACADEMIC PRESS 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 16 PY 1999 VL 287 IS 5 BP 859 EP 865 DI 10.1006/jmbi.1999.2658 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 187WV UT WOS:000079812000006 PM 10222196 ER PT J AU Stebbins, CE Kaelin, WG Pavletich, NP AF Stebbins, CE Kaelin, WG Pavletich, NP TI Structure of the VHL-ElonginC-ElonginB complex: Implications for VHL tumor suppressor function SO SCIENCE LA English DT Article ID HIPPEL-LINDAU GENE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CARCINOMA; SOMATIC MUTATIONS; F-BOX; PROTEIN; PRODUCT; UBIQUITIN; BINDING; FAMILY AB Mutation of the VHL tumor suppressor is associated with the inherited von Hippel-Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ELonginC-ELonginB complex and regulates Levels of hypoxia-inducible protei ns. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ELonginC and another between ELonginC and ELonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ELonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway. C1 Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. Cornell Univ, Joan & Sanford I Weill Grad Sch Med Sci, Dept Biochem & Struct Biol, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA. RP Pavletich, NP (reprint author), Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, 1275 York Ave, New York, NY 10021 USA. NR 41 TC 537 Z9 550 U1 4 U2 17 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 16 PY 1999 VL 284 IS 5413 BP 455 EP 461 DI 10.1126/science.284.5413.455 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187NE UT WOS:000079792200038 PM 10205047 ER PT J AU Niklason, LE Gao, J Abbott, WM Hirschi, KK Houser, S Marini, R Langer, R AF Niklason, LE Gao, J Abbott, WM Hirschi, KK Houser, S Marini, R Langer, R TI Functional arteries grown in vitro SO SCIENCE LA English DT Article ID SMOOTH-MUSCLE CELLS; BLOOD-VESSEL; CONSCIOUS DOGS; COLLAGEN; ELASTIN; VEIN; DIFFERENTIATION; PATHOGENESIS; DENSITY AB A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography. C1 Duke Univ, Dept Anesthesia, Durham, NC 27710 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. MIT, Dept Comparat Med, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Niklason, LE (reprint author), Duke Univ, Dept Anesthesia, Durham, NC 27710 USA. FU NHLBI NIH HHS [HL60435, K08HL03492] NR 30 TC 1070 Z9 1135 U1 11 U2 164 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 16 PY 1999 VL 284 IS 5413 BP 489 EP 493 DI 10.1126/science.284.5413.489 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187NE UT WOS:000079792200048 PM 10205057 ER PT J AU Padial, LR Abascal, VM Moreno, PR Weyman, AF Levine, RA Palacios, IF AF Padial, LR Abascal, VM Moreno, PR Weyman, AF Levine, RA Palacios, IF TI Echocardiography can predict the development of severe mitral regurgitation after percutaneous mitral valvuloplasty by the Inoue technique SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BALLOON VALVULOPLASTY; VALVOTOMY; VALVE; MECHANISMS; STENOSIS; SINGLE; DILATATION AB Severe mitral regurgitation (MR) following mitral balloon valvuloplasty is a major complication of this procedure. We recently described a new echocardiographic score that can predict the development of severe MR following mitral valvuloplasty with the double balloon technique. The present study was designed to test the usefulness of this score for predicting severe MR in patients undergoing the procedure using the Inoue balloon technique, From 117 consecutive patients who underwent mitral valvuloplasty using the Inoue technique, 14 (11.9%) developed sever MR after the procedure. A good quality echocardiogram before mitral valvuloplasty was available in 11 patients. These 11 patients were matched by age, sex, mitral valve area, and degree of MR before valvuloplasty with 69 randomly selected patients who did not develop severe MR after Inoue valvuloplasty. The total MR-echocardiographic (MR-echo) score was significantly greater in the severe MR group (10.5 +/- 1.4 vs 8.2 +/- 1.1; p <0.001). In addition, the component grades for the anterior leaflet (2.9 +/- 0.5 vs 2.2 +/- 0.4; p <0.001), posterior leaflet (2.6 +/- 0.7 vs 1.9 +/- 0.8), commissures (2.4 +/- 0.8 vs 2.0 +/- 0.5; p <0.05) and subvalvular apparatus (2.6 +/- 0.5 vs 1.9 +/- 0.4; p <0.001) were also higher in the MR group. Using a total score of greater than or equal to 10 as a cut-oft point for predicting severe MR with the Inoue technique, a sensitivity of 82%, specificity of 91%, accuracy of 90%, and negative predictive value of 97% were obtained. Stepwise logistic regression analysis identified the MR-echo score as the only independent predictor for developing severe MR with the Inoue technique (p <0.0001). Thus, the MR-echo score can also predict the development of: severe MR Following mitral balloon valvuloplasty using the Inoue technique, (C) 1999 by Excerpta Medica, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. NR 24 TC 15 Z9 22 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1999 VL 83 IS 8 BP 1210 EP 1213 DI 10.1016/S0002-9149(99)00061-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 185GE UT WOS:000079659100013 PM 10215286 ER PT J AU Roberts, WC Cooper, DKC AF Roberts, WC Cooper, DKC TI David Kempton Cartwright Cooper, MD: A conversation with the editor SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID BRAIN-DEATH; CARDIAC TRANSPLANTATION; HEART-TRANSPLANTATION; DISCORDANT XENOTRANSPLANTATION; ORGAN XENOTRANSPLANTATION; HYPOTHERMIC PERFUSION; HYPERACUTE REJECTION; NATURAL ANTIBODIES; HORMONAL-THERAPY; CHACMA BABOON C1 Baylor Univ, Med Ctr, Baylor Cardiovasc Inst, Dallas, TX 75246 USA. Massachusetts Gen Hosp, Immunol Surg Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Roberts, WC (reprint author), Baylor Univ, Med Ctr, Baylor Cardiovasc Inst, Dallas, TX 75246 USA. NR 80 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1999 VL 83 IS 8 BP 1253 EP 1262 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 185GE UT WOS:000079659100021 PM 10215294 ER PT J AU Freedman, R Adler, LE Gault, J Harris, JG Nagamoto, HT Olincy, A Ross, RG Stevens, K Waldo, M Leonard, S AF Freedman, R Adler, LE Gault, J Harris, JG Nagamoto, HT Olincy, A Ross, RG Stevens, K Waldo, M Leonard, S TI Parsing the phenotype of schizophrenia: Deficits in inhibitory mechanisms SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 22 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600024 ER PT J AU Fava, M AF Fava, M TI Clinical strategies for depression relapse during SSRI treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 29 BP 9S EP 9S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600031 ER PT J AU Savage, CR Deckersbach, T Wilhelm, S Rauch, SL Baer, L Jenike, MA AF Savage, CR Deckersbach, T Wilhelm, S Rauch, SL Baer, L Jenike, MA TI Learning strategies disrupt verbal and nonverbal memory in OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 55 BP 18S EP 18S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600057 ER PT J AU Amin, F Calkin, PA Silverman, JM Smith, CJ Densmore, D Siever, LJ AF Amin, F Calkin, PA Silverman, JM Smith, CJ Densmore, D Siever, LJ TI Dopamine and anhedonia in relatives of schizophrenic probands SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Bronx VA Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 111 BP 35S EP 35S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600111 ER PT J AU Nahas, Z McConnell, K Collins, S Molloy, M Oliver, NC Risch, SC Christie, S Arana, GW George, MS AF Nahas, Z McConnell, K Collins, S Molloy, M Oliver, NC Risch, SC Christie, S Arana, GW George, MS TI Could left prefrontal rTMS modify negative symptoms and attention in schizophrenia? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 120 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600120 ER PT J AU Shurman, B Wirshing, D Manschreck, TC Marder, S Wirshing, W AF Shurman, B Wirshing, D Manschreck, TC Marder, S Wirshing, W TI Risperidone improves language production compared to Haldol SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Schizophrenia Res Unit, Los Angeles, CA 90073 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 129 BP 40S EP 40S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600129 ER PT J AU Ghaemi, SN Sachs, GS Goodwin, FK AF Ghaemi, SN Sachs, GS Goodwin, FK TI Divalproex vs. lithium in the treatment of bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA 02114 USA. George Washington Univ, Ctr Neurosci Med Progress & Soc, Washington, DC 20037 USA. RI Ghaemi, Nassir/J-4934-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 204 BP 64S EP 64S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600204 ER PT J AU Fava, M Rosenbaum, J Judge, R Hoog, S Millard, D Koke, S AF Fava, M Rosenbaum, J Judge, R Hoog, S Millard, D Koke, S TI Fluoxetine versus sertraline and paroxetine in major depression: Long-term changes in weight SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 3 Z9 3 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 239 BP 74S EP 75S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600239 ER PT J AU Nahas, Z Speer, AM Molloy, M Oliver, NC Arana, GW Ballenger, JC Risch, SC George, MS AF Nahas, Z Speer, AM Molloy, M Oliver, NC Arana, GW Ballenger, JC Risch, SC George, MS TI Role of stimulation frequency in the antidepressant effect of left prefrontal rTMS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 256 BP 79S EP 80S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600256 ER PT J AU Hamner, MB Ulmer, HG Horne, DF George, MS Arana, GW AF Hamner, MB Ulmer, HG Horne, DF George, MS Arana, GW TI Procaine administration in posttraumatic stress disorder: A pilot study of tolerability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 295 BP 90S EP 91S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600294 ER PT J AU Seidman, LJ Farone, SV Kremen, WS Toomey, R Goldstein, JM Tourville, J Makris, N Kennedy, D Caviness, VS Tsuang, MT AF Seidman, LJ Farone, SV Kremen, WS Toomey, R Goldstein, JM Tourville, J Makris, N Kennedy, D Caviness, VS Tsuang, MT TI Neuropsychological and brain structural endophenotypes to schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Morphometric Anal, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Kennedy, David/H-3627-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 309 BP 95S EP 95S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600308 ER PT J AU George, MS Insel, T Leckman, J Lorberbaum, J Baxter, LR Schlaepfer, T MacLean, PA AF George, MS Insel, T Leckman, J Lorberbaum, J Baxter, LR Schlaepfer, T MacLean, PA TI The limbic system in complex mammalian behaviors: Studies stemming from the life work of Dr. Paul MacLean SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Funct Neuroimaging Div, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. Emory Univ, Yerkes Primate Ctr, Atlanta, GA 30322 USA. Yale Univ, Ctr Child Study, New Haven, CT USA. Univ Alabama, Dept Psychiat, Birmingham, AL USA. Univ Bern, Psychiat Neuroimaging Grp, NIMH, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 316 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600315 ER PT J AU Adler, CM Elman, I Weisenfeld, N Kesstler, L Pickar, D Breier, A AF Adler, CM Elman, I Weisenfeld, N Kesstler, L Pickar, D Breier, A TI Effects of 2-deoxyglucose-induced glucoprivation on striatal dopamine release in healthy volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 349 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600348 ER PT J AU Dougherty, DD Shin, LM Alpert, NM Pitman, RK Orr, SP Lasko, M Macklin, ML Fischman, AJ Rauch, SL AF Dougherty, DD Shin, LM Alpert, NM Pitman, RK Orr, SP Lasko, M Macklin, ML Fischman, AJ Rauch, SL TI Regional cerebral blood flow during transiently induced anger in healthy men SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Vet Affairs Res Serv, Manchester, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 371 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600370 ER PT J AU Arciniegas, D Olincy, A Topkoff, J McRae, K Cawthra, E Reite, ML Adler, LE AF Arciniegas, D Olincy, A Topkoff, J McRae, K Cawthra, E Reite, ML Adler, LE TI Impaired auditory gating following traumatic brain injury SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Psychiat Serv, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Denver Res Inst, Denver, CO 80220 USA. RI Arciniegas, David/A-3792-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 388 BP 120S EP 121S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600387 ER PT J AU Deckersbach, T Otto, MW Pollack, MH Florin, I AF Deckersbach, T Otto, MW Pollack, MH Florin, I TI Memory functioning in panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Marburg, Marburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 392 BP 122S EP 122S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600391 ER PT J AU Shin, LM Dougherty, DD Rauch, SL Lasko, M Macklin, ML Alpert, NM Fischman, AJ Orr, SP Pitman, RK AF Shin, LM Dougherty, DD Rauch, SL Lasko, M Macklin, ML Alpert, NM Fischman, AJ Orr, SP Pitman, RK TI Activation of anterior paralimbic structures during induced guilt in healthy subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Tufts Univ, Medford, MA 02155 USA. VA Res Serv, Manchester, NH 03103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 423 BP 130S EP 131S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600422 ER PT J AU Lorberbaum, JP George, MS Johnson, MR Emmanuel, NP Book, SW Mintzer, O Morton, A Nahas, Z Bohning, DE Vincent, D Shastri, A Hamner, M Arana, GW Ballenger, JC Lydiard, RB AF Lorberbaum, JP George, MS Johnson, MR Emmanuel, NP Book, SW Mintzer, O Morton, A Nahas, Z Bohning, DE Vincent, D Shastri, A Hamner, M Arana, GW Ballenger, JC Lydiard, RB TI Feasibility of using fMRI in social phobics undergoing a public speaking task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 429 BP 132S EP 133S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600428 ER PT J AU Tenebank, CC Nahas, N Speer, AM Molloy, LM Stallings, LE Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Risch, SC George, MS AF Tenebank, CC Nahas, N Speer, AM Molloy, LM Stallings, LE Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Risch, SC George, MS TI Paralimbic activity declines with depression severity and improves with TMS response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 428 BP 132S EP 132S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600427 ER PT J AU Tsuang, D Larson, EB Bowen, J McCormick, M Teri, L Nochlin, D Leverenz, J Peskind, ER Lim, A Raskind, M Thompson, ML Mirra, S Gearing, M Schellenberg, G Kukull, W AF Tsuang, D Larson, EB Bowen, J McCormick, M Teri, L Nochlin, D Leverenz, J Peskind, ER Lim, A Raskind, M Thompson, ML Mirra, S Gearing, M Schellenberg, G Kukull, W TI The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer's disease in a community-based case series SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 445 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600444 ER PT J AU Koenigsberg, HW Siever, LJ New, AS Mitropoulou, V Harvey, P Bergman, A AF Koenigsberg, HW Siever, LJ New, AS Mitropoulou, V Harvey, P Bergman, A TI Affective instability in the personality disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Mt Sinai Med Ctr, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 SU S MA 451 BP 140S EP 140S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189NN UT WOS:000079911600450 ER PT J AU Burt, T Sachs, GS Demopulos, C AF Burt, T Sachs, GS Demopulos, C TI Donepezil in treatment-resistant bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; cholinesterase inhibitors; treatment resistant; mania; donepezil; lithium ID REM-SLEEP INDUCTION; ALZHEIMERS-DISEASE; MOOD; PROPHYLAXIS; MARKER; TRIAL AB Background: A considerable percentage of patients with bipolar disorder do not respond or do not tolerate conventional treatment. Cholinesterase (ChE) inhibitors have been suggested to possess depressogenic and antimanic properties. Methods: We report a case series of treatment-resistant bipolar patients (n = 11) to whom we administered the ChE inhibitor donepezil. Four patients met criteria for current manic episode, 5 for mixed episode, I for hypomanic episode, and I for major depressive episode. Donepezil was added to current medication on an open-label basis. Ratings were based on a retrospective chart review. Results: Of the II patients, 6 (54.5%) demonstrated marked improvement (improvement in CGI-S greater than or equal to 2), 3 (27.2%) demonstrated slight improvement; I did not respond, and I did not tolerate the medication. Among those patients who had marked improvement (i.e., responders, n = 6), improvement was observed within 2 weeks or less in 5 of them (83%). Patients experienced only minor side effects, Conclusions: These pilot data suggest the efficacy and safety of donepezil in the treatment of bipolar disorder To our knowledge this is the first published report on the use of donepezil in the treatment of mood disorders. Controlled, randomized, double-blind studies are necessary to validate these preliminary observations. (C) 1999 Society of Biological Psychiatry. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RI Burt, Tal/O-1951-2013 OI Burt, Tal/0000-0002-5853-6110 NR 28 TC 49 Z9 51 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1999 VL 45 IS 8 BP 959 EP 964 DI 10.1016/S0006-3223(98)00320-5 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 189FA UT WOS:000079892700003 PM 10386177 ER PT J AU Shpall, EJ Wheeler, CA Turner, SA Yanovich, S Brown, RA Pecora, AL Shea, TC Mangan, KF Williams, SF LeMaistre, CF Long, GD Jones, R Davis, MW Murphy-Filkins, R Parker, WRL Glaspy, JA AF Shpall, EJ Wheeler, CA Turner, SA Yanovich, S Brown, RA Pecora, AL Shea, TC Mangan, KF Williams, SF LeMaistre, CF Long, GD Jones, R Davis, MW Murphy-Filkins, R Parker, WRL Glaspy, JA TI A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; QUALITY-OF-LIFE; IN-VIVO; FUNCTIONAL ASSESSMENT; LYMPHOMA PATIENTS; HEMATOPOIESIS; ENGRAFTMENT; COMBINATION AB This randomized study compared the number of leukaphereses required to collect an optimal target yield of 5 x 10(6) CD34(+) peripheral blood progenitor cells/kg, using either stem cell factor (SCF) at 20 mu g/kg/d in combination with Filgrastim at 10 mu g/kg/d or Filgrastim alone at 10 mu g/kg/d. from 203 patients with high-risk stage II, III. or IV breast cancer. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield of CD34(+) cells had been reached or a maximum of 5 leukaphereses performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n = 103) reached the CD34(+) cell target yield. There was a clinically and statistically significant reduction (P < .05) in the number of leukaphereses required to reach the target yield for the patients receiving SCF plus Filgrastim (median, 4 leukaphereses) compared with patients receiving Filgrastim alone (median, 6 or more leukapherses; ie. <50% of patients reached the target in 5 leukaphereses). All patients receiving SCF were premedicated with antihistamines, albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and not associated with life-threatening or fatal toxicity. In conclusion, SCF plus Filgrastim is a more effective peripheral blood progenitor cell (PBPC)-mobilization regimen than Filgrastim alone. In addition to the potential for reduced leukapheresis-related morbidity and costs, SCF offers additional options for obtaining cells for further graft manipulation. (C) 1999 by The American Society of Hematology. C1 Univ Colorado, Hlth Sci Ctr, Bone Marrow Transplant Program, Denver, CO 80262 USA. Beth Israel Hosp, Dana Farber Canc Inst, Bone Marrow Transplant Programs, Boston, MA 02215 USA. Amgen Inc, Bone Marrow Transplant Programs, Thousand Oaks, CA 91320 USA. Washington Univ, Sch Med, Bone Marrow Transplant Programs, St Louis, MO USA. Hackensack Univ, Med Ctr, Bone Marrow Transplant Programs, Hackensack, NJ USA. Univ N Carolina, Lineberger Canc Res Ctr, Bone Marrow Transplant Programs, Chapel Hill, NC 27599 USA. Temple Univ, Ctr Canc, Bone Marrow Transplant Programs, Philadelphia, PA 19122 USA. Univ Chicago, Med Ctr, Bone Marrow Transplant Programs, Chicago, IL 60637 USA. S Texas Canc Inst, Bone Marrow Transplant Programs, San Antonio, TX USA. Stanford Med Ctr, Bone Marrow Transplant Programs, Stanford, CA USA. Univ Calif Los Angeles, Sch Med, Bowyer Oncol Ctr, Bone Marrow Transplant Program, Los Angeles, CA USA. RP Shpall, EJ (reprint author), Univ Colorado, Hlth Sci Ctr, Bone Marrow Transplant Program, 4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [R01-CA61508]; NCRR NIH HHS [M01-RR00865, M01RR00046] NR 47 TC 75 Z9 79 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1999 VL 93 IS 8 BP 2491 EP 2501 PG 11 WC Hematology SC Hematology GA 184YY UT WOS:000079642400008 PM 10194427 ER PT J AU Reed, GL Houng, AK Fitzgerald, ML AF Reed, GL Houng, AK Fitzgerald, ML TI Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: Implications for platelet secretion SO BLOOD LA English DT Article ID GRANULE MEMBRANE-PROTEIN; SYNAPTIC VESICLE DOCKING; PLASMA-MEMBRANE; BINDING PROTEIN; KINASE-C; PHORBOL ESTERS; YEAST SEC1; CELL-LINE; IDENTIFICATION; RADIOIMMUNOASSAY AB In response to thrombin and other extracellular activators, platelets secrete molecules from large intracellular vesicles (granules) to initiate thrombosis. Little is known about the molecular machinery responsible for vesicle docking and secretion in platelets and the linkage of that machinery to cell activation. We found that platelet membranes contain a full complement of interacting proteins-VAMP, SNAP-25, and syntaxin 4-that are necessary for vesicle docking and fusion with the plasma membrane. Platelets also contain an uncharacterized homologue of the Sec1p family that appears to regulate vesicle docking through its binding with a cognate syntaxin. This platelet Sec1 protein (PSP) bound to syntaxin 4 and thereby excluded the binding of SNAP-25 with syntaxin 4, an interaction critical to vesicle docking. As predicted by its sequence, PSP was detected predominantly in the platelet cytosol and was phosphorylated in vitro by protein kinase C (PKC), a secretion-linked kinase, incorporating 0.87 +/- 0.11 mol of PO4 per mole of protein. PSP was also specifically phosphorylated in permeabilized platelets after cellular stimulation by phorbol esters or thrombin and this phosphorylation was blocked by the PKC inhibitor Ro-31-8220. Phosphorylation by PKC in vitro inhibited PSP from binding to syntaxin 4. Taken together, these studies indicate that platelets, like neurons and other cells capable of regulated secretion, contain a unique complement of interacting vesicle docking proteins and PSP, a putative regulator of vesicle docking. The PKC-dependent phosphorylation of PSP in activated platelets and its inhibitory effects on syntaxin 4 binding provide a novel functional link that may be important in coupling the processes of cell activation, intracellular signaling, and secretion. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Hungtington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL57314-01] NR 62 TC 75 Z9 77 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1999 VL 93 IS 8 BP 2617 EP 2626 PG 10 WC Hematology SC Hematology GA 184YY UT WOS:000079642400022 PM 10194441 ER PT J AU Bastian, LS Kwiatkowski, BA Breininger, J Danner, S Roth, G AF Bastian, LS Kwiatkowski, BA Breininger, J Danner, S Roth, G TI Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets transcription factor Fli-1 SO BLOOD LA English DT Article ID C-MPL LIGAND; IIB GENE; 5'-FLANKING REGION; EXPRESSION; FAMILY; GATA; BINDING; MEMBER; ALPHA; CELLS AB Glycoprotein (GP) IX is a subunit of the von Willebrand receptor, GPIb-V-IX, which mediates adhesion of platelets to the subendothelium of damaged blood vessels. Previous characterization of the GPIX promoter identified a functional Ets site that, when disrupted, reduced promoter activity. However, the Ets protein(s) that regulated GPIX promoter expression was unknown. In this study, transient cotransfection of several GPIX promoter/reporter constructs into 293T kidney fibroblasts with a Fli-1 expression vector shows that the oncogenic protein Fli-1 can transactivate the GPIX promoter when an intact GPIX Ets site is present. In addition, Fli-1 binding of the GPIX Ets site was identified in antibody supershift experiments in nuclear extracts derived from hematopoietic human erythroleukemia cells. Comparative studies showed that Fli-1 was also able to transactivate the GPIb alpha and, to a lesser extent, the GPIIb promoter. Immunoblot analysis identified Fli-1 protein in lysates derived from platelets. In addition, expression of Fli-1 was identified immunohistochemically in megakaryocytes derived from CD34(+) cells treated with the megakaryocyte differentiation and proliferation factor, thrombopoietin. These results suggest that Fli-1 is likely to regulate lineage-specific genes during megakaryocytopoiesis. (C) 1999 by The American Society of Hematology. C1 VA Puget Sound Hlth Care Syst, Hematol Sect, Med Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Hematol Sect, Res Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Dept Oncol, Seattle, WA 98195 USA. RP Roth, G (reprint author), VA Puget Sound Hlth Care Syst, Hematol Sect, Med Serv, M-S 111,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL39947, F32 HL09265]; NIDDK NIH HHS [R01-DK49855-01] NR 55 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1999 VL 93 IS 8 BP 2637 EP 2644 PG 8 WC Hematology SC Hematology GA 184YY UT WOS:000079642400024 PM 10194443 ER PT J AU Wang, X Christiani, DC Mark, EJ Nelson, H Wiencke, JK Gunn, L Wain, JC Kelsey, KT AF Wang, X Christiani, DC Mark, EJ Nelson, H Wiencke, JK Gunn, L Wain, JC Kelsey, KT TI Carcinogen exposure, p53 alteration, and K-ras mutation in synchronous multiple primary lung carcinoma SO CANCER LA English DT Article DE lung carcinoma; p53; K-ras; synchronous multiple primary tumors; cigarette smoking; asbestos ID CIGARETTE-SMOKING; CANCER PATIENTS; GENE; ADENOCARCINOMA; EXPRESSION; DIAGNOSIS; TISSUE; TUMORS; MARKER; HEAD AB BACKGROUND. Synchronous multiple primary lung tumors (SMPLT) have been estimated to occur in 1% of lung carcinoma patients. Criteria for SMPLT diagnosis include different cancer histologies, location in different lobes of the lung, or genetic discordance. Patients with SMPLT have a poor clinical prognosis with decreased 5-year disease survival, despite diagnosis at an early stage. Field cancerization (the induction of somatic mutation in large clones of epithelial cells after carcinogen exposure) has been proposed to be an integral process involved in the development of SMPLT. Host factors also may contribute to the development of SMPLT. METHODS. The authors investigated the occurrence of p53 and K-rns alterations in tumors from SMPLT patients and also studied the association between carcinogen exposure and polymorphic metabolic traits in SMPLT patients, comparing these patients with individuals with one primarily lung tumor. RESULTS. In a case-control study of lung carcinoma susceptibility, 6 patients were identified whose 33 multiple tumors met the criteria of SMPLT. The incidence was 3.6% (16 of 451 patients), which was higher than many previously published series. Among the multiple tumors, 73% (24 of 33 tumors) were adenocarcinomas. Patients with SMPLT smoked more (73.0 pack-years vs. 56.2 pack-years; P = 0.07) and longer (45.8 years vs. 37.0 years; P < 0.03) than patients with only 1 tumor. For those patients who stopped smoking, patients with SMPLT had stopped smoking more recently than those with a single primary tumor (3.4 years vs. 7.3 years; P = 0.08). A total of 39% of SMPLT tumors (13 of 33 tumors) had detectable p53 alterations; 36% had genetic changes in p53 measured by polymerase chain reaction-single strand conformation polymorphism, and 33% showed positive immunostaining for p53 protein. This was comparable to the occurrence of p53 mutations and immunostaining in single tumor cases (30%). Age, gender, family history of cancer, and the prevalence of polymorphic metabolic traits previously associated with lung carcinoma susceptibility did not differ among SMPLT patients compared with patients with a single tumor. CONCLUSIONS. The patients with SMPLT had significantly more tobacco exposure, and their tumors apparently bad independently arising p53 and K-rns mutations, suggesting that field cancerization may be important in lung carcinogenesis. (C) 1999 American Cancer Society. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA 02115 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, ES04705, ES8357] NR 30 TC 28 Z9 29 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1999 VL 85 IS 8 BP 1734 EP 1739 PG 6 WC Oncology SC Oncology GA 184WF UT WOS:000079636200013 PM 10223567 ER PT J AU Lee, D Prowse, DM Brissette, JL AF Lee, D Prowse, DM Brissette, JL TI Association between mouse nude gene expression and the initiation of epithelial terminal differentiation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE winged helix transcription factor; Whn; Hfh 11; hair follicles; epidermis ID OUTER ROOT SHEATH; HAIR FOLLICLE; TRANSGENIC MICE; ANTIBODY KI-67; PROTEIN; LOCUS; RAT; ACTIVATION; EPIDERMIS; MUTATIONS AB Loss-of-function mutations in Whn (Hfh 11), a winged-helix/forkhead transcription factor, result in the nude mouse phenotype. To determine the whn expression pattern during development, we utilized mice in which a beta-galactosidase reporter gene was placed under the control of the wild-type whn promoter by homologous recombination (M. Nehls et al., 1996, Science 272, 886-889). Sites of reporter expression were confirmed by immunohistochemical staining for Whn protein or by in situ hybridization for whn mRNA. At all developmental stages, whn expression is restricted to epithelial cells. In addition to the skin and thymus, whn is expressed in the developing nails, nasal passages, tongue, palate, and teeth. In embryonic epidermis, suprabasal cells induce whn expression at the same time that terminal differentiation markers first appear. As the epidermis matures, whn promoter activity is found primarily in the first suprabasal layer, which contains keratinocytes in the early stages of terminal differentiation. In developing and mature anagen hair follicles, whn is expressed at high levels in the postmitotic precursor cells of the hair shaft and inner root sheath. Though principally associated with terminal differentiation, whn expression is also detected in progenitor cell compartments; in the hair bulb matrix and basal epidermal layer, a small subclass of cells expresses whn, while in the outer root sheath, whn promoter activity is induced as the follicle completes its elongation. Within these compartments, rare cells exhibit both whn expression and the nuclear proliferation marker Ki-67. The results suggest that whn expression encompasses the transition from a proliferative to a postmitotic state and that whn regulates the initiation of terminal differentiation. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA. RP Brissette, JL (reprint author), Massachusetts Gen Hosp E, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 36 TC 75 Z9 77 U1 1 U2 1 PU ACADEMIC PRESS INC 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 APR 15 PY 1999 VL 208 IS 2 BP 362 EP 374 DI 10.1006/dbio.1999.9221 PG 13 WC Developmental Biology SC Developmental Biology GA 189TX UT WOS:000079923200010 PM 10191051 ER PT J AU Stone, E Heagerty, P Vittinghoff, E Douglas, JM Koblin, BA Mayer, KH Celum, CL Gross, M Woody, GE Marmor, M Seage, GR Buchbinder, SP AF Stone, E Heagerty, P Vittinghoff, E Douglas, JM Koblin, BA Mayer, KH Celum, CL Gross, M Woody, GE Marmor, M Seage, GR Buchbinder, SP TI Correlates of condom failure in a sexually active cohort of men who have sex with men SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE condoms; condom failure; gay; anal sex; lubricant; HIV; SES; amphetamines; poppers ID HOMOSEXUAL MEN; VAGINAL INTERCOURSE; UNITED-STATES; LATEX CONDOMS; BREAKAGE; SLIPPAGE; BEHAVIOR; RISK; EXPERIENCE; LUBRICANTS AB Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure. C1 Permanente Med Grp, Oakland, CA USA. Fred Hutchinson Canc Res Ctr, HIVNET Stat Ctr, Seattle, WA 98104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Denver Dept Publ Hlth, Denver, CO USA. New York Blood Ctr, Lab Epidemiol, New York, NY 10021 USA. Fenway Community Hlth Ctr, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. ABT Associates Inc, Cambridge, MA 02138 USA. ABT Associates Inc, Bethesda, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NYU, Med Ctr, New York, NY 10016 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. RP Buchbinder, SP (reprint author), San Francisco Dept Publ Hlth, 25 Van Ness Ave,Suite 500, San Francisco, CA 94102 USA. OI Marmor, Michael/0000-0001-6605-2661 FU PHS HHS [N01-A1-35176, N01-A1-45200] NR 32 TC 46 Z9 46 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 15 PY 1999 VL 20 IS 5 BP 495 EP 501 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189EX UT WOS:000079892400013 PM 10225233 ER PT J AU Cariappa, A Kim, TJ Pillai, S AF Cariappa, A Kim, TJ Pillai, S TI Accelerated emigration of B lymphocytes in the Xid mouse SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED IMMUNODEFICIENCY; RECEPTOR SIGNAL-TRANSDUCTION; BONE-MARROW; CELL DEVELOPMENT; TYROSINE KINASE; LIGHT CHAIN; IMMUNOGLOBULIN HEAVY; CD22-DEFICIENT MICE; TRANSGENIC MICE; DEFICIENT MICE AB The B cell receptor is required for the emigration of newly generated B lymphocytes and for their maintenance in the periphery, A specific maintenance defect was noted in fraction I (IgD(high)lgM(low)) B cells in Sid mice (which harbor a mutation in Btk), Although Bcl-2 levels in fractions I and Il (IgD(high)IgM(high)) are equivalent in normal and Xid B cells, a novel peak of Bcl-2(low) fraction III (IgD(low)IgM(high)) B cells was noted in the Xid mouse. Since this B cell population resembled bone marrow immature B cells,,ve examined the emigration of newly formed B cells in normal and Xid mice. These studies revealed the accelerated emigration of newly formed Xid B cells. We conclude that distinct Btk-independent and Btk-dependent signals mediate emigration and maintenance events during peripheral B cell maturation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 149 13th St,Charlestown Navy Yard, Boston, MA 02129 USA. RI Kim, Tae Jin/D-6544-2011 OI Kim, Tae Jin/0000-0001-9802-0568 FU NCI NIH HHS [CA69618]; NIAID NIH HHS [AI33507] NR 54 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4417 EP 4423 PG 7 WC Immunology SC Immunology GA 184KV UT WOS:000079612100008 PM 10201977 ER PT J AU Gollob, JA Schnipper, CP Murphy, EA Ritz, J Frank, DA AF Gollob, JA Schnipper, CP Murphy, EA Ritz, J Frank, DA TI The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; SIGNAL-TRANSDUCTION PATHWAY; NATURAL-KILLER; TYROSINE PHOSPHORYLATION; T-CELLS; MAP KINASE; HUMAN-LYMPHOCYTES; FACTOR NKSF; IFN-GAMMA; TH1 CELLS AB IL-12 and IL-2 can stimulate mitogen- or CD3-activated T cells to proliferate, produce IFN-gamma, and kill tumor cells. The magnitude of these functional responses is greatly augmented when T cells are activated by the combination of IL-12 and IL-2. Although peripheral blood T cells are largely unresponsive to these cytosines without prior activation, a small subset of CD8(+) T cells (CD8(+)CD(18bright)) is strongly activated by the combination of IL-12! and IL-2. In this report He show that the functional synergy between IL-12 and IL-2 in CD8(+)CD18(bright) T cells correlates with the activation of the stress kinases, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase (SAPK)Jun N-terminal kinase, but not with the activation of the extracellular signal-regulated kinases, The functional synergy between IL-2 and IL-12 is also associated with a prominent increase in STAT1 and STAT3 serine phosphorylation over that observed with IL-12 or IL-2 alone, By contrast, STAT tryosine phosphorylation is not augmented over that seen with either cytokine alone, A specific inhibitor of p38 MAP kinase completely inhibits the serine phosphorylation of STAT1 and STAT3 induced by IL-12 and IL-2 and abrogates the functional synergy between IL-12 and IL-2 without affecting STAT tryosine phosphorylation, This suggests that p38 MAP kinase may play an important role in regulating STAT serine phosphorylation in response to the combination of IL-IZ and IL-2, Furthermore, these findings indicate that the optimal activation of T cells by IL-12 and IL-2 may depend on an interaction between the p38 MAP kinase and Janus kinase/STAT signaling pathways. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gollob, JA (reprint author), Beth Israel Med Ctr, Div Hematol Oncol, 330 Brookline Ave,East Campus,Room KS 158,Kirstei, Boston, MA 02215 USA. EM jgollob@bidme.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 49 TC 107 Z9 108 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4472 EP 4481 PG 10 WC Immunology SC Immunology GA 184KV UT WOS:000079612100015 PM 10201984 ER PT J AU Fridkis-Hareli, M Neveu, JM Robinson, RA Lane, WS Gauthier, L Wucherpfennig, KW Sela, M Strominger, JL AF Fridkis-Hareli, M Neveu, JM Robinson, RA Lane, WS Gauthier, L Wucherpfennig, KW Sela, M Strominger, JL TI Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; HISTOCOMPATIBILITY COMPLEX-MOLECULES; ANTIGEN-PRESENTING CELLS; ALPHA-BETA-HETERODIMERS; CLASS-II MOLECULES; SYNTHETIC COPOLYMER-1; CRYSTAL-STRUCTURE; PEPTIDE BINDING; 3-DIMENSIONAL STRUCTURE AB Copolymer 1 (Cop 1, poly (Y, E, A, K)) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), Cop 1 binds promiscuously, with high affinity and in a peptide-specific manner to purified MS-associated HLA-DR2 (DRB1*1501) and rheumatoid arthritis-associated HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules, In the present work at least 95% of added Cop 1 could be bound to recombinant "empty" HLA-DR1 and -DR4, and 80% could be bound to HLA-DR2 proteins. Amino acid composition, HPLC profiles, and sequencing patterns of Cop 1 eluted by acid extraction from HLA-DR molecules were similar to those of the unseparated Cop 1, Protruding N-terminal ends of Cop 1 bound to HLA-DR1, -DR2, or -DR4 molecules were then treated with aminopeptidase I, followed by elution, HPLC, and pool sequencing. In contrast to untreated or unbound Cop I, this material exhibited distinct motifs at some positions with increases in levels of E at the first and second cycles, of Ii at the second and third cycles, and of Y (presumably at P1 of the bound peptide) at the third to fifth cycles, regardless of the HLA-DR molecule employed. No preference was seen at the following cycles that were mainly A. These first pooled HLA-DR binding epitopes provide clues to the components of Cop 1 that are biologically active in suppressing MS and possibly rheumatoid arthritis. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Microchem Facil, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Strominger, JL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA. EM jlstrom@fas.harvard.edu FU NCI NIH HHS [R35-CA 47554]; NIAID NIH HHS [N01-AI 45198] NR 46 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4697 EP 4704 PG 8 WC Immunology SC Immunology GA 184KV UT WOS:000079612100041 PM 10202010 ER PT J AU Brander, C Goulder, PJR Luzuriaga, K Yang, OO Hartman, KE Jones, NG Walker, BD Kalams, SA AF Brander, C Goulder, PJR Luzuriaga, K Yang, OO Hartman, KE Jones, NG Walker, BD Kalams, SA TI Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in utero HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSES; PERIPHERAL-BLOOD; CD8(+) CELLS; STIMULATION; SPECIFICITY; REPLICATION; REPERTOIRE; EXHAUSTION; MECHANISMS AB To address the issue of clonal exhaustion in humans, we monitored HLA class I-restricted, epitope-specific CTL responses in an in utero HIV-I-infected infant from 3 mo through 5 years of age. Serial functional CTL precursor assays demonstrated persistent, vigorous, and broadly directed HIV-1 specific CTL activity with a dominant response against an epitope in HIV-1 Gag-p17 (SLYNTVATL, aa 77-85). A clonal CTL response directed against the immunodominant, HLA-A*0201-restricted epitope was found to persist over the entire observation period, as shown by TCR analysis of cDNA libraries generated from PBMC. The analysis of autologous viral sequences did not reveal any escape mutations within the targeted epitope, and viral load measurement indicated ongoing viral replication, Furthermore, inhibition of viral replication assays indicated that the epitope was properly processed from autologous viral protein. These data demonstrate that persistent exposure to high levels of viral Ag does not necessarily lead to clonal exhaustion and that epitope-specific clonal CTL responses induced within the first weeks of life can persist for years without inducing detectable viral escape variants. C1 Massachusetts Gen Hosp E, Ctr AIDS Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Univ Massachusetts, Sch Med, Dept Pediat, Boston, MA 02129 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp E, Ctr AIDS Res, 149 13th St,Room S214, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI39966, U19AI38584] NR 30 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4796 EP 4800 PG 5 WC Immunology SC Immunology GA 184KV UT WOS:000079612100053 PM 10202022 ER PT J AU Merfeld, DM Zupan, L Peterka, RJ AF Merfeld, DM Zupan, L Peterka, RJ TI Humans use internal models to estimate gravity and linear acceleration SO NATURE LA English DT Article ID SQUIRREL-MONKEY; VESTIBULOOCULAR REFLEX; SEMICIRCULAR CANALS; ECCENTRIC ROTATION; OCULAR RESPONSES; VIEWING DISTANCE; ROLL TILT; MOTION; ORIENTATION; INTEGRATION AB Because sensory systems often provide ambiguous information, neural processes must exist to resolve these ambiguities. It is likely that similar neural processes are used by different sensory systems. For example, many tasks require neural processing to distinguish linear acceleration from gravity(1), but Einstein's equivalence principle states that all linear accelerometers must measure both linear acceleration and gravity. Here we investigate whether the brain uses internal models, defined as neural systems that mimic physical principles, to help estimate linear acceleration and gravity(2-4). Internal models may be used in motor control(5-7), sensorimotor integration(8-10) and sensory processing(11-14), but direct experimental evidence for such models is limited. To determine how humans process ambiguous gravity and linear acceleration cues, subjects were tilted after being rotated at a constant velocity about an Earth-vertical axis. We show that the eye movements evoked by this post-rotational tilt include a response component that compensates for the estimated Linear acceleration even when no actual linear acceleration occurs. These measured responses are consistent with our internal model predictions that the nervous system can develop a non-zero estimate of linear acceleration even when no true linear acceleration is present. C1 Oregon Hlth Sci Univ, Inst Neurol Sci, Portland, OR 97209 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 247 Z9 252 U1 1 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 15 PY 1999 VL 398 IS 6728 BP 615 EP 618 DI 10.1038/19303 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 186WX UT WOS:000079754700056 PM 10217143 ER PT J AU Freedman, AS Nielsen, GP Barest, GD AF Freedman, AS Nielsen, GP Barest, GD TI A 60-year-old woman with epidural and paraspinal masses - High-grade, Burkitt-like B cell lymphoma, probably arising in soft tissue. Nocardiosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; PRIMARY MALIGNANT-LYMPHOMA; ASTEROIDES INFECTION; NEOPLASTIC DISEASE; DIAGNOSIS; INVOLVEMENT; MANIFESTATIONS; MENINGITIS; METASTASES; DISORDERS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 41 TC 3 Z9 3 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 15 PY 1999 VL 340 IS 15 BP 1188 EP 1196 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 185TZ UT WOS:000079687700008 ER PT J AU FitzGerald, MJ Arsura, M Bellas, RE Yang, W Wu, M Chin, L Mann, KK DePinho, RA Sonenshein, GE AF FitzGerald, MJ Arsura, M Bellas, RE Yang, W Wu, M Chin, L Mann, KK DePinho, RA Sonenshein, GE TI Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc SO ONCOGENE LA English DT Article DE Max; Myc; Mad/Mxi; apoptosis; proliferation ID HELIX-LOOP-HELIX; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; IN-VIVO; NEOPLASTIC TRANSFORMATION; GROWTH-FACTOR; CELL-GROWTH; B-CELLS; S-PHASE; HLA-A AB dMax, a naturally occurring splice variant of the Myc binding protein Mas, lacks the DNA binding basic region and helix 1 of the Helix-Loop-Helix domain; dMax interacts with c-Myc in vitro and in vivo, and inhibits E-bos Myc site driven transcription in transient transfection assays, Here we have investigated the expression, function and interactions of dMax, RT/PCR analyses detected dmax mRNA in multiple tissues of the developing, newborn and adult mouse. Functionally, dMax reduced the ability of c-Myc to cooperate,vith the progression factor A-Myb to promote S phase entry of quiescent smooth muscle cells. In contrast, dMax failed to ablate inhibition of initiator element (Inr)-mediated transcription by c-Myc in Jurkat T cells. In in vitro protein:protein association assays, dMax interacted with c-Myc, N-Myc, L-Myc, Mad1, Mxi1, Mad3 and Mad4, but not,vith itself or wild-type Max, These interactions required an intact leucine zipper. Inhibition of E-box-mediated transactivation by induction of dMax overexpression resulted in apoptosis of WEHI 231 B cells. Thus, dMax is a widely expressed, naturally occurring protein, with the capacity to bind most members of the Myc/Max superfamily; dMax has little effect on Inr-mediated repression by c-Myc, but can significantly decrease E-bos-mediated events promoting proliferation and cell survival. C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Sonenshein, GE (reprint author), Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. FU NCI NIH HHS [CA36355, T32-CA64070] NR 62 TC 11 Z9 12 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 15 PY 1999 VL 18 IS 15 BP 2489 EP 2498 DI 10.1038/sj.onc.1202611 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 186AC UT WOS:000079703300009 PM 10229200 ER PT J AU Bouma, BE Tearney, GJ AF Bouma, BE Tearney, GJ TI Power-efficient nonreciprocal interferometer and linear-scanning fiber-optic catheter for optical coherence tomography SO OPTICS LETTERS LA English DT Article AB A nonreciprocal fiber-optic interferometer is demonstrated in an optical coherence tomography (OCT) system. The increased power efficiency of this system provides a 4.1-dB advantage over standard Michelson rotary optical junction that is required in circumferential scanning systems. These advancements have permitted the clinical implementation of OCT imaging in the human gastrointestinal tract. (C) 1999 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 11 TC 114 Z9 116 U1 1 U2 11 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 APR 15 PY 1999 VL 24 IS 8 BP 531 EP 533 DI 10.1364/OL.24.000531 PG 3 WC Optics SC Optics GA 187EH UT WOS:000079773600010 PM 18071562 ER PT J AU Sablinski, T Emery, DW Monroy, R Hawley, RJ Xu, YX Gianello, P Lorf, T Kozlowski, T Bailin, M Cooper, DKC Cosimi, AB Sachs, DH AF Sablinski, T Emery, DW Monroy, R Hawley, RJ Xu, YX Gianello, P Lorf, T Kozlowski, T Bailin, M Cooper, DKC Cosimi, AB Sachs, DH TI Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; IN-VITRO; TRANSPLANTATION; TOLERANCE; DONOR; CELLS; RECONSTITUTION; EXPRESSION; ANTIBODY; BLOOD AB Background. Mixed allogeneic hematopoietic chimerism has previously been reliably achieved and shown to induce tolerance to fully MHC-mismatched allografts in mice and monkeys. However, the establishment of hematopoietic chimerism has been difficult to achieve in the discordant pig-to-primate xenogeneic model. Methods. To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusion of pig bone marrow (BM), Monkey anti-pig natural antibodies were immunoadsorbed by extracorporeal perfusion of monkey blood through a pig liver, immediately before the intravenous infusion of porcine BM (day 0). Cyclosporine was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monkey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. Results. Both monkeys recovered from pancytopenia within 4 weeks of whole body irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 days. Methylcellulose colony assays at days 180 and 300 revealed that about 2% of the myeloid progenitors in the BM of the cytokine-treated recipient were of pig origin, whereas no chimerism was detected in the BM of the untreated control monkey at similar times. The chimeric animal was less responsive by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that had rejected a porcine kidney transplant. Conclusion. To our knowledge, this is the first report of long-term survival of discordant xenogeneic BM in a primate recipient. C1 Harvard Univ, Transplantat Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Transplant Unit, Sch Med, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, MGH E,Bldg 149-9019, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL54038]; NIAID NIH HHS [1PO1 AI39755] NR 32 TC 36 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 BP 972 EP 977 DI 10.1097/00007890-199904150-00007 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700007 PM 10221480 ER PT J AU Alexander, S Refaeli, Y Abbas, A Lichtman, A AF Alexander, S Refaeli, Y Abbas, A Lichtman, A TI IL-2 regulates flip expression in human CD4(+) lymphocytes SO TRANSPLANTATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 262 BP S72 EP S72 DI 10.1097/00007890-199904150-00290 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700290 ER PT J AU Baid, S Pascual, M Mauiyyedi, S Chung, R Collins, B Tolkoff-Rubin, N Williams, WW Delmonico, FL Cosimi, AB Colvin, RB AF Baid, S Pascual, M Mauiyyedi, S Chung, R Collins, B Tolkoff-Rubin, N Williams, WW Delmonico, FL Cosimi, AB Colvin, RB TI Association of hepatitis C infection with chronic transplant glomerulopathy and de novo membrano-proliferative glomerular lesions in renal allografts SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 82 BP S27 EP S27 DI 10.1097/00007890-199904150-00110 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700111 ER PT J AU Crespo, M Pascual, M Tolkoff-Rubin, N Duan, JM Fitzpatrick, D Collins, AB Cosimi, AB Colvin, R Saidman, SL AF Crespo, M Pascual, M Tolkoff-Rubin, N Duan, JM Fitzpatrick, D Collins, AB Cosimi, AB Colvin, R Saidman, SL TI De novo production of anti-HLA donor specific antibodies during acute renal allograft rejection SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 324 BP S87 EP S87 DI 10.1097/00007890-199904150-00352 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700351 ER PT J AU Fishman, JA Doran, MT Cosimi, AB Flood, JG Rubin, RH AF Fishman, JA Doran, MT Cosimi, AB Flood, JG Rubin, RH TI Dosing of intravenous ganciclovir for prophylaxis and treatment of cytomegalovirus infection in solid organ transplant recipients SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 371 BP S99 EP S99 DI 10.1097/00007890-199904150-00399 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700397 ER PT J AU Haller, GW Esnaola, N Yamada, K Wu, A Shimizu, A Colvin, RB Sykes, M Sachs, DH AF Haller, GW Esnaola, N Yamada, K Wu, A Shimizu, A Colvin, RB Sykes, M Sachs, DH TI Induction of T cell tolerance in miniature swine with allogeneic thymus transplants across a class I barrier SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 247 BP S68 EP S68 DI 10.1097/00007890-199904150-00275 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700273 ER PT J AU Haller, GW Kunisaki, SM Germana, S LeGuern, C Sachs, DH AF Haller, GW Kunisaki, SM Germana, S LeGuern, C Sachs, DH TI MLR responses to allogenic MHC class II peptides requires priming of the responder SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 141 BP S42 EP S42 DI 10.1097/00007890-199904150-00169 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700169 ER PT J AU Ito, H Wekerle, T Kurtz, J Sayegh, MH Hill, J Chandraker, A Pearson, DA Swenson, KG Zhao, G Sykes, M AF Ito, H Wekerle, T Kurtz, J Sayegh, MH Hill, J Chandraker, A Pearson, DA Swenson, KG Zhao, G Sykes, M TI Induction of mixed hematopoietic chimerism and tolerance with suboptimal recipient T cell depletion, 3Gy tbi and anti-CD154 or CTLA4Ig: Toward a clinical regimen useful for cadaveric donors SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 109 BP S34 EP S34 DI 10.1097/00007890-199904150-00137 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700137 ER PT J AU Koulmanda, M Smith, RN Shea, S Laufer, TM Auchincloss, H AF Koulmanda, M Smith, RN Shea, S Laufer, TM Auchincloss, H TI Xenograft survival of fetal pig islets in mice with CD4+T cells but class II-/- APC SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 857 BP S221 EP S221 DI 10.1097/00007890-199904150-00881 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700880 ER PT J AU Kurtz, J Wekerle, T Ito, H Shaffer, J Sykes, M AF Kurtz, J Wekerle, T Ito, H Shaffer, J Sykes, M TI An unexpected role for CD28 and lack of a role for CD40L signaling in peripheral deletion of donor-reactive CD4(+) T cells and establishment of mixed chimerism through costimulatory blockade SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 453 BP S120 EP S120 DI 10.1097/00007890-199904150-00481 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700480 ER PT J AU McKay, D Tao, L Yu, CL Burakoff, S AF McKay, D Tao, L Yu, CL Burakoff, S TI Alloantigen-unresponsiveness results in defects in intracellular signaling and transcriptional activation of the IL-2 promotor SO TRANSPLANTATION LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 886 BP S228 EP S228 DI 10.1097/00007890-199904150-00910 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700910 ER PT J AU Menard, M Mawulawde, K Yamada, K Schwarze, M Lee, RS Allison, K Pillsbury, E Houser, S Sachs, D Madsen, J AF Menard, M Mawulawde, K Yamada, K Schwarze, M Lee, RS Allison, K Pillsbury, E Houser, S Sachs, D Madsen, J TI Acute rejection and cardiac allograft vasculopathy (CAV) following thymoheart transplantation in miniswine SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 258 BP S71 EP S71 DI 10.1097/00007890-199904150-00286 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700286 ER PT J AU Rosen, RH Lenz, J Rose, S Rabkin, J Corless, CL Chou, S AF Rosen, RH Lenz, J Rose, S Rabkin, J Corless, CL Chou, S TI Donor polymorphism of tumor necrosis factor (TNF) genes associated with variable severity of hepatitis C (HCV) recurrence following liver transplantation SO TRANSPLANTATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med Pathol & Liver Transplantat, Portland, OR 97201 USA. Prometheus Labs, San Diego, CA 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 33 BP S15 EP S15 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700061 ER PT J AU Strehlau, J Nashan, B Von Schnakenburg, C Demirci, G Strasburg, A Strom, TB Ehrich, JHH AF Strehlau, J Nashan, B Von Schnakenburg, C Demirci, G Strasburg, A Strom, TB Ehrich, JHH TI Organ-specific T-cell growth factor and CTL gene activation in renal and liver transplant rejection SO TRANSPLANTATION LA English DT Meeting Abstract C1 Hannover Med Sch, Dept Pediat Nephrol, D-3000 Hannover, Germany. Hannover Med Sch, Dept Transplant Surg, D-3000 Hannover, Germany. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 965 BP S248 EP S248 DI 10.1097/00007890-199904150-00989 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700988 ER PT J AU Theodore, P Simon, A Sackstein, R Sykes, M AF Theodore, P Simon, A Sackstein, R Sykes, M TI Porcine cells adhere to human fibronectin independently of VLA-5: Implications for porcine to human xenotransplantation. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 510 BP S134 EP S134 DI 10.1097/00007890-199904150-00538 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700538 ER PT J AU Turgeon, N Fishman, JA Doran, M Basgoz, N Tolkoff-Rubin, NE Cosimi, AB Rubin, RH AF Turgeon, N Fishman, JA Doran, M Basgoz, N Tolkoff-Rubin, NE Cosimi, AB Rubin, RH TI Prevention or recurrent cytomegalovirus disease in renal and liver transplant recipients: Effect of oral ganciclovir. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 478 BP S126 EP S126 DI 10.1097/00007890-199904150-00506 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700506 ER PT J AU Turgeon, N Hovingh, GK Fishman, JA Doran, M Basgoz, N Tolkoff-Rubin, NE Cosimi, AB Rubin, RH AF Turgeon, N Hovingh, GK Fishman, JA Doran, M Basgoz, N Tolkoff-Rubin, NE Cosimi, AB Rubin, RH TI Safety and efficacy of granulocyte-colony stimulating factor in kidney and liver transplant recipients. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 359 BP S96 EP S96 DI 10.1097/00007890-199904150-00387 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700385 ER PT J AU Waltz, DA Lillehei, CW Reilly, JJ Swanson, SJ Ginns, LC Wain, JC O'Connor, KJ Delmonico, FL AF Waltz, DA Lillehei, CW Reilly, JJ Swanson, SJ Ginns, LC Wain, JC O'Connor, KJ Delmonico, FL TI Prioritization of lung transplant recipients by hospitalization status shortens waiting time without affecting post-transplant survival. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Organ Bank, Newton, MA 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 96 BP S30 EP S30 DI 10.1097/00007890-199904150-00124 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700124 ER PT J AU Wekerle, T Sayegh, MH Kurtz, J Ronquillo, JV Dong, V Swenson, KG Zhao, G Sykes, M AF Wekerle, T Sayegh, MH Kurtz, J Ronquillo, JV Dong, V Swenson, KG Zhao, G Sykes, M TI Substantial donor chimerism and tolerance across a full MHC barrier without host pre-conditioning SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02129 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 110 BP S34 EP S34 DI 10.1097/00007890-199904150-00138 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700139 ER PT J AU Wekerle, T Turka, LA Sayegh, MH Kurtz, J Ito, H Wells, AD Shaffer, J Sykes, M AF Wekerle, T Turka, LA Sayegh, MH Kurtz, J Ito, H Wells, AD Shaffer, J Sykes, M TI Early deletion after bone marrow transplantation with costimulatory blockade is Fas-dependent and is prevented by BCL-X-L overexpression SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Univ Penn, Philadelphia, PA 19104 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 941 BP S242 EP S242 DI 10.1097/00007890-199904150-00965 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700964 ER PT J AU Wu, A Yamada, K Awwad, M Shimizu, A Watts, A Gojo, S Neville, D Cooper, DKC Sykes, M Sachs, DH AF Wu, A Yamada, K Awwad, M Shimizu, A Watts, A Gojo, S Neville, D Cooper, DKC Sykes, M Sachs, DH TI Prolonged xenogeneic skin graft survival after xenogenic porcine thymic transplantation in a non-human primate model SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Biotransplant Inc, Boston, MA USA. NIH, Bethesda, MD 20892 USA. 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 1011 BP S259 EP S259 DI 10.1097/00007890-199904150-01035 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910701033 ER PT J AU Yamada, A Dong, VM Kishimoto, K Laufer, TM Sayegh, MH Auchincloss, H AF Yamada, A Dong, VM Kishimoto, K Laufer, TM Sayegh, MH Auchincloss, H TI Long-term survival of cardiac allografts induced by costimulatory blockade may require indirect recognition SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 45 BP S18 EP S18 DI 10.1097/00007890-199904150-00073 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700073 ER PT J AU Yamada, K Shimizu, A Ierino, FL Gargollo, P Barth, R Colvin, RB Sachs, DH AF Yamada, K Shimizu, A Ierino, FL Gargollo, P Barth, R Colvin, RB Sachs, DH TI T cell reconstitution and the mechanism of tolerance induction by allogeneic thymokidney transplants in miniature swine SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Barth, Rolf/B-2542-2014 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 936 BP S240 EP S240 DI 10.1097/00007890-199904150-00960 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700959 ER PT J AU Yamada, K Fishbein, J Gianello, PR Ierino, FL Shimizu, A Colvin, RB Sachs, DH AF Yamada, K Fishbein, J Gianello, PR Ierino, FL Shimizu, A Colvin, RB Sachs, DH TI Influence of the thymus on sensitization and the requirement of antigen for the maintenance of tolerance to renal allografts in miniature swine SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 246 BP S68 EP S68 DI 10.1097/00007890-199904150-00274 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700274 ER PT J AU Johansen, KL Mulligan, K Schambelan, M AF Johansen, KL Mulligan, K Schambelan, M TI Anabolic effects of nandrolone decanoate in patients receiving dialysis - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN GROWTH-HORMONE; CHRONIC-RENAL-FAILURE; DEPENDENT DIABETES-MELLITUS; HEMODIALYSIS-PATIENTS; MAINTENANCE HEMODIALYSIS; CARDIOVASCULAR-DISEASE; SERUM-LIPOPROTEIN; BODY-COMPOSITION; CAPD PATIENTS; RISK FACTOR AB Context Patients receiving dialysis commonly experience malnutrition, reduced muscle mass (sarcopenia), and fatigue for which no effective treatment has been identified. Anabolic steroids are known to increase muscle mass and strength in healthy individuals, but their effect on the sarcopenia and fatigue associated with long-term dialysis has not been evaluated. Objective To assess the effects of an anabolic steroid, nandrolone decanoate, on lean body mass (LBM), functional status, and quality of life in dialysis patients. Design Randomized, double-blind, placebo-controlled trial conducted between April 1996 and July 1997. Setting Hospital-based outpatient dialysis unit. Patients Twenty-nine patients undergoing dialysis for at least 3 months. Intervention Nandrolone decanoate, 100 mg (n = 14), or placebo (n = 15) by intramuscular injection once a week for 6 months. Main Outcome Measures Weight, LBM, fatigue, grip strength, walking and stair-climbing times, and treadmill performance after 3 and 6 months of treatment. Results Lean body mass increased significantly in patients given nandrolone compared with patients given placebo (mean change [SD], +4.5 [2.3] kg; P<.001 compared with baseline). This effect was significantly greater than the change in LBM in the placebo group (mean change [SD], +1.9 [1.6] kg; P = .003 compared with baseline; P = .005 compared with nandrolone group). Serum creatinine levels increased in the nandrolone group (+168 [203] mmol/L [1.9 {2.3} mg/dL]; P = .02) but not in the placebo group (-4.0 [177] mmol/L [0.04 {2.0} mg/dL]; P = .95), suggesting an increase in muscle mass. Time to complete the walking and stair-climbing test decreased from 36.5 to 32.7 seconds in the nandrolone group, while those in the placebo group increased from 38.7 to 42.1 seconds (P = .05). Peak oxygen consumption increased in the individuals in the nandrolone group who performed treadmill tests, but not to a statistically significant degree. Grip strength did not change in either group. Conclusions Treatment with nandrolone for 6 months resulted in a significant increase in LBM associated with functional improvement in patients undergoing dialysis. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Nephrol, San Francisco, CA USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Endocrinol, San Francisco, CA USA. RP Johansen, KL (reprint author), San Francisco Vet Affairs Med Ctr, Nephrol Sect, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. EM johanse@itsa.ucsf.edu FU NCRR NIH HHS [RR-00083]; NIDDK NIH HHS [DK-45833] NR 40 TC 147 Z9 149 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1999 VL 281 IS 14 BP 1275 EP 1281 DI 10.1001/jama.281.14.1275 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 184TC UT WOS:000079628700031 PM 10208142 ER PT J AU Rumsfeld, JS MaWhinney, S McCarthy, M Shroyer, ALW VillaNueva, CB O'Brien, M Moritz, TE Henderson, WG Grover, FL Sethi, GK Hammermeister, KE AF Rumsfeld, JS MaWhinney, S McCarthy, M Shroyer, ALW VillaNueva, CB O'Brien, M Moritz, TE Henderson, WG Grover, FL Sethi, GK Hammermeister, KE TI Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TERM MORTALITY; DISEASE; DEPRESSION; RISK AB Context Health-related quality of life has not been evaluated as a predictor of mortality following coronary artery bypass graft (CABG) surgery. Evaluation of health status as a mortality predictor may be useful for preoperative risk stratification. Objective To determine whether the Physical and Mental Component Summary scores from the preoperative Short-Form 36 (SF-36) health status survey predict mortality following CABG surgery after adjustment for known clinical risk variables. Design Prospective cohort study conducted between September 1992 and December. 1996. Setting Fourteen Veterans Affairs hospitals. Patients Of the 3956 patients undergoing CABG surgery only and who were enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study, the 2480 who completed a preoperative SF-36. Main Outcome Measure All-cause mortality within 180 days after surgery. Results A total of 117 deaths (4.7%) occurred within 180 days of CABG surgery. The Physical Component Summary of the preoperative SF-36 was a statistically significant risk factor for 6-month mortality after adjustment for known clinical risk factors for mortality following CABG surgery. In multivariate analysis, a 10-point lower SF-36 Physical Component Summary score had an odds ratio (OR) of 1.39 (95% confidence interval [CI], 1.11-1.77; P = .006) for predicting mortality. The SF-36 Mental Component Summary score was not associated with 6-month mortality in multivariate analyses (OR, 1.09; 95% CI, 0.92-1.29; P = .31). Conclusions The Physical Component Summary score from the preoperative SF-36 is an independent risk factor for mortality following CABG surgery. The baseline Mental Component Summary score does not appear to be predictive of mortality. Preoperative patient: self-report of the physical component of health status may be helpful for risk stratification and clinical decision making for patients undergoing CABG surgery. C1 Denver Vet Affairs Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiothorac Surg, Denver, CO USA. Denver Vet Affairs Med Ctr, Surg Serv, Denver, CO 80220 USA. Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. Hines Vet Affairs Med Ctr, Vet Affairs Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. Tucson Vet Affairs Med CTr, Cardiothorac Surg Sect, Tucson, AZ USA. Univ Arizona, Hlth Sci Ctr, Dept Surg, Tucson, AZ USA. RP Rumsfeld, JS (reprint author), Denver Vet Affairs Med Ctr, Cardiol Sect, 1055 Clermont St, Denver, CO 80220 USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 30 TC 280 Z9 285 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1999 VL 281 IS 14 BP 1298 EP 1303 DI 10.1001/jama.281.14.1298 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 184TC UT WOS:000079628700034 PM 10208145 ER PT J AU Singh, JP Larson, MG Manolio, TA O'Donnell, CJ Lauer, M Evans, JC Levy, D AF Singh, JP Larson, MG Manolio, TA O'Donnell, CJ Lauer, M Evans, JC Levy, D TI Blood pressure response during treadmill testing as a risk factor for new-onset hypertension - The Framingham Heart Study SO CIRCULATION LA English DT Article DE tests; hypertension; trials ID EXERCISE HYPERTENSION; SUBMAXIMAL EXERCISE; YOUNG-ADULTS; FOLLOW-UP; DISEASE; GENDER; AGE; MEN AB Background-Although systolic blood pressure (SBP) response to exercise has been shown to predict subsequent hypertension in small samples of men, this association has not been studied in a large population-based sample of middle-aged men and women. The purpose of this study was to examine, in normotensive subjects, the relations of SEP and diastolic blood pressure (DBP) during the exercise and recovery periods of a graded treadmill test to the risk of developing new-onset hypertension. Methods and Results-BP data from exercise testing in 1026 men and 1284 women (mean age, 42+/-10 years; range, 20 to 69 years) from the Framingham Offspring Study who were normotensive at baseline were related to the incidence of hypertension 8 years later. New-onset hypertension, defined as an SEP greater than or equal to 140 mm Hg or DBP greater than or equal to 90 mm Hg or the initiation of antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%). Exaggerated SEP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of SEP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than the 95th percentile during the second stage of exercise and third minute of recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05) and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in men in a multivariable model that included exercise duration and peak exercise BP (OR, 1.92; CI, 1.00, 3.69). Baseline resting SEP (chi(2), 23.4 in men and 34.7 in women) and DBP (chi(2), 11.3 in men and 13.1 in women) had stronger associations with new-onset hypertension than exercise DBP (chi(2), 16.4 in men and 6.1 in women) and recovery SEP (chi(2), 6.5 in men and 2.1 in women) responses. Conclusions-An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. An elevated recovery SEP was predictive of hypertension in men. These findings may reflect subtle pathophysiological features in the preclinical stage of hypertension. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. Beth Israel Hosp, Div Cardiol, Boston, MA 02215 USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov NR 31 TC 230 Z9 249 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 13 PY 1999 VL 99 IS 14 BP 1831 EP 1836 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 184WC UT WOS:000079635900009 PM 10199879 ER PT J AU Chen, YNP Sharma, SK Ramsey, TM Jiang, L Martin, MS Baker, K Adams, PD Bair, KW Kaelin, WG AF Chen, YNP Sharma, SK Ramsey, TM Jiang, L Martin, MS Baker, K Adams, PD Bair, KW Kaelin, WG TI Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID S-PHASE ENTRY; DNA-BINDING; CYCLIN-A; RETINOBLASTOMA PROTEIN; MAMMALIAN-CELLS; E2F-1; APOPTOSIS; EXPRESSION; TRANSCRIPTION; CANCER AB Recent studies identified a short peptide motif that serves as a docking site for cyclin/cyclin-dependent kinase (cdk) 2 complexes. Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell membrane-permeable forms of such peptides preferentially induced transformed cells to undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription factors is a common event during transformation and was sufficient to sensitize cells to the cyclin/cdk2 inhibitory peptides, These results suggest that deregulation of E2F and inhibition of cdk2 are synthetically lethal and provide a rationale for the development of cdk2 antagonists as antineoplastic agents. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Nova Pharmaceut Corp, Novartis Inst Biomed Res, Summit, NJ 07901 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 282 Z9 289 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 13 PY 1999 VL 96 IS 8 BP 4325 EP 4329 DI 10.1073/pnas.96.8.4325 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500024 PM 10200261 ER PT J AU Cheng, XF Boas, DA AF Cheng, XF Boas, DA TI Systematic diffuse optical image errors resulting from uncertainty in the background optical properties SO OPTICS EXPRESS LA English DT Article ID PHOTON-DENSITY WAVES; LIGHT TRANSPORT; TURBID MEDIA; TOMOGRAPHY; RECONSTRUCTION; SPECTROSCOPY; SIMULATIONS; SCATTERING; ABSORPTION; TISSUE AB We investigated the diffuse optical image errors resulting from systematic errors in the background scattering and absorption coefficients, Gaussian noise in the measurements, and the depth at which the image is reconstructed when using a 2D linear reconstruction algorithm for a 3D object. The fourth Born perturbation approach was used to generate reflectance measurements and k-space tomography was used for the reconstruction. Our simulations using both single and dual wavelengths show large systematic errors in the absolute reconstructed absorption coefficients and corresponding hemoglobin concentrations, while the errors in the relative oxy- and deoxy- hemoglobin concentrations are acceptable. The greatest difference arises from a systematic error in the depth at which an image is reconstructed. While an absolute reconstruction of the hemoglobin concentrations can deviate by 100% for a depth error of +/-1 mm, the error in the relative concentrations is less than 5%. These results demonstrate that while quantitative diffuse optical tomography is difficult, images of the relative concentrations of oxy- and deoxy- hemoglobin are accurate and robust. Other results, not presented, confirm that these findings hold for other linear reconstruction techniques (i. e. SVD and SIRT) as well as for transmission through slab geometries. (C) 1999 Optical Society of America. C1 Tufts Univ, Ctr Electroopt Technol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Cheng, XF (reprint author), Tufts Univ, Ctr Electroopt Technol, Medford, MA 02155 USA. NR 26 TC 32 Z9 32 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD APR 12 PY 1999 VL 4 IS 8 BP 299 EP 307 PG 9 WC Optics SC Optics GA 185ZD UT WOS:000079700800008 PM 19396286 ER PT J AU Adams, GB Pym, AS Poznansky, MC McClure, MO Weber, JN AF Adams, GB Pym, AS Poznansky, MC McClure, MO Weber, JN TI The in vivo effects of combination antiretroviral drug therapy on peripheral blood CD34(+) cell colony forming units from HIV type 1 infected patients SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS-1; AIDS-RELATED COMPLEX; BONE-MARROW; HIV-1-INFECTED DONORS; STIMULATING FACTOR; ANTIVIRAL THERAPY; PROGENITOR CELLS; DISEASE; ABNORMALITIES; INHIBITION AB This study investigated the effects of a combination antiretroviral drug regimen (indinavir and two nucleoside analogs or ritonavir and saquinavir) on the levels of CD34(+) colony-forming units (CFU-Cs) in the peripheral blood of HIV-1(+) patients, Ten patients who were receiving combination antiretroviral drug therapy were studied and their peripheral blood CD34+ CFU-Cs were measured prior to, 1 month after, and 4 to 6 months after the commencement of therapy, The levels of CD4(+) T cells increased significantly in these patients (paired t test, p = 0.0027) and plasma viral load became undetectable in all but one patient studied. Measurements of the CFU-Cs showed that their levels tended to increase on the commencement of therapy, nd these levels became significantly higher than baseline by 4-6 months (paired t test, p = 0.0293), Analysis of the different colony phenotype demonstrated that the main contributor to this increase consisted of burst-forming unit erythroid (BFU-E) cells, These data also demonstrated that there was an inverse correlation between the rise in CFU-Cs at 4-6 months compared with CD4(+) cell, CD8(+) cell, and neutrophil counts, and hemoglobin concentration, at baseline. The demonstrated increase in the levels of CD34(+) CFU-Cs suggests that HIV-1 may have an inhibitory effect on these cells in vivo, and that this inhibition may be abrogated by suppression of viral replication. C1 Imperial Coll, Sch Med, Jefferiss Res Trust Labs, Dept Genitourinary Med & Communicable Dis, London W2 1PG, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 02129 USA. RP Weber, JN (reprint author), Imperial Coll, Sch Med, Jefferiss Res Trust Labs, Dept Genitourinary Med & Communicable Dis, Norfolk Pl, London W2 1PG, England. NR 27 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 1999 VL 15 IS 6 BP 551 EP 559 DI 10.1089/088922299311079 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 185JL UT WOS:000079665700007 PM 10221532 ER PT J AU Jacobs, IJ Skates, SJ MacDonald, N Menon, U Rosenthal, AN Davies, AP Woolas, R Jeyarajah, AR Sibley, K Lowe, DG Oram, DH AF Jacobs, IJ Skates, SJ MacDonald, N Menon, U Rosenthal, AN Davies, AP Woolas, R Jeyarajah, AR Sibley, K Lowe, DG Oram, DH TI Screening for ovarian cancer: a pilot randomised controlled trial SO LANCET LA English DT Article ID SERUM CA-125 LEVELS; CA 125; ULTRASONOGRAPHY; SONOGRAPHY; COLOR; STRATEGIES; CARCINOMA; DIAGNOSIS; PROTOCOL; MARKERS AB Background The value of screening for ovarian cancer is uncertain. We did a pilot randomised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography. Methods Postmenopausal women aged 45 years or older were randomised to a control group (n=10 977) or screened group (n=10 958). Women randomised to screening were offered three annual screens that involved measurement of serum CA 125, pelvic ultrasonography if CA 125 was 30 U/mL or more, and referral for gynaecological opinion if ovarian volume was 8.8 mt or more on ultrasonography. All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube tinder cancers). Findings Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in six and 23 had false positive screening results. The positive predictive value was 20.7%. During 7-year follow-up, ten further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months (p=0.0112), The number of death's from an index cancer did not differ significantly between the control and screened groups (18 of 10 977 vs nine of 10 958, relative risk 2.0 [95% CI 0.78-5.13]). Interpretation These results show that a multimodal approach to ovarian cancer screening in a randomised trial is feasible acid justify a larger randomised trial to see whether screening affects mortality, C1 Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, Dept Gynaecol Oncol, Gynaecol Canc Res Unit, London EC1A 7BE, England. Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, Dept Pathol, London EC1A 7BE, England. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA USA. RP Jacobs, IJ (reprint author), St Bartholomews Hosp, London EC1A 7BE, England. RI Menon, Usha/C-4716-2008; Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 25 TC 331 Z9 340 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 10 PY 1999 VL 353 IS 9160 BP 1207 EP 1210 DI 10.1016/S0140-6736(98)10261-1 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 186TB UT WOS:000079744100007 PM 10217079 ER PT J AU Pandey, P Avraham, S Kumar, S Nakazawa, A Place, A Ghanem, L Rana, A Kumar, V Majumder, PK Avraham, H Davis, RJ Kharbanda, S AF Pandey, P Avraham, S Kumar, S Nakazawa, A Place, A Ghanem, L Rana, A Kumar, V Majumder, PK Avraham, H Davis, RJ Kharbanda, S TI Activation of p38 mitogen-activated protein kinase by PYK2/related adhesion focal tyrosine kinase-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; N-TERMINAL KINASE; C-JUN; MAP KINASE; IONIZING-RADIATION; STRESS-RESPONSE; GENE-EXPRESSION; ABL; PHOSPHORYLATION; CALCIUM AB The stress-activated p38 mitogen-activated protein kinase (p38 MAPK), a member of the subgroup of mammalian kinases, appears to play an important role in regulating inflammatory responses, including cytokine secretion and apoptosis, The upstream mediators that link extracellular signals with the p38 MAPK signaling pathway are currently unknown. Here we demonstrate that pp125 focal adhesion kinase-related tyrosine kinase RAFTK (also known as PYK2, CADTK) is activated specifically by methylmethane sulfonate (MMS) and hyperosmolarity but not by ultraviolet radiation, ionizing radiation, or cis-platinum. Overexpression of RAFTK leads to the activation of p38 MAPK, Furthermore, overexpression of a dominant-negative mutant of RAFTK (RAFTK K-M) inhibits MMS-induced p38 MAPK activation. MKK3 and MKK6 are known potential constituents of p38 MAPK signaling pathway, whereas SEK1 and MEK1 are upstream activators of SAPK/JNK and ERK pathways, respectively. We observe that the dominant-negative mutant of MKK3 but not of MKK6, SEK1, or MEK1 inhibits RAFTK-induced p38 MAPK activity. Furthermore, the results demonstrate that treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N'.N'-tetraacetic acid, tetra(acetoxymethyl)-ester, a membrane-permeable calcium chelator, inhibits MMS-induced activation of RAFTK and p38 MAPK. Taken together, these findings indicate that RAFTK represents a stress-sensitive mediator of the p38 MAPK signaling pathway in response to certain cytotoxic agents. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Inst Med, Deaconess Med Ctr, Div Expt Med & Hematol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Howard Hughes Med Inst,Program Mol Med, Worcester, MA 01605 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ghanem, Louis/R-3733-2016 OI Ghanem, Louis/0000-0002-7723-5241 FU NCI NIH HHS [CA75216, CA65861]; NHLBI NIH HHS [R01 HL55445] NR 37 TC 117 Z9 117 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 1999 VL 274 IS 15 BP 10140 EP 10144 DI 10.1074/jbc.274.15.10140 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185HT UT WOS:000079663500036 PM 10187797 ER PT J AU Walters, RW Grunst, T Bergelson, JM Finberg, RW Welsh, MJ Zabner, J AF Walters, RW Grunst, T Bergelson, JM Finberg, RW Welsh, MJ Zabner, J TI Basolateral localization of fiber receptors limits adenovirus infection from the apical surface of airway epithelia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEDIATED GENE-TRANSFER; CYSTIC-FIBROSIS; TRACHEAL EPITHELIUM; NASAL EPITHELIUM; HELA-CELLS; COOPERATIVE BINDING; IN-VITRO; VIRUS; ENTRY; VECTOR AB Recent identification of two receptors for the adenovirus fiber protein, coxsackie B and adenovirus type 2 and 5 receptor (CAR), and the major histocompatibility complex (MHC) Class I alpha-2 domain allows the molecular basis of adenoviral infection to be investigated. Earlier work has shown that human airway epithelia are resistant to infection by adenovirus, Therefore, we examined the expression and localization of CAR and MHC Class I in an in vitro model of well differentiated, ciliated human airway epithelia. We found that airway epithelia express CAR and MHC Class I. However, neither receptor was present in the apical membrane; instead, both were polarized to the basolateral membrane. These findings explain the relative resistance to adenovirus infection from the apical surface. In contrast, when the virus was applied to the basolateral surface, gene transfer was much more efficient because of an interaction of adenovirus fiber with its receptors, In addition, when the integrity of the tight junctions was transiently disrupted, apically applied adenovirus gained access to the basolateral surface and enhanced gene transfer. These data suggest that the receptors required for efficient infection are not available on the apical surface, and interventions that allow access to the basolateral space where fiber receptors are located increase gene transfer efficiency. C1 Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Physiol & Biophys, Iowa City, IA 52242 USA. Childrens Hosp Philadelphia, Div Immunol & Infect Dis, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zabner, J (reprint author), Univ Iowa, Coll Med, Howard Hughes Med Inst, Dept Internal Med, 500 EMRB, Iowa City, IA 52242 USA. EM Joseph-Zabner@uiowa.edu RI Finberg, Robert/E-3323-2010 NR 57 TC 256 Z9 263 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 1999 VL 274 IS 15 BP 10219 EP 10226 DI 10.1074/jbc.274.15.10219 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185HT UT WOS:000079663500046 PM 10187807 ER PT J AU Lin, Y Sun, L Nguyen, LV Rachubinski, RA Goodman, HM AF Lin, Y Sun, L Nguyen, LV Rachubinski, RA Goodman, HM TI The pex16p homolog SSE1 and storage organelle formation in Arabidopsis seeds SO SCIENCE LA English DT Article ID YEAST YARROWIA-LIPOLYTICA; PEROXISOME BIOGENESIS; THALIANA; PROTEIN; MUTANTS; PLANTS; BODIES AB Mature Arabidopsis seeds are enriched in storage proteins and lipids, but lack starch. In the shrunken seed 1 (sse1) mutant, however, starch is favored over proteins and lipids as the major storage compound. SSE1 has 26 percent identity with Pex16p in Yarrowia lipolytica and complements pex16 mutants defective in the formation of peroxisomes and the transportation of plasma membrane- and cell wall-associated proteins, In Arabidopsis maturing seeds, SSE1 is required for protein and oil body biogenesis, both of which are endoplasmic reticulum-dependent. Starch accumulation in sse1 suggests that starch formation is a default storage deposition pathway. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Alberta, Dept Anat & Cell Biol, Edmonton, AB T6G 2H7, Canada. RP Lin, Y (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NR 17 TC 76 Z9 79 U1 1 U2 5 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 9 PY 1999 VL 284 IS 5412 BP 328 EP 330 DI 10.1126/science.284.5412.328 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 184WH UT WOS:000079636400045 PM 10195899 ER PT J AU Passafaro, M Sheng, M AF Passafaro, M Sheng, M TI Synaptogenesis: The MAP location of GABA receptors SO CURRENT BIOLOGY LA English DT Article ID GLYCINE-RECEPTOR; LOCALIZATION; GEPHYRIN; PROTEIN AB Microtubule-associated proteins (MAPs) have been identified as binding partners for ionotropic GABA(A) and GABA, receptors, These interactions suggest a potential role for MAPs in the cytoskeletal anchoring of receptor ion channels at specific subcellular sites, such as synapses. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Passafaro, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 10 TC 10 Z9 12 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 8 PY 1999 VL 9 IS 7 BP R261 EP R263 DI 10.1016/S0960-9822(99)80159-6 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 186MD UT WOS:000079732800013 PM 10209115 ER PT J AU Kirchhausen, T AF Kirchhausen, T TI Cell biology - Boa constrictor or rattlesnake? SO NATURE LA English DT Editorial Material ID DYNAMIN; RINGS C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. NR 9 TC 19 Z9 19 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 1999 VL 398 IS 6727 BP 470 EP 471 DI 10.1038/18989 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 185HQ UT WOS:000079662800027 PM 10206640 ER PT J AU Becker, AE Grinspoon, SK Klibanski, A Herzog, DB AF Becker, AE Grinspoon, SK Klibanski, A Herzog, DB TI Current concepts - Eating disorders SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; FOLLOW-UP; WOMEN; PSYCHOTHERAPY; OSTEOPOROSIS; THERAPY; ANTIDEPRESSANTS; DISTURBANCES; PREGNANCY C1 Harvard Univ, Sch Med, Harvard Eating Disorders Ctr, Boston, MA 02116 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Herzog, DB (reprint author), Harvard Univ, Sch Med, Harvard Eating Disorders Ctr, 356 Boylston St, Boston, MA 02116 USA. FU NCRR NIH HHS [5M01 RR01066]; NIDDK NIH HHS [R01 DK5265]; NIMH NIH HHS [5R01 MH38333] NR 70 TC 229 Z9 241 U1 5 U2 11 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 8 PY 1999 VL 340 IS 14 BP 1092 EP 1098 DI 10.1056/NEJM199904083401407 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 184AK UT WOS:000079587000007 PM 10194240 ER PT J AU Harmon, DC Drucker, EA Aisenberg, AC Mark, EJ Vonsattel, JP Richardson, EP AF Harmon, DC Drucker, EA Aisenberg, AC Mark, EJ Vonsattel, JP Richardson, EP TI Case records of the Massachusetts General Hospital - A 53-year-old man with acute renal failure, cortical blindness, and respiratory distress - Signet-ring-cell carcinoma of the stomach, with widespread metastases, including leptomeningeal carcinomatosis. Disseminated intravascular coagulation. Cerebral cortico-subcortical infarcts. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEPATITIS-B VIRUS; POLYARTERITIS-NODOSA; ASSOCIATION; AUTOANTIBODIES; VASCULITIS; INFECTION C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02115 USA. RP Harmon, DC (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. NR 23 TC 1 Z9 1 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 8 PY 1999 VL 340 IS 14 BP 1099 EP 1106 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 184AK UT WOS:000079587000008 ER PT J AU Richardson, WS Wilson, MC Guyatt, GH Cook, DJ Nishikawa, J AF Richardson, WS Wilson, MC Guyatt, GH Cook, DJ Nishikawa, J CA Evidence-Based Med Working Grp TI Users' guides to the medical literature - XV. How to use an article about disease probability for differential diagnosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NOTHING GOES WRONG; INFECTIVE ENDOCARDITIS; DECISION-MAKING; PRIMARY-CARE; HELP ME; PREVENTION; NUMERATORS; DIZZINESS; JUDGMENT; THERAPY C1 McMaster Univ, Dept Clin Epidemiol, Hamilton, ON L8S 4L8, Canada. McMaster Univ, Dept Biostat, Hamilton, ON L8S 4L8, Canada. Audie L Murphy Mem Vet Hosp, Dept Ambulatory Care, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. RP Guyatt, GH (reprint author), McMaster Univ, Hlth Sci Ctr, 1200 Main St W,Room 2C12, Hamilton, ON L8N 3Z5, Canada. NR 35 TC 75 Z9 78 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 1999 VL 281 IS 13 BP 1214 EP 1219 DI 10.1001/jama.281.13.1214 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 181VW UT WOS:000079464400037 PM 10199432 ER PT J AU Kaelin, WG AF Kaelin, WG TI The emerging p53 gene family SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR-SUPPRESSOR GENE; LARGE T-ANTIGEN; WILD-TYPE P53; MUTANT P53; DNA-DAMAGE; P73 GENE; P53-MEDIATED TRANSACTIVATION; TRANSCRIPTIONAL ACTIVITY; SV40-TRANSFORMED CELLS AB Perturbation of p53 protein function is a common, if not universal, finding in human cancer. Tumor suppression by p53 is due, at least in part, to its ability to activate transcription of certain genes involved in cell cycle control and apoptosis (programmed cell death), Two additional members of the mammalian p53 family, p73 and p51, which is also known as p40, p63, KET, or p73L, were recently identified, Both of these proteins share substantial sequence homology with p53 and can, at least when overproduced, activate p53-responsive promoters and induce apoptosis, Nonetheless, data on differences between these proteins and p53 are emerging, For example, p73 is not induced by DNA damage and is not targeted for inactivation by viral oncoproteins such as simian virus 40 (SV40) T antigen, adenovirus E1B 55K, and human papillomavirus E6. In contrast to p53, neither p73 nor p51 appears to be frequently mutated in human cancers on the basis of the limited studies reported to date. Finally, unlike p53, cells produce multiple p73 and p51 isoforms as a result of alternative splicing, and production of p73 and p51 appears to be restricted to certain tissues. Additional studies are required to determine the role, if any, that p73 and p51 play in cell growth control and carcinogenesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Mayer Bldg,Rm 457,44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 87 TC 119 Z9 129 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 1999 VL 91 IS 7 BP 594 EP 598 DI 10.1093/jnci/91.7.594 PG 5 WC Oncology SC Oncology GA 185KK UT WOS:000079668000009 PM 10203277 ER PT J AU Wiencke, JK Thurston, SW Kelsey, KT Varkonyi, A Wain, JC Mark, EJ Christiani, DC AF Wiencke, JK Thurston, SW Kelsey, KT Varkonyi, A Wain, JC Mark, EJ Christiani, DC TI Early age at smoking initiation and tobacco carcinogen DNA damage in the lung SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CANCER RISK ASSESSMENT; MOLECULAR EPIDEMIOLOGY; CIGARETTE-SMOKING; ADDUCT LEVELS; ORAL-MUCOSA; TISSUES; CELLS; SUSCEPTIBILITY; EXPOSURE; ASSAY AB Background: DNA adducts formed as a consequence of exposure to tobacco smoke may be involved in carcinogenesis, and their presence may indicate a high risk of lung cancer, To determine whether DNA adducts can be used as a "dosimeter" for cancer risk, we measured the adduct levels in nontumorous lung tissue and blood mononuclear cells from patients with lung cancer, and we collected data from the patients on their history of smoking. Methods: We used the P-32-postlabeling assay to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143 patients and in blood mononuclear cells from 54 of these patients, From the smoking histories, we identified exposure variables associated with increased DNA adduct levels by use of multivariate analyses with negative binomial regression models, Results/ Conclusions: We found statistically significant interactions for variables of current and former smoking and for other smoking variables (e.g., pack-years [number of packs smoked per day x years of smoking] or years smoked), indicating that the impact of smoking variables on DNA adduct levels may be different in current and former smokers. Consequently, our analyses indicate that models for current and former smokers should be considered separately. In current smokers, recent smoking intensity (cigarettes smoked per day) was the most important variable. In former smokers, age at smoking initiation was inversely associated with DNA adduct levels. A highly statistically significant correlation (r =.77 [Spearman's correlation]; two sided P<.001) was observed between DNA adduct levels in blood mononuclear cells and lung tissue. Implications: Our results in former smokers suggest that smoking during adolescence may produce physiologic changes that lead to increased DNA adduct persistence or that young smokers may be markedly susceptible to DNA adduct formation and have higher adduct burdens after they quit smoking than those who started smoking later in life. C1 Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Wiencke, JK (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Lab Mol Epidemiol, 500 Parnassus Ave, San Francisco, CA 94143 USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [P42ES04705, ES08357, ES00002] NR 39 TC 157 Z9 158 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 1999 VL 91 IS 7 BP 614 EP 619 DI 10.1093/jnci/91.7.614 PG 6 WC Oncology SC Oncology GA 185KK UT WOS:000079668000012 PM 10203280 ER PT J AU Moir, RD Atwood, CS Romano, DM Laurans, MH Huang, XD Bush, AI Smith, JD Tanzi, RE AF Moir, RD Atwood, CS Romano, DM Laurans, MH Huang, XD Bush, AI Smith, JD Tanzi, RE TI Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations SO BIOCHEMISTRY LA English DT Article ID RECEPTOR-RELATED PROTEIN; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE BRAIN; HUMAN CEREBROSPINAL-FLUID; E IN-VITRO; SECONDARY STRUCTURE; FIBRIL FORMATION; E EPSILON-4; ALPHA-2-MACROGLOBULIN RECEPTOR; TERMINAL FRAGMENT AB The epsilon 4 allele of apolipoprotein E (APOE) has been found to be a risk factor for late-onset Alzheimer's disease (AD). While the pathogenic mechanism of APOE in AD is not yet clear, APOE isoforms appear to differentially influence the aggregation of A beta, the principal component of Alzheimer-associated beta-amyloid deposits. To date, no data are available for the propensity of A beta to aggregate in the presence of APOE under conditions where these components are at physiological concentrations (in cerebrospinal fluid, APOE and A beta are approximate to 100 nM and approximate to 5 nM, respectively). We employed a novel in vitro filtration assay for detecting zinc(II)- and copper(II)-induced aggregation of A beta in solutions containing concentrations of the peptide that are similar to those reported for human cerebrospinal fluid. The potential for resolubilization with EDTA and the relative densities of zinc- and copper-induced A beta aggregates were also compared. Zinc-induced A beta aggregates were found to be denser and less easily resolubilized than copper-induced precipitates. Metal-induced aggregation of A beta was studied in the presence of purified apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 under conditions that approximate the physiological concentrations and ratios of these proteins. In the presence of all three APOE isoforms, zinc-induced aggregation of A beta was attenuated, while precipitation with copper was enhanced. Consistent with the increased risk for AD associated with the epsilon 4 allele of APOE, metal-induced aggregation of A beta was highest for both zinc and copper in the presence of apolipoprotein E4. Our data are consistent with a role for APOE as an in vivo molecular chaperone for A beta. C1 Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Charlestown, MA 02129 USA. Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10021 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 88 TC 98 Z9 100 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 6 PY 1999 VL 38 IS 14 BP 4595 EP 4603 DI 10.1021/bi982437d PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188EP UT WOS:000079834100041 PM 10194381 ER PT J AU Cornford, EM Hyman, S AF Cornford, EM Hyman, S TI Blood-brain barrier permeability to small and large molecules SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE GLUT1 glucose transporter; immunogold electron microscopy; MCT1; MCT2; monocarboxylic acid transporter ID GLUT1 GLUCOSE-TRANSPORTER; CENTRAL-NERVOUS-SYSTEM; ELECTRON-MICROSCOPIC IMMUNOGOLD; PEPTIDE DRUG-DELIVERY; INTRACAROTID INFUSION; WATER PERMEABILITY; TUMOR BARRIER; RAT-BRAIN; IN-VIVO; NEUROTROPHIC FACTOR AB The objective of this article is to provide the reader with an update of some of the BBB research highlights which have occurred in recent times, and to review the impact and contributions of immunogold electron microscopic studies on our understanding of the brain capillary endothelium. Glucose and monocarboxylic acids are two small molecules which this review will focus upon; and advances in immunogold characterization of the GLUT1 glucose transporter and the MCT1 and MCT2 monocarboxylic acid nutrient transporters will be discussed. Human serum albumin is chosen as a representative large molecule, and it has recently been shown that immunogold identification of this protein can serve as an indicator of compromised BBB function in a variety of pathophysiological conditions. (C) 1999 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, SW Reg VA Epilepsy Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90095 USA. RP Cornford, EM (reprint author), W Los Angeles Vet Affairs Med Ctr, SW Reg VA Epilepsy Ctr, W127B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 112 TC 53 Z9 54 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD APR 5 PY 1999 VL 36 IS 2-3 BP 145 EP 163 DI 10.1016/S0169-409X(98)00082-9 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180CE UT WOS:000079366800002 ER PT J AU Scremin, OU Holschneider, DP Chen, K Li, MG Shih, JC AF Scremin, OU Holschneider, DP Chen, K Li, MG Shih, JC TI Cerebral cortical blood flow maps are reorganized in MAOB-deficient mice SO BRAIN RESEARCH LA English DT Article DE cerebral blood flow; monoamine oxidase; phenylethylamine; autoradiography; iodo-antipyrine; mouse ID PLATELET MONOAMINE-OXIDASE; PIRIFORM CORTEX; BETA-PHENYLETHYLAMINE; BRAIN-BARRIER; MIGRAINE; RAT; AMPHETAMINE; HEADACHE; AMINES; INHIBITION AB Cerebral cortical blood flow (CBF) was measured autoradiographically in conscious mice without the monoamine oxidase B (MAOB) gene (KO, n = 11) and the corresponding wild-type animals (WILD, n = 11). Subgroups of animals of each genotype received a continuous intravenous infusion over 30 min of phenylethylamine (PEA), an endogenous substrate of MAOB, (8 nmol g(-1) min(-1) in normal saline at a volume rate of 0.11 mu l g(-1) min(-1)) or saline at the same volume rate. Maps of relative CBF distribution showed predominance of midline motor and sensory area CBF in KO mice over WILD mice that received saline. PEA enhanced CBF in lateral frontal and piriform cortex in both KO and WILD mice. These changes may reflect a differential activation due to chronic and acute PEA elevations on motor and olfactory function, as well as on the anxiogenic effects of this amine. In addition to its effects on regional CBF distribution, PEA decreased CBF globally in KO mice (range -31% to -41% decrease from control levels) with a lesser effect in WILD mice. It is concluded that MAOB may normally regulate CBF distribution and its response to blood PEA. (C) 1999 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. RP Scremin, OU (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 317, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu FU NIA NIH HHS [5-K12-AG-00521, K12 AG000521]; NIMH NIH HHS [R37 MH39085, K05 MH 00796, R37 MH039085] NR 49 TC 18 Z9 18 U1 0 U2 0 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 3 PY 1999 VL 824 IS 1 BP 36 EP 44 DI 10.1016/S0006-8993(99)01167-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 180GL UT WOS:000079377700004 PM 10095040 ER PT J AU Ganesh, S Amano, K Delgado-Escueta, AV Yamakawa, K AF Ganesh, S Amano, K Delgado-Escueta, AV Yamakawa, K TI Isolation and characterization of mouse homologue for the human epilepsy gene, EPM2A SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROGRESSIVE MYOCLONUS EPILEPSY; PROTEIN-TYROSINE PHOSPHATASES; FORM AB Mutations in the novel gene, EPM2A, have been shown recently to cause the progressive myoclonus epilepsy of Lafora type. EPM2A is predicted to encode a putative protein-tyrosine phosphatase but its specific role in normal brain function and in the Lafora disease is not known. As a first step towards understanding the cellular function of EPM2A in an animal model, we have isolated cDNA clones for mouse EPM2A and analyzed its expression, Sequence analyses of the mouse cDNA clones revealed a complete ORF that supports the 5' coding sequence predicted for human EPM2A from the genomic sequence. When compared to EPM2A, the mouse homologue, named Epa2a, shows 86% identity at the nucleotide level and 88% identity and 93% similarity at the amino acid level. Similar to the human counterpart, Epm2a showed ubiquitous expression in Northern with a major transcript size of 3.5 kb. We have mapped the Epm2a to the proximal region of mouse chromosome 10 which is the syntenic region for human chromosome band, 6q24. Our results suggest that EPM2A is highly conserved in mammals and might have a conserved function. (C) 1999 Academic Press. C1 Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. W Los Angeles DVA Med Ctr, Los Angeles, CA 90073 USA. RP Yamakawa, K (reprint author), Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. RI Ganesh, Subramniam/B-4131-2009; Yamakawa, Kazuhiro/N-5050-2015 NR 17 TC 16 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 2 PY 1999 VL 257 IS 1 BP 24 EP 28 DI 10.1006/bbrc.1999.0402 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 184MC UT WOS:000079615100005 PM 10092504 ER PT J AU Medvedev, AE Blanco, JCG Qureshi, N Vogel, SN AF Medvedev, AE Blanco, JCG Qureshi, N Vogel, SN TI Limited role of ceramide in lipopolysaccharide-mediated mitogen-activated protein kinase activation, transcription factor induction, and cytokine release SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; DIPHOSPHORYL LIPID-A; LPS BINDING-PROTEIN; MURINE MACROPHAGES; BACTERIAL LIPOPOLYSACCHARIDE; RHODOPSEUDOMONAS-SPHAEROIDES; ACID SPHINGOMYELINASE; INDUCED APOPTOSIS AB The involvement of ceramide in lipopolysaccharide-mediated activation of mouse macrophages was studied. Lipopolysaccharide cell-permeable ceramide analogs, and bacterial sphingomyelinase led to phosphorylation of the extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38 kinase and induced AP-1 DNA binding in C3H/OuJ (Lps(n)) but not in C3H/HeJ (Lps(d)) macrophages. Lipopolysaccharide and ceramide mimetics showed distinct kinetics of mitogen-activated protein kinase phosphorylation and AP-1 induction and activated AP-1 complexes with different subunit compositions. Lipopolysaccharide-activated AP-1 consisted of c-Fos, Jun-E, Jun-D, and c-Jun, while C-2-ceramide induced Jun-D and c-Jun only. Lipopolysaccharide and, less potently, C-2-ceramide or sphingomyelinase, stimulated AP-1-dependent reporter gene transcription in RAW 264.7 cells. Unlike lipopolysaccharide, C-2-ceramide failed to activate NF-kappa B and did not induce production of tumor necrosis factor or interleukin-6. The lipopolysaccharide antagonist, Rhodobacter sphaeroides diphosphoryl lipid A, inhibited lipopolysaccharide activation of NF-kappa B and AP-1 but did not block C-2-ceramide-induced AP-1. Pretreatment of C3H/OuJ macrophages with C-2-ceramide greatly diminished AP-1 induction following subsequent C-2-ceramide stimulation. However, lipopolysaccharide-induced transcription factor activation and cytokine release were not influenced, In contrast, lipopolysaccharide pretreatment inhibited both lipopolysaccharide- and C-2-ceramide-mediated responses. Thus, ceramide partially mimics lipopolysaccharide in activating the mitogen-activated protein kinases and AP-1 but not in mediating NF-kappa B induction or cytokine production, suggesting a limited role in lipopolysaccharide signaling. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Vogel, SN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vogel@bob.usuf2.usuhs.mil FU NIAID NIH HHS [AI-18797]; NIGMS NIH HHS [GM-50870] NR 74 TC 42 Z9 43 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9342 EP 9350 DI 10.1074/jbc.274.14.9342 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800031 PM 10092612 ER PT J AU Kieber-Emmons, T Lin, CM Foster, MH Kleyman, TR AF Kieber-Emmons, T Lin, CM Foster, MH Kleyman, TR TI Antiidiotypic antibody recognizes an amiloride binding domain within the alpha subunit of the epithelial Na+ channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM-CHANNEL; CONFORMATIONAL SEARCH; NEUTRALIZING ANTIBODY; INDUCED HYPERKALEMIA; MEMBRANE TOPOLOGY; CELL-LINE; PEPTIDE; PROTEIN; ANTIGEN; IDENTIFICATION AB We previously raised an antibody (RA6.3) by an antidiotypic approach which was designed to be directed against an amiloride binding domain on the epithelial Na+ channel (ENaC). This antibody mimicked amiloride in that it inhibited transepithelial Na+ transport across A6 cell monolayers. RA6.3 recognized a 72-kDa polypeptide in A6 epithelia treated with tunicamycin, consistent with the size of nonglycosylated Xenopus laevis alpha ENaC. RA6.3 specifically recognized an amiloride binding domain within the alpha-subunit of mouse and bovine ENaC. The deduced amino acid sequence of RA6.3 was used to generate a three-dimensional model structure of the antibody. The combining site of RA6.3 was epitope mapped using a novel computer-based strategy. Organic residues that potentially interact with the RA6.3 combining site were identified by data base screening using the program LUDI. Selected residues docked to the antibody in a manner corresponding to the ordered linear array of amino acid residues within an amiloride binding domain on the alpha-subunit of ENaC, A synthetic peptide spanning this domain inhibited the binding of RA6.3 to alpha ENaC. This analysis provided a novel approach to develop models of antibody-antigen interaction as well as a molecular perspective of RA6.3 binding to an amiloride binding domain within alpha ENaC. C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. RP Kleyman, TR (reprint author), Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM kleyman@mail.med.upenn.edu FU NIDDK NIH HHS [DK50268] NR 68 TC 21 Z9 21 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 2 PY 1999 VL 274 IS 14 BP 9648 EP 9655 DI 10.1074/jbc.274.14.9648 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800070 PM 10092651 ER PT J AU Kosslyn, SM Pascual-Leone, A Felician, O Camposano, S Keenan, JP Thompson, WL Ganis, G Sukel, KE Alpert, NM AF Kosslyn, SM Pascual-Leone, A Felician, O Camposano, S Keenan, JP Thompson, WL Ganis, G Sukel, KE Alpert, NM TI The role of Area 17 in visual imagery: Convergent evidence from PET and rTMS SO SCIENCE LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON EMISSION TOMOGRAPHY; OCCIPITAL CORTEX; PERCEPTION; CONNECTIVITY AB Visual imagery is used in a wide range of mental activities, ranging from memory to reasoning, and also plays a role in perception proper. The contribution of early visual cortex, specifically Area 17, to Visual mental imagery was examined by the use of two convergent techniques. In one, subjects closed their eyes during positron emission tomography (PET) while they visualized and compared properties (for example, relative length) of sets of stripes. The results showed that when people perform this task, Area 17 is activated. In the other, repetitive transcranial magnetic stimulation (rTMS) was applied to medial occipital cortex before presentation of the same task. Performance was impaired after rTMS compared with a sham control condition; similar results were obtained when the subjects performed the task by actually Looking at the stimuli. In sum, the PET results showed that when patterns of stripes are visualized, Area 17 is activated, and the rTMS results showed that such activation underlies information processing. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Lab Magnet Brain Stimulat,Behav Neurol Unit, Boston, MA 02215 USA. RP Kosslyn, SM (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. RI Pascual-Leone, Alvaro/G-6566-2011; Felician, Olivier/F-1212-2011; OI Ganis, Giorgio/0000-0001-6175-2618 FU NEI NIH HHS [R01 EY12091]; NIMH NIH HHS [R01 MH57980] NR 29 TC 424 Z9 439 U1 0 U2 24 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 2 PY 1999 VL 284 IS 5411 BP 167 EP 170 DI 10.1126/science.284.5411.167 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182QE UT WOS:000079509000060 PM 10102821 ER PT J AU Small, SD Wuerz, RC Simon, R Shapiro, N Conn, A Setnik, G AF Small, SD Wuerz, RC Simon, R Shapiro, N Conn, A Setnik, G TI Demonstration of high-fidelity simulation team training for emergency medicine SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE patient safety; performance; teamwork; team training; emergency medicine; simulation ID COMPREHENSIVE ANESTHESIA SIMULATION; PATIENT SIMULATOR; HUMAN ERROR; COORDINATION; PERFORMANCE; MANAGEMENT; INCIDENTS; EDUCATION; CARE AB Emergency medicine (EM) presents many cognitive, social, and systems challenges to practitioners. Coordination and communication under stress between and among individuals and teams representing a number of disciplines are critical for optimal care of the patient. The specialty is characterized by uncertainty, complexity, rapidly shifting priorities, a dependence on teamwork, and elements common to other risky domains such as perioperative medicine and aviation. High-fidelity simulators have had a long tradition in aviation, and in the past few years have begun to have a significant impact in anesthesiology. A national, multicenter research program to document the costs of teamwork failures in EM and provide a remedy in the form of an Emergency Team Coordination Course has developed to the point that high-fidelity medical simulators will be added to the hands-on training portion of the course. This paper describes an evolving collaborative effort by members of the Center for Medical Simulation, the Harvard Emergency Medicine Division, and the MedTeams program to design, demonstrate, and refine a high-fidelity EM simulation course to improve EM clinician performance, increase patient safety, and decrease liability. The main objectives of the paper are: 1) to present detailed specifications of tools and techniques for high-fidelity medical simulation; 2) to share the results of a proof-of-concept EM simulation workshop introducing multiple mannequin/three-patient scenarios; and 3) to focus on teamwork applications. The authors hope to engage the EM community in a wide-ranging discussion and hands-on exploration of these methods. C1 Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Div Emergency Med, Boston, MA USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. Ctr Med Simulat, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Dynam Res Corp, MedTeams, Crew Performance Grp, Boston, MA USA. Mt Auburn Hosp, Dept Emergency Med, Boston, MA USA. RP Small, SD (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol, 55 Fruit St, Boston, MA 02114 USA. RI Shapiro, Nathan/F-1718-2016 NR 47 TC 125 Z9 127 U1 1 U2 10 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 1999 VL 6 IS 4 BP 312 EP 323 DI 10.1111/j.1553-2712.1999.tb00395.x PG 12 WC Emergency Medicine SC Emergency Medicine GA 187PT UT WOS:000079796100013 PM 10230983 ER PT J AU Barnett, PG AF Barnett, PG TI The cost-effectiveness of methadone maintenance as a health care intervention SO ADDICTION LA English DT Article ID FOLLOW-UP; ZIDOVUDINE THERAPY; HEROIN-ADDICTION; MORTALITY-RATES; OPIOID ADDICTS; DEATH RATES; HIV; PROGRAMS AB Aims. Cost-effectiveness analysis using life-years of survival as the measure of treatment benefit is widely used in the economic evaluation of health care interventions but has not been applied to substance abuse treatment. The cost-effectiveness of methadone maintenance was evaluated to demonstrate the feasibility of applying this method to substance abuse treatment. Design. A literature review was undertaken to determine the effect of methadone treatment on the rate of mortality associated with opiate addiction. Information was also obtained on the average cost and duration of treatment. A two-state Markov model was used to estimate the incremental effect of methadone on the life span and treatment cost of a cohort of 25-year-old heroin users. Findings. Providing opiate addicts with access to methadone maintenance has an incremental cost-effectiveness ratio of $5915 per life-year gained (that is, for every year of life that is saved by providing methadone to opiate addicts, an additional $5915 in treatment costs are incurred). One-way sensitivity analysis determined that the ratio was less than $10 000 per-life year over a wide range of modeling assumptions. Conclusions. The ratio determined for methadone is lower than that of many common medical therapies, and well within the $50 000 threshold for judging cost-effectiveness. Even if decision makers do not wish use the same ratio that is applied to the general population, this method allows substance abuse treatment enhancements to be compared to improvements in health services offered to individuals with substance abuse disorders. Future work will require information on the impact of methadone treatment on the cost of health care and public programs, the indirect costs incurred by patients, and adjustments to reflect quality of life. C1 US Dept Vet Affairs, Ctr Hlth Care Evaluat, VA Palo Alto Hlth Care Syst, Program Evaluat & Resource Ctr, Menlo Park, CA 94025 USA. RP Barnett, PG (reprint author), US Dept Vet Affairs, Ctr Hlth Care Evaluat, VA Palo Alto Hlth Care Syst, Program Evaluat & Resource Ctr, 795 Willow Rd,152 MPD, Menlo Park, CA 94025 USA. FU NIDA NIH HHS [1-Y01 DA 40032] NR 30 TC 66 Z9 69 U1 2 U2 4 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 1999 VL 94 IS 4 BP 479 EP 488 DI 10.1046/j.1360-0443.1999.9444793.x PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 186RD UT WOS:000079742000003 PM 10605844 ER PT J AU Johansen, KL AF Johansen, KL TI Physical functioning and exercise capacity in patients on dialysis SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article DE exercise; end-stage renal disease; physical functioning; exercise capacity ID STAGE RENAL-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; HEMODIALYSIS-PATIENTS; SUBMAXIMAL EXERCISE; SKELETAL-MUSCLE; MAINTENANCE DIALYSIS; FAILURE; RECIPIENTS; METABOLISM; TOLERANCE AB Patients on dialysis have extremely limited exercise capacity, and poor physical functioning has been linked to low quality of life and high mortality in this population. The reason for the debility of patients on dialysis is far from clear despite years of study. The anemia of chronic renal disease is clearly a contributing factor, but uremic myopathy and resulting decreased muscle oxygen utilization have a significant impact on the physical functioning of patients on dialysis as well. Although it is likely that factors related to uremia adversely affect muscle function, some of the abnormalities demonstrated in uremic muscle are consistent with disuse atrophy. The clear contribution of anemia and the possible role of limited physical activity have led to studies of the effects of erythropoietin and aerobic exercise training on exercise capacity in end-stage renal disease patients. Both of these interventions result in increased exercise capacity. Thus vigorous treatment of anemia and uremia and encouragement of physical activity are important interventions to maximize the physical functioning of patients on dialysis. In addition, more studies are needed to clarify the causes of debility in this population and the impact of interventions on physical functioning, quality of life, and mortality. (C) 1999 by the National Kidney Foundation, Inc. C1 San Francisco VAMC, Nephrol Sect, San Francisco, CA 94121 USA. RP Johansen, KL (reprint author), San Francisco VAMC, Nephrol Sect, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. NR 42 TC 78 Z9 84 U1 3 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1073-4449 J9 ADV RENAL REPLACE TH JI Adv. Renal Replace. Ther. PD APR PY 1999 VL 6 IS 2 BP 141 EP 148 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 229JV UT WOS:000082191700005 PM 10230881 ER PT J AU Goss, KA Alharethi, R Laposata, M AF Goss, KA Alharethi, R Laposata, M TI Fatty acid ethyl ester synthesis in the preparation of scotch whiskey SO ALCOHOL LA English DT Article DE ethanol; lipids; fatty acids; alcoholism; ethanol abuse; addiction ID ETHANOL; CELLS AB Fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites present in human organs commonly damaged by ethanol abuse, have been implicated as mediators of organ damage. FAEE are additives in various foods and beverages to provide flavor or fragrance, and therefore are common dietary lipid constituents. We hypothesized that FAEE could be generated during alcoholic beverage production because fatty acids are present within microorganisms and ethanol is generated during the fermentation process. In this report, we demonstrate that FAEE are present in commercially available scotch beverages, and that in the preparation of scotch, FALL can be produced during the fermentation reaction as a result of FAEE synthase activity in the yeast. Following ingestion of scotch, preformed FAEE are delivered to GI tract. The consequences of ingestion of FALL in scotch, if any, remain to be determined. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Dept Pathol,Harvard Med Sch, Boston, MA 02114 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Dept Pathol,Harvard Med Sch, Room 235 Gray Bldg,32 Fruit St, Boston, MA 02114 USA. NR 11 TC 7 Z9 7 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD APR PY 1999 VL 17 IS 3 BP 241 EP 245 DI 10.1016/S0741-8329(98)00057-3 PG 5 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 186XK UT WOS:000079756000009 PM 10231172 ER PT J AU Asthana, S Raffaele, KC Greig, NH Schapiro, MB Blackman, MR Soncrant, TT AF Asthana, S Raffaele, KC Greig, NH Schapiro, MB Blackman, MR Soncrant, TT TI Neuroendocrine responses to intravenous infusion of physostigmine in patients with Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE physostigmine; HPA-axis; Alzheimer disease; memory; cortisol ID CORTICOTROPIN-RELEASING HORMONE; CEREBROSPINAL-FLUID; MEMORY; ARECOLINE; PITUITARY; ACETYLCHOLINE; CORTISOL; DEMENTIA; TACRINE; SYSTEM AB We have reported that physostigmine, a reversible cholinesterase inhibitor, enhances verbal memory in patients with Alzheimer disease (AD). To elucidate the mechanism of cognition enhancement, plasma hormones were measured during high-dose acute and low-dose chronic steady-state intravenous infusions of physostigmine in nine subjects with AD. High-dose hormone responses were measured during and for 24 h after the infusion of physostigmine 1-1.5 mg over 45-60 min. Chronic responses were measured during continuous intravenous infusions of physostigmine at doses (0.5-25 mg/day) that escalated over 2 weeks, and then during 1 week infusion of the dose that optimized cognition (2-12 mg/day) or placebo administered in a randomized double-blind, crossover design. A replicable improvement in verbal memory was found in five subjects. High-dose physostigmine infusion that produced noxious side effects resulted in significant elevation above baseline in plasma levels of adrenocorticotrophic hormone (ACTH) (p = 0.0001), cortisol (p = 0.0001), and beta-endorphin (p = 0.0001). Chronic physostigmine administration, in the absence of adverse effects, produced no significant elevation in ACTH (p = 0.08), cortisol (p = 0.70), or beta-endorphin (p = 0.82). These results indicate that high-dose physostigmine activates the hypothalamic-pituitary-adrenal (HPA) axis, likely representing a "stress response." In contrast, cognition-enhancing doses do not produce a peripheral corticosteroid response. Thus, physostigmine-induced memory improvement is independent of the activation of the HPA axis. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. Johns Hopkins Univ, Sch Med, Hopkins Bayview Med Ctr, Baltimore, MD USA. RP Asthana, S (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, GRECC 182 B, Tacoma, WA 98493 USA. NR 40 TC 5 Z9 5 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 1999 VL 13 IS 2 BP 102 EP 108 DI 10.1097/00002093-199904000-00008 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 268NQ UT WOS:000084422800008 PM 10372954 ER PT J AU Schwartz, MW Baskin, DG Kaiyala, KJ Woods, SC AF Schwartz, MW Baskin, DG Kaiyala, KJ Woods, SC TI Model for the regulation of energy balance and adiposity by the central nervous system SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE body weight; adipose tissue; food intake; insulin; leptin; neuropeptide Y; glucocorticoids; obesity; energy balance; central nervous system; homeostasis; central effector pathways; arcuate nucleus; paraventricular nucleus; review ID CORTICOTROPIN-RELEASING-FACTOR; REDUCES FOOD-INTAKE; OBESE ZUCKER RATS; MESSENGER-RIBONUCLEIC-ACID; INCREASED HYPOTHALAMIC CONTENT; NEUROPEPTIDE-Y CONCENTRATIONS; BODY-WEIGHT; GENE-EXPRESSION; CEREBROSPINAL-FLUID; IN-VIVO AB In 1995, we described a new model for adiposity regulation. Since then, data regarding the biology of body weight regulation has accumulated at a remarkable rate and has bath modified and strengthened our understanding of ibis homeostatic system. In this review we integrate new information into a revised model for further understanding this important regulatory process. Our model of energy homeostasis proposes that long-term adiposity-related signals such as insulin and leptin influence the neuronal activity of central effector pathways that serve as controllers of energy balance. C1 Univ Washington, Dept Med, Harborview Med Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Biol Struct, Harborview Med Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Harborview Med Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. RP Schwartz, MW (reprint author), Univ Washington, Dept Med, Harborview Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mschwart@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-12829, DK-52989]; NINDS NIH HHS [NS-32273] NR 180 TC 171 Z9 179 U1 0 U2 4 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 BP 584 EP 596 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 181GX UT WOS:000079434100003 PM 10197558 ER PT J AU Sibulesky, L Hayes, KC Pronczuk, A Weigel-DiFranco, C Rosner, B Berson, EL AF Sibulesky, L Hayes, KC Pronczuk, A Weigel-DiFranco, C Rosner, B Berson, EL TI Safety of < 7500RE (< 25000IU) vitamin A daily in adults with retinitis pigmentosa SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin A; supplementation; triacylglycerols; liver enzymes; retinal degeneration; retinitis pigmentosa; retinol; adults ID LIVER-FUNCTION TESTS; RETINYL ESTERS; A TOXICITY; LIQUID-CHROMATOGRAPHY; RANDOMIZED TRIAL; ALPHA-TOCOPHEROL; HEPATIC-INJURY; PLASMA RETINOL; LUNG-CANCER; CAROTENE AB Background: Vitamin A supplementation is being used successfully to treat some forms of cancer and the degenerative eye disease retinitis pigmentosa. The daily biological need for vitamin A is estimated to be 800 retinol equivalents (RE)fd (2667 IU/d) for adult women and 1000 RE/d (3300 IU/d) for adult men; doses greater than or equal to 7500 RE (greater than or equal to 25000 IU)/d are considered potentially toxic over the long term. Objective: We assessed the safety in adults of long-term vitamin A supplementation with doses above the daily biological need but less than 7500 RE (less than 25000 IU)/d. Design: Adults aged 18-54 y with retinitis pigmentosa but in generally good health (n = 146) were supplemented with 4500 RE (15000 IU) vitamin A/d for less than or equal to 12 y (group A) and compared with a similar group (n = 149) that received 23 RE (75 IU)ld (trace group). Mean total consumption of vitamin A in group A was 5583 RE (18609 IU)/d (range: 4911-7296 RE/d, or 16369-24318 IU/d) and that in the trace group was 1053 RE (3511 IU)/d (range: 401-3192 RE/d, or 1338-10638 IU/d). Results: Patients in group A showed an 8% increase in mean serum retinol concentration at 5 y and an 18% increase at 12 y (P less than 0.001); no retinol value exceeded the upper normal limit (3.49 mu mol/L, or 100 mu g/dL). Mean serum retinyl esters were elevated approximate to 1.7-fold at 5 y and remained relatively stable there after. No clinical symptoms or signs of liver toxicity attributable to vitamin A excess were detected. Conclusions: Prolonged daily consumption of less than 7500 RE (less than 25000 IU) vitamin A/d can be considered safe in this age group. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Brandeis Univ, Foster Biomed Res Lab, Waltham, MA 02254 USA. RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [U10-EY11030, U10-EY02014] NR 41 TC 43 Z9 44 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 BP 656 EP 663 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 181GX UT WOS:000079434100011 PM 10197566 ER PT J AU Renshaw, AA Cronin, JA Minter, LJ Nappi, D Whitman, T Jiroutek, M Cibas, ES AF Renshaw, AA Cronin, JA Minter, LJ Nappi, D Whitman, T Jiroutek, M Cibas, ES TI Performance characteristics of rapid (30-second) prescreening - Implications for calculating the false-negative rate and comparison with other quality assurance techniques SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cytopathology; cytology; quality control; Papanicolaou smear; statistics; false-negative rate; errors; screening; accuracy; uterine cervix ID CERVICAL SMEARS; PAPNET AB Rapid (30-second) prescreening of cervicovaginal smears can be used to detect false-negative cases and determine the false-negative rate of primary screening, but the performance characteristics have not been evaluated fully. A test set of 242 cases including 80 originally false-negative cases were rapidly screened by 4 different cytotechnologists on 2 occasions. Intraobserver and interobserver reproducibility were good. Median specificity for each round of observations was 89% (range, 30%-96%). Median sensitivity for all true-positive cases was 78% (range, 63%-97%); for all false-negative cases it was 59% (range, 38%-89%). The relative sensitivity of rapid screening for true-positive and false-negative cases varied with the diagnosis. Rapid screening detected almost the same percentage of false-negative cases of atypical squamous cells of uncertain significance (ASCUS) as true-positive ASCUS cases (median ratio, 1.12; range, 0.72-1.52). The median ratio of false-negative to true-positive ASCUS cases was significantly different than the ratio for low-grade plus high-grade squamous intraepithelial lesions (0.68; range, 0.50-0.96). Although performance varies between individuals, in this test population the reproducibility, specificity, and sensitivity were good. Because it detects more false-negative cases at a lower cost per case than routine rescreening, rapid prescreening should be considered as an alternative to current quality control measures. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cytol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Renshaw, AA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 21 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 1999 VL 111 IS 4 BP 517 EP 522 PG 6 WC Pathology SC Pathology GA 180KM UT WOS:000079385100010 PM 10191772 ER PT J AU Blumenfeld, A Slaugenhaupt, SA Liebert, CB Temper, V Maayan, C Gill, S Lucente, DE Idelson, M MacCormack, K Monahan, MA Mull, J Leyne, M Mendillo, M Schiripo, T Mishori, E Breakefield, X Axelrod, FB Gusella, JF AF Blumenfeld, A Slaugenhaupt, SA Liebert, CB Temper, V Maayan, C Gill, S Lucente, DE Idelson, M MacCormack, K Monahan, MA Mull, J Leyne, M Mendillo, M Schiripo, T Mishori, E Breakefield, X Axelrod, FB Gusella, JF TI Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NERVE GROWTH-FACTOR; TORSION DYSTONIA; ASHKENAZI JEWS; HUMAN GENOME; LINKAGE MAP; DNA; POPULATION; POLYMORPHISMS; LOCALIZATION; DIAGNOSIS AB Familial dysautonomia (FD) is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems and by Ashkenazi Jewish ancestry. We previously had mapped the defective gene (DYS) to an 11-cM segment of chromosome 9q31-33, flanked by D9S53 and D9S105. By using 11 new polymorphic loci, we now have narrowed the location of DYS to <0.5 cM between the markers 43B1GAGT and 157A3. Two markers in this interval, 164D1 and D9S1677, show no recombination with the disease. Haplotype analysis confirmed this candidate region and revealed a major haplotype shared by 435 of 441 FD chromosomes, indicating a striking founder effect. Three other haplotypes, found on the remaining 6 FD chromosomes, might represent independent mutations. The frequency of the major FD haplotype in the Ashkenazim (5 in 324 control chromosomes) was consistent with the estimated DYS carrier frequency of 1 in 32, and none of the four haplotypes associated with FD was observed on 492 non-FD chromosomes from obligatory carriers. It is now possible to provide accurate genetic testing both for families with FD and for carriers, on the basis of close flanking markers and the capacity to identify >98% of FD chromosomes by their haplotype. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Unit Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. NYU, Med Ctr, Dept Pediat, Dysautonomia Diagnost & Treatment Ctr, New York, NY 10016 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 42 TC 45 Z9 46 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 1110 EP 1118 DI 10.1086/302339 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900022 PM 10090896 ER PT J AU Ormsby, BL Hori, MT Tuck, ML AF Ormsby, BL Hori, MT Tuck, ML TI Eicosapentaenoic acid is a potent inhibitor of angiotensin II-induced calcium signals in vascular smooth muscle cells SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE vascular smooth muscle; calcium; angiotensin II; phospholipids C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA GLAHCS, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 8A EP 8A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600026 ER PT J AU Takagawa, Y Hori, MT Tuck, ML AF Takagawa, Y Hori, MT Tuck, ML TI Effect of insulin on bradykinin-induced intracellular calcium mobilization in cultured human endothelial cells. SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE vascular endothelium; calcium; bradykinin; insulin C1 Vet Adm GLHCS, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 23A EP 23A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600066 ER PT J AU Zusman, R Atlas, S Kochar, M Adler, E Levy, E AF Zusman, R Atlas, S Kochar, M Adler, E Levy, E TI Efficacy and safety of omapatrilat, a vasopeptidase inhibitor. SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE omapatrilat; vasopeptidase inhibitor; dose-ranging study; antihypertensive efficacy; safety C1 Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA. Zablocki VAMC, Milwaukee, WI USA. Bronx VAMC, Bronx, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 125A EP 125A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600434 ER PT J AU Christiani, DC Ye, T Zhang, S Wegman, DH Eisen, EA Ryan, LA Olenchock, SA Pothier, L Dai, H AF Christiani, DC Ye, T Zhang, S Wegman, DH Eisen, EA Ryan, LA Olenchock, SA Pothier, L Dai, H TI Cotton dust and endotoxin exposure and long-term decline in lung function: Results of a longitudinal study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupation; vegetable dust; chronic lung disease; China; byssinosis; cotton dust ID ANIMAL FEED-INDUSTRY; REPUBLIC-OF-CHINA; TEXTILE WORKERS; RESPIRATORY-DISEASE; INHALED ENDOTOXIN; GUINEA-PIGS; RESPONSE RELATIONSHIPS; PULMONARY-FUNCTION; BYSSINOSIS; INHALATION AB Background: To evaluate the relationship between long-term exposure to cotton dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11-year follow-up study of cotton textile workers in Shanghai, China. Methods: Workers at a nearby silk-thread manufacturing mill were used as a referent population. Ninety percent of the original cohort of 445 cotton and 467 silk textile workers both active and retired - were identified for testing in the 11th year: Questionnaires and spirometric testing were performed, as well as cotton dust and endotoxin sampling at three points over the 11-year follow-up period: at baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick-leave, 84% of the original cohort had complete health and environmental data. Results: The data were reanalyzed using generalized estimating equations feedback model which allow for subject transfer over time between work areas, various exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the second 6 years of follow-up (-18 mls/yr). During the same periods, the average decline among silk workers was slightly higher in the first period, but was more consistent (-30 mls/yr vs. -27 mls/yr), and these differences could nor be explained by worker selection or dropout. Wizen cumulative exposure to dust and endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss, cumulative dust, but not endotoxin, was associated with 11-year loss im FEV1 after adjustments for confounders. There was evidence of feedback between dust-exposure levels and FEV1, indicating the existence of a healthy-worker survivor effect. After accounting for a healthy-worker survivor effect, we found a significant relationship between dust exposure and FEV1 decline. Conclusions: Our results suggest that cotton dust is more strongly associated with chronic airflow limitation than associated endotoxins. Further work is needed to clarify potential reversibility after cessation of exposure, and the relative contributions of dust, endotoxin, and tobacco to chronic respiratory impairment in cotton and other vegetable-exposed workers. Am. J. Ind. Med. 35:321-331, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Shanghai Med Univ, Inst Prevent Med, Dept Med, Shanghai 200032, Peoples R China. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. Shanghai Text Bur, Hosp 1, Dept Occupat Med, Shanghai, Peoples R China. NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [ES00002, T32ES07142]; NIOSH CDC HHS [R01OH02421] NR 54 TC 59 Z9 60 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 1999 VL 35 IS 4 BP 321 EP 331 DI 10.1002/(SICI)1097-0274(199904)35:4<321::AID-AJIM1>3.0.CO;2-L PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 173KT UT WOS:000078980300001 PM 10086207 ER PT J AU Lipsky, BA Baker, CA McDonald, LL Suzuki, NT AF Lipsky, BA Baker, CA McDonald, LL Suzuki, NT TI Improving the appropriateness of vancomycin use by sequential interventions SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID RESISTANT ENTEROCOCCUS-FAECIUM; UNIVERSITY MEDICAL-CENTER; INFECTION; OUTBREAK; EXPERIENCE; USAGE AB Background: Vancomycin usage is directly associated with the incidence of vancomycin-resistant enterococci. Optimal methods to reduce inappropriate use have not been delineated. We determined the appropriateness of vancomycin prescribing at our hospital on the basis of national guidelines and assessed the effect of sequential administrative and educational interventions. Methods: In this prospective 3-phase study conducted in a Veterans Affairs Medical Center, we monitored vancomycin prescribing at baseline and in 2 follow-up periods. Administrative interventions included discussions with service chiefs and revising routine perioperative antibiotic prophylaxis orders. Educational interventions included in-services about vancomycin-resistant enterococci and appropriate vancomycin prescribing. In each monitoring period, 50 consecutive new vancomycin orders that could be evaluated were classified for appropriateness and categorized by indication. Results: At baseline, 70% of vancomycin use was inappropriate. Surgical services accounted for 84% of orders. Interventions targeted services with high or frequently inappropriate vancomycin use. After administrative interventions, inappropriate vancomycin use dropped to 40% of orders (P =.003). Improvements were noted in targeted services. Educational interventions further decreased inappropriate vancomycin use, but the effect appeared transient. Conclusions: The simple, nonrestrictive administrative interventions used resulted in a statistically significant (30%) reduction in inappropriate vancomycin prescribing. However, educational interventions provided only transient benefit on institutional prescribing patterns. C1 Vet Affairs Puget Sound Hlth Care Syst, GIMC Antibiot Res Clin 111M, Seattle, WA 98108 USA. RP Lipsky, BA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GIMC Antibiot Res Clin 111M, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 32 TC 31 Z9 32 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD APR PY 1999 VL 27 IS 2 BP 84 EP 90 DI 10.1016/S0196-6553(99)70086-6 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 186AY UT WOS:000079705600003 PM 10196484 ER PT J AU Wolf, GL AF Wolf, GL TI Using enhanced computed tomography to measure renal function and fractional vascular volume SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID GLOMERULAR-FILTRATION RATE; IOHEXOL C1 Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Wolf, GL (reprint author), Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Boston, MA 02114 USA. NR 6 TC 5 Z9 5 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 1999 VL 33 IS 4 BP 804 EP 806 DI 10.1016/S0272-6386(99)70240-4 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 182PJ UT WOS:000079507100030 PM 10196030 ER PT J AU Brown, JH Lustrin, ES Lev, MH Ogilvy, CS Taveras, JM AF Brown, JH Lustrin, ES Lev, MH Ogilvy, CS Taveras, JM TI Reduction of aneurysm clip artifacts on CT angiograms: A technical note SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CIRCLE; WILLIS AB We describe a head tilt technique for use with CT angiography that reduces beam-hardening artifacts in patients with aneurysm clips, This simple maneuver directs the artifacts away from pertinent anatomy, thus increasing the chances for diagnostic accuracy. No significant changes in the CT angiographic protocol are required, and the maneuver can easily be combined with other artifact-minimizing strategies. C1 St Elizabeth Hosp, Dept Radiol, Elizabeth, NJ USA. Long Isl Jewish Med Ctr, Dept Radiol, New Hyde Park, NY 11042 USA. Massachusetts Gen Hosp, Dept Radiol, Cerebrovasc Surg Neurosurg Serv, Boston, MA 02114 USA. RP Brown, JH (reprint author), Diagnost Imaging Elizabeth, 415 Morris Ave, Elizabeth, NJ 07208 USA. NR 5 TC 23 Z9 25 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 1999 VL 20 IS 4 BP 694 EP 696 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 191FC UT WOS:000080011000034 PM 10319984 ER PT J AU Schaumberg, DA Moyes, AL Gomes, JAP Dana, MR AF Schaumberg, DA Moyes, AL Gomes, JAP Dana, MR CA Multicenter Pediat Keratoplasty Study TI Corneal transplantation in young children with congenital hereditary endothelial dystrophy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PENETRATING KERATOPLASTY AB PURPOSE: To describe the surgical success rate and visual results of penetrating keratoplasty in a series of young children with congenital hereditary endothelial dystrophy and to summarize the current literature on outcomes of keratoplasty for congenital hereditary endothelial dystrophy, with particular attention to the timing of surgery. METHODS: The authors conducted a retrospective study of children aged 12 years and younger who underwent penetrating keratoplasty between 1975 and 1994 at four participating eye centers, and who were followed for at least 6 months postoperatively, For this report, 21 corneal transplants performed in 16 eyes of nine patients with congenital hereditary endothelial dystrophy were studied. Patients' median age at the time of first kerato plasty was 40 months (range, 3 months to 10 years). RESULTS: During a mean follow up period of over 70 months (range, 6 to 240 months), 11 (69%) of 16 eyes retained full graft clarity. The 2-year survival rate of first grafts was 71% (95% confidence interval, 47% to 95%), Postoperative visual acuity improvement of 1 or more Snellen lines was seen in five of 10 eyes in which the patients were old enough for accurate assessment of visual acuity; however, just four of these 10 eyes attained a visual acuity of 20/200 or better. CONCLUSIONS: Penetrating keratoplasty for congenital hereditary endothelial dystrophy in children has a reasonable chance of surgical success when performed at a young age; however, the prognosis for improved visual acuity in children appears to be more guarded, Decisions on the timing of surgical intervention for congenital hereditary endothelial dystrophy should be made on a case by-case basis. Although the threat of irreversible amblyopia in untreated eyes and good surgical success rates even among very young children argue for the consideration of relatively early surgical intervention in the most severely affected cases, there is evidence to support delaying surgery in some cases. (Am J Ophthalmol 1999;127:373-378, (C) 1999 by Elsevier Science Inc. All rights reserved.). C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Dept Ophthalmol, Kansas City, KS 66103 USA. Eyecare Midwest Kansas City, Kansas City, MO USA. Univ Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. Santa Casa SP, Sao Paulo, Brazil. Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Schaumberg, DA (reprint author), Harvard Univ, Sch Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. NR 11 TC 19 Z9 20 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 1999 VL 127 IS 4 BP 373 EP 378 DI 10.1016/S0002-9394(98)00435-8 PG 6 WC Ophthalmology SC Ophthalmology GA 182YW UT WOS:000079526600001 PM 10218688 ER PT J AU Jimenez, RE Z'graggen, K Hartwig, W Graeme-Cook, F Warshaw, AL Fernandez-del Castillo, C AF Jimenez, RE Z'graggen, K Hartwig, W Graeme-Cook, F Warshaw, AL Fernandez-del Castillo, C TI Immunohistochemical characterization of pancreatic tumors induced by dimethylbenzanthracene in rats SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article; Proceedings Paper CT 1998 Meeting of the American-Pancreatic-Association CY NOV 05-06, 1998 CL CHICAGO, ILLINOIS SP Amer Pancreat Assoc ID DIFFERENTIATION MARKERS; INTERMEDIATE FILAMENTS; TUBULAR COMPLEXES; CELL-CARCINOMA; DUCT; ADENOCARCINOMA; CANCER; CYTOKERATINS; ENDOCRINE; ORIGIN AB Dimethylbenzanthracene (DMBA) induces pancreatic adenocarcinomas in rats 9 months after carcinogen exposure, with precursor lesions (tubular complexes) developing 1 month after initiation of treatment. Because previous studies have suggested an acinar cell of origin for these tumors, we investigated the expression pattern of ductal, acinar, and islet cell markers in these cancers to gain insight into their phenotype and cell of origin. Pancreatic neoplasms were induced in rats by implantation of DMBA into the head of the pancreas. Lesions studied included 10 early tubular complexes (DMBA for 2 weeks), 8 tubular complexes (DMBA for 1 month), and 10 adenocarcinomas (DMBA for 9 months). Normal rat pancreas served as a control, For comparison, 5 human ductal adenocarcinomas were also evaluated. immunohistochemistry with ductal (keratin, cytokeratin 19, cytokeratin 20), acinar (chymotrypsin), and islet (chromogranin A) cell markers was performed to analyze the tissues. Rat tubular complexes and adenocarcinomas revealed strong expression of keratin, cytokeratin 19, and cytokeratin 20 in the cytoplasm of all neoplastic cells, absence of chymotrypsin, and rare immunoreactivity to chromogranin A. Human adenocarcinomas showed strong expression of keratin and cytokeratin 19 in all neoplastic cells, expression of cytokeratin 20 in 5-20% of cells, and absence of chymotrypsin and chromogranin A. Pancreatic adenocarcinomas induced by DMBA in rats express markers consistent with a ductal phenotype, as observed in human tumors, Ductal marker expression in early tumor stages suggests a ductal cell of origin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, WACC 336, Boston, MA 02114 USA. NR 37 TC 39 Z9 40 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1223 EP 1229 DI 10.1016/S0002-9440(10)65374-6 PG 7 WC Pathology SC Pathology GA 184MU UT WOS:000079616600030 PM 10233860 ER PT J AU van Gorder, MA Della Pelle, P Henson, JW Sachs, DH Cosimi, AB Colvin, RB AF van Gorder, MA Della Pelle, P Henson, JW Sachs, DH Cosimi, AB Colvin, RB TI Cynomolgus polyoma virus infection - A new member of the polyoma virus family causes interstitial nephritis, ureleritis, and enteritis in immunosuppressed cynomolgus monkeys SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RENAL-TRANSPLANT RECIPIENTS; BONE-MARROW TRANSPLANTS; BK-VIRUS; HEMORRHAGIC CYSTITIS; ALLOGRAFT RECIPIENTS; MONOCLONAL-ANTIBODY; SIMIAN VIRUS-40; JC-VIRUS; DISEASE AB Polyoma virus infection causes acute interstitial nephritis and ureteral stenosis in humans but has rarely been noted in other species. In the present study, a hitherto unknown polyoma virus was detected in 12 of 57 cynomolgus monkeys after 3 to 11 weeks of immunosuppression given to promote acceptance of renal allografts or xenografts, This virus, termed cynomolgus polyoma virus (CPV), is antigenically and genomically related to simian virus 40 (SV40), The tubular epithelial nuclei of the collecting ducts in the medulla and cortex reacted with an antibody for the SV40 large T antigen and by electron microscopy contained densely packed paracrystalline arrays of 30- to 32-nm diameter viral particles. A polymerase chain reaction analysis of DNA extracted from affected kidneys detected polyoma virus sequences using primers for a highly conserved region of the large T antigen of polyoma virus. Sequence analysis showed 7 base substitutions and 3 to 5 deletions in the 123-nucleotide segment of amplified products, compared with the corresponding portion of SV40, yielding 84% homology at the amino acid level. CPV caused interstitial nephritis in six renal allografts, a xenograft kidney, and six native kidneys. Infected animals showed renal dysfunction and had tubulointerstitial nephritis with nuclear inclusions, apoptosis, and progressive destruction of collecting ducts. CPV was detected in the urothelium of graft ureters, associated with ureteritis and renal infection, Viral infection was demonstrable in smooth muscle cells of the ureteric wall, which showed apoptosis, One animal had diarrhea and polyoma virus infection in the smooth muscle cells of the muscularis propria of the intestine. Spontaneous resolution occurred in one case; no animal had virus detected in tissues more than 3 months after transplantation. Thus, immunosuppression predisposes cynomolgus monkeys to a polyoma virus infection with clinical consequences quite similar to BK virus infection in humans, including renal dysfunction. We also suggest that this may be the pathogenetic basis for the significant incidence of late onset, isolated ureteral stenosis observed in these recipients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Warren 225,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01 HL018646, P01-HL18646] NR 38 TC 58 Z9 58 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1273 EP 1284 DI 10.1016/S0002-9440(10)65379-5 PG 12 WC Pathology SC Pathology GA 184MU UT WOS:000079616600035 PM 10233865 ER PT J AU Thorell, A Nygren, J Hirshman, MF Hayashi, T Nair, KS Horton, ES Goodyear, LJ Ljungqvist, O AF Thorell, A Nygren, J Hirshman, MF Hayashi, T Nair, KS Horton, ES Goodyear, LJ Ljungqvist, O TI Surgery-induced insulin resistance in human patients: relation to glucose transport and utilization SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose transport; nonoxidative glucose disposal; glycogen synthesis ID SUBSTRATE OXIDATION RATES; HUMAN SKELETAL-MUSCLE; DIABETIC-PATIENTS; PROTEIN-CONCENTRATION; PLASMA-MEMBRANE; GLUT4; TRANSLOCATION; METABOLISM; HYPERINSULINEMIA; EXPRESSION AB To investigate the underlying molecular mechanisms for surgery-induced insulin resistance in skeletal muscle, six otherwise healthy patients undergoing total hip replacement were studied before, during, and after surgery. Patients were studied under basal conditions and during physiological hyperinsulinemia (60 mu U/ml). Biopsies of vastus lateralis muscle were used to measure GLUT-4 translocation, glucose transport, and glycogen synthase activities. Surgery reduced insulin-stimulated glucose disposal (P < 0.05) without altering the insulin-stimulated increase in glucose oxidation or suppression of endogenous glucose production. Preoperatively, insulin infusion increased plasma membrane GLUT-4 in all six subjects (P < 0.05), whereas insulin-stimulated GLUT-4 translocation only occurred in three patients postoperatively (not significant). Moreover, nonoxidative glucose disposal rates and basal levels of glycogen synthase activities in muscle were reduced postoperatively (P ( 0.05). These findings demonstrate that peripheral insulin resistance develops immediately postoperatively and that this condition might be associated with perturbations in insulin-stimulated GLUT-4 translocation as well as nonoxidative glucose disposal, presumably at the level of glycogen synthesis. C1 Karolinska Inst, Huddinge Univ Hosp, Dept Surg, S-17176 Stockholm, Sweden. Karolinska Inst, Karolinska Univ Hosp, Dept Surg, S-17176 Stockholm, Sweden. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Mayo Clin, Div Endocrinol & Metab, Rochester, MN 55905 USA. RP Thorell, A (reprint author), Huddinge Univ Hosp, Dept Surg, S-14186 Huddinge, Sweden. FU NCRR NIH HHS [RR-00585]; NIAMS NIH HHS [R01 AR-42238]; NIDDK NIH HHS [DK-41973] NR 43 TC 46 Z9 55 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 1999 VL 276 IS 4 BP E754 EP E761 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 185CG UT WOS:000079650100020 PM 10198313 ER PT J AU Million, M Tache, Y Anton, P AF Million, M Tache, Y Anton, P TI Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE astressin; myeloperoxidase; corticotropin-releasing factor; brain; colon; food intake; 2,4,6-trinitrobenzenesulfonic acid ID CORTICOTROPIN-RELEASING FACTOR; PITUITARY-ADRENAL AXIS; INFLAMMATORY BOWEL-DISEASE; COLONIC MOTOR FUNCTION; C-FOS EXPRESSION; ULCERATIVE-COLITIS; RESPONSES; HORMONE; ANTAGONIST; IMMUNE AB We assessed the role of central corticotropin-releasing factor (CRF) in stress-induced worsening of colitis :in inbred rat strains with hypo (Lewis/N) and hyper (Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both strains as assessed on day 7 by macroscopic scoring, histological evaluation, tissue myeloperoxidase (MPO) activity, and decrease in food intake and body weight. Colitis was inhibited by daily intracerebroventricular injections of CRF in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71 and 22% further increase in MPO activity, respectively). The CRF antagonist astressin injected intracerebroventricularly enhanced the colitis response to stress and caused mortality in both strains. Fischer rats had higher plasma corticosterone levels 20 min after stress alone on day I and after TNB plus stress on days 1 and 3 compared with Lewis. These data show that central CRF restrains the proinflammatory action of stress in experimental colitis. C1 Univ Calif Los Angeles, Inst Brain Res, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. RP Million, M (reprint author), Univ Calif Los Angeles, Inst Brain Res, Div Digest Dis, Dept Med, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmuluget@ucla.edu FU NIDDK NIH HHS [DK-41301, R01-DK-33061] NR 51 TC 85 Z9 85 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1999 VL 276 IS 4 BP G1027 EP G1036 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 184UL UT WOS:000079632100029 PM 10198347 ER PT J AU Nozu, T Martinez, V Rivier, J Tache, Y AF Nozu, T Martinez, V Rivier, J Tache, Y TI Peripheral urocortin delays gastric emptying: role of CRF receptor 2 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE corticotropin-releasing factor; NBI-27914; antalarmin; astressin; postoperative gastric ileus; abdominal surgery ID CORTICOTROPIN-RELEASING FACTOR; CENTRAL-NERVOUS-SYSTEM; STRESS-RELATED ALTERATIONS; COLONIC MOTOR FUNCTION; INDUCED INHIBITION; RATS; ANTAGONIST; PITUITARY; HORMONE; BINDING AB Urocortin, a new mammalian member of the corticotropin-releasing factor (CRF) family has been proposed to be the endogenous ligand for CRF receptor 2 (CRF-R2). We studied the influence of intravenous urocortin on gastric emptying and the role of CRF-R2 in peptide action and postoperative gastric ileus in conscious rats. The intravenous doses of rat CRF and rat urocortin producing 50% inhibition of gastric emptying were 2.5 and 1.1 mu g/kg, respectively. At these intravenous doses, CRF and urocortin have their actions fully reversed by the CRF-R1/CRF-R2 antagonist astressin at antagonist/agonist ratios of 5:1 and 67:1, respectively. Astressin (12 mu g/kg iv) completely prevented abdominal surgery-induced 54% inhibition of gastric emptying 3 h after surgery while having no effect on basal gastric emptying. The selective nonpeptide CRF-R1 antagonists antalarmin (20 mg/kg ip) and NBI-27914 (400;mu g/kg iv) did not influence intravenous CRF-, urocortin- or surgery-induced gastric stasis. These results as well as earlier ones showing that or-helical CRF(9-41) (a CRF-RB more selective antagonist) partly prevented postoperative ileus indicate that peripheral CRF-RB may be primarily:ly involved in intravenous urocortin-, CRF-, and abdominal surgery-induced gastric stasis. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92038 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 203, Los Angeles, CA 90073 USA. EM ytache@ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-26741, DK-41301, DK-33061] NR 56 TC 47 Z9 47 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1999 VL 276 IS 4 BP G867 EP G874 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 184UL UT WOS:000079632100011 PM 10198329 ER PT J AU Solomon, TE Walsh, JH Bussjaeger, L Zong, YM Hamilton, JW Ho, FJ Lee, TD Reeve, JR AF Solomon, TE Walsh, JH Bussjaeger, L Zong, YM Hamilton, JW Ho, FJ Lee, TD Reeve, JR TI COOH-terminally extended secretins are potent stimulants of pancreatic secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE posttranslational processing; amidation; radioimmunoassay; physiology ID MOLECULAR-CLONING; PLASMA SECRETIN; FUNCTIONAL EXPRESSION; ADENYLATE-CYCLASE; PORCINE SECRETIN; SODIUM OLEATE; RAT SECRETIN; FORM; RECEPTOR; BIOACTIVITY AB Posttranslational processing of preprosecretin generates several COOH-terminally extended forms of secretin and alpha-carboxyl amidated secretin. We used synthetic canine secretin analogs with COOH-terminal -amide,-Gly, or -Gly-Lys-Arg to examine the effects of COOH-terminal extensions of secretin on bioactivity and detection in RIA Synthetic products were purified by reverse-phase and ion-exchange HPLC and characterized by reverse-phase isocratic HPLC and amino acid, sequence, and mass spectral analyses. Secretin and secretin-Gly were noted to coelute during reverse-phase HPLC. In RIA using eight, different antisera raised against amidated secretin, COOH-terminally extended secretins had little or no cross-reactivity. Bioactivity was assessed by measuring pancreatic responses in anesthetized rats. Amidated canine and porcine secretins were equipotent. Secretin-Gly and secretin-Gly-Lys-Arg had potencies of 81 +/- 9% (P > 0.05) and 176 +/- 13% (P < 0.01), respectively, compared with amidated secretin, and the response to secretin-Gly-Lys-Arg lasted significantly longer These data demonstrate that 1) amidated secretin and secretin;Gly are not separable under some chromatographic conditions, 2) current RIA may not detect bioactive COOH-terminally extended forms of secretin in tissue extracts or blood, and 3) the secretin receptor mediating stimulation of pancreatic secretion recognizes both amidated and COOH-terminally extended secretins. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Kansas City Dept Vet Affairs Med Ctr, Kansas City, MO 64128 USA. Univ Kansas, Med Ctr, Dept Biochem, Kansas City, KS 66160 USA. City Hope Res Inst, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. RP Solomon, TE (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 111, Los Angeles, CA 90073 USA. EM solomont@ucla.edu FU NIDDK NIH HHS [DK-41301] NR 43 TC 13 Z9 13 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1999 VL 276 IS 4 BP G808 EP G816 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 184UL UT WOS:000079632100004 PM 10198322 ER PT J AU Song, M Yang, H Walsh, JH Ohning, G Wong, H Tache, Y AF Song, M Yang, H Walsh, JH Ohning, G Wong, H Tache, Y TI Intracisternal TRH analog increases gastrin release and corpus histidine decarboxylase activity in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE enterochromaffin-like cell; gastrin monoclonal antibody; vagus; thyrotropin-releasing hormone ID ENTEROCHROMAFFIN-LIKE CELLS; MESSENGER-RNA ABUNDANCE; ACID-SECRETION; ECL CELLS; HISTAMINE-SECRETION; ANESTHETIZED RATS; VAGAL REGULATION; SOMATOSTATIN; STOMACH; ACTIVATION AB Thyrotropin-releasing hormone (TRH) acts in brain stem nuclei to induce vagally mediated stimulation of gastric secretion. The effects of intracisternal injection of the TRH analog RX-77368 on plasma gastrin levels and corpus histidine decarboxylase (HDC) activity were studied in 48-h fasted conscious rats. RX-77368 (25-100 ng) increased plasma gastrin levels by threefold at 30 min, which remained significantly higher than control at 2 and 4 h postinjection. Corpus HDC activity began to increase at 2 h and reached a peak at 4 h postinjection with a 21-fold maximum response observed at 50 ng. Morphological changes in the appearance of corpus HDC-immunoreactive cells correlated well with HDC activity. Pretreatment with gastrin monoclonal antibody completely prevented RX-77368 stimulatory effects on HDC activity. Atropine significantly attenuated gastrin increase at 30 min by 26%. These results indicated that in conscious fasted rats, TRH analog acts in the brain to increase corpus HDC activity in the enterochromaffin-like cells, which involves gastrin release stimulated by central TRH analog. C1 W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu FU NIDDK NIH HHS [DK-30110, DK-17294, DK-50255] NR 49 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1999 VL 276 IS 4 BP G901 EP G908 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 184UL UT WOS:000079632100015 PM 10198333 ER PT J AU Gruning, W Arnould, T Jochimsen, F Sellin, L Ananth, S Kim, E Walz, G AF Gruning, W Arnould, T Jochimsen, F Sellin, L Ananth, S Kim, E Walz, G TI Modulation of renal tubular cell function by RGS3 SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renal tubular epithelial cells; kidney development; chemotaxis; G protein; regulators of G protein signaling ID GTPASE-ACTIVATING PROTEINS; LYSOPHOSPHATIDIC ACID; PHOSPHOLIPASE-C; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; TRANSITION-STATE; MESANGIAL CELLS; CORE DOMAIN; RAT-KIDNEY; FAMILY AB The recently discovered family of regulators of G protein signaling (RGS) accelerates the intrinsic GTPase activity of certain G alpha subunits, thereby terminating G protein signaling. Particularly high mRNA levels of one family member, RGS3, are found in the adult kidney. To establish the temporal and spatial renal expression pattern of RGS3, a polyelonal antiserum was raised against the COOH terminus of RGS3. Staining of mouse renal tissue at different gestational stages revealed high levels of RGS3 within the developing and mature tubular epithelial cells. We tested whether RGS3 can modulate tubular migration, an important aspect of tubular development, in response to G protein-mediated signaling. Several mouse intermedullary collecting duet (mIMCD-3) cell lines were generated that expressed RGS3 under the control of an inducible promoter. Lysophosphatidic acid (LPA) is a potent chemoattractant that mediates its effects through heterotrimeric G proteins. We found that induction of RGS3 significantly reduced LPA-mediated cell migration in RGS3-expressing mIMCD-3 clones, whereas chemotaxis induced by hepatocyte growth factor remained unaffected by RGS3. Our findings suggest that RGS3 modulates tubular functions during renal development and in the adult kidney. C1 Harvard Univ, Sch Med, Beth Israel Med Ctr, Dept Med,Renal Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Walz, G (reprint author), Harvard Univ, Sch Med, Beth Israel Med Ctr, Dept Med,Renal Div, 330 Brookline Ave, Boston, MA 02215 USA. EM gwalz@bidmc.harvard.edu FU NIDDK NIH HHS [R01-DK-52897]; NIMH NIH HHS [MH-01147] NR 61 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 1999 VL 276 IS 4 BP F535 EP F543 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 185JK UT WOS:000079665500006 PM 10198412 ER PT J AU Shin, LM McNally, RJ Kosslyn, SM Thompson, WL Rauch, SL Alpert, NM Metzger, LJ Lasko, NB Orr, SP Pitman, RK AF Shin, LM McNally, RJ Kosslyn, SM Thompson, WL Rauch, SL Alpert, NM Metzger, LJ Lasko, NB Orr, SP Pitman, RK TI Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Psychobiology of Posttraumatic Stress Disorder CY SEP 07-10, 1996 CL NEW YORK, NEW YORK SP New York Acad Sci ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON EMISSION TOMOGRAPHY; FUNCTIONAL NEUROANATOMY; SYMPTOM PROVOCATION; FACIAL EXPRESSIONS; VISUAL-IMAGERY; HUMAN AMYGDALA; HAPPINESS; ANXIETY; SADNESS AB Objective: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). Method: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Results: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. Conclusions: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. VA Res Serv, Manchester, NH USA. Harvard Med Sch, Boston, MA USA. RP Shin, LM (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, E Bldg 149,Room 9147,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH-48559, MH-01215] NR 47 TC 387 Z9 395 U1 7 U2 26 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 1999 VL 156 IS 4 BP 575 EP 584 PG 10 WC Psychiatry SC Psychiatry GA 184CV UT WOS:000079592500012 PM 10200737 ER PT J AU Lieberman, E Cohen, A Lang, J Frigoletto, F Goetzl, L AF Lieberman, E Cohen, A Lang, J Frigoletto, F Goetzl, L TI Maternal intrapartum temperature elevation as a risk factor for cesarean delivery and assisted vaginal delivery SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID EPIDURAL ANALGESIA; RANDOMIZED TRIAL; LABOR; CHORIOAMNIONITIS; FEVER; ASSOCIATION; DYSTOCIA; HYPERTHERMIA; MANAGEMENT; NULLIPARAS AB Objectives. This study investigated the association of intrapartum temperature elevation with cesarean delivery and assisted vaginal delivery. Methods. Participants were 1233 nulliparous women with singleton, term pregnancies in vertex presentations who had spontaneous labors and were afebrile (temperature; 99.5 degrees F [37.5 degrees C]) at admission for delivery. Rates of cesarean and assisted vaginal deliveries according to highest intrapartum temperature were examined by epidural status. Results. Women with maximum intrapartum temperatures higher than 99.5 degrees F were 3 times as likely to experience cesarean (25.2% vs 7.2%) or assisted vaginal delivery (25.2% vs 8.5%). The association was present in epidural users and nonusers and persisted after birthweight, epidural use, and labor length had been controlled. In adjusted analyses, temperature elevation was associated with a doubling in the risk of cesarean delivery (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5, 3.4) and assisted vaginal delivery (OR = 2.1, 95% CI = 1.4, 3.1). Conclusions. Modest temperature elevation developing during labor was associated with higher rates of cesarean and assisted vaginal deliveries. More frequent temperature elevation among women with epidural analgesia may explain in part the higher rates of cesarean and assisted vaginal deliveries observed with epidural use. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Cambridge, MA 02138 USA. RP Lieberman, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. FU NICHD NIH HHS [R01-HD26813] NR 27 TC 31 Z9 31 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 1999 VL 89 IS 4 BP 506 EP 510 DI 10.2105/AJPH.89.4.506 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 180HH UT WOS:000079379700010 PM 10191792 ER PT J AU Fujino, Y Kirmse, M Hess, D Kacmarek, RM AF Fujino, Y Kirmse, M Hess, D Kacmarek, RM TI The effect of mode, inspiratory time, and positive end-expiratory pressure on partial liquid ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; GAS-EXCHANGE; INVERSE RATIO; LUNG INJURY; I/E RATIOS; FAILURE; MECHANICS; SHEEP AB Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positive end-expiratory pressure (PEEP) set above the lower inflection point (LIP) of the pressure-volume (P-V) curve regardless of mode of ventilation or inspiratory to expiratory time (I:E) ratio and that the efficiency of ventilation would be greatest with volume-controlled ventilation (VCV) compared with pressure-controlled ventilation (PGV) and with long inspiratory time as compared with short inspiratory time. Lung injury was induced in 14 sheep by lavage, 10 of which were studied. Sheep were then assigned to high-PEEP (Group H, n = 5) and low-PEEP (Group L, n = 5) groups. In Group H applied PEEP was set at the LIP and in Group L applied PEEP was set at 5 cm H2O after the lung was filled with perflubron (PFB). We randomly compared VCV and PCV with I:E ratios of 1:2, 1:1, and 2:1. Peak inspiratory pressure and VT were adjusted to maintain a constant end-inspiratory plateau pressure (Pplat) of about 25 cm H2O in both groups and a constant total PEEP of about 5 cm H2O in Group L and about 12 cm H2O in Group H. There were no differences in oxygenation among modes in Group H. In Group L VCV 2:1 and all of the PCV modes in Group L had a lower Pao, than VCV 1:1 (p < 0.05). Pao, and V-D/V-T were significantly different (p < 0.05) among modes. V-D/V-T was highest during PCV 1:2 with PEEP of 5 cm H2O (p < 0.05). Quasi-static compliance in Group H was higher than in Group L (p < 0.05). We conclude that during low PEEP gas exchange deteriorated in VCV with long inspiratory time and in PCV. Oxygenation was enhanced during VCV 1:1 when compared with VCV at longer I:E ratios or PCV at any I:E ratio. With PEEP set at the LIP, adequate gas exchange and improved lung mechanics could be obtained in all modes assessed. C1 Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept Lab, Resp Care Ellison 401, Boston, MA 02114 USA. NR 25 TC 27 Z9 28 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 1999 VL 159 IS 4 BP 1087 EP 1095 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 184XE UT WOS:000079638400010 PM 10194150 ER PT J AU Jones, R Jacobson, M Steudel, W AF Jones, R Jacobson, M Steudel, W TI alpha-smooth-muscle actin and microvascular precursor smooth-muscle cells in pulmonary hypertension SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CONTRACTILE INTERSTITIAL-CELLS; GROWTH-FACTOR-BETA; RAT LUNG; ALVEOLAR MYOFIBROBLASTS; CYTOSKELETAL FEATURES; ISOFORM EXPRESSION; IN-VITRO; DIFFERENTIATION; MICROVESSELS; LOCALIZATION AB Little is known of the molecular basis of smooth-muscle cell development in the microvessels of the adult lung in pulmonary hypertension (PH). Using quantitative and immunogold electron microscopy techniques we report the development of microvascular precursor smooth-muscle cells (PSMCs) expressing alpha-smooth-muscle actin (alpha SMA), a first marker of smooth-muscle cell differentiation, in rats with hyperoxic PH. Increase in the frequency of distal (alveolar wall) vessels with alpha SMA cells preceded (P-chi 2 < 0.02, Day 4) the increase in proximal (alveolar duct) vessels (P-chi 2 < < 0.02, Day 14). The smallest vessel with cells expressing alpha SMA (< 50 mu m in diameter) increased most with time (P-chi 2 < 0.001). Immunopositive PSMCs were rare in normal lung and frequent in hyperoxia, Well-developed filament arrays decorated with alpha SMA were detected in intermediate cells early in hyperoxia (Day 4). Similar filament networks were detected later in fibroblasts recruited to vessel walls (Days 7 to 14). By Day 28, cells derived from fibroblasts formed several layers in the vessel wall and expressed dense alpha SMA filament arrays, in either a central domain or mesh. Thus, intermediate cells are the source of cells expressing alpha SMA early in the microvessels in hyperoxic pulmonary hypertension and fibroblasts of cells in the late stage-the time of intense neomuscularization of the microvessels. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Mol & Cell Biol Lab, Boston, MA USA. RP Jones, R (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Mol & Cell Biol Lab, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL RO1 45737] NR 35 TC 50 Z9 52 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1999 VL 20 IS 4 BP 582 EP 594 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 186YF UT WOS:000079758200006 PM 10100989 ER PT J AU Mehta, A Dreyer, KJ Montgomery, M Wittenberg, J AF Mehta, A Dreyer, KJ Montgomery, M Wittenberg, J TI A World Wide Web Internet engine for collaborative entry and peer review of radiologic teaching files SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SERVER AB OBJECTIVE, Radiologists can now use the Internet as a dissemination medium for radiologic teaching files. This has greatly increased the availability of radiologic information to a larger number of people. However, the creation of the teaching files themselves remains a static and labor-intensive process. As a partial solution to this problem, we set out to create a World Wide Web-based Internet engine for the collaborative entry and peer review of radiologic teaching files. CONCLUSION. We created a system that facilitates, simplifies, and improves the generation of radiologic teaching files. We used the Internet to help promote the creation of teaching files in a more timely, efficient, and effective manner. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mehta, A (reprint author), 8 Whittier Pl,Ste 19D, Boston, MA 02114 USA. NR 5 TC 21 Z9 23 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 APR PY 1999 VL 172 IS 4 BP 893 EP 896 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 178VJ UT WOS:000079289600004 PM 10587117 ER PT J AU Grant, EG Duerinckx, AJ El Saden, S Melany, ML Hathout, G Zimmerman, P Cohen, SN Singh, R Baker, JD AF Grant, EG Duerinckx, AJ El Saden, S Melany, ML Hathout, G Zimmerman, P Cohen, SN Singh, R Baker, JD TI Doppler sonographic parameters for detection of carotid stenosis: Is there an optimum method for their selection? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ARTERY STENOSIS; ENDARTERECTOMY TRIAL; DUPLEX CRITERIA; ATHEROSCLEROTIC DISEASE; COST-EFFECTIVENESS; ULTRASOUND; 70-PERCENT; ULTRASONOGRAPHY; PERFORMANCE AB OBJECTIVE. A wide range of Doppler threshold values for carotid stenosis is found in the literature. We undertook this study to compare methods of derivation and to determine if an optimum strategy of threshold selection exists for a high-risk population. MATERIALS AND METHODS. From the sonograms of all patent internal carotid arteries, peak systolic velocity in the internal carotid artery (ICA(PSV)) and the ratio of peak systolic velocity in the internal carotid artery to that of the common carotid artery (ICA(PSV)/CCA(PSV)) were compared with the percentage of angiographically determined stenosis, Receiver operating characteristic curves were generated for levels of stenosis greater than or equal to 60% and greater than or equal to 70%. Doppler thresholds were chosen on the basis of maximum accuracy and on the basis of greater than or equal to 90% sensitivity and specificity. Patients were then segregated into symptomatic and asymptomatic cohorts, and the above process was repeated. An effectiveness analysis was also conducted using various Doppler thresholds. Thresholds derived using these three methods were compared and optimal values chosen. RESULTS. Of 333 carotid arteries that fit inclusion criteria, 132 were found in asymptomatic patients and 201 in symptomatic patients. Maximum accuracy, greater than or equal to 90% sensitivity and specificity, and effectiveness analysis each produced different ranges of thresholds. We chose final thresholds that maintained patient outcome profiles. For asymptomatic patients at the greater than or equal to 60% stenosis level, thresholds were ICA(PSV) = 200 cm/sec and ICA(PSV)/CCA(PSV) = 3.0. For symptomatic patients with stenosis greater than or equal to 70%, thresholds were ICA(PSV) = 175 cm/sec and ICA(PSV)/CCA(PSV) = 2.5. CONCLUSION. Considerable latitude exists in the choice of carotid Doppler thresholds. We propose a rational strategy for threshold selection based on a combination of three commonly used methods. Our observations indicate that it appears advisable to consider symptomatic and asymptomatic patients separately and to apply appropriately derived thresholds. C1 W Los Angeles Vet Affairs Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Radiol Sci, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP Grant, EG (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 27 TC 26 Z9 28 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 APR PY 1999 VL 172 IS 4 BP 1123 EP 1129 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 178VJ UT WOS:000079289600047 PM 10587159 ER PT J AU Eichhorn, JH Bell, DA Young, RH Scully, RE AF Eichhorn, JH Bell, DA Young, RH Scully, RE TI Ovarian serous borderline tumors with micropapillary and cribriform patterns - A study of 40 cases and comparison with 44 cases without these patterns SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE serous borderline tumor; micropapillary; cribriform; prognosis ID TERM FOLLOW-UP; PERITONEAL IMPLANTS; HISTOLOGIC FEATURES; EPITHELIAL TUMORS; MICROINVASION; CARCINOMA; MALIGNANCY; PROGNOSIS AB A group of investigators have proposed that the presence of micropapillary or cribriform patterns within ovarian serous tumors diagnosed as borderline according to World Health Organization (WHO) criteria identifies a subset of these neoplasms that are apt to be associated with invasive peritoneal implants and therefore should be designated as "micropapillary carcinoma." The authors of the current article identified 40 serous borderline tumors that showed one or both of these patterns, using the earlier investigators' published criteria for so-called micropapillary carcinoma, and compared them with 44 tumors that lacked these patterns (controls). Twenty-six patients with micropapillary tumors were aged 21 to 76 years (mean 38); 11 with cribriform tumors were aged 34 to 79 years (mean 60); and 3 with tumors having both patterns were aged 21 to 58 years (mean 38); the control patients were aged 22 to 83 years (mean 54). An advanced stage, bilaterality, and ovarian surface growth were features of the "micropapillary" tumors more often than of the control tumors. Except for a postoperative death related to sepsis, all Ii patients with Stage I tumors with either or both patterns who were followed until their death, or for at least 5 years (mean 7.9 years), survived without evidence of disease; a twelfth patient had a recent removal of recurrent pelvic tumor at 2.8 years and was alive at 3.3 years. Six of the eight patients with Stage II or III tumors with either or both patterns who were followed for at least 5 years (mean 7.5 years) survived disease-free. No deaths from tumor or progressive recurrences occurred in 27 control cases with 5-14 (mean 7.9) years of follow-up data. The two tumor-related deaths in the entire series, one from a micropapillary tumor and one from a cribriform tumor, occurred in patients who had Stage III tumors with invasive peritoneal implants. No patient with "micropapillary" tumors and noninvasive implants had progressive disease. Two women with "micropapillary" tumors and two control subjects had stable recurrent tumor or a newly developed tumor in a contralateral ovary that had been spared during the initial operation. Our findings confirm those of previous investigators that noninvasive serous tumors with a micropapillary or cribriform pattern or both patterns may be accompanied by invasive peritoneal implants more often than tumors without such patterns and that in such cases the disease is likely to be progressive and fatal. Since so-called micropapillary carcinomas lack obvious stromal invasion within the ovary, and their prognosis when they spread to the peritoneum is much closer to that associated with typical Stage II and III serous borderline tumors than to that associated with similarly staged serous carcinomas, the authors believe that this newly described category of tumors should remain as a subset within the borderline category, with a notation that their prognosis is poor if they are associated with invasive peritoneal implants. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Eichhorn, JH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Warren 120,32 Fruit St, Boston, MA 02114 USA. NR 28 TC 139 Z9 154 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 1999 VL 23 IS 4 BP 397 EP 409 DI 10.1097/00000478-199904000-00004 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 183TQ UT WOS:000079569900004 PM 10199469 ER PT J AU Ang, S Koski, G Hilgenberg, AD D'Ambra, MN AF Ang, S Koski, G Hilgenberg, AD D'Ambra, MN TI Permanent neurologic deficit after circulatory arrest for ascending aortic surgery: Role of neuroprotectants and aprotinin SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 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 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 1999 VL 88 IS 4 SU S BP U24 EP U24 PG 1 WC Anesthesiology SC Anesthesiology GA 185GH UT WOS:000079659400020 ER PT J AU D'Ambra, MN Whitbourne, PGS Venegas, J AF D'Ambra, MN Whitbourne, PGS Venegas, J TI Changes in clotting viscoelasticity caused by cardiopulmonary bypass (CPB) surgery. SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia, 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 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 1999 VL 88 IS 4 SU S BP U25 EP U25 PG 1 WC Anesthesiology SC Anesthesiology GA 185GH UT WOS:000079659400021 ER PT J AU Schaumberg, DA Ridker, PM Glynn, RJ Christen, WG Dana, MR Hennekens, CH AF Schaumberg, DA Ridker, PM Glynn, RJ Christen, WG Dana, MR Hennekens, CH TI High levels of plasma C-reactive protein and future risk of age-related cataract SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE C-reactive protein; physicians' health study; cataract; risk factor; epidemiology; inflammation ID CARDIOVASCULAR-DISEASE; PROGNOSTICATORS; CYTOKINES; CAROTENE; UVEITIS; ASPIRIN; MEN AB PURPOSE: Chronic intraocular inflammation, with or without systemic inflammation, is associated with increased risk of cataract. Whether systemic inflammation alone is associated with cataract is unknown. This study examined the association between plasma C-reactive protein (CRP), a marker of systemic inflammation, and risk of cataract. METHODS: In the Physicians' Health Study, we recently analyzed plasma CRP levels in baseline blood specimens from 543 men who later developed cardiovascular disease, and 543 who did not. These data provided a cost-efficient means to explore whether baseline plasma CRP is associated with future risk of age-related cataract. After excluding 252 men with prior diagnosis of cataract or missing: data, we followed the remaining 834 men defined by baseline CRP level for 11 years for incident cataract. We used proportional hazards regression models, stratified by cardiovascular disease status. RESULTS: Baseline CRP was significantly higher among men who later developed cataract than levels among those who remained free of cataract, P = 0.02 (median 1.53 versus 1.23 mg/L). In a multivariable model adjusted for cardiovascular disease, randomized aspirin and beta carotene assignments, age, diabetes, cigarette smoking, alcohol consumption, body mass index, exercise, and parental history of myocardial infarction, the levels of CRP remained significantly associated with development of cataract (P = 0.001); but the association was less significant in a model using log CRP levels (P = 0.038). In exploratory analyses of a threshold effect, the excess risk was significant only among men with levels at or above the 97.5th centile (6.17 mg/L); compared to those with lower levels, the relative risk in these men was 3.00 (95% confidence interval, 1.53 to 5.91; P = 0.002). Relative risks associated with CRP levels at or above versus below the 85th, 90th, and 95th percentiles were not significant (relative risks 1.29, 1.50, and 1.77, respectively). CONCLUSIONS: Overall, our results suggest that elevated levels of CRP are associated with future risk of cataract in these apparently healthy men. This early report raises the possibility that systemic inflammation may play a role in the pathogenesis of age-related cataract. Ann Epidemiol 1999;9:166-171. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiovasc Dis, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Ophthalmol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Schaumberg, DA (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NEI NIH HHS [EY06633, EY00365]; NHLBI NIH HHS [HL26490] NR 30 TC 48 Z9 48 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 1999 VL 9 IS 3 BP 166 EP 171 DI 10.1016/S1047-2797(98)00049-0 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 177HU UT WOS:000079205200004 PM 10192648 ER PT J AU Schulz, JB Weller, M Moskowitz, MA AF Schulz, JB Weller, M Moskowitz, MA TI Caspases as treatment targets in stroke and neurodegenerative diseases SO ANNALS OF NEUROLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; CEREBELLAR GRANULE NEURONS; TROPHIC FACTOR WITHDRAWAL; INTERLEUKIN-1-BETA CONVERTING-ENZYME; TRANSIENT GLOBAL-ISCHEMIA; CELL-DEATH; BRAIN INJURY; DNA FRAGMENTATION; CYTOCHROME-C; IN-VIVO AB Apoptosis is one of the most exciting and intensely investigated areas of biology and medicine today. Cysteine proteases called caspases serve as the executioners of apoptosis, a form of cell suicide. Hypoxic/ischemic cell death proceeds in part, by apoptosis, particularly within the periinfarct zone or ischemic penumbra. During ischemia, activated caspases dismantle the cell by cleaving multiple substrates including cytoskeletal proteins and enzymes essential for cell repair. Strategies that inhibit caspase activity block cell death in experimental models of mild ischemia, and preserve neurological function. The therapeutic window for caspase inhibition is substantially longer than for glutamate receptor antagonists, and treatment combinations with both classes of drugs decrease ischemic injury and expand the treatment window synergistically, Hence, the caspases are now recognized as novel therapeutic targets for central nervous system diseases in which cell death is prominent. This article will review the evidence and the potential importance of caspase inhibition to cerebral ischemia and briefly summarize an emerging body of data implicating caspases in cell death accompanying neurodegenerative disorders. C1 Univ Tubingen, Sch Med, Dept Neurol, Neurodegenerat Lab, D-72076 Tubingen, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Neurol Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Neurosurg Serv, Charlestown, MA USA. RP Schulz, JB (reprint author), Univ Tubingen, Sch Med, Dept Neurol, Neurodegenerat Lab, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. RI Moskowitz, Michael/D-9916-2011; Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 NR 80 TC 245 Z9 272 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1999 VL 45 IS 4 BP 421 EP 429 DI 10.1002/1531-8249(199904)45:4<421::AID-ANA2>3.0.CO;2-Q PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 182ND UT WOS:000079504300002 PM 10211465 ER PT J AU Breathnach, O Donnellan, P Collins, D McNicholas, W Crown, J AF Breathnach, O Donnellan, P Collins, D McNicholas, W Crown, J TI Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: Case report and review of the literature SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; cytomegalovirus pneumonia; dexamethasone; ganciclovir; standard dose chemotherapy regimen ID OPPORTUNISTIC PULMONARY INFECTIONS; BONE-MARROW TRANSPLANTATION; VIRUS PNEUMONIA; BRONCHOALVEOLAR LAVAGE; GANCICLOVIR; RECIPIENTS; COMBINATION; THERAPY; CMV; IMMUNOGLOBULIN AB Cytomegalovirus (CMV) pneumonia in the setting of nontransplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy. C1 Dana Farber Canc Ctr, Thorac Oncol Program, Boston, MA 02115 USA. St Vincents Univ Hosp, Div Oncol, Dublin, Ireland. St Vincents Univ Hosp, Div Pulm, Dublin, Ireland. RP Breathnach, O (reprint author), Dana Farber Canc Ctr, Thorac Oncol Program, 44 Binney St, Boston, MA 02115 USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 1999 VL 10 IS 4 BP 461 EP 465 DI 10.1023/A:1008360927507 PG 5 WC Oncology SC Oncology GA 202XX UT WOS:000080678400021 PM 10370790 ER PT J AU Sheridan, RL Baryza, MJ Pessina, MA O'Neill, KM Cipullo, HM Donelan, MB Ryan, CM Schulz, JT Schnitzer, JJ Tompkins, RG AF Sheridan, RL Baryza, MJ Pessina, MA O'Neill, KM Cipullo, HM Donelan, MB Ryan, CM Schulz, JT Schnitzer, JJ Tompkins, RG TI Acute hand burns in children: Management and long-term outcome based on a 10-year experience with 698 injured hands SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Burn-Association CY MAR 18-21, 1998 CL CHICAGO, ILLINOIS SP Amer Burn Assoc ID EXCISION; THERAPY AB Objective To document long-term results associated with an coordinated plan of cave for acutely burned hands in children. Summary and Background Data Optimal hand function is a crucial component of a high-quality survival after burn injury. This can be achieved only with a coordinated approach to the injuries. Long-term outcomes associated with such a plan of care have not been previously reported. Methods Over a 10-year period, 495 children with 698 acutely burned hands were managed at a regional pediatric burn facility; 219 children with 395 injured hands were followed in the authors' outpatient clinic for at least 1 year and an average of >5 years. The authors' approach to the acutely burned hand emphasizes ranging and splinting throughout the hospital stay, prompt sheet autograft wound closure as soon as practical, and the selective use of axial pin fixation and flaps. Long-term follow-up, hand therapy, and reconstructive surgery are emphasized. Results Normal functional results were seen in 97% of second-degree and 85% of third-degree injuries; in children with burns involving underlying tendon and bone, 70% could perform activities of daily living and 20% had normal function. Reconstructive hand surgery was required in 4.4% of second-degree burns. 32% of third-degree burns, and 85% of those with injuries involving underlying bone and tendon. Conclusions When managed in a coordinated long-term program, the large majority of children with serious hand burns can be expected to have excellent functional results. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Sheridan, RL (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. FU NIGMS NIH HHS [T32GM07035, P50 GM21700] NR 35 TC 35 Z9 36 U1 2 U2 4 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 APR PY 1999 VL 229 IS 4 BP 558 EP 564 DI 10.1097/00000658-199904000-00016 PG 7 WC Surgery SC Surgery GA 181QT UT WOS:000079453900016 PM 10203090 ER PT J AU Fournier, B Gravel, A Hooper, DC Roy, PH AF Fournier, B Gravel, A Hooper, DC Roy, PH TI Strength and regulation of the different promoters for chromosomal beta-lactamases of Klebsiella oxytoca SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI PROMOTER; CATABOLITE-ACTIVATOR PROTEIN; TANDEM PROMOTERS; RNA-POLYMERASE; DNA; TRANSCRIPTION; RESISTANCE; GENE; REPLICATION; SEQUENCES AB The two groups of chromosomal P-lactamases from Klebsiella oxytoca (OXY-1 and OXY-2) can be overproduced 73- to 223-fold, due to point mutations in the consensus sequences of their promoters. The different versions of promoters from bla(OXY-1) and bla(OXY-2) were cloned upstream of the chloramphenicol acetyltransferase (CAT) gene of pKK232-8, and their relative strengths were determined in Escherichia coli and in K, oxytoca, The three different mutations in the OXY beta-lactamase promoters resulted in a 4- to 31-fold increase in CAT activity compared to that of the wild-type promoter. The G --> T transversion in the first base of the -10 consensus sequence caused a greater increase in the promoter strength of the wild-type promoter than the two other principal mutations (a G-to-A transition of the fifth base of the -10 consensus sequence and a T-to-A transversion of the fourth base of the -35 sequence). The strength of the promoter carrying a double mutation (transition in the Pribnow box and the transversion in the -35 hexamer) was increased 15- to 61-fold in comparison to that of the wild-type promoter. A change from 17 to 16 bp between the -35 and -10 consensus sequences resulted in a ninefold decrease of the promoter strength, The expression of the bla(OXY) promoter in E. coli differs from that in K. oxytoca, particularly for promoters carrying strong mutations. Furthermore, the bla(OXY) promoter appears not to be controlled by DNA supercoiling or an upstream curved DNA, but it is dependent on the gene copy number. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. CHU Laval, Lab Infectiol, St Foy, PQ, Canada. CHU Laval, Serv Infectiol, St Foy, PQ, Canada. RP Fournier, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI023988, AI23988, R37 AI023988] NR 31 TC 24 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1999 VL 43 IS 4 BP 850 EP 855 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 183LQ UT WOS:000079555400018 PM 10103190 ER PT J AU Rajadhyaksha, M Anderson, RR Webb, RH AF Rajadhyaksha, M Anderson, RR Webb, RH TI Video-rate confocal scanning laser microscope for imaging human tissues in vivo SO APPLIED OPTICS LA English DT Article ID IN-VIVO; HUMAN-SKIN; REFRACTIVE-INDEX; OPTICAL-PROPERTIES; HUMAN EPIDERMIS; INVIVO; CONTRAST; LIGHT; OPHTHALMOSCOPE; DERMATOLOGY AB We have built a video-rate confocal scanning laser microscope for reflectance imaging of human skin and oral mucosa in vivo. Design and imaging parameters were determined for optimum resolution and contrast. Mechanical skin-holding fixtures and oral tissue clamps were made for stable objective lens-to-tissue contact such that gross tissue motion relative to the microscope was minimized. Confocal imaging was possible to maximum depths of 350 mu m in human skin and 450 mu m in oral mucosa, with measured lateral resolution of 0.5-1 mu m and axial resolution (section thickness) of 3-5 mu m at the 1064-nm wavelength. This resolution is comparable with that of conventional microscopy of excised biopsies (histology). Normal and abnormal tissue morphology and dynamic processes were observed. (C) 1999 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs, Dept Dermatol, Boston, MA 02114 USA. RP Rajadhyaksha, M (reprint author), Massachusetts Gen Hosp, Wellman Labs, Dept Dermatol, Bartlett Hall Ext 630,50 Blossom St, Boston, MA 02114 USA. NR 63 TC 187 Z9 193 U1 4 U2 12 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 1999 VL 38 IS 10 BP 2105 EP 2115 DI 10.1364/AO.38.002105 PG 11 WC Optics SC Optics GA 184TU UT WOS:000079630200028 PM 18319771 ER PT J AU Ross, EV McKinlay, JR Anderson, RR AF Ross, EV McKinlay, JR Anderson, RR TI Why does carbon dioxide resurfacing work? A Review SO ARCHIVES OF DERMATOLOGY LA English DT Review ID DIFFERENTIAL SCANNING CALORIMETRY; CO2-LASER TISSUE ABLATION; RESIDUAL THERMAL-DAMAGE; YAG LASER ABLATION; HIGH-ENERGY; PULSED CO2-LASER; ER-YAG; COLLAGEN DENATURATION; BIOLOGICAL TISSUES; ACNE SCARS AB Despite the unquestionable efficacy of carbon dioxide laser skin resurfacing, mechanisms for cosmetic enhancement remain poorly characterized. Histological studies have provided some insight into the cascade of events from initial laser impact to final skin rejuvenation. However, there are few comprehensive studies of gross and microscopic wound healing. Additionally, the literature is fragmented; excellent individual articles appear in journals from widely disparate disciplines. For example, some reports relevant to laser skin resurfacing are "sequestered" in the engineering literature. This article is intended to update the physician on laser skin resurfacing based on the broadest review of the current literature. It proceeds from a discussion of initial laser-tissue interactions, such as collagen denaturation, to examination of longterm biological sequlae. At some cost tp scientific rigor, mathematical models describing laser-tissue interactions are not presented. C1 USN, Med Ctr, Dept Dermatol, San Diego, CA 92152 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Ross, EV (reprint author), USN, Med Ctr, Dept Clin Res, San Diego, CA 92134 USA. NR 97 TC 88 Z9 89 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 1999 VL 135 IS 4 BP 444 EP 454 DI 10.1001/archderm.135.4.444 PG 11 WC Dermatology SC Dermatology GA 185MD UT WOS:000079672000011 PM 10206052 ER PT J AU George, MS Lisanby, SH Sackeim, HA AF George, MS Lisanby, SH Sackeim, HA TI Transcranial magnetic stimulation - Applications in neuropsychiatry SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID HUMAN MOTOR CORTEX; DORSOLATERAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; ECHOPLANAR BOLD FMRI; RTMS IMPROVES MOOD; ELECTROCONVULSIVE-THERAPY; BRAIN-STIMULATION; EVOKED-POTENTIALS; MACAQUE MONKEY; CORTICAL HYPEREXCITABILITY AB In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing. Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity-transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs; from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium. C1 Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. New York State Psychiat Inst & Hosp, Dept Biol Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, 171 Ashley Ave, Charleston, SC 29425 USA. EM georgem@musc.edu FU NIMH NIH HHS [MH35636] NR 148 TC 340 Z9 347 U1 1 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 1999 VL 56 IS 4 BP 300 EP 311 DI 10.1001/archpsyc.56.4.300 PG 12 WC Psychiatry SC Psychiatry GA 182NE UT WOS:000079504400001 PM 10197824 ER PT J AU Perry, JR Louis, DN Cairncross, JG AF Perry, JR Louis, DN Cairncross, JG TI Current treatment of oligodendrogliomas SO ARCHIVES OF NEUROLOGY LA English DT Review ID CHEMOTHERAPY; GLIOMAS; ADULTS AB That a neurological review is dedicated specifically to the oligodendroglioma is testimony to a decade of progress. The unique molecular features and chemosensitivity of the oligodendroglioma were not appreciated 10 years ago; yet today, these features merit such interest to clinicians and pathologists alike that the oligodendroglioma is separated from other types of primary brain tumors in both the laboratory and in practice. C1 London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. Univ Toronto, Toronto Sunnybrook Reg Canc Ctr, Dept Med Neurol, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Lab, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Cairncross, JG (reprint author), London Reg Canc Ctr, Dept Med Oncol, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. NR 12 TC 34 Z9 34 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 1999 VL 56 IS 4 BP 434 EP 436 DI 10.1001/archneur.56.4.434 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 184NA UT WOS:000079617200007 PM 10199331 ER PT J AU Coday, MP Colby, K AF Coday, MP Colby, K TI Nailing down the diagnosis - Imaging intraocular foreign bodies SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Massachusetts Eye & Ear Infirm, Clin Res Ctr, Boston, MA 02114 USA. RP Colby, K (reprint author), Massachusetts Eye & Ear Infirm, Clin Res Ctr, 243 Charles St, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 1999 VL 117 IS 4 BP 548 EP 548 PG 1 WC Ophthalmology SC Ophthalmology GA 185MF UT WOS:000079672200024 PM 10206593 ER PT J AU Som, PM Curtin, HD Mancuso, AA AF Som, PM Curtin, HD Mancuso, AA TI An imaging-based classification for the cervical nodes designed as an adjunct to recent clinically based nodal classifications SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SQUAMOUS-CELL-CARCINOMA; NECK DISSECTION; LYMPH-NODES; HEAD; CANCER; METASTASES; CT AB Over the past 18 years, numerous classifications have been proposed to distinguish among the diverse nodal levels. Some classifications have used surgical landmarks, others physical assessment criteria. These classifications do not agree precisely and exhibit sufficient variation that competent physicians could arrive at slightly different staging of the patient's nodal disease. In the past 2 decades, computed tomography and magnetic resonance imaging have offered progressively more refined anatomical precision, reproducibility, and visualization of deep, clinically inaccessible structures. Because the majority of patients with head and neck malignancies presently undergo sectional imaging prior to treatment planning, we felt: a need to integrate anatomical imaging criteria with the 2 most commonly used nodal classifications: those of the American Joint Committee on Cancer and those of the American Academy of Otolaryngology-Head and Neck Surgery. The imaging-based nodal classification proposed herein has been developed in. consultation with surgeons interested in such classifications in the hope that the resultant classification would find ready acceptance by both clinicians and imagers. It is our desire that the best attributes of imaging, combined with those of the physical assessment, can result in a better and more consistently reproducible nodal staging than is possible by either approach alone. C1 CUNY, Mt Sinai Sch Med, Dept Radiol, New York, NY 10021 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Florida, Coll Med, Shands Hosp, Gainesville, FL USA. RP Som, PM (reprint author), Mt Sinai Hosp, Dept Radiol, 1 Gustave Levy Pl, New York, NY 10029 USA. NR 22 TC 126 Z9 147 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD APR PY 1999 VL 125 IS 4 BP 388 EP 396 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 184MY UT WOS:000079617000003 PM 10208676 ER PT J AU Cooper, RA Boninger, ML Rentschler, A AF Cooper, RA Boninger, ML Rentschler, A TI Evaluation of selected ultralight manual wheelchairs using ANSI/RESNA standards SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID STABILITY AB Objectives: To provide data for clinicians and wheelchair users to compare the durability, strength, stability, and cost effectiveness of four different ultralight wheelchair models, and to compare the results of this study with those published for lightweight wheelchairs. Design: Standards testing and cost-effectiveness analysis of four wheelchair models from different manufacturers (12 wheelchairs total). Results: There were significant differences (p less than or equal to .05) in the fatigue life and value (equivalent cycles per dollar) among the ultralight wheelchairs tested. There was also a significant difference (p less than or equal to.05) in rearward stability tilt angle for the least and most stable configurations. There were no differences in forward and lateral stability. The ultralight wheelchairs (1,009,108 cycles) had significantly (p less than or equal to .05) higher fatigue lives than previously reported for lightweight wheelchairs (187,370 cycles). The lightweight wheelchairs had a mean value of 210 cycles per dollar compared to 673 cycles per dollar for the ultralight wheelchairs. The difference in value for the lightweight and ultralight wheelchairs was statistically significant (p less than or equal to .05). Conclusion: There were differences in the fatigue life and value among the four models of ultralight manual wheelchairs tested. This indicates that ultralight manual wheelchairs are not all of equal quality. The fatigue life and value of the ultralight manual wheelchairs were significantly higher than those previously reported far lightweight manual wheelchairs. This indicates that ultralight wheelchairs may be of higher quality than lightweight manual wheelchairs. Clinicians and consumers should seriously consider selecting an ultralight manual wheelchair to meet their wheelchair mobility needs. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151 R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr Hlth Syst, Div Phys Med & Rehabil, Pittsburgh, PA USA. Vet Affairs Pittsburgh Hlth Care Syst, Human Engn Res Labs, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151 R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 19 TC 26 Z9 26 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 1999 VL 80 IS 4 BP 462 EP 467 DI 10.1016/S0003-9993(99)90287-3 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 184TG UT WOS:000079629100018 PM 10206612 ER PT J AU Masiakos, PT Islam, S Doody, DP Schnitzer, JJ Ryan, DP AF Masiakos, PT Islam, S Doody, DP Schnitzer, JJ Ryan, DP TI Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the New-England-Surgical-Society CY SEP 25-27, 1998 CL TORONTO, CANADA SP New England Surg Soc ID PERMISSIVE HYPERCAPNIA; MECHANICAL VENTILATION; DISTRESS-SYNDROME; CLINICAL-TRIAL; LIFE-SUPPORT; PRESSURE; MORTALITY; SURVIVAL; ECMO; CHILDREN AB Hypothesis: Extracorporeal membrane oxygenation (ECMO) is effective in nonneonatal acute respiratory failure under certain circumstances. Design: Retrospective medical. record review. Setting: The intensive care unit of a tertiary care hospital. Patients: Thirty-four nonneonatal patients (mean age, 22 years; range, 8 days to 56 years),with ratios of the PaO2 to the fraction of inspired oxygen persistently below 70, who were treated with ECMO after maximal ventilator therapy had failed (mean time of ventilator therapy, 6.9 days; range, 1-41 days). The mean ECMO duration was 304 hours (range, 56-934 hours). Patients were grouped into 7 categories based on their diagnosis: sepsis or sepsis syndrome (n = 3), bacterial or fungal pneumonia (n = 10), viral pneumonia (n = 5), trauma or burn (n = 2), inhalation injury without burn (n = 1), immunocompromised state (due to transplantation or chemotherapy) (n = 8), and acute respiratory failure of unknown origin (n = 5). Main Outcome Measure: Survival to hospital discharge following ECMO therapy. Results: Overall survival was 53% (18 patients). All 6 patients (100%) with viral pneumonias or isolated inhalation injuries survived. Of 13 patients with bacterial pneumonia, sepsis, or sepsis syndrome not complicated by multiorgan failure, 10 (77%) survived. In contrast, all but 1 of the immunocompromised patients died. Survival in patients who were intubated for less than 9 days before ECMO was 64%, whereas survival fell precipitously to 22% for patients who experienced mechanical ventilation for 9 or more days before the implementation of ECMO. Finally, the proportion of patients who died while receiving ECMO therapy was greater when the ECMO duration exceeded 300 hours (62% vs 38%; P<.05). Conclusions: Nonneonatal survival with ECMO therapy is strongly dependent on the diagnosis. Pre-ECMO intubation for less than 9 days had little effect on survival. Survival rates decreased when the length of time of receiving ECMO exceeded 300 hours. C1 Massachusetts Gen Hosp, Dept Surg, Pediat Surg Serv, Harvard Med Sch, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Dept Surg, Pediat Surg Serv, Harvard Med Sch, 40 Fruit St,WRN 1131, Boston, MA 02114 USA. NR 22 TC 25 Z9 25 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1999 VL 134 IS 4 BP 375 EP 379 DI 10.1001/archsurg.134.4.375 PG 5 WC Surgery SC Surgery GA 184DG UT WOS:000079594200006 PM 10199309 ER PT J AU Gadd, MA Cosimi, AB Yu, J Duncan, LM Yu, L Flotte, TJ Souba, WW Ott, MJ Wong, LS Sober, AJ Mihm, MC Haluska, FG Tanabe, KK AF Gadd, MA Cosimi, AB Yu, J Duncan, LM Yu, L Flotte, TJ Souba, WW Ott, MJ Wong, LS Sober, AJ Mihm, MC Haluska, FG Tanabe, KK TI Outcome of patients with melanoma and histologically negative sentinel lymph nodes SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the New-England-Surgical-Society CY SEP 25-27, 1998 CL TORONTO, CANADA SP New England Surg Soc ID EARLY-STAGE MELANOMA; MALIGNANT-MELANOMA; DISSECTION; METASTASES; IMMEDIATE AB Hypothesis: Patients with melanoma and histologically negative sentinel lymph nodes identified by lymphatic mapping have a very good prognosis. Design: Cohort study with follow-up information obtained from medical records and telephone interviews. Setting and Patients: Of all patients with cutaneous melanoma who underwent intraoperative sentinel lymph node mapping between November 15, 1993, and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial location. The median tumor thickness was 1.8 mm (range, 0.36-12.0,mm) and 11 tumors (12%) were ulcerated. Interventions: Patients underwent intraoperative sentinel lymph node mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy following wide excision of the primary lesion. Main Outcome Measures: Site of initial recurrence and time to initial recurrence. Results: The median follow-up for all patients was 23 months (range, 2-54 months). Eleven patients (12%) developed melanoma recurrences, and 78 (88%) patients remain disease free. Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without involvement of regional lymph nodes: 2 with distant metastases and 2 with in transit metastases. The median time to recurrence was 12 months (range, 2-35 months). Sentinel lymph nodes were reanalyzed using serial sections and immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was identified in 3 (43%). Conclusions: The risk for melanoma recurrence is relatively low in patients with histologically negative sentinel nodes identified by lymphatic mapping. Longer follow-up will improve our understanding of the prognostic value of this procedure. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox Bldg 626, Boston, MA 02114 USA. NR 20 TC 113 Z9 114 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1999 VL 134 IS 4 BP 381 EP 387 DI 10.1001/archsurg.134.4.381 PG 7 WC Surgery SC Surgery GA 184DG UT WOS:000079594200008 PM 10199310 ER PT J AU Ott, MJ Tanabe, KK Gadd, MA Stark, P Smith, BL Finkelstein, DM Souba, WW AF Ott, MJ Tanabe, KK Gadd, MA Stark, P Smith, BL Finkelstein, DM Souba, WW TI Multimodality management of Merkel cell carcinoma SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the New-England-Surgical-Society CY SEP 25-27, 1998 CL TORONTO, CANADA SP New England Surg Soc ID CUTANEOUS NEUROENDOCRINE CARCINOMA; TRABECULAR CARCINOMA; METASTATIC DISEASE; RADIATION-THERAPY; SKIN; DIAGNOSIS; RECURRENT; TUMOR AB Hypothesis: Merkel cell carcinoma is a rare dermal neuroendocrine carcinoma whose optimal treatment and prognostic factors are poorly defined. We hypothesize that high-risk patients with Merkel cell carcinoma are best treated with multimodality therapy. Design: A retrospective review of all patients (N = 33) with Merkel cell carcinoma treated at the Massachusetts General Hospital from January 1, 1980, to August 24, 1997. Median follow-up time was 37 months (range, 6-157 months). Patients: Adequate data for evaluation were available for 31 patients. Male to female distribution was 14 men and 17 women, with a median patient age of 68 years. Main Outcome Measure: Stage at presentation; factors associated with recurrence; and the effects of surgery, radiation therapy (XRT), and chemotherapy on recurrence, salvage, and survival rates. Results: There were 12 extremity, 11 head and neck, and 8 truncal tumors. There were 22 isolated primary tumors, 8 with additional clinically positive lymph nodes, and 1 with distant disease. Therapy was local excision with or without XRT in 19 patients, local resection and lymphadenectomy with or without XRT in 8 patients, and XRT alone in 4 patients with head and neck tumors. Fifteen patients developed recurrences (7 local, 8 nodal, and 10 distant). Median time to recurrence was 8 months (range, 3-48 months). There were 7 tumor-related deaths, 6 of which were associated with truncal lesions (P<.001). No locoregional recurrences occurred inpatients with margins of resection of 2 cm or greater or adequate XRT, A multivariate analysis selected truncal location (P = .005) and nodal disease (P = .05) as predictors of mortality. Remission was possible in 5 patients with locoregional and 2 patients with distant recurrences. Conclusions: Merkel cell carcinoma is an aggressive dermal cancer with frequent nodal metastases; truncal tumors have the worst prognosis. Locoregional recurrence correlates with inadequate margins and lack of XRT, but remission is possible with multimodality therapy. C1 Harvard Univ, Div Surg Oncol, Dept Surg, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. Harvard Univ, Dept Biostat, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ott, MJ (reprint author), Harvard Univ, Div Surg Oncol, Dept Surg, Massachusetts Gen Hosp,Med Sch, 626 Cox Bldg,100 Blossom St, Boston, MA 02114 USA. NR 22 TC 128 Z9 129 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1999 VL 134 IS 4 BP 388 EP 392 DI 10.1001/archsurg.134.4.388 PG 5 WC Surgery SC Surgery GA 184DG UT WOS:000079594200010 PM 10199311 ER PT J AU Chien, GL Mohtadi, K Wolff, RA Van Winkle, DM AF Chien, GL Mohtadi, K Wolff, RA Van Winkle, DM TI Naloxone blockade of myocardial ischemic preconditioning does not require central nervous system participation SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE myocardial infarction; ischemic preconditioning; naloxone; rabbits ID INTACT RAT-HEART; OPIOID RECEPTORS; MORPHINE ANALGESIA; GENE-EXPRESSION; BETA-ENDORPHIN; MESSENGER-RNA; AGONIST; INFARCTION; ANTAGONIST; MECHANISM AB Objective The hypothesis that naloxone blockade of ischemic preconditioning (IP)-induced infarct limitation does not require central nervous system participation was evaluated using quaternary naloxone in anesthetized rabbits (Study I) and naloxone hydrochloride in isolated rabbit hearts (Study II). Methods In Study I, rabbits underwent 30 min coronary artery occlusion and 180 min reperfusion. IP was elicited with a 5 min coronary artery occlusion beginning 15 min before the 30 min occlusion. Intravenous naloxone methiodide, 12.9 mg/kg, was bolused 10 or 1 min before IF. In Study II, rabbit hearts underwent 15 min coronary artery occlusion and 120 min reperfusion. IP was elicited with 2 cycles of 5 min coronary artery occlusion plus 5 min reperfusion, beginning 20 min before the 45 min occlusion. Naloxone hydrochloride, 1 mu mol/L or 100 mu mol/L, was added to the buffer perfusate for 25 min preceding the long coronary artery occlusion. In both studies, infarct size was assessed with tetrazolium, normalized to risk volume, and analyzed using ANOVA. Results In both studies, IP reduced infarct size compared to control (6.3 +/- 2.3 vs. 29.5 +/- 4.4, P = 0.007, Study I; 11.8 +/- 4.7 vs. 47.7 +/- 6.7, P = 0.03, Study II). In Study I, IP was not blocked when naloxone methiodide was given 10 min before IP (13.8 +/- 1.8 vs. 42.3 +/- 5.4, P = 0.004) but was blocked when given 1 min before IP (25.3 +/- 7.2 vs. 28.4 +/- 5.0, Pr ns). In Study II, infarct size was intermediate in the 1 mu mol/L naloxone hydrochloride+IP group (19.0 +/- 6.5 vs. 48.9 +/- 8.4, P = ns) but IP was blocked by 100 mu mol/L naloxone hydrochloride (62.6 +/- 4.5 vs. 56.2 +/- 6.7, P = ns). Conclusion Naloxone blockade of IP-induced infarct limitation involves a cardiac mechanism. C1 Portland Vet Affairs Med Ctr, Anesthesiol Serv, Dept Anesthesiol, Portland, OR 97201 USA. RP Van Winkle, DM (reprint author), Portland Vet Affairs Med Ctr, Anesthesiol Serv, Dept Anesthesiol, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 34 TC 34 Z9 38 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD APR PY 1999 VL 94 IS 2 BP 136 EP 143 DI 10.1007/s003950050136 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 188NV UT WOS:000079855100009 PM 10326662 ER PT J AU Hamner, MB Frueh, BC Ulmer, HG Arana, GW AF Hamner, MB Frueh, BC Ulmer, HG Arana, GW TI Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc DE posttraumatic stress; anxiety; psychosis; depression; comorbidity; alcohol abuse ID AUDITORY HALLUCINATIONS; UNIPOLAR DEPRESSION; SYMPTOMS; PTSD AB Background: Psychotic symptoms may be present in up to 40% of patients with combat-related posttraumatic stress disorder (PTSD). In this study, we hypothesized that severity of psychotic symptoms would also reflect severity of PTSD symptoms in patients with well-defined psychotic features. Methods: Forty-five Vietnam combat veterans with PTSD but without a primary psychotic disorder diagnosis underwent a Structured Clinical Interview for DSM-III-R with Psychotic Screen, and the Clinician Administered PTSD Scale (CAPS). Patients identified as having psychotic features (PTSD-P), (n = 22) also received the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Results: There was a significant positive correlation between the Caps and PANSS global ratings (p < .001) and the HDRS and PANSS (p < .03) in the PTSD-P patients. Many CAPS and PANSS subscales also demonstrated significant intercorrelations; however, the CAPS-B subscale (reexperiencing) and the PANSS positive symptom scale were not correlated, suggesting that psychotic features may not necessarily be influenced or accounted for by more severe reexperiencing symptoms. Fifteen (68%) of the PTSD-P patients had major depression (MDD). Both CAPs and PANSS ratings were significantly higher in the PTSD-P patients with comorbid MDD. Conclusions: As postulated, patients with more severe psychosis ratings are likely to have more severe PTSD disease burden if psychotic features are present. This study further documents the occurrence of psychotic features in PTSD that are not necessarily due to a primary psychotic disorder, suggesting that this may be a distinct subtype; however, a significant interaction likely exists between PTSD, depression, and psychotic features. (C) 1999 Society of Biological Psychiatry. C1 Ralph H Johnson VA Med Ctr, Dept Psychiat, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, Dept Psychiat, 109 Bee St, Charleston, SC 29401 USA. NR 38 TC 95 Z9 96 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1999 VL 45 IS 7 BP 846 EP 852 DI 10.1016/S0006-3223(98)00301-1 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 182VM UT WOS:000079518900007 PM 10202572 ER PT J AU Savage, CR Baer, L Keuthen, NJ Brown, HD Rauch, SL Jenike, MA AF Savage, CR Baer, L Keuthen, NJ Brown, HD Rauch, SL Jenike, MA TI Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; memory; executive function; organizational strategies; frontal-striatal ID GLUCOSE METABOLIC RATES; POSITRON-EMISSION-TOMOGRAPHY; FRONTAL-LOBE DYSFUNCTION; SYMPTOM PROVOCATION; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; COGNITIVE DEFICITS; STRIATAL FUNCTION; NEUROPSYCHOLOGY; BEHAVIOR AB Background: Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. Methods: We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. Results: OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. Conclusions: Immediate nonverbal memory problems in OCD subjects wee mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD. Biol Psychiatry 1999;45:905-916 (C) 1999 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychol, Cambridge, MA 02138 USA. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, 149-9102,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 78 TC 263 Z9 278 U1 12 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1999 VL 45 IS 7 BP 905 EP 916 DI 10.1016/S0006-3223(98)00278-9 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 182VM UT WOS:000079518900014 PM 10202579 ER PT J AU Ross, RJ Ball, WA Sanford, LD Morrison, AR Dinges, DF Silver, SM Kribbs, NB Mulvaney, FD Gehrman, PR McGinnis, DE AF Ross, RJ Ball, WA Sanford, LD Morrison, AR Dinges, DF Silver, SM Kribbs, NB Mulvaney, FD Gehrman, PR McGinnis, DE TI Rapid eye movement sleep changes during the adaptation night in combat veterans with posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE hyperarousal; posttraumatic stress disorder; rapid eye movement sleep; phasic activity ID DISTURBANCE AB Background: Hyperarousal in posttraumatic stress disorder (PTSD) is manifested during sleep as well as waking. Elevated rapid eye movement sleep (REMS) phasic activity, likely signifying central nervous system alerting, has been identified in PTSD. The authors reasoned that PTSD compared to control subjects would show particularly increased REMS phasic activity on the first night of polysomnography, with adaptation to a novel environment. Methods: First-night polysomnograms of 17 veterans with PTSD were compared with those of 11 control subjects. Sleep was also studied in subsets of both groups over two nights. Results: On the first night, the PTSD subjects had a higher density of rapid eye movements in the first REMS period. This measure was increased on the first compared to the second night, but there was no interaction effect between night and group. Conclusions: REMS changes are again demonstrated in veterans with PTSD. Introduction to a novel environment activated a REMS phasic process, but not differentially in PTSD compared to control subjects. Biol Psychiatry 1999;45:938-941 (C) 1999 Society of Biological Psychiatry. C1 Vet Affairs Med Ctr, Behav Hlth Serv 116A, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Coatesville, PA USA. RP Ross, RJ (reprint author), Vet Affairs Med Ctr, Behav Hlth Serv 116A, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [MH42903] NR 16 TC 23 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1999 VL 45 IS 7 BP 938 EP 941 DI 10.1016/S0006-3223(98)00233-9 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 182VM UT WOS:000079518900020 PM 10202585 ER PT J AU Brownell, AL Jenkins, BG Isacson, O AF Brownell, AL Jenkins, BG Isacson, O TI Dopamine imaging markers and predictive mathematical models for progressive degeneration in Parkinson's disease SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE dopamine transporters; L-DOPA; MPTP; MRS; Parkinson's disease; PET ID POSITRON EMISSION TOMOGRAPHY; COCAINE RECOGNITION SITES; MPTP-INDUCED PARKINSONISM; PRIMATE MODEL; INVITRO MATURATION; BINDING-SITES; MOTOR SYMPTOMS; LIGAND-BINDING; BASAL GANGLIA; D2 RECEPTORS AB We conducted PET imaging studies of modulation of dopamine transporter function and MRS studies of neurochemicals in idiopathic primate Parkinson's disease (PD) model induced by long-term, low-dose administration of MPTP. MR spectra showed striking similarities of the control spectrum of the primate and human striatum as well as MPTP-treated primate (six months after cessation of MPTP), and Parkinson's disease patient striatum (68 year old male; Hoehn-Yahr scale II; 510 mg/d L-DOPA). The choline/creatine ratio was similar in the MPTP model and human parkinsonism, suggesting a possible glial abnormality. The progressive degeneration of dopamine re-uptake sires observed in our PD model can be expressed by a time dependent exponential equation N(t) = N-0 exp (-(0.072 +/- 0.016) t), where N-0 represents intact entities (dopamine re-uptake sites before MPTP) and 0.072 per month is the rate of degeneration. When the signs of PD appear, N(t) is about 0.3-0.4 times N-0. Interestingly, this biological degenerative phenomena has similar progression to that observed in cell survival theory. According to this theory and calculated degeneration rate, predictive models can be produced for regeneration and protective treatments. (C) 1999 Elsevier, Paris. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. McLean Hosp, Neurogenerat Labs, Belmont, MA 02178 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [P51RR00168-36] NR 82 TC 16 Z9 17 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD APR PY 1999 VL 53 IS 3 BP 131 EP 140 DI 10.1016/S0753-3322(99)80078-X PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 200EJ UT WOS:000080526400004 PM 10349501 ER PT J AU Pootanakit, K Brunken, WJ AF Pootanakit, K Brunken, WJ TI Combination of cross-species RNA solution hybridization and immunoprecipitation aids in the cloning of RT-PCR products SO BIOTECHNIQUES LA English DT Article ID GENERATION; PROBES C1 Massachusetts Gen Hosp East, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Boston Coll, Chestnut Hill, MA 02167 USA. RP Pootanakit, K (reprint author), Massachusetts Gen Hosp East, Cutaneous Biol Res Ctr, 3rd Floor,Bldg 149,Charlestown Navy Yard,13th St, Boston, MA 02129 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 1999 VL 26 IS 4 BP 616 EP + PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185UL UT WOS:000079689200004 PM 10343895 ER PT J AU Rebel, VI Tanaka, M Lee, JS Hartnett, S Pulsipher, M Nathan, DG Mulligan, RC Sieff, CA AF Rebel, VI Tanaka, M Lee, JS Hartnett, S Pulsipher, M Nathan, DG Mulligan, RC Sieff, CA TI One-day ex vivo culture allows effective gene transfer into human nonobese diabetic severe combined immune-deficient repopulating cells using high-titer vesicular stomatitis virus G protein pseudotyped retrovirus SO BLOOD LA English DT Article ID HUMAN HEMATOPOIETIC-CELLS; BONE-MARROW CELLS; HUMAN ADENOSINE-DEAMINASE; BLOOD CD34(+) CELLS; STEM-CELL; PERIPHERAL-BLOOD; IMMUNODEFICIENT MICE; INITIATING CELLS; PROGENITOR CELLS; LEUKEMIA-VIRUS AB Retrovirus-mediated gene transfer into long-lived human pluripotent hematopoietic stem cells (HSCs) is a widely sought but elusive goal. A major problem is the quiescent nature of most HSCs, with the perceived requirement for ex vivo prestimulation in cytokines to induce stem cell cycling and allow stable gene integration. However, ex vivo culture may impair stem cell function, and could explain the disappointing clinical results in many current gene transfer trials, To address this possibility, we examined the ex vivo survival of nonobese diabetic/severe combined immune-deficient (NOD/SCID) repopulating cells (SRCs) over 3 days. After 1 day of culture, the SRC number and proliferation declined twofold, and was further reduced by day 3; self-renewal was only detectable in noncultured cells. To determine if the period of ex vivo culture could be shortened, we used a vesicular stomatitis virus G protein (VSV-G) pseudotyped retrovirus vector that was concentrated to high titer, The results showed that gene transfer rates were similar without or with 48 hours prestimulation. Thus, the use of high-titer VSV-G pseudotyped retrovirus may minimize the loss of HSCs during culture, because efficient gene transfer can be obtained without the need for extended ex vivo culture. (C) 1999 by The American Society of Hematology. C1 Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Sieff, CA (reprint author), Dana Farber Canc Inst, Div Pediat Hematol & Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [1 P50 HL54785, R01 HL55709] NR 47 TC 60 Z9 60 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1999 VL 93 IS 7 BP 2217 EP 2224 PG 8 WC Hematology SC Hematology GA 180GH UT WOS:000079377400011 PM 10090930 ER PT J AU Finklestein, SP Ren, JM Kawamata, T Kaplan, PL Charette, MF AF Finklestein, SP Ren, JM Kawamata, T Kaplan, PL Charette, MF TI OP-1 (BMP-7) enhancement of recovery following stroke SO BONE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tokyo Womens Med Coll, Tokyo 162, Japan. Creat Biomol Inc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 1999 VL 24 IS 4 MA 89 BP 431 EP 431 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 184DN UT WOS:000079594900102 ER PT J AU Bird, TD Nochlin, D Poorkaj, P Cherrier, M Kaye, J Payami, H Peskind, E Lampe, TH Nemens, E Boyer, PJ Schellenberg, GD AF Bird, TD Nochlin, D Poorkaj, P Cherrier, M Kaye, J Payami, H Peskind, E Lampe, TH Nemens, E Boyer, PJ Schellenberg, GD TI A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L) SO BRAIN LA English DT Article DE frontotemporal dementia; tau; mutations ID PONTO-NIGRAL DEGENERATION; MULTIPLE SYSTEM TAUOPATHY; ALZHEIMERS-DISEASE CERAD; PRESENILE-DEMENTIA; APOLIPOPROTEIN-E; NEURODEGENERATIVE DISORDERS; NEUROFIBRILLARY TANGLES; DUTCH FAMILIES; PICKS-DISEASE; PARKINSONISM AB We investigated three separate families (designated D, F and G) with frontotemporal dementia that have the same molecular mutation in exon 10 of the tau gene (P301L), The families share many clinical characteristics, including behavioural aberrations, defective executive functions, language deficits, relatively preserved constructional abilities and frontotemporal atrophy on imaging studies, However, Family D has an earlier mean age of onset and shorter duration of disease than Families F and G (49.0 and 5.1 years versus 61-64 and 7.3-8.0 years, respectively), Two members of Families D and F had neuropathological studies demonstrating lobar atrophy, but the brain from Family D had prominent and diffuse circular, intraneuronal, neurofibrillary tangles not seen in Family F. The brain from Family F had ballooned neurons typical of Pick's disease type B not found in Family D, A second autopsy from Family D showed neurofibrillary tangles in the brainstem with a distribution similar to that found in progressive supranuclear palsy. These three families demonstrate that a missense mutation in the exon 10 microtubule-binding domain of the tau protein gene can produce severe behavioural abnormalities with frontotemporal lobar atrophy and microscopic tau pathology, However, the findings in these families also emphasize that additional unidentified environmental and/or genetic factors must be producing important phenotypic variability on the background of an identical mutation, Apolipoprotein E genotype does not appear to be such a factor influencing age of onset in this disease. C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bird, TD (reprint author), GRECC 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG 05136, AG 08017] NR 45 TC 163 Z9 166 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 1999 VL 122 BP 741 EP 756 DI 10.1093/brain/122.4.741 PN 4 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 189VF UT WOS:000079926300012 PM 10219785 ER PT J AU Hedley-Whyte, ET AF Hedley-Whyte, ET TI In memory of Dr Edward Peirson Richardson - Obituary SO BRAIN PATHOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hedley-Whyte, ET (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 1999 VL 9 IS 2 BP 415 EP 417 PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 182AL UT WOS:000079476300018 ER PT J AU Doherty, CP Meredith, GE Farrell, M Toland, J Staunton, H AF Doherty, CP Meredith, GE Farrell, M Toland, J Staunton, H TI Radiological determination of the posterior limits of the temporal lobe for volumetric analysis SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE MRI; language lateralization; association cortex; Brodmann's area; Sylvian fissure; planum temporale ID LEFT-RIGHT ASYMMETRY; MAGNETIC-RESONANCE; PLANUM TEMPORALE; MR IMAGES; CORTEX; EPILEPSY AB The posterior peri-Sylvian area is the most highly lateralized part of the human brain due to its specialised role in language. Currently, there is no clearly defined posterior boundary of the temporal lobe which takes account of language lateralization and which can be reliably determined radiologically. However, there have been a number of recent advances in magnetic resonance technology including volume visualisation techniques which have as their goal the realistic three-dimensional representation of the brain which is acquired in two-dimensional slices. These have enabled the identification of precise macroanatomical and cytoarchitectural boundaries from which an efficient and reproducible posterior limit may be demarcated. Such limit standardisation is important for volumetric investigations of both neurological and psychiatric disease. Magnetic resonance imaging (MRI) scans of 20 normal subjects (10 male and 10 female), aged between 18 and 42 years, were acquired as part of a study of normal temporal lobe volume variation. In order to demonstrate the method of posterior limit placement, a thin slice (1.5 mm) 3D spoiled gradient magnetic resonance image of the brain of a 30 year-old right-handed male, without neurological disease, was acquired on a 1.5 tesla GE magnetic resonance machine. The data set was transferred via network to the hard disk of a 166 MHz Pentium processor PC. A software package called MEASURE allowed reformation of the data set in all three orthogonal planes. Then, using a high resolution algorithm, the brain was aligned along the newly proposed posterior plane which runs from the Limit of the Sylvian fissure, identified on a 3D rendering, to the posterior/inferior splenium. It is hoped that this procedure will be utilised as a standard method for radiological determination of the Limit of the posterior temporal lobe in order to allow volumetric measurements of this structure to be compared in a meaningful way. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Royal Coll Surg Ireland, Beaumont Hosp, Dept Clin Neurol Sci, Dublin 9, Ireland. Royal Coll Surg Ireland, Dept Anat, Dublin 2, Ireland. RP Doherty, CP (reprint author), Massachusetts Gen Hosp, Div Neurol, Wang Ambulatory Care Ctr 835, 32 Fruit St, Boston, MA 02114 USA. EM cpdoherty@partners.org NR 40 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD APR PY 1999 VL 4 IS 1 BP 1 EP 10 DI 10.1016/S1385-299X(98)00053-1 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 184ZF UT WOS:000079643100001 PM 10234447 ER PT J AU Barnes, CJ Lee, M AF Barnes, CJ Lee, M TI Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2-dimethylhydrazine-induced colon tumours in rats SO BRITISH JOURNAL OF CANCER LA English DT Article DE aspirin; carcinogenesis; chemoprevention; colon; rat ID CYCLOOXYGENASE-2 LEVELS; COLORECTAL-CANCER; CARCINOGENESIS; SULINDAC; ADENOMAS; DRUGS; RISK; PROSTAGLANDINS; REGRESSION; EXPRESSION AB In order to establish an optimal timing and duration of aspirin treatment in the chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats, colon tumours were induced using an established protocol and aspirin was given in the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results indicate that only aspirin treatment throughout the entire carcinogenic period significantly reduced tumour incidence and volume whereas intermittent aspirin dosing increased tumour number and/or volume, suggesting that aspirin must be used for an extended period in order to gain any chemopreventive benefit. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Vet Affairs Med Ctr, San Antonio, TX 78284 USA. RP Lee, M (reprint author), Univ Mississippi, Med Ctr, Dept Med, Div Digest Dis, 2500 N State St, Jackson, MS 39216 USA. FU NCI NIH HHS [P30 CA 54174] NR 32 TC 11 Z9 12 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 1999 VL 79 IS 11-12 BP 1646 EP 1650 DI 10.1038/sj.bjc.6690263 PG 5 WC Oncology SC Oncology GA 179FD UT WOS:000079314400003 PM 10206272 ER PT J AU Tatsuta, N Suzuki, H Mochizuki, T Koya, K Kawakami, M Shishido, T Motoji, N Kuroiwa, H Shigematsu, A Chen, LB AF Tatsuta, N Suzuki, H Mochizuki, T Koya, K Kawakami, M Shishido, T Motoji, N Kuroiwa, H Shigematsu, A Chen, LB TI Pharmacokinetic analysis and antitumor efficacy of MKT-077, a novel antitumor agent SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE MKT-077; mitochondria; pharmacokinetics; delocalized lipophilic cation; antitumor agent ID RHODAMINE-123; DYE AB MKT-077 (1-ethyl-2-{[3 -ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-oxothiazolidin-2-ylidenemethyl} pyridinium chloride), a novel rhodacyanine dye in phase I/II clinical trials, may provide a new approach to cancer therapy based on the accumulation in the mitochondria of the cells of certain carcinomas, for example, those of the colon, breast and pancreas. To support the development of MKT-077 for clinical application as an intravenous (i.v.) therapy, we investigated the metabolic fate of [C-14]MKT-077 in BDF1 mice as well as the distribution of MKT-077 in experimental LS174T tumor-bearing mice using a high-performance liquid chromatography (HPLC) method. The plasma levels of C-14 after i.v. administration of [C-14]MKT-077 declined in a triphasic manner. In the first distribution phase, the levels of C-14 decreased with a T-1/2 of similar to 5 min. In the second and terminal phase, the T-1/2 of C-14 was 2.8-4.6 h and 16.2 h, respectively. C-max (1 min after injection) increased from 0.3 to 1.5 mu g/ml linearly, but less than proportionately between the doses. The AUC((0-infinity)) at 0.3, 1 and 3 mg/kg were 0.030 +/- 0.002, 0.60 +/- 0.12 and 1.73 +/- 0.25 mu g . h/ml, respectively. Plasma clearance was similar to 1.8 1/h per kg (at doses of 1 and 3 mg/kg). The steady state volume of distribution (6.8 and 25.1 1/ kg) indicated that MKT-077 distributed as a lipid-soluble molecule. The mean residence time (MRT) was 4.1 (at a dose of 1 mg/kg) and 14.1 h (at a dose of 3 mg/kg). In the first rapid phase (5 min after dosing), C-14 radioactivity was detected in most of the tissues and organs, most strongly in the kidney cortex, and not in the central nervous system and testes. In the terminal phase (24 h after dosing), C-14 contents increased in the intestinal tract, and in the kidney and liver were nearly to the background level. After i.v. bolus administration at a dose of 3 mg/kg of [C-14]MKT-077, the predominant route of elimination of the radioactivity was via the feces, and recoveries of total radioactivity in urine and feces corresponded to 33.5% and 61.1%, respectively. More than 60% was recovered within 24 h and 95% within 1 week. MKT-077 was primarily excreted in unmetabolized form with five unidentified metabolites found in the urine and plasma. Intact MKT-077 was retained in the tumor tissue longer than in plasma and kidney in LS174T tumor-bearing mice receiving MKT-077 at an i.v. therapeutic dose (10 mg/kg). This accumulation decreased very slowly, suggesting that the high membrane potentials of tumor cell mitochondria may help retain the drug in tumors. C1 Shionogi BioRes Corp, Lexington, MA 02173 USA. Fuji Photo Film Co Ltd, Ashigara Res Labs, Kanagawa 25001, Japan. Inst Whole Body Metab, Chiba 27014, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tatsuta, N (reprint author), Shionogi BioRes Corp, 45 Hartwell Ave, Lexington, MA 02173 USA. EM tatsuta@erols.com NR 21 TC 15 Z9 16 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 1999 VL 43 IS 4 BP 295 EP 301 DI 10.1007/s002800050898 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 168GU UT WOS:000078684100005 PM 10071980 ER PT J AU Bowen, DJ Patenaude, AF Vernon, SW AF Bowen, DJ Patenaude, AF Vernon, SW TI Psychosocial issues in cancer genetics: From the laboratory to the public - Introduction SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID WOMEN C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Sch Publ Hlth, Houston, TX 77225 USA. RP Bowen, DJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave,N-MP702, Seattle, WA 98109 USA. NR 12 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1999 VL 8 IS 4 BP 326 EP 328 PN 2 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 187DB UT WOS:000079770100003 PM 10207636 ER PT J AU Li, FP AF Li, FP TI Psychosocial aspects of cancer genetic testing findings from the Cancer Genetics Studies Consortium - Introduction SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1999 VL 8 IS 4 BP 326 EP 326 PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 187DB UT WOS:000079770100002 ER PT J AU Korsmeyer, SJ AF Korsmeyer, SJ TI BCL-2 gene family and the regulation of programmed cell death SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT General-Motors-Cancer-Research-Foundation 20th Annual Scientific Conference - Developmental Biology and Cancer CY JUN 09-10, 1998 CL BETHESDA, MARYLAND SP Gen Motors Canc Res Fdn ID P53-DEPENDENT APOPTOSIS; TRANSGENIC MICE; HOMOLOG BAK; IN-VIVO; LYMPHOID HYPERPLASIA; SEQUENCE SIMILARITY; POLYCYSTIC KIDNEY; BH3 DOMAIN; E1B 19K; C-MYC AB The BCL-2 gene was identified at the chromosomal breakpoint of t(14; 18)-bearing human follicular B cell lymphomas. BCL-2 proved to block programmed cell death rather than promote proliferation. Transgenic mice that overexpress Bcl-2 in the B cell lineage demonstrate extended cell survival and progress to high-grade lymphomas. Thus, BCL-2 initiated a new category of oncogenes, regulators of cell death. Bcl-2-deficient mice demonstrate fulminant apoptosis of lymphocytes, profound renal cell death and loss of melanocytes, BCL-2 protein duels with its counteracting twin, a partner known as BAX, When BAX is in excess, cells execute a death command; but, when BCL-2 dominates, the program is inhibited and cells survive. Bax-deficient mice display cellular hyperplasia, confirming its role as a proapoptotic molecule. An expanded family of BCL-2-related proteins shares homology clustered within four conserved regions termed BCL-2 homology 1 through 4 (BH1-4), These novel domains control the ability of these proteins to dimerize and function. An amphipathic alpha helix, BH3, is of particular importance for the proapoptotic family members. BID and BAD represent an evolving set of proapoptotic molecules, which bear sequence homology only at BH3, They appear to reside more proximal in the pathway serving as death ligands. BAD connects upstream signal transduction paths with the BCL-2 family, modulating this checkpoint for apoptosis, In the presence of survival factor interleukin-3, cells phosphorylate BAD on two serine residues. This inactivated BAD is held by the 14-3-3 protein, freeing BCL-X-L and BCL-2 to promote survival. Activation of BAX results in the initiation of apoptosis, Downstream events in this program include mitochondrial dysfunction, as well as Caspase activation. The pro- and antiapoptotic BCL-2 family members represent central regulators in an evolutionarily conserved pathway of cell death. Aberrations in the BCL-2 family result in disordered homeostasis, a pathogenic event in diseases, including cancer. C1 Washington Univ, Sch Med, Howard Hughes Med Inst, Div Mol Oncol, St Louis, MO 63110 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Harvard Med Sch, Smith 758,1 Jimmy Fund Way, Boston, MA 02115 USA. NR 73 TC 344 Z9 370 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1999 VL 59 IS 7 SU S BP 1693S EP 1700S PG 8 WC Oncology SC Oncology GA 183YH UT WOS:000079582000006 PM 10197582 ER PT J AU Chen, JJ Silver, D Cantor, S Livingston, DM Scully, R AF Chen, JJ Silver, D Cantor, S Livingston, DM Scully, R TI BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT General-Motors-Cancer-Research-Foundation 20th Annual Scientific Conference - Developmental Biology and Cancer CY JUN 09-10, 1998 CL BETHESDA, MARYLAND SP Gen Motors Canc Res Fdn ID CANCER SUSCEPTIBILITY GENE; EMBRYONIC CELLULAR PROLIFERATION; OVARIAN-CANCER; TRANSCRIPTIONAL ACTIVATION; STRAND EXCHANGE; MEIOTIC CELLS; BREAST-CANCER; PROTEIN; REPAIR; MOUSE AB The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian canter and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51, We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex, The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells. Thus, BRCA1 and BRCA2 participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function in postreplicational repair processes activated during the DNA synthesis stage of the cell cycle. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013 NR 33 TC 69 Z9 73 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1999 VL 59 IS 7 SU S BP 1752S EP 1756S PG 5 WC Oncology SC Oncology GA 183YH UT WOS:000079582000024 PM 10197592 ER PT J AU Oesterle, SN Hayase, M Schuler, G Migyel, CM Cumberland, D Katoh, O Reifart, N AF Oesterle, SN Hayase, M Schuler, G Migyel, CM Cumberland, D Katoh, O Reifart, N TI A novel stent delivery catheter: The Intella Trinity balloon SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; stents; coronary artery disease ID CORONARY-ARTERY DISEASE; ANGIOPLASTY AB The Trinity catheter is a novel multiballoon device designed to facilitate stent delivery by providing for predilatation, stent deployment, and further expansion on a single shaft. The device was tested extensively in a canine model with a variety of stents before being used in a limited human feasibility trial in Europe. A description of the device and its initial human application is presented. Cathet Cardiovasc. Intervent 46:498-502, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Leipzig, Herzzentrum, D-7010 Leipzig, Germany. Univ Madrid, San Carlos Hosp, Madrid 3, Spain. No Gen Hosp, Sheffield S5 7AU, S Yorkshire, England. Katsura Med Ctr, Kyoto, Japan. Kardiol Inst, Taunus, Germany. RP Oesterle, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. EM oesterle.stephen@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR PY 1999 VL 46 IS 4 BP 498 EP 502 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 181VN UT WOS:000079463400024 PM 10216024 ER PT J AU Emerman, CL Woodruff, PG Cydulka, RK Gibbs, MA Pollack, CV Camargo, CA AF Emerman, CL Woodruff, PG Cydulka, RK Gibbs, MA Pollack, CV Camargo, CA CA MARC Investigators TI Prospective multicenter study of relapse following treatment for acute asthma among adults presenting to the emergency department SO CHEST LA English DT Article DE asthma; emergency medicine; follow-up studies; peak expiratory flow rate; relapse ID ACUTE BRONCHIAL-ASTHMA; PEAK EXPIRATORY FLOW; CONTROLLED TRIAL; ROOM TREATMENT; MANAGEMENT; PREDNISONE; OUTCOMES; METHYLPREDNISOLONE; HOSPITALIZATION; EXACERBATIONS AB Study objective: To identify factors associated with relapse following treatment for acute asthma among adults presenting to the emergency department(ED). Design: Prospective inception cohort study performed during October 1996 to December 1996 and April 1997 to June 1997, as part of the Multicenter Asthma Research Collaboration. Setting: Thirty-six EDs in 18 states. Patients: ED patients, aged 18 to 54 years, with physician diagnosis of acute asthma. For the present analysis, we restricted the cohort to patients sent home from the ED (n = 971), then further excluded patients with comorbid respiratory conditions (n 32). This left 939 eligible subjects to have follow-up data. Interventions: None. Measurements and results: Two weeks after being sent home from the ED, patients were contacted by telephone. A relapse was defined as an urgent or unscheduled visit to any physician for worsening asthma symptoms during the 14-day follow-up period. Complete follow-up data were available for 641 patients, of whom 17% reported relapse (95% confidence interval, 14 to 20). There was no significant difference in peak expiratory flow rate (PEFR) between patients who suffered relapse and those who did not. In a multivariate logistic regression analysis (controlling for age, gender, race, and primary care provider status), patients who suffered relapse were more Likely to have a history of numerous ED (odds ratio [OD] 1.3 per 5 visits) and urgent clinic visits (OR 1.4 per 5 visits) for asthma in the past year, use a home nebulizer (OR 2.2), report multiple triggers of their asthma (OR 1.1 per trigger), and report a longer duration of symptoms (OR 2.5 for 1 to 7 days). Conclusion: Among patients sent home from the ED following acute asthma therapy, 17% will have a relapse and PEFR does not predict who will develop this outcome. By contrast, several historical features were associated with increased risk. Further research should focus on ways to decrease the relapse rate among these high-risk patients. The clinician may wish to consider these historical factors when making ED decisions. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Emerman, CL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03533, HL-07427] NR 43 TC 81 Z9 82 U1 0 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 1999 VL 115 IS 4 BP 919 EP 927 DI 10.1378/chest.115.4.919 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 185EV UT WOS:000079655900008 PM 10208187 ER PT J AU Schwartz, DR Maroo, A Malhotra, A Kesselman, H AF Schwartz, DR Maroo, A Malhotra, A Kesselman, H TI Negative pressure pulmonary hemorrhage SO CHEST LA English DT Article DE negative pressure pulmonary edema; pulmonary hemorrhage; stress failure ID UPPER AIRWAY-OBSTRUCTION; STRESS FAILURE; HEART-DISEASE; SLEEP-APNEA; EDEMA; CAPILLARIES; RABBITS; INJURY; ADULTS AB Negative pressure pulmonary edema, a well-recognized phenomenon, is the formation of pulmonary edema following an acute upper airway obstruction (UAO), To our knowledge, diffuse alveolar hemorrhage, has not been reported previously as a complication of an UAO. We describe a case of negative pressure pulmonary hemorrhage, and we propose that its etiology is stress failure, the mechanical disruption of the alveolar-capillary membrane. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Schwartz, DR (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. OI schwartz, david/0000-0002-5058-5575 NR 25 TC 45 Z9 52 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 1999 VL 115 IS 4 BP 1194 EP 1197 DI 10.1378/chest.115.4.1194 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 185EV UT WOS:000079655900050 PM 10208229 ER PT J AU Rowinsky, EK Jiroutek, M Bonomi, P Johnson, D Baker, SD AF Rowinsky, EK Jiroutek, M Bonomi, P Johnson, D Baker, SD TI Paclitaxel steady-state plasma concentration as a determinant of disease outcome and toxicity in lung cancer patients treated with paclitaxel and cisplatin SO CLINICAL CANCER RESEARCH LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; OVARIAN-CANCER; CELL-LINES; PHASE-I; TAXOL; PHARMACOKINETICS; METABOLISM; PHARMACODYNAMICS; DISPOSITION; LEUKEMIA AB The principal purpose of this study was to evaluate relationships between paclitaxel plasma steady-state concentration (C-ss) and both disease outcome and toxicity in patients with non-small cell lung cancer (NSCLC) treated with paclitaxel and cisplatin in an Eastern Cooperative Oncology Group (ECOG) Phase III study E5592. Chemotherapy-naive patients with stage IIIb and IV NSCLC were randomized to treatment with either 75 mg/m(2) cisplatin i.v. on day 1 and 100 mg/m(2) etopside i.v. on days 1-3 (EC arm) or 75 mg/m(2) cisplatin i.v. combined with either a low dose of paclitaxel (135 mg/m(2), 24-h i.v. infusion; PC arm) or a higher dose of paclitaxel (250 mg/m(2) i.v., 24-h i.v. infusion) with granulocyte colony-stimulating factor (PCG arm). End-of-24-h-infusion paclitaxel concentrations, which have been demonstrated to be nearly equal to C(ss)s on this schedule, were obtained during the first and second courses in patients on the PC and PCG arms. Relationships between the average paclitaxel C-ss (C-ss,(avg)) and the best response to treatment, time to treatment failure (TTF), survival, and worst grade of leukopenia and neurotoxicity were evaluated by univariate analysis. A multivariate model was used to assess the influence of paclitaxel C-ss in conjunction with other potentially relevant patient variables that may affect disease outcome, including the paclitaxel treatment arm, age, sex, performance status, weight loss during the previous 6 months, and disease stage. Paclitaxel C-ss in both courses 1 and 2 were obtained in 71 patients treated with PC and 75 patients treated with PCG. Although C-ss,(avg)s in patients treated with PC and PCG were significantly different (median, 0.32 versus 0.81 mu mol/liter; P < 0.0001), response rates were not (33.8 versus 26.7%; P = 0.3719). In addition, there were no differences between the PC and PCG arms in TTF (median, 5.1 versus 5.5 months, P = 0.6201) or survival (median, 11.6 versus 11.3 months, P = 0.7173). Combined analysis of paclitaxel concentrations from both treatment arms revealed no significant difference in paclitaxel C-ss,(avg) between responders and nonresponders [median, 0.40 (range, 0.16-1.6) mu mol/liter versus 0.55 (range, 0.11-3.6)], and C-ss,(avg)s were similar in patients segregated according to whether they had a complete response, partial response, stable disease, or progressive disease as their best response to treatment (P = 0.7612). In addition, the relationship between C-ss,(avg) and TTF was weak (r(2) = 0.00003, P = 0.94), as was the relationship between C-ss,(avg) and survival (P = 0.1267). With regard to the principal toxicities, neither the propensity to develop neuromuscular and neurosensory toxicity nos the worst grade of these adverse effects were related to C-ss,(avg) (P = 0.5000 and 0.2033, respectively); however, the relationship between C-ss,(avg) and the worst grade of leukopenia experienced was marginally significant (P = 0.0796). In a multivariate model, neither the combined effect of relevant demographic and stratification variables nor paclitaxel C-ss,(avg) predicted for either response (P = 0.1544) or TTF (P = 0.2574), whereas the combined effect of all covariates predicted for survival (P = 0.0249). With regard to individual covariates, a lower disease stage (stage IIIb) was the only significant positive determinant of response (P = 0.0195), and a lower ECOG performance status (= 0) was the only significant positive determinant of survival (P = 0.0121) in the multivariate model. In summary, paclitaxel C-ss,(avg) was not a determinant of response, TTF, or survival in patients with advanced NSCLC treated with paclitaxel as a 24-h i.v. infusion combined with cisplatin. On the basis of both the clinical and pharmacodynamic results of E5592, there is no compelling reason to treat patients with advanced NSCLC with paclitaxel on a 24-h i.v. schedule at doses of >135 mg/m(2) in combination with cisplatin, although higher doses are associated with higher paclitaxel C(ss)s. C1 Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. RP Rowinsky, EK (reprint author), Canc Therapy & Res Ctr S Texas, Inst Drug Dev, 8122 Datapoint Dr,Suite 700, San Antonio, TX 78229 USA. EM erowinsk@saci.org FU NCI NIH HHS [CA23318, CA49957, CA25988] NR 41 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1999 VL 5 IS 4 BP 767 EP 774 PG 8 WC Oncology SC Oncology GA 185QD UT WOS:000079680300008 PM 10213211 ER PT J AU Vollmer, RT Kantoff, PW Dawson, NA Vogelzang, NJ AF Vollmer, RT Kantoff, PW Dawson, NA Vogelzang, NJ TI A prognostic score for hormone-refractory prostate cancer: Analysis of two Cancer and Leukemia Group B studies SO CLINICAL CANCER RESEARCH LA English DT Article ID CLINICAL-TRIALS; END-POINT; ANTIGEN; MARKER; CHEMOTHERAPY; THERAPY AB Previously, we have shown that serial measurements of prostate-specific antigen (PSA) in hormone-refractory prostate cancer (HRPC) can be used to calculate an average relative velocity (rva) of PSA, Together, the level of PSA and the rva formed a two-variable model for survival time that worked at any time during the course of HRPC, Here, we have added serial measurements of hemoglobin and weight to test whether they improve the prior model based on PSA alone. Data from two Cancer and Leukemia Group B studies (9181 and 9182) on HRPC were combined to study the relationship between survival and serial measurements of PSA, serum hemoglobin, and patient weight. Altogether, there were 348 patients who could be evaluated. We used the Cox proportional hazard model for survival time with the interval censored method to accommodate time-dependent covariates, and tests for significance were two sided. Log (PSA), rva, log (hemoglobin), and log [weight (in kg)] were all significantly related to survival time during the course of HRPC (P < 3.0 x 10(-5)). Together, they formed a prognostic score based upon the relative hazard. Higher values of this score implied higher probability of death as the next observed event. Serial measurements of PSA, hemoglobin, and weight provide a prognostic score that can be applied continuously during the course of HRPC, Changes in the score may provide a reproducible measure of treatment effect. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27705 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, Boston, MA 02115 USA. Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Vollmer, RT (reprint author), Vet Affairs Med Ctr, Durham, NC 27705 USA. FU NCI NIH HHS [CA47577, CA26806, CA41287] NR 27 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1999 VL 5 IS 4 BP 831 EP 837 PG 7 WC Oncology SC Oncology GA 185QD UT WOS:000079680300016 PM 10213219 ER PT J AU Rosenthal, DI Hornicek, FJ Wolfe, MW Jennings, LC Gebhardt, MC Mankin, HJ AF Rosenthal, DI Hornicek, FJ Wolfe, MW Jennings, LC Gebhardt, MC Mankin, HJ TI Decreasing length of hospital stay in treatment of osteoid osteoma SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PREOPERATIVE LOCALIZATION; CT GUIDANCE; EXCISION; RESECTION; ABLATION; REMOVAL; LESIONS; TALUS; BONE AB Ninety-eight operative procedures were performed for treatment of osteoid osteoma since 1978 at the authors' institution. During these years there was a progressive decrease in the length of hospital stay, decreasing from a mean of 6.8 days between 1978 and 1980 to 2.6 days between 1994 and 1996. Factors that influenced the length of stay after a surgical procedure include patient age, lesion location, choice of procedure, and surgeon. However, the decline in length of stay with time is independent of these factors, and antedates the era of managed care. Increased reliance on more conservative surgical procedures has markedly diminished the length of hospital stay required in the care of these patients. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA 02115 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,White 239, Boston, MA 02114 USA. NR 35 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 1999 IS 361 BP 186 EP 191 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 184KJ UT WOS:000079611100024 PM 10212612 ER PT J AU Lipsky, BA Miller, B Schwartz, R Henry, DC Nolan, T McCabe, A Magner, DJ Talbot, GH AF Lipsky, BA Miller, B Schwartz, R Henry, DC Nolan, T McCabe, A Magner, DJ Talbot, GH TI Sparfloxacin versus ciprofloxacin for the treatment of community-acquired, complicated skin and skin-structure infections SO CLINICAL THERAPEUTICS LA English DT Article ID THERAPY; PENETRATION; PATHOGENS; TISSUES AB Fluoroquinolones have been shown to be effective in the treatment of complicated skin and skin-structure infections, in part because of their broad-spectrum antibacterial activity against causative pathogens that are resistant to older antimicrobial agents. We enrolled 603 adult patients (>58% male, >85% white) in a double-masked, double-dummy, randomized, multicenter trial to compare the efficacy and tolerability of sparfloxacin (400-mg loading dose followed by 200 mg once daily) with those of ciprofloxacin (750 mg twice daily) for 10 days in the treatment of community-acquired, complicated skin and skin-structure infections. The primary efficacy variable was clinical response, based on assessment of signs and symptoms, in the clinically assessable population. Patients in the sparfloxacin and ciprofloxacin groups were comparable with respect to demographic characteristics, underlying diseases, medical history, and laboratory test results. Wound infection was the most common diagnosis, and Staphylococcus aureus was the most frequently isolated pathogen. For the 475 clinically assessable patients, the clinical success rate (percentage of patients cured or improved) was 90.1% (210/233) with sparfloxacin and 87.2% (211/242) with ciprofloxacin. In this analysis (95% confidence interval [CI], -2.8 to 8.6) and the intent-to-treat analyses (95% CI, -4.2 to 6.2), results with spar floxacin were statistically equivalent to those with ciprofloxacin (95% CI, -1 to 15.3). For bacteriologically assessable patients, eradication rates were 87.0% (141/162) with sparfloxacin and 79.9% (123/154) with ciprofloxacin (95% CI, -1 to 15.3). Eradication rates of S aureus and coagulase-negative staphylococcal infections were 90.2% (101/112) with sparfloxacin and 77.9% (88/113) with ciprofloxacin. For patients with 2 or more pathogens at baseline (mixed infections), bacteriologic success was 87.6% for sparfloxacin and 77.9% for ciprofloxacin. Pseudomonas aeruginosa infections were eradicated or presumed eradicated in 71.4% (10/14) of sparfloxacin-treated patients and 87.5% (7/8) of ciprofloxacin-treated patients. Overall success rates in the bacteriologically assessable patients for sparfloxacin (84.6% [137/162]) and ciprofloxacin (78.6% [121/154]) were statistically equivalent (95% CI, -2.5 to 14.5). Tolerability was assessed in all patients who received study medication. The overall frequency of treatment-related adverse events was comparable in the 2 treatment groups (26.5% sparfloxacin, 23.3% ciprofloxacin). Drug-related adverse events involving the digestive system occurred in 7.1% of sparfloxacin-treated patients and 19.0% of ciprofloxacin-treated patients; photosensitivity reactions were reported in 11.1% of patients in the sparfloxacin group and 0.7% of patients in the ciprofloxacin group (P < 0.001). The mean change in QT,interval from baseline to the maximum on-treatment value was greater in the sparfloxacin group (9 milliseconds) than in the ciprofloxacin group (3 milliseconds) (P = 0.005; 95% CI, 0.002 to 0.010). The efficacy of sparfloxacin was comparable to that of ciprofloxacin in the treatment of community-acquired, complicated skin and skin-structure infections, including those caused by staphylococci, the most common pathogens. Sparfloxacin's once-daily regimen, high skin-tissue penetration, and improved activity against gram-positive cocci make it a therapeutic alternative to ciprofloxacin for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QT(c) interval. C1 VA Puget Sound Hlth Care Syst, Gen Internal Med Clin 111M, Seattle, WA 98108 USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Gen Internal Med Clin 111M, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 24 TC 19 Z9 19 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD APR PY 1999 VL 21 IS 4 BP 675 EP 690 DI 10.1016/S0149-2918(00)88319-8 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 197YB UT WOS:000080393000006 PM 10363733 ER PT J AU Watkins, KE Shaner, A Sullivan, G AF Watkins, KE Shaner, A Sullivan, G TI The role of gender in engaging the dually diagnosed in treatment SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article ID MENTAL-DISORDERS; SEX-DIFFERENCES; SCHIZOPHRENIA; ADDICTION; ILLNESS; ALCOHOL; WOMEN; ABUSE AB Individuals with both a serious mental illness and substance abuse are particularly difficult to engage in treatment. Given known gender differences in both substance abuse and schizophrenia, we examined the impact of gender on treatment engagement. Qualitative interviews with ten males and eleven females focused on how the client perceived the engagement process, and what obstacles they faced. While both males and females are difficult to engage, the interviews suggest that they experience the process differently and that they face different obstacles. We discuss the implication for service providers, C1 Univ Calif Los Angeles, Robert Wood Johnson Clin Sch Program, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, W Los Angeles, CA USA. Ctr Mental Healthcare Res Freeway Med Tower, Little Rock, AR USA. RP Watkins, KE (reprint author), Rand Corp, 1700 Main St, Santa Monica, CA 90407 USA. FU NIMH NIH HHS [MH30911] NR 24 TC 19 Z9 19 U1 2 U2 3 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD APR PY 1999 VL 35 IS 2 BP 115 EP 126 DI 10.1023/A:1018716629998 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 181VA UT WOS:000079462100002 PM 10412621 ER PT J AU Rosowsky, A AF Rosowsky, A TI PT523 and other aminopterin analogs with a hemiphthaloyl-L-ornithine side chain: Exceptionally tight-binding inhibitors of dihydrofolate reductase which are transported by the reduced folate carrier but cannot form polyglutamates SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID METHOTREXATE ANALOGS; BIOLOGICAL-ACTIVITY; HUMAN HEAD; IN-VITRO; ANTIFOLATE; CELLS AB Nonpolyglutamatable antifolates are potentially of therapeutic interest for the treatment of tumors that are inherently refractory, or have become resistant, to classical antifolates as a result of decreased expression of the enzyme folylpolyglutamate synthetase. An interesting class of water-soluble nonpolyglutamatable analogs of aminopterin (AMT) have been developed, which are much more cytotoxic because they bind more tightly to dihydrofolate reductase (DHFR) and also utilize the reduced folate carrier (RFC) pathway more efficiently for influx into the cell. This review summarizes the in vitro and in vivo preclinical data on the initial lead compound, N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523). In addition, the synthesis and in vitro biochemical and biological properties of several types of second-generation analogs are discussed. Analogs modified in the B-ring of the pteridine moiety have been found to be of particular interest because their affinity for DHFR and their influx rate into cells via the RFC pathway are even greater than those of PT523. The hemiphthaloylornithine moiety, which is larger and more hydrophobic than the glutamate side chain of classical antifolates, appears to be chiefly responsible for the exceptionally high biological potency of PT523 and its B-ring analogs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA70349, CA25394] NR 21 TC 22 Z9 22 U1 0 U2 0 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD APR PY 1999 VL 6 IS 4 BP 329 EP 352 PG 24 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 195LT UT WOS:000080252900004 PM 10101216 ER PT J AU Hood, JK Silver, PA AF Hood, JK Silver, PA TI In or out? Regulating nuclear transport SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID KAPPA-B-ALPHA; CYCLIN-CDK COMPLEX; EXPORT FACTOR CRM1; PROTEIN IMPORT; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; PORE COMPLEX; DNA-DAMAGE; PHOSPHORYLATION AB The compartmentalization of proteins within the nucleus or cytoplasm of a eukaryotic cell offers opportunity for regulation of cell cycle progression and signalling pathways. Nuclear localization of proteins is determined by their ability to interact with specific nuclear import and export factors. In the past year, substrate phosphorylation has emerged as a common mechanism for controlling this interaction. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hood, JK (reprint author), Harvard Univ, Sch Med, Smith 922,44 Binney St, Boston, MA 02115 USA. EM jhood@student.med.harvard.edu; pamela_silver@dfci.harvard.edu NR 47 TC 114 Z9 116 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 1999 VL 11 IS 2 BP 241 EP 247 DI 10.1016/S0955-0674(99)80032-5 PG 7 WC Cell Biology SC Cell Biology GA 184CL UT WOS:000079591700011 PM 10209150 ER PT J AU Cortes, M Wong, E Koipally, J Georgopoulos, K AF Cortes, M Wong, E Koipally, J Georgopoulos, K TI Control of lymphocyte development by the Ikaros gene family SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID TRANSCRIPTION FACTOR; CENTROMERIC HETEROCHROMATIN; SIGNAL-TRANSDUCTION; HISTONE ACETYLATION; CHROMATIN; MUTATION; COMPLEX; HELIOS; AIOLOS AB Lymphoid cell differentiation relies on precisely orchestrated gene activation and repression events. Gene targeting studies have demonstrated crucial roles for the transcription factors Ikaros and Aiolos in regulating multiple stages of B and T cell development. Recent experiments suggest that Ikaros and Aiolos set B cell antigen-receptor (BCR)- and TCR-mediated signal ng thresholds and that the molecules exist within T cells in nuclear complexes that contain nucleosome remodeling and histone deacetylase activities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Cortes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. NR 23 TC 101 Z9 102 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 1999 VL 11 IS 2 BP 167 EP 171 DI 10.1016/S0952-7915(99)80028-4 PG 5 WC Immunology SC Immunology GA 183ZL UT WOS:000079584800007 PM 10322160 ER PT J AU Hobert, O Tessmar, K Ruvkun, G AF Hobert, O Tessmar, K Ruvkun, G TI The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons SO DEVELOPMENT LA English DT Article DE LIM homeobox; Caenorhabditis elegans; axogenesis; GABA; uterus ID SECRETORY-EXCRETORY SYSTEM; NUCLEOTIDE-GATED CHANNEL; NAIL-PATELLA SYNDROME; LMX1B MUTANT MICE; C-ELEGANS; NERVOUS-SYSTEM; MOTOR-NEURONS; DEVELOPMENTAL CONTROL; HOMEODOMAIN PROTEIN; ACTIVITY BLOCKADE AB We describe here the functional analysis of the C, elegans LIM homeobox gene lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, CNS, kidney and eye development. lim-6 is expressed in a small number of sensory-, inter- and motorneurons, in epithelial cells of the uterus and in the excretory system. Loss of lim-6 function affects late events in the differentiation of two classes of GABAergic motorneurons which control rhythmic enteric muscle contraction. lim-6 is required to specify the correct axon morphology of these neurons and also regulates expression of glutamic acid decarboxylase, the rate limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrine outputs of the nervous system, In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is also required in epithelial cells for uterine morphogenesis. We compare the function of lim-6 to those of other LIM homeobox genes in C, elegans and suggest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroanatomical and neural function defects. C1 Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol, Boston, MA 02114 USA. RI Tessmar-Raible, Kristin/F-9642-2011 NR 74 TC 81 Z9 110 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 1999 VL 126 IS 7 BP 1547 EP 1562 PG 16 WC Developmental Biology SC Developmental Biology GA 188LJ UT WOS:000079848200019 PM 10068647 ER PT J AU Giorgino, F Logoluso, F Davalli, AM Napoli, R Laviola, L Hirshman, MF Horton, ES Weir, GC Smith, RJ AF Giorgino, F Logoluso, F Davalli, AM Napoli, R Laviola, L Hirshman, MF Horton, ES Weir, GC Smith, RJ TI Islet transplantation restores normal levels of insulin receptor and substrate tyrosine phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle and myocardium of streptozocin-induced diabetic rats SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; GLUCOSE-TRANSPORT ACTIVITY; GLYCOGEN-SYNTHASE ACTIVITY; C-FOS EXPRESSION; 3T3-L1 ADIPOCYTES; PHOSPHOTYROSINE PROTEIN; SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; ANIMAL-MODELS; KINASE AB Insulin-dependent diabetes in rats is characterized by abnormalities of post-binding insulin signaling reactions that are not fully corrected by exogenous insulin therapy. The aim of this study was to investigate the effects of islet transplantation on insulin signaling in skeletal muscle and myocardium of streptozocin (STZ)-induced diabetic rats. Control rats, untreated diabetic rats, and diabetic rats transplanted with syngeneic islets under the kidney capsule were studied. Compared with controls, diabetic rats were characterized by multiple insulin signaling abnormalities in skeletal muscle, which included 1) increased insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrates IRS-1 and IRS-2, 2) increased substrate tyrosine phosphorylation in the basal state, 3) a decreased amount of IRS-1 protein, 4) markedly elevated basal and insulin-stimulated phosphatidylinositol (PI) 3-kinase activity in anti-IRS-l immunoprecipitates from total tissue extracts, and 5) increased PI 3-kinase activity in low-density microsomes, A similar augmentation of insulin receptor and substrate tyrosine phosphorylation in response to STZ-diabetes was also found in myocardium, although with lower magnitude than that found in skeletal muscle, In addition, STZ-diabetes resulted in decreased IRS-1 and increased IRS-2 protein levels in myocardium. Islet transplantation fully corrected the diabetes-induced changes in protein tyrosine phosphorylation and PI 3-kinase activity and normalized IRS-1 and IRS-2 protein content in both skeletal muscle and myocardium, Thus, insulin delivered into the systemic circulation by pancreatic islets transplanted under the kidney capsule can adequately correct altered insulin signaling mechanisms in insulinopenic diabetes. C1 Univ Bari, Sch Med, Ist Clin Med, I-70124 Bari, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Univ Bari, Sch Med, Ist Clin Med, Piazza Giulio Cesare 11, I-70124 Bari, Italy. EM giorginf@tin.it RI Giorgino, Francesco/K-7262-2016; OI Giorgino, Francesco/0000-0001-7372-2678; NAPOLI, Raffaele/0000-0002-3366-2321; Laviola, Luigi/0000-0001-8860-5845 FU NIDDK NIH HHS [DK-36836, DK-35449, DK-50657] NR 67 TC 20 Z9 20 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 1999 VL 48 IS 4 BP 801 EP 812 DI 10.2337/diabetes.48.4.801 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180UG UT WOS:000079403100017 PM 10102697 ER PT J AU Baskin, DG Breininger, JF Schwartz, MW AF Baskin, DG Breininger, JF Schwartz, MW TI Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus SO DIABETES LA English DT Article ID PROOPIOMELANOCORTIN MESSENGER-RNA; OBESE GENE-PRODUCT; BODY-WEIGHT; OB/OB MICE; RIBONUCLEIC-ACID; ZUCKER RATS; OB PROTEIN; MOUSE; EXPRESSION; BRAIN AB The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus, To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor (Ob-Rb), Thus, mRNAs encoding NPY and pro-opiomelanocortin (POMC) were colocalized in the arcuate nucleus of fed and fasted rats by fluorescence in situ hybridization in combination,vith isotopic in situ hybridization for Ob-Rb mRNA, In fed animals, 47% of arcuate nucleus neurons containing NPY mRNA also contained Ob-Rb mRNA, compared with 79% of POMC neurons (P < 0.01), After a 2-day fast, the number of arcuate nucleus neurons with NPY mRNA increased 50% (P < 0.05); the number of these that coexpressed Ob-Rb increased twofold (P = 0.013), Furthermore, Ob-Rb mRNA hybridization in individual NPY neurons increased by 64% (P < 0.02), In contrast, the number of POMC neurons that coexpressed Ob-Rb was unchanged. A significant interpretation of these findings is that the NPY neurons that do not express detectable levels of Ob-Rb mRNA are not activated by fasting, whereas the NPY neurons that are activated by fasting are the ones that express Ob-Rb, These data demonstrate a significant physiological difference between NPY neurons that express Ob-Rb and those that do not. The results support the conclusion that the effect of food intake on NPY neurons is mediated by the direct action of leptin via Ob-Rb receptors expressed by these NPY cells. The results also indicate that expression of Ob-Rb is a defining phenotypic characteristic of the subset of arcuate nucleus NPY neurons that are activated by fasting and play a central role in the adaptive response to negative energy balance. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. RP Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Mail Stop 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM baskindg@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-17047, DK-52989]; NINDS NIH HHS [NS32273] NR 42 TC 216 Z9 224 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 1999 VL 48 IS 4 BP 828 EP 833 DI 10.2337/diabetes.48.4.828 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180UG UT WOS:000079403100020 PM 10102700 ER PT J AU Trief, PM Aquilino, C Paradies, K Weinstock, RS AF Trief, PM Aquilino, C Paradies, K Weinstock, RS TI Impact of the work environment on glycemic control and adaptation to diabetes SO DIABETES CARE LA English DT Article ID DEPRESSION; STRESS AB OBJECTIVE - To evaluate quantitatively whether the work environments of adults with diabetes relate to the adequacy of metabolic control and/or to the individual's adaptation to diabetes and to explore qualitatively the interactions between an individual's life at work and ways of coping with diabetes. RESEARCH DESIGN AND METHODS - A total of 129 insulin-requiring adults who were employed outside of the home were assessed on a single occasion. They completed two work system measures (The Work Environment Scale and The Work Apgar Scale) and two quality-of-life measures (The Diabetes Quality of Life Scale and The Appraisal of Diabetes Scale). Subjects also participated in a semi structured interview concerning the interaction of work and diabetes. Glycemic control was assessed by using HbA(1c) results. Demographic data (age, sex, diabetes type, duration of diabetes, number of diabetes-related medical complications) were gathered from the charts. RESULTS - Concerning glycemic control, neither of the work system measures was a significant predictor of HbA(1c). Concerning psychosocial adaptation, supervisor support was found to be a significant predictor of positive appraisal and diabetes-related satisfaction. Involvement and coworker cohesion also predicted aspects of diabetes-related quality of life. Interview themes showed that for a minority (18%), diabetes affected choice of work and that for a majority (60%), diabetes affected relationships at work and raised financial/job concerns (49%). Most adjust their diet, blood glucose testing, and exercise regimen through work-related modifications. CONCLUSIONS - For insulin-treated adults with diabetes, work system variables do not directly relate to glycemic control, bur they do relate to psychosocial adaptation Future work should examine further the specific aspects of the workplace that might affect adaptation, with the goal being to develop worksite interventions that target not only the employee with diabetes bur also their supervisors and coworkers. C1 SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Vet Adm Med Ctr, Syracuse, NY 13210 USA. Joslin Diabet Ctr, Syracuse, NY USA. RP Trief, PM (reprint author), SUNY Hlth Sci Ctr, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM triefp@vax.cs.hscsyr.edu NR 28 TC 18 Z9 21 U1 2 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 1999 VL 22 IS 4 BP 569 EP 574 DI 10.2337/diacare.22.4.569 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179GJ UT WOS:000079317900006 PM 10189533 ER PT J AU Bray, GA Culbert, IW Champagne, CM Dawson, L Eberhardt, B Greenway, FL Guillory, FG Hebert, AA Jeffirs, ML Kennedy, BM Lovejoy, JC Morris, LH Melancon, LE Reed, L Perault, J Ryan, DH Sanford, DA Smith, KG Smith, LL St Amant, JA Tulley, RT Vicknair, PC Williamson, D Zachwieja, JJ Polonsky, KS Matulik, MJ Clarke, B DeSandre, C Ehrmann, DA Hilbrich, RM McNabb, WL Morrone, D Semenske, AR Stepp, KA Tobian, JA Watson, PG Caro, JF Goldstein, BJ Graziani, CM Kunkel, EJ Laine, CA Louis, DZ Smith, KA Spandirfer, J Yuen, EJ Goldberg, RB Rowe, P Calles, J Donahue, RP Florez, HJ Giannella, A O'Hara, P Prineas, R Haffner, SM Montez, MG Miettinen, H Mobley, CM Mykkanen, LA Hamman, RF Nash, PV Calonge, BN Hill, JO Jortberg, BT Regensteiner, JG Reusch, J Schiltz, CM Seagle, H VanDorsten, B Horton, ES Lawton, KE Arky, RA Bryant, M Burke, JP Caballero, E Callaphan, KM Ganda, OP Franklin, T Jackson, SD Jacobsen, AM Kula, LM Kocal, M Malloy, MA Nicosia, M Oldmixon, CF Pan, J Quitingon, M Rubtchinsky, S Seely, EW Schweizer, D Simonson, D Smith, F Solomon, CG Warram, J Kahn, SE Montgomery, BK Berger, M Boyko, EJ Fujimoto, WY Greenbaum, CJ Knopp, RH McCann, BS Lipkin, EW Nguyen, TT Palmer, JP Schwartz, RS Talbot-Lawson, C Wan, D Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Frieson, SL Imseis, R Kennedy, CL Lambeth, HC Lichtermann, LC Oktaei, H O'Toole, ML Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, BJ Metzger, BE Johnson, MK Fitzgibbon, M Heard, D Johnson, CKH McPherson, D Molitch, ME Moore, M Pitts, T Schinleber, PA Nathan, DM McKitrick, C Abbott, K Anderson, E Cagliero, E Cohen, M Crowell, S Delahanty, L Levina, E Michel, T O'Keefe, J Poulos, A Ronan, L Rosal, M Salerno, M Shagensky, C Steiner, B Young, A Olefsky, JM Carrion-Petersen, ML Barrett-Connor, E Beltran, M Caenepeel, K Edelman, SV Ford, RO Garcia, J Henry, RR Hill, M Horne, J Leos, D Mudaliar, S Pollard, A Torio, J Pi-Sunyer, FX Lee, JE Allison, DB Aronoff, NJ Barreras, IM Crandall, JP Foo, ST Orlando, SJ Parkes, K Rooney, ES Van Wye, GEH Viscovich, KA Prince, MJ Kukman, SM Dotson, YF Fineberg, ES Guare, JC Ignaut, JM Jackson, MA Kirkman, MS Marrero, DG Porter, DB Rowland, ND Wheeler, ML Ratner, RE Youssef, G Bronsord, M Cheatham, WW Boggs, G Evans, C Levatan, C Kellum, T Nair, AK Passaro, MD Saad, MF Khan, A Aziz, A Bernaba, B Budgett, MD Cosenza, C Hagar, JE Isagholian, K Jinagouda, SD Kamdar, VV Kumar, D Khawaja, Q Kelada, BL Lui, G Marston, AR Mehta, V Sharma, AR Szamos, K Vargas, A Vargas, B Zambrana, N Dagogo-Jack, S Santiago, AE Brendle, JS Fisher, EB Gherardini, DC Heins, JM Marsala, JM Raspberry, CC Santiago, JV Stephan, CL Saudek, CD Bradley, VL Brancati, FL Cappelli, S Charleston, JB Rubin, RR Stewart, KJ Sullivan, E Schade, DS Adams, KS Atler, LF Bowling, DA Boyle, PJ Burge, MR Canady, JL Chai, L Dorin, RI Facio, E Guillen, M Gutierrez, M Johannes, C Katz, P King, C McCalman, R Rassam, A Senter, W Waters, D Shamoon, H Brown, JO Cox, L Duffy, H Engel, S Friedler, A Howard-Century, CJ Longchamp, N Pompi, D Walker, EA Wylie-Rosett, J Zonszein, J Wing, RR Kramer, MK Barr, S Clifford, L Culyba, R Frazier, M Harris, L Harrier, S Henderson, W Jeffries, S Koenning, G Maholic, K Mullen, M Noel, A Orchard, T Smith, CF Smith, M Viteri, J Wilson, T Williams, KV Zgibor, J Arakaki, RF Latimer, RW Baker-Ladao, NK Beddow, RM Dias, LM Dupont, DA Fukuhara, LL Mau, MK Odom, SK Perry, RU Tokunaga, JS Knowler, WC Hoskin, MA Andre, VL Acton, KJ Antone, S Baptisto, NM Bennett, PH Bird, EC Dacawyma, TS Hanson, RL Jackson, MC Jay, PA Kobus, KM Roumain, J Rowse, DH Roy, RJ Yazzie, M Cooeyate, NJ Chavez, M Broussard, BA Ghahate, JM Hughte, G Ingraham, LE Kaskalla, RS Kessler, D Nashboo, Y Poirier, S Percy, CA Barber, R Benson, MB Duncan, R Glass, M Gohdes, D Grant, W Horse, E Morgan, T Reidy, M Bain, R Bambad, J Brenneman, T Dunegan, C Edelstein, SL Grimes, KL Jones, S Jones, TL Klepac, H Lachin, JM Mucik, P Orlosky, R Rochon, J Stimpson, CE Van Aerden, C Eastman, R Garfield, S Harris, M Andres, R Engelgau, M Narayan, V Williamson, D Herman, W Chandler, WL Marcovina, SM McMillan, T Rautaharju, PM Rautaharju, FSR Mayer-Davis, EJ O'Leary, DH Funk, LRC O'Leary, KA Scherzinger, AL Stamm, ER Gillis, BP Kriska, AM Huffmyer, C Meier, A Venditti, EM Wing, RR Haffner, SM Ratner, RE Olefsky, JM Santiago, JV Saudek, CD Knowler, WC Montez, MG Fujimoto, WY Hamman, RF Nathan, DM AF Bray, GA Culbert, IW Champagne, CM Dawson, L Eberhardt, B Greenway, FL Guillory, FG Hebert, AA Jeffirs, ML Kennedy, BM Lovejoy, JC Morris, LH Melancon, LE Reed, L Perault, J Ryan, DH Sanford, DA Smith, KG Smith, LL St Amant, JA Tulley, RT Vicknair, PC Williamson, D Zachwieja, JJ Polonsky, KS Matulik, MJ Clarke, B DeSandre, C Ehrmann, DA Hilbrich, RM McNabb, WL Morrone, D Semenske, AR Stepp, KA Tobian, JA Watson, PG Caro, JF Goldstein, BJ Graziani, CM Kunkel, EJ Laine, CA Louis, DZ Smith, KA Spandirfer, J Yuen, EJ Goldberg, RB Rowe, P Calles, J Donahue, RP Florez, HJ Giannella, A O'Hara, P Prineas, R Haffner, SM Montez, MG Miettinen, H Mobley, CM Mykkanen, LA Hamman, RF Nash, PV Calonge, BN Hill, JO Jortberg, BT Regensteiner, JG Reusch, J Schiltz, CM Seagle, H VanDorsten, B Horton, ES Lawton, KE Arky, RA Bryant, M Burke, JP Caballero, E Callaphan, KM Ganda, OP Franklin, T Jackson, SD Jacobsen, AM Kula, LM Kocal, M Malloy, MA Nicosia, M Oldmixon, CF Pan, J Quitingon, M Rubtchinsky, S Seely, EW Schweizer, D Simonson, D Smith, F Solomon, CG Warram, J Kahn, SE Montgomery, BK Berger, M Boyko, EJ Fujimoto, WY Greenbaum, CJ Knopp, RH McCann, BS Lipkin, EW Nguyen, TT Palmer, JP Schwartz, RS Talbot-Lawson, C Wan, D Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Frieson, SL Imseis, R Kennedy, CL Lambeth, HC Lichtermann, LC Oktaei, H O'Toole, ML Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, BJ Metzger, BE Johnson, MK Fitzgibbon, M Heard, D Johnson, CKH McPherson, D Molitch, ME Moore, M Pitts, T Schinleber, PA Nathan, DM McKitrick, C Abbott, K Anderson, E Cagliero, E Cohen, M Crowell, S Delahanty, L Levina, E Michel, T O'Keefe, J Poulos, A Ronan, L Rosal, M Salerno, M Shagensky, C Steiner, B Young, A Olefsky, JM Carrion-Petersen, ML Barrett-Connor, E Beltran, M Caenepeel, K Edelman, SV Ford, RO Garcia, J Henry, RR Hill, M Horne, J Leos, D Mudaliar, S Pollard, A Torio, J Pi-Sunyer, FX Lee, JE Allison, DB Aronoff, NJ Barreras, IM Crandall, JP Foo, ST Orlando, SJ Parkes, K Rooney, ES Van Wye, GEH Viscovich, KA Prince, MJ Kukman, SM Dotson, YF Fineberg, ES Guare, JC Ignaut, JM Jackson, MA Kirkman, MS Marrero, DG Porter, DB Rowland, ND Wheeler, ML Ratner, RE Youssef, G Bronsord, M Cheatham, WW Boggs, G Evans, C Levatan, C Kellum, T Nair, AK Passaro, MD Saad, MF Khan, A Aziz, A Bernaba, B Budgett, MD Cosenza, C Hagar, JE Isagholian, K Jinagouda, SD Kamdar, VV Kumar, D Khawaja, Q Kelada, BL Lui, G Marston, AR Mehta, V Sharma, AR Szamos, K Vargas, A Vargas, B Zambrana, N Dagogo-Jack, S Santiago, AE Brendle, JS Fisher, EB Gherardini, DC Heins, JM Marsala, JM Raspberry, CC Santiago, JV Stephan, CL Saudek, CD Bradley, VL Brancati, FL Cappelli, S Charleston, JB Rubin, RR Stewart, KJ Sullivan, E Schade, DS Adams, KS Atler, LF Bowling, DA Boyle, PJ Burge, MR Canady, JL Chai, L Dorin, RI Facio, E Guillen, M Gutierrez, M Johannes, C Katz, P King, C McCalman, R Rassam, A Senter, W Waters, D Shamoon, H Brown, JO Cox, L Duffy, H Engel, S Friedler, A Howard-Century, CJ Longchamp, N Pompi, D Walker, EA Wylie-Rosett, J Zonszein, J Wing, RR Kramer, MK Barr, S Clifford, L Culyba, R Frazier, M Harris, L Harrier, S Henderson, W Jeffries, S Koenning, G Maholic, K Mullen, M Noel, A Orchard, T Smith, CF Smith, M Viteri, J Wilson, T Williams, KV Zgibor, J Arakaki, RF Latimer, RW Baker-Ladao, NK Beddow, RM Dias, LM Dupont, DA Fukuhara, LL Mau, MK Odom, SK Perry, RU Tokunaga, JS Knowler, WC Hoskin, MA Andre, VL Acton, KJ Antone, S Baptisto, NM Bennett, PH Bird, EC Dacawyma, TS Hanson, RL Jackson, MC Jay, PA Kobus, KM Roumain, J Rowse, DH Roy, RJ Yazzie, M Cooeyate, NJ Chavez, M Broussard, BA Ghahate, JM Hughte, G Ingraham, LE Kaskalla, RS Kessler, D Nashboo, Y Poirier, S Percy, CA Barber, R Benson, MB Duncan, R Glass, M Gohdes, D Grant, W Horse, E Morgan, T Reidy, M Bain, R Bambad, J Brenneman, T Dunegan, C Edelstein, SL Grimes, KL Jones, S Jones, TL Klepac, H Lachin, JM Mucik, P Orlosky, R Rochon, J Stimpson, CE Van Aerden, C Eastman, R Garfield, S Harris, M Andres, R Engelgau, M Narayan, V Williamson, D Herman, W Chandler, WL Marcovina, SM McMillan, T Rautaharju, PM Rautaharju, FSR Mayer-Davis, EJ O'Leary, DH Funk, LRC O'Leary, KA Scherzinger, AL Stamm, ER Gillis, BP Kriska, AM Huffmyer, C Meier, A Venditti, EM Wing, RR Haffner, SM Ratner, RE Olefsky, JM Santiago, JV Saudek, CD Knowler, WC Montez, MG Fujimoto, WY Hamman, RF Nathan, DM CA Diabet Prevention Program Res Grp TI The Diabetes Prevention Program - Design and methods for a clinical trial in the prevention of type 2 diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; POLYCYSTIC-OVARY-SYNDROME; INSULIN-RESISTANCE; BLOOD-PRESSURE; METABOLIC ABNORMALITIES; PHYSICAL-ACTIVITY; LONGITUDINAL DATA; PIMA-INDIANS; METFORMIN; MELLITUS AB The Diabetes Prevention Program is a randomized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk individuals with elevated fasting plasma glucose concentrations and impaired glucose tolerance. The 27 clinical centers in the U.S. are recruiting at least 3,000 participants of both sexes, similar to 50% of whom are minority patients and 20% of whom are greater than or equal to 65 years old, to be assigned at random to one of three intervention groups. an intensive lifestyle intervention focusing on a healthy diet and exercise and two masked medication treatment groups-metformin or placebo-combined with standard diet and exercise recommendations. Participants are being recruited during a 2 2/3-year period, and all will be followed for an additional 3 1/3 to 5 years after the close of recruitment to a common closing dare in 2002. The primary outcome is the development of diabetes, diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria. The 3,000 participants will provide 90% power to detect a 33% reduction in an expected diabetes incidence rate of at least 6.5% per year in the placebo group. Secondary outcomes include cardiovascular disease and its risk factors; changes in glycemia, beta-cell function, insulin sensitivity obesity diet, physical activity and health-related quality; of life: and occurrence of adverse events. A fourth treatment group troglitazone combined with standard diet and exercise recommendations-was included initially but discontinued because of the liver toxicity of the drug. This randomized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in individuals at high risk. C1 Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Chicago, Chicago, IL 60637 USA. Jefferson Med Coll, Philadelphia, PA USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Colorado, Hlth Sci Ctr, Computed Tomog Scan Reading Unit, Boulder, CO 80309 USA. Joslin Diabet Ctr, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. Univ Tennessee, Knoxville, TN 37996 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. St Lukes Roosevelt Hosp, New York, NY USA. Indiana Univ, Bloomington, IN 47405 USA. Medlantic Res Inst, Washington, DC USA. Univ So Calif, UCLA Sch Med, Los Angeles, CA 90089 USA. Washington Univ, St Louis, MO USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Albert Einstein Coll Med, Bronx, NY USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Hawaii, Honolulu, HI 96822 USA. NIDDKD, Program Off, Bethesda, MD USA. NIA, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Bowman Gray Sch Med, Epicare Ctr, Winston Salem, NC USA. Univ S Carolina, Nutr Coding Ctr, Columbia, SC 29208 USA. New England Med Ctr, Cent Carotid Ultrasound Unit, Boston, MA USA. RP Bray, GA (reprint author), George Washington Univ, Ctr Biostat, DPP Coordinating Ctr, 6110 Execut Blvd 750, Rockville, MD 20852 USA. OI Shamoon, Harry/0000-0002-5014-5211; Kahn, Steven/0000-0001-7307-9002 NR 67 TC 343 Z9 345 U1 3 U2 31 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1999 VL 22 IS 4 BP 623 EP 634 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179GJ UT WOS:000079317900016 ER PT J AU King, GL Wakasaki, H AF King, GL Wakasaki, H TI Theoretical mechanisms by which hyperglycemia and insulin resistance could cause cardiovascular diseases in diabetes SO DIABETES CARE LA English DT Article; Proceedings Paper CT Conference on Therapeutic Approaches to Type 2 Diabetes CY DEC 10-12, 1997 CL SCOTTSDALE, ARIZONA SP Indiana Univ, Diabet Res & Training Ctr, Eli Lilly & Co ID PROTEIN-KINASE-C; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-BETA; D-ALPHA-TOCOPHEROL; GENE-EXPRESSION; ACTIVATION; RATS; MELLITUS; GLUCOSE; PATHOGENESIS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP King, GL (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY05110, EY09178-05]; NIDDK NIH HHS [DK53105-01] NR 41 TC 48 Z9 53 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1999 VL 22 SU 3 BP C31 EP C37 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179YY UT WOS:000079359000008 PM 10189560 ER PT J AU Saini, S Sharma, R AF Saini, S Sharma, R TI Role of X-ray imaging in the development of drugs SO DRUG INFORMATION JOURNAL LA English DT Article DE plain film radiography; computed tomography; drug development ID CT AB X-ray imaging plays a crucial role in the diagnosis of pathology of virtually every organ system of the human body. It has provided a crucial insight into the pathogenesis and patho-physiology of many diseases. Radiological modalities have been used as a measure of drug efficacy and an objective means of comparing various drug regimens. This article describes the current role of X-ray imaging in the development of drugs and outlines the possibilities in the future. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1999 VL 33 IS 2 BP 635 EP 640 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 204GP UT WOS:000080756000033 ER PT J AU Lipton, A Berenson, JR AF Lipton, A Berenson, JR TI Bisphosphonate treatment of lytic bone metastases SO DRUGS & AGING LA English DT Article ID BREAST-CANCER; MULTIPLE-MYELOMA; CONTROLLED TRIAL; INTRAVENOUS PAMIDRONATE; CLODRONATE; DIPHOSPHONATE; MULTICENTER; CARCINOMA; EFFICACY; WOMEN AB Tumour-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by tumour products or indirectly through an influence on other cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Pamidronate is a second-generation aminobisphosphonate that is a potent inhibitor of osteoclastic activity. In multiple myeloma, a phase III study has shown that the proportion of patients at the end of 21 months who had any skeletal event was significantly lower in the pamidronate group (38%) than in the placebo group (58%). The therapeutic benefit was independent of the type of antimyeloma chemotherapy. Patients who received pamidronate had significant decrease in bone pain and delayed deterioration in performance status and quality of life. Overall there was no survival advantage in patients who received pamidronate. In similar fashion, in 2 phase III breast cancer trials, patients who received pamidronate had fewer skeletal events, decrease in bone pain and analgesic use, and slower deterioration of performance status that in those patients receiving placebo. Again, there was no survival advantage in these patients. Recent studies suggest that the bisphosphonates clodronate can prevent the development of bone metastases in patients with breast cancer. C1 Penn State Univ, Milton S Hershey Med Ctr, Dept Haematol Oncol, Hershey, PA 17033 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Lipton, A (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Haematol Oncol, Hershey, PA 17033 USA. NR 26 TC 7 Z9 9 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD APR PY 1999 VL 14 IS 4 BP 241 EP 246 DI 10.2165/00002512-199914040-00001 PG 6 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 189FP UT WOS:000079894100001 PM 10319239 ER PT J AU Le Cam, L Polanowska, J Fabbrizio, E Olivier, M Philips, A Eaton, EN Classon, M Geng, Y Sardet, C AF Le Cam, L Polanowska, J Fabbrizio, E Olivier, M Philips, A Eaton, EN Classon, M Geng, Y Sardet, C TI Timing of cyclin E gene expression depends on the regulated association of a bipartite repressor element with a novel E2F complex SO EMBO JOURNAL LA English DT Article DE cell cycle; cyclin E; E2F; pocket protein; transcriptional repression ID B-MYB TRANSCRIPTION; CELL-CYCLE; RETINOBLASTOMA PROTEIN; DNA-REPLICATION; ADENOVIRUS E1A; IN-VIVO; SITE; P107; PRB; PROMOTER AB Transient induction of the cyclin E gene in late G(1) gates progression into S. We show that this event is controlled via a cyclin E repressor module (CERM), a novel bipartite repressor element located near the cyclin E transcription start site. GERM consists of a variant E2F-binding site and a contiguous upstream AT-rich sequence which cooperate during G(0)/G(1) to delay cyclin E expression until late G(1). CERM binds the protein complex CERC, which disappears upon progression through G(0)-G(1) and reappears upon entry into the following G(1). CERC disappearance correlates kinetically with the liberation of the GERM module in vivo and cyclin E transcriptional induction, CERC contains E2F4/DP1 and a pocket protein, and sediments faster than classical E2F complexes in a glycerol gradient, suggesting the presence of additional components in a novel high molecular weight complex. Affinity purified CERC binds to CERM but not to canonical E2F sites, thus displaying behavior different from known E2F complexes. In cells nullizygous for members of the Rb family, CERC is still detectable and CERM-dependent repression is functional. Thus p130, p107 and pRb function interchangeably in CERC. Notably, the CERC-CERM complex dissociates prematurely in pRb(-/-) cells in correspondence with the premature expression of cyclin E. Thus, we identify a new regulatory module that controls repression of G(1)-specific genes in G(0)/G(1). C1 Inst Genet Mol, CNRS, UMR 5535, F-34293 Montpellier 5, France. Whitehead Inst, Cambridge, MA 02145 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sardet, C (reprint author), Inst Genet Mol, CNRS, UMR 5535, 1919 Route Mende, F-34293 Montpellier 5, France. EM sardet@igm.cnrs-mop.fr RI Polanowska, Jolanta/P-9117-2016; Le Cam, Laurent/O-1408-2016 OI Polanowska, Jolanta/0000-0001-7666-7010; NR 45 TC 69 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 1 PY 1999 VL 18 IS 7 BP 1878 EP 1890 DI 10.1093/emboj/18.7.1878 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185FW UT WOS:000079658300016 PM 10202151 ER PT J AU Moy, EV Hu, H Christiani, DC AF Moy, EV Hu, H Christiani, DC TI A retired shipyard worker with rapidly progressive pulmonary interstitial fibrosis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE asbestos; lung; pulmonary interstitial fibrosis ID GLUTATHIONE-S-TRANSFERASE; COMPUTED-TOMOGRAPHY; LUNG-DISEASE; ASBESTOS; SILICOSIS; CANCER AB We present a case of progressive interstitial fibrosis in a retired shipyard worker who was exposed to asbestos during the postwar era of the late 1940s and 1950s, when asbestos exposures in the workplace were not regulated. Forty years later, at 63 years of age, the patient presented with restrictive lung disease. The patient was diagnosed with asbestos-related pleural disease and parenchymal asbestosis. He remained stable for the next 7 years, bur then he began to manifest rapid clinical progression, which raised the possibility of an unusual variant of asbestosis, a concomitant interstitial process, or an unrelated disease. Lung biopsy was not undertaken because of the patient's low pulmonary reserve and limited treatment options. An empiric trial of oral steroids was initiated, but his pulmonary status continued to deteriorate and he died of pulmonary failure at 72 years of age. Many diseases result in pulmonary interstitial fibrosis. Ideally, open lung biopsy should be performed, but this procedure inevitably causes complications in many patients with end-stage restrictive lung disease. Furthermore, while the presence of asbestos bodies in tissue sections is a sensitive and specific marker of asbestos exposure, neither this finding nor any other charge is a marker indicative of asbestosis or the severity of asbestosis. With the;enactment of the Asbestos Standard in the United States, asbestos exposures have been decreasing in this country. However, industries that produce asbestos products and wastes continue to expand in developing countries. Prevention of asbestos-related lung disease should be a global endeavor, and asbestos exposures should be regulated in both developed and developing countries. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Ctr Occupat & Environm Med, Boston, MA 02115 USA. Massachusetts Resp Hosp, S Braintree, MA 02184 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Hu, H (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. OI Hu, Howard/0000-0002-3676-2707 FU NIEHS NIH HHS [ES00002] NR 36 TC 1 Z9 1 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1999 VL 107 IS 4 BP 321 EP 327 DI 10.2307/3434601 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 187HZ UT WOS:000079782400024 PM 10090713 ER PT J AU Goldmann, WH Niles, JL Arnaout, MA AF Goldmann, WH Niles, JL Arnaout, MA TI Interaction of purified human proteinase 3 (PR3) with reconstituted lipid bilayers SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE calorimetry; hydrophobic photolabeling; light scattering; proteinase 3-lipid interaction; Wegener's granulomatosis ID NEUTROPHIL SERINE PROTEINASE; WEGENERS GRANULOMATOSIS; DISEASE-ACTIVITY; TALIN; ANTIBODIES; ANTIGEN; ACTIN; AZUROCIDIN; MEMBRANES; DIAGNOSIS AB Proteinase 3 (PR3), the major target autoantigen in Wegener's granulomatosis is a serine proteinase that is normally stored intracellularly in the primary granules of quiescent neutrophils and monocytes. Upon cell activation, a significant portion of this antigen is detected on the cell surface membrane. The nature of the association of PR3 with the membrane and its functional significance are unknown. We investigated the interaction of purified human PR3 with mixtures of zwitterionic (dimyristoyl-L-alpha-phosphatidylcholine, DMPC) and anionic (dimyristoyl-L-alpha-phosphatidylglycerol, DMPG) phospholipids in reconstituted lipid bilayers using differential scanning calorimetry and lipid photolabeling, and measured the affinity of this interaction using spectrophotometry. Two other primary granule constituents, human neutrophil elastase (HNE) and myeloperoxidase (MPO) were investigated for comparison. In calorimetric assays, using lipid vesicles of mixed DMPC/DMPG, increasing PR3 concentrations (protein/lipid molar ratio from 0 to 1 : 110) induced a significant decrease of the main chain transition enthalpy and a shift in chain melting temperatures which is indicative of partial insertion of PR3 into the hydrophobic region of the lipid membranes. This was confirmed by hydrophobic photolabeling using liposomes containing trace amounts of the photoactivable [I-125]-labeled phosphatidylcholine analog TID-PC/16. The molar affinity of PR3, EWE, and MPO to lipid vesicles of different DMPC/DMPG ratios was then determined by spectrophotometry. At a DMPC/DMPG ratio of 1 : 1, molar affinities of PR3, K-d = 4.5 +/- 0.3 mu M; HNE, 14.5 +/- 1.2 mu M; and MPO, 50 +/- 5 mu M (n = 3) were estimated. The lipid-associated PR3 exhibited two-fold lower V-max and K-m values, and its enzyme activity was slightly more inhibited (K-i) by the natural alpha(1)-proteinase inhibitor (alpha(1)-PI) or an autoantibody to PR3. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Leukocyte Biol & Inflammat Program, Bldg 149, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 FU NIDDK NIH HHS [DK42722] NR 25 TC 35 Z9 35 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD APR PY 1999 VL 261 IS 1 BP 155 EP 162 DI 10.1046/j.1432-1327.1999.00259.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185FQ UT WOS:000079657800021 PM 10103046 ER PT J AU Bacha, EA Wright, CD Grillo, HC Wain, JC Moncure, A Keel, SB Donahue, DM Mathisen, DJ AF Bacha, EA Wright, CD Grillo, HC Wain, JC Moncure, A Keel, SB Donahue, DM Mathisen, DJ TI Surgical treatment of primary pulmonary sarcomas SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE primary pulmonary sarcoma; surgery; malignant fibrous histiocytoma ID MALIGNANT FIBROUS HISTIOCYTOMA; LUNG AB Objective: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. Methods: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. Results: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P < 0.05). Conclusions: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass fan be a useful adjunct when tumors involve a resectable area of the heart or great vessels. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Thorac Surg Unit, Fruit St, Boston, MA 02114 USA. NR 11 TC 33 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD APR PY 1999 VL 15 IS 4 BP 456 EP 460 DI 10.1016/S1010-7940(99)00045-7 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 195AM UT WOS:000080227000021 PM 10371121 ER PT J AU Felsenfeld, AJ AF Felsenfeld, AJ TI Bone, parathyroid hormone and the response to the rapid induction of hypocalcaemia SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID CALCIUM; HUMANS C1 W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 1999 VL 29 IS 4 BP 274 EP 277 PG 4 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 193HU UT WOS:000080130500002 PM 10231337 ER PT J AU Lin, MTS Levy, ML Bowden, PE Magro, C Baden, L Baden, HP Roop, DR AF Lin, MTS Levy, ML Bowden, PE Magro, C Baden, L Baden, HP Roop, DR TI Identification of sporadic mutations in the helix initiation motif of keratin 6 in two pachyonychia congenita patients: further evidence for a mutational hot spot SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE pachyonychia congenita; keratin K6; mutational hot spot; genodermatosis ID EPIDERMOLYTIC HYPERKERATOSIS; EXPRESSION; PATTERNS; CELLS AB Pachyonychia congenita (PC) is a rare, autosomal dominant, ectodermal dysplasia characterized most distinctly by the presence of symmetric nail hypertrophy, In the Jadassohn-Lewandowsky form, or PC-1, additional cutaneous manifestations may include palmoplantar hyperkeratosis, hyperhidrosis, follicular keratoses, and oral leukokeratosis. Mutations have previously been identified in the 1A helix initiation motif of either keratin 6 or keratin 16 in patients with PC-1, In the current study, we have identified 2 sporadic, heterozygous mutations in the IA helix region of the K6 isoform (K6a), The first mutation identified was a 3 base pair deletion (K6a Delta N171), The second mutation was a C-to-A transversion resulting in an amino acid substitution (K6a N171K). These data, in combination with previous reports, provide further evidence that this location is a mutational hot spot. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Wales Coll Med, Dept Dermatol, Cardiff CF4 4XN, S Glam, Wales. Harvard Univ, Beth Israel Hosp, Sch Med, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Dept Pathol, Pathol Serv, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Roop, DR (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NICHD NIH HHS [HD25479] NR 19 TC 14 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD APR PY 1999 VL 8 IS 2 BP 115 EP 119 DI 10.1111/j.1600-0625.1999.tb00357.x PG 5 WC Dermatology SC Dermatology GA 188MA UT WOS:000079849700005 PM 10232401 ER PT J AU Castle, SC Uyemura, K Crawford, W Wong, W Klaustermeyer, WB Makinodan, T AF Castle, SC Uyemura, K Crawford, W Wong, W Klaustermeyer, WB Makinodan, T TI Age-related impaired proliferation of peripheral blood mononuclear cells is associated with an increase in both IL-10 and IL-12 SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; interleukin-10; interleukin-12; Staphylococcus entertoxin B; superantigen ID HUMAN T-CELLS; INTERLEUKIN-10 PRODUCTION; CYTOKINE PRODUCTION; B7/CD28 INTERACTION; SUBSETS; DYSREGULATION; EXPRESSION AB Reflective of age-associated decline in immune function among elderly individuals is a decrease in in vitro T cell proliferative ability. Impaired T cell proliferation in the elderly may result from disruption of the well-balanced network of regulatory cytokines produced during an immune response. The purpose of this study was to identify age-related changes in the production of interleukin (IL)-10 and IL-12, and to determine whether in vitro T cell proliferation can be enhanced in the elderly by modulation of these two key cytokines. The superantigen Staphyloccocus enterotoxin B (SEB) was used to stimulate proliferation and IL-10 and IL-12 production in peripheral blood mononuclear cells (PBMC) in vitro. Proliferation was determined by standard tritiated thymidine uptake. Cytokine levels in culture supermatants were measured by ELISA, We observed impaired SEE-induced proliferation of PBMC in the elderly that is comparable to that seen with the polyclonal mitogen Con A, This age-related decline in proliferation was associated with increased production of both IL-10 and IL-12, Modulation of PBMC proliferative response with either recombinant IL-12 or IL-10-neutralizing antibodies can boost proliferation of elderly PBMC to the levels seen in unmodulated young controls. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Univ Calif Los Angeles, Ctr Geriatr Res Educ & Clin, W Los Angeles VA Med Ctr, Multicampus Div Geriatr & Gerontol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Microbiol & Immunol, Los Angeles, CA 90024 USA. RP Castle, SC (reprint author), Univ Calif Los Angeles, Ctr Geriatr Res Educ & Clin, W Los Angeles VA Med Ctr, Multicampus Div Geriatr & Gerontol, 11301 Wilshire Ave,Bldg 220,Room 314, Los Angeles, CA 90073 USA. NR 23 TC 43 Z9 44 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD APR PY 1999 VL 34 IS 2 BP 243 EP 252 DI 10.1016/S0531-5565(98)00064-3 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 180JK UT WOS:000079382300009 PM 10363790 ER PT J AU Kupfer, G Naf, D Garcia-Higuera, I Wasik, J Cheng, A Yamashita, T Tipping, A Morgan, N Mathew, CG D'Andrea, AD AF Kupfer, G Naf, D Garcia-Higuera, I Wasik, J Cheng, A Yamashita, T Tipping, A Morgan, N Mathew, CG D'Andrea, AD TI A patient-derived mutant form of the Fanconi anemia protein, FANCA, is defective in nuclear accumulation SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE Fanconi anemia; mitomycin C; leukemia; cancer susceptibility ID GROUP-C PROTEIN; CHROMOSOMAL INSTABILITY; GENE FAA; CELLS; COMPLEMENTATION; LOCALIZATION; APOPTOSIS; INACTIVATION; POLYPEPTIDE; EXPRESSION AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A-H). Three FA genes, corresponding to complementation groups A, C, and G, have been cloned, but the function of the encoded FA proteins remains unknown. We recently demonstrated that the FANCA and FANCC proteins bind and form a nuclear complex, In the current study, we identified a homozygous mutation in the FANCA gene (3329A>C) in an Egyptian FA patient from a consanguineous family. This mutant FANCA allele is predicted to encode a mutant FANCA protein, FANCA(H1110P), in which histidine 1110 is changed to proline, Initially, me characterized the FANCA(H1110P) protein, expressed in an Epstein Parr virus (EBV)-immortalized lymphoblast Line derived from the patient. Unlike wild-type FANCA protein expressed in normal lymphoblasts, FANCA(H1110P) was not phosphorylated and failed to bind to FANCC. To test directly the effect of this mutation on FANCA function, we used retroviral-mediated transduction to express either wildtype FANCA or FANCA(H1110P) protein in the FA-A fibroblast line, GM6914. Unlike mild-type FANCA, the mutant protein failed to complement the mitomycin C sensitivity of these cells, In addition, the FANCA(H1110P) protein mas defective in nuclear accumulation in the transduced cells. The characteristics of this mutant protein underscore the importance of FANCA phosphorylation, FANCA/FANCC binding, and nuclear accumulation in the function of the FA pathway. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Tokyo, Japan. UMDS, Guys Hosp, Div Med & Mol Genet, London, England. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM a_dandrea@farber.harvard.edu RI Morgan, Neil/A-5475-2009; Garcia-Higuera, Irene/L-5004-2014; Mathew, Christopher/G-3434-2015 OI Morgan, Neil/0000-0001-6433-5692; Mathew, Christopher/0000-0003-4178-1838 FU NHLBI NIH HHS [R01-HL52725, P01HL54785]; PHS HHS [K08-H103420] NR 37 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 1999 VL 27 IS 4 BP 587 EP 593 DI 10.1016/S0301-472X(99)00022-3 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 185VB UT WOS:000079690600002 PM 10210316 ER PT J AU Sato, T Laver, JH Aiba, Y Ogawa, M AF Sato, T Laver, JH Aiba, Y Ogawa, M TI NK cell colony formation from human fetal thymocytes SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE clonal cell culture; human natural killer cell; fetal thymocyte; natural killer cell colony ID NATURAL-KILLER-CELLS; RECEPTOR-GAMMA-CHAIN; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW-CELLS; IL-2 RECEPTOR; INTERLEUKIN-2 IL-2; FUNCTIONAL COMPONENT; CULTURE; DIFFERENTIATION; COMPLEXES AB We established a clonal cell culture system for human natural killer (NK) cells from fetal thymoctes . Thymocytes of 16 to 22 gestational weeks were cultured in methylcellulose in the presence of interleukin (IL)-7, IL-15, and steel factor (SF), After 14 days in incubation, large, diffuse colonies consisting of small cells,were identified. Cells in the colonies vr-ere medium- to large-sized granular lymphocytes, expressing CD56 but not CD3, and revealed lytic activity against K562 cells, Colony-forming units (CFU)NK were enriched in lineage negative (Lin(-)) CD34(++) subpopulations of fetal thymocytes, whereas a smaller number of CFU-NK also existed in Lin(-)CD34(+) and Lin(-)CD34(-) subpopulations. Cytokine requirement for the WR cell colony formation was examined under serum-free conditions. As a single agent, only IL-15, but not IL-2, IL-7, or SF, supported NK cell colony formation. IL-15 had synergy with IL-7 and SF independently, and the maximal number of colonies were obtained when the three cytokines were present. IL-2 also supported NK cell colony formation in the presence of SF, When IL-2 was added to cultures containing IL-15 alone, IL-15 plus SF, or IL-15, SF, and IL-7, the numbers of NK cell colonies were reduced relative to those without IL-2, These results indicate that IL-2 may regulate IL-15-responsive Nti cell progenitors. This clonal culture system will be a useful tool in the investigation of NK cell ontogeny, (C) 1999 International Society for Experimental Hematology, Published by Elsevier Science Inc. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Ogawa, M (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM ogawam@musc.edu NR 35 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 1999 VL 27 IS 4 BP 726 EP 733 DI 10.1016/S0301-472X(99)00005-3 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 185VB UT WOS:000079690600016 PM 10210330 ER PT J AU Takahashi, T Bhide, PG Goto, T Miyama, S Caviness, VS AF Takahashi, T Bhide, PG Goto, T Miyama, S Caviness, VS TI Proliferative behavior of the murine cerebral wall in tissue culture: Cell cycle kinetics and checkpoints SO EXPERIMENTAL NEUROLOGY LA English DT Article DE neocortical development; cell cycle; mouse; organotypic explants; tissue culture ID NEOCORTICAL NEURONOGENESIS; DROSOPHILA EMBRYOGENESIS; VENTRICULAR ZONE; G1 PHASE; EPITHELIUM; NEURONS; MARKER; GLUTAMATE; PROTEIN; MODEL AB Cerebral wall from embryonic day 13 mice was cultured in a three-dimensional collagen matrix in defined, serum-free medium. The cerebral wall retained its normal architecture, including the radial glial fiber system, for up to 19 h in culture. The cell cycle was initially blocked at the S/G2/M and the G1/S phase transitions, resulting in a transient synchronization of the proliferative cells. The transient blockades correspond, we suggest, to the G2 checkpoint and G1 restriction point, adaptive mechanisms of normal proliferative cells. The blocks were relieved within a few hours of explantation with restoration of the interkinetic nuclear migration and flow of cells through the cycle phases. The duration of the reestablished cell cycle and those of G1, S, and combined G2-M phases were estimated to be 19.2, 6.3-8.3, 8.8, and 2.0-4.0 h, respectively. The leaving (Q) fraction of the cycle (0.64) was twice the in vivo value. Two-thirds of the Q fraction cells remained in the ventricular epithelium, resulting in a substantially low growth fraction of 0.73 compared with 1.0 in vivo. The embryonic murine cerebral explant, cultured in minimum essential medium, should be favorable for studies of cycle modulatory actions of cell external influences such as growth factors or neurotransmitters. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo 160, Japan. RP Takahashi, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU NINDS NIH HHS [NS12005, NS32657] NR 36 TC 18 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC 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 APR PY 1999 VL 156 IS 2 BP 407 EP 417 DI 10.1006/exnr.1999.7023 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 189LK UT WOS:000079906200015 PM 10328945 ER PT J AU Mueller, LA Camilleri, M Emslie-Smith, AM AF Mueller, LA Camilleri, M Emslie-Smith, AM TI Mitochondrial neurogastrointestinal encephalomyopathy: Manometric and diagnostic features SO GASTROENTEROLOGY LA English DT Article ID OCULOGASTROINTESTINAL MUSCULAR-DYSTROPHY; CHRONIC INTESTINAL PSEUDOOBSTRUCTION; FAMILIAL VISCERAL MYOPATHY; OPHTHALMOPLEGIA; DISEASE; DISORDER; DEFICIENCY; MOTILITY; TRANSIT; MNGIE C1 Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. RP Camilleri, M (reprint author), Mayo Clin, Gastroenterol Res Unit, Alfred 2-435,200 1st St SW, Rochester, MN 55905 USA. NR 27 TC 34 Z9 34 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 BP 959 EP 963 DI 10.1016/S0016-5085(99)70080-6 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 180EL UT WOS:000079372600026 PM 10092319 ER PT J AU Akiba, Y Guth, PH Engel, E Kaunitz, JD AF Akiba, Y Guth, PH Engel, E Kaunitz, JD TI Luminal acid produces duodenal hyperemia via trans-epithelial proton transport and afferent nerve capsaicin receptors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0473 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400474 ER PT J AU Akiba, Y Guth, PH Engel, E Kaunitz, JD AF Akiba, Y Guth, PH Engel, E Kaunitz, JD TI Repeated acid exposure creates acute adaptation of intracellular pH by activation of Na+: HCO(3)(-)cotransport in rat duodenal mucosa SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0472 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400473 ER PT J AU Akiba, Y Tomikawa, M Sarfeh, IJ Tarnawski, AS Kaunitz, JD AF Akiba, Y Tomikawa, M Sarfeh, IJ Tarnawski, AS Kaunitz, JD TI Mechanisms of impairment of gastric defense mechanisms to luminal acid and ethanol in portal hypertensive rats SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif Irvine, VAMC, Long Beach, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0471 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400472 ER PT J AU Andres, PG Awane, M Reinecker, HC AF Andres, PG Awane, M Reinecker, HC TI Conversion of the IL-17 and IL-1 beta signal transduction pathways in the activation of NF-B is mediated by TRAF-6. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, GRJ 711, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2788 BP A639 EP A639 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402789 ER PT J AU Beck, PL Xavier, R Ezedi, I Mizoguchi, E Mashimo, H Bhan, AK Podolsky, DK AF Beck, PL Xavier, R Ezedi, I Mizoguchi, E Mashimo, H Bhan, AK Podolsky, DK TI Paradoxical roles of different nitric oxide synthase isoforms in colonic injury. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 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 APR PY 1999 VL 116 IS 4 MA G3459 BP A798 EP A798 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403460 ER PT J AU Beck, PL Brandwein, SL Comiskey, M Terhorst, C Podolsky, DK AF Beck, PL Brandwein, SL Comiskey, M Terhorst, C Podolsky, DK TI Synergistic interactions between epithelial and immune defects in the development of experimental colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 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 APR PY 1999 VL 116 IS 4 MA G3457 BP A797 EP A797 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403458 ER PT J AU Beck, PL Xavier, R Ezedi, I Mizoguchi, E Mizoguchi, A Bhan, AK Podolsky, DK AF Beck, PL Xavier, R Ezedi, I Mizoguchi, E Mizoguchi, A Bhan, AK Podolsky, DK TI The role of T cell subsets and chemokines tn the regulation of the inflammatory response in dextran sodium sulfate-induced colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 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 APR PY 1999 VL 116 IS 4 MA G3458 BP A797 EP A797 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403459 ER PT J AU Beck, PL Podolsky, DK AF Beck, PL Podolsky, DK TI Intestinal trefoil factor reduces the severity of chemotherapy and radiotherapy-induced intestinal mucositis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2133 BP A486 EP A486 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402134 ER PT J AU Carta, M Atzei, A Cugia, L Idda, M Casu, M Dore, MP Realdi, G AF Carta, M Atzei, A Cugia, L Idda, M Casu, M Dore, MP Realdi, G TI Low incidence of Helicobacter pylori reinfection three years after eradication SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Med Sassari, Sassari, Italy. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0571 BP A132 EP A132 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400572 ER PT J AU Carter, EA Schiffrin, EJ Tompkins, RG Hillier, S Fischman, AJ AF Carter, EA Schiffrin, EJ Tompkins, RG Hillier, S Fischman, AJ TI Continuous infusion of tumor necrosis factor (TNF) produces chronic intestinal inflammation and increased Tc99m DTPA excretion in rats SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2954 BP A678 EP A678 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402955 ER PT J AU Chen, D Wang, TC Dockray, GJ Varro, A Zhao, CM Hakansson, R Koh, TJ AF Chen, D Wang, TC Dockray, GJ Varro, A Zhao, CM Hakansson, R Koh, TJ TI Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin deficient mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Lund, Lund, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0587 BP A136 EP A136 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400588 ER PT J AU Chen, D Zhao, CM Koh, TJ Hakansson, R Wang, TC AF Chen, D Zhao, CM Koh, TJ Hakansson, R Wang, TC TI ECL cell hypotrophy but not hypoplasia in antrectomized rats and gastrin deficient mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Lund, Lund, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2613 BP A596 EP A596 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402614 ER PT J AU Chung, RT Rosenberg, PM Farrell, JJ Abraczinskas, DR Ochoa, E Graeme-Cook, FM Dienstag, JL AF Chung, RT Rosenberg, PM Farrell, JJ Abraczinskas, DR Ochoa, E Graeme-Cook, FM Dienstag, JL TI HCV-induced fibrosing cholestatic hepatitis in HIV infection: A newly recognized clinical syndrome. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA L0076 BP A1197 EP A1197 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405185 ER PT J AU Colucci, R Fleming, JV Raychowdhury, R Wang, TC AF Colucci, R Fleming, JV Raychowdhury, R Wang, TC TI Feedback inhibition of histidine decarboxylase is mediated by decreased activation of GAS-RE elements SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2619 BP A598 EP A598 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402620 ER PT J AU Cugia, L Atzei, A Carta, M Idda, M Bilotta, M Dore, MP Bindi, B Bianco, P Meloni, M Sanna, A Realdi, G AF Cugia, L Atzei, A Carta, M Idda, M Bilotta, M Dore, MP Bindi, B Bianco, P Meloni, M Sanna, A Realdi, G TI New triple therapy for H-pylori infection that is effective in a region with a high rate of antibiotic resistance SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Med Sassari, Sassari, Italy. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Reg Hosp, Sassari, Italy. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0613 BP A142 EP A142 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400614 ER PT J AU Dore, MP Yamaoka, Y Realdi, G Graham, DY Sepulveda, AR AF Dore, MP Yamaoka, Y Realdi, G Graham, DY Sepulveda, AR TI Helicobacter infection in sheep: Vehicle for transmission or ancestral host? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Med Sassari, Sassari, Italy. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G0649 BP A150 EP A150 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400650 ER PT J AU Dore, MP Osato, MS Malaty, HM Graham, DY AF Dore, MP Osato, MS Malaty, HM Graham, DY TI Confirmation of the ability to culture Helicobacter pylori from the feces of infected patients SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G0648 BP A150 EP A150 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400649 ER PT J AU Farrell, RJ Menconi, MJ Keates, AC Kelly, CP AF Farrell, RJ Menconi, MJ Keates, AC Kelly, CP TI P-glycoprotein (PGP-170) inhibition reduces cortisol and cyclosporin efflux from human intestinal epithelial (caso-2) cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. BIDMC, DANA 601, Boston, MA USA. NR 0 TC 1 Z9 2 U1 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3888 BP A894 EP A895 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403889 ER PT J AU Freedman, SD Katz, MH Parker, EM Clark, PM Laposata, M Urman, SM Alvarez, JG AF Freedman, SD Katz, MH Parker, EM Clark, PM Laposata, M Urman, SM Alvarez, JG TI Role of arachidonic and docosahexanoic acids in the pathological manifestations of cystic fibrosis (CF) in CFTR (-/-) mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G4870 BP A1123 EP A1123 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404871 ER PT J AU Fusunyan, RD Nanthakumar, NN Sanderson, IR Baldeon, ME Walker, WA AF Fusunyan, RD Nanthakumar, NN Sanderson, IR Baldeon, ME Walker, WA TI IL-8 secretion is a function of enterocyte differentiation in Caco-2 cells in response to stimulation with proinflammatory mediators SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3832 BP A881 EP A881 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403833 ER PT J AU Gaspard, JP Graeme-Cook, F Warshaw, AL Jensen, RT Chung, DC AF Gaspard, JP Graeme-Cook, F Warshaw, AL Jensen, RT Chung, DC TI Loss of imprinting and overexpression of IGF-II in pancreatic endocrine tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G4836 BP A1115 EP A1115 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404837 ER PT J AU Gewirtz, AT Siber, AM Madara, JL McCormick, BA AF Gewirtz, AT Siber, AM Madara, JL McCormick, BA TI Specific apical intestinal epithelial-S typhimurium interactions, disociable from bacterial invasion mediate epithelial orchestration of neutrophil movement SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA USA. Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3353 BP A773 EP A773 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403353 ER PT J AU Gilbert, RJ Hahn, PF Sica, G Zeytinoglu, H Colby, J Edelman, RR AF Gilbert, RJ Hahn, PF Sica, G Zeytinoglu, H Colby, J Edelman, RR TI Utility of MRI in association with an endorectal surface coil in the clinical staging of patients with adenocarcinoma of the rectum SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cambridge Hosp, Cambridge, MA 02139 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G1803 BP A411 EP A411 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401804 ER PT J AU Guan, RJ Fu, Y Holt, PR Pardee, AB AF Guan, RJ Fu, Y Holt, PR Pardee, AB TI Association of K-ras mutations with p16 methylation in human colon cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst D602, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G1820 BP A415 EP A415 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401821 ER PT J AU Guan, RJ Fu, Y Pardee, AB AF Guan, RJ Fu, Y Pardee, AB TI Identification of a differentiation related, PPAR gamma and methylation regulated putative metastasis suppresser gene Drg-1 in human colon cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst D602, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G1819 BP A415 EP A415 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401820 ER PT J AU Gukovskaya, AS Zaninovic, V Lam, H Mouria, M Neil, L Pandol, SJ AF Gukovskaya, AS Zaninovic, V Lam, H Mouria, M Neil, L Pandol, SJ TI Neutrophils regulate trypsin activation in cerulein pancreatitis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 3 Z9 3 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 APR PY 1999 VL 116 IS 4 MA G4892 BP A1128 EP A1129 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404893 ER PT J AU Gukovskaya, AS Gukovsky, I Mouria, M Pandol, SJ AF Gukovskaya, AS Gukovsky, I Mouria, M Pandol, SJ TI Cerulein stimulates apoptosis in pancreatic acinar cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 3 Z9 3 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 APR PY 1999 VL 116 IS 4 MA G4891 BP A1128 EP A1128 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404892 ER PT J AU Gukovsky, I Jung, Y Periskic, S Zaninovic, V Kim, S Gukovskaya, AS Tsukamoto, H Pando, SJ AF Gukovsky, I Jung, Y Periskic, S Zaninovic, V Kim, S Gukovskaya, AS Tsukamoto, H Pando, SJ TI Ethanol diet sensitizes pancreas to CCK-8 induced activation of NF-KB and cytokine mRNA expression SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G4893 BP A1129 EP A1129 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404894 ER PT J AU Gukovsky, I Gukovskaya, A Mouria, M Pandol, SJ AF Gukovsky, I Gukovskaya, A Mouria, M Pandol, SJ TI Detachment from extracellular matrix stimulates NF-kappa B activation and apoptosis in pancreatic cancer cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G1822 BP A416 EP A416 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401823 ER PT J AU Hanauer, SB Rutgeerts, PJ D'Haens, G Targan, SR Kam, L Present, DH Mayer, L Wagner, C LaSorda, J Sands, B Livingston, RA AF Hanauer, SB Rutgeerts, PJ D'Haens, G Targan, SR Kam, L Present, DH Mayer, L Wagner, C LaSorda, J Sands, B Livingston, RA TI Delayed hypersensitivity to infliximab (Remicaide (R)) re-infusion after a 2-4 year interval without treatment SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Acad Ziekenhuis, Louvain, Belgium. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Centocor Inc, Malvern, PA 19355 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 29 Z9 30 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 APR PY 1999 VL 116 IS 4 MA G3174 BP A731 EP A731 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403175 ER PT J AU Hartwig, W Jimenez, RE Kelliher, A Preffer, F Warshaw, AL Fernandez-del Castillo, C AF Hartwig, W Jimenez, RE Kelliher, A Preffer, F Warshaw, AL Fernandez-del Castillo, C TI Serum changes induced by trypsin during acute pancreatitis result in neutrophil activation and remote organ injury SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA S0103 BP A1317 EP A1317 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405711 ER PT J AU Hartwig, W Carter, E Jimenez, RE Werner, J Fernandez-del Castillo, C Warshaw, AL AF Hartwig, W Carter, E Jimenez, RE Werner, J Fernandez-del Castillo, C Warshaw, AL TI Activity of neutrophils sequestered in the lungs is increased in severe but not in mild experimental pancreatitis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G4905 BP A1131 EP A1131 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404906 ER PT J AU Inoue, N Podolsky, DK AF Inoue, N Podolsky, DK TI Collaboraton of a goblet cell-specific and nonspecific regulatory elements in the regulation of human intestinal trefoil factor gene expression. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2779 BP A636 EP A636 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402780 ER PT J AU Iwakiri, D Itoh, H Podolsky, DK AF Iwakiri, D Itoh, H Podolsky, DK TI Goblet cell-specific transcription of mouse intestinal trefoil factor gene is regulated by tissue specific silencer inhibitor. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2681 BP A613 EP A613 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402682 ER PT J AU Jensen, DM Jensen, ME King, J Cheng, S Kowal, J Lam, F Fontana, L Gornbein, J AF Jensen, DM Jensen, ME King, J Cheng, S Kowal, J Lam, F Fontana, L Gornbein, J TI Prevalence of H.pylor and outcomes of patients with ulcer hemorrhage related to NSAID utilization: Results of screening for a large multicenter US trial SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, VA Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0869 BP A199 EP A199 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400870 ER PT J AU Kearney, DJ Brousal, A AF Kearney, DJ Brousal, A TI Effect of Helicobacter pylori treatment on outpatient pharmacy costs SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 3 Z9 3 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 APR PY 1999 VL 116 IS 4 MA G0296 BP A70 EP A70 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400297 ER PT J AU Kearney, DJ Brousal, A AF Kearney, DJ Brousal, A TI Treatment of Helicobacter pylori infection in clinical practice in the United States: Results from 224 patients SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0295 BP A69 EP A69 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400296 ER PT J AU Keates, AC Keates, S Kelly, CP AF Keates, AC Keates, S Kelly, CP TI Human colonic enterocytes produce MIP-3 alpha a memory CD4(+) T-cell directed C-C chemokine SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. BIDMC, DANA 601, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3243 BP A747 EP A747 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403244 ER PT J AU Keates, S Keates, AC Peek, RM Kelly, CP AF Keates, S Keates, AC Peek, RM Kelly, CP TI cag+ and cag- H-pylori strains differ in their ability to activate map kinases in AGS gastric epithelial cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G0920 BP A211 EP A211 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400921 ER PT J AU Kinoshita, K Taupin, D Itoh, H Podolsky, DK AF Kinoshita, K Taupin, D Itoh, H Podolsky, DK TI Structure-function analysis of human intestinal trefoil factor: Dissociation of distinct cell response pathways. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2446 BP A557 EP A557 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402447 ER PT J AU Kinugasa, T MacDermott, RP Reinecker, HC AF Kinugasa, T MacDermott, RP Reinecker, HC TI IL-17 is a regulator of intestinal epithelial cell barrier function. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit GRJ 711, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2518 BP A574 EP A575 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402519 ER PT J AU Koh, TJ Dockray, GJ Varro, A Cahill, RJ Dangler, CA Fox, JG Wang, TC AF Koh, TJ Dockray, GJ Varro, A Cahill, RJ Dangler, CA Fox, JG Wang, TC TI Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Liverpool, Liverpool L69 3BX, Merseyside, England. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2699 BP A617 EP A617 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402700 ER PT J AU Kushak, R VanCott, E Drapeau, C Winter, H AF Kushak, R VanCott, E Drapeau, C Winter, H TI Effect of algae Aphantizomenon flos aquae on digestive enzyme activity and polyunsaturated fatty acids level in blood plasma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2455 BP A559 EP A559 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402456 ER PT J AU Kyne, L Warny, M Qamar, A Fatimi, A Wei, JY Lamont, JT Kelly, CP AF Kyne, L Warny, M Qamar, A Fatimi, A Wei, JY Lamont, JT Kelly, CP TI Natural immunity against Clostridium difficile toxin A protects against diarrhea and pseudomembranous colitis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. BIDMC, DANA 601, Boston, MA USA. NR 0 TC 3 Z9 3 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3889 BP A895 EP A895 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403890 ER PT J AU Lee, S Chang, H Livingston, EH AF Lee, S Chang, H Livingston, EH TI Risk assessment for Roux-en-Y gastric bypass (RYGB) complications. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA S0149 BP A1329 EP A1329 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405757 ER PT J AU Luedtke-Heckenkamp, K Xavier, R Podolky, DK Reinecker, HC AF Luedtke-Heckenkamp, K Xavier, R Podolky, DK Reinecker, HC TI The lymphocyte specific IL-17 promoter is under autocrine control and regulated by T-cell activation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit GRJ 711, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2519 BP A575 EP A575 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402520 ER PT J AU Mashimo, H Kim, CD Goyal, RK AF Mashimo, H Kim, CD Goyal, RK TI Neuronal nitric oxide synthase ts major mediator of electrical field stimulated lower esophageal sphincter relaxation: Use of gene knockout mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Vet Adm Med Ctr W Roxbury, W Roxbury, MA USA. Harvard Univ, Sch Med, W Roxbury, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G4505 BP A1036 EP A1037 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404506 ER PT J AU McLaughlin, J Koh, TJ Wang, TC AF McLaughlin, J Koh, TJ Wang, TC TI Gastrin activates the human heparin binding-EGF promoter via a PKC MAP kinase-dependent pathway in AGS cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G2736 BP A626 EP A626 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402737 ER PT J AU McLaughlin, J Wang, TC Koh, TJ AF McLaughlin, J Wang, TC Koh, TJ TI PACAP regulates the histidine decarboxylase promoter via dual (PKA/PKC) signalling pathways. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Univ, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G2735 BP A626 EP A626 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402736 ER PT J AU Mouria, M Gukovskaya, AS Gukovsky, I Pandol, SJ AF Mouria, M Gukovskaya, AS Gukovsky, I Pandol, SJ TI Effects of polyphenols on apoptosis and NF-kappa B activation in pancreatic cancer cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2064 BP A470 EP A470 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402065 ER PT J AU Mura, D Deliperi, R Fastame, L Cugia, L Cossu, PA Pisanu, G Dore, MP Realdi, G AF Mura, D Deliperi, R Fastame, L Cugia, L Cossu, PA Pisanu, G Dore, MP Realdi, G TI Interferon therapy of HCV cirrhosis reduces the incidence of HCC, and decompensation, and significantly improves survival: A 5 year comparative trial SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Med Sassari, Sassari, Italy. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA L0310 BP A1251 EP A1251 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405419 ER PT J AU Ohtsuka, Y Sanderson, IR AF Ohtsuka, Y Sanderson, IR TI Chemokine secretion by epithelial cells increases neutrophil recruitment in the intestine in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 St Bartholomews & Royal London Sch Med & Dent, London, England. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3415 BP A787 EP A787 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403416 ER PT J AU Okumura, A Takehara, T Tsuji, N Hanada, S Takahashi, H AF Okumura, A Takehara, T Tsuji, N Hanada, S Takahashi, H TI Characterization of tumoricidal soluble factors that induce apoptosis of human colon cancer cells resistant to Fas- and TNF receptor-mediated cytotoxicity. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2258 BP A514 EP A514 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402259 ER PT J AU Ooi, CJ Willett, CG Zeitman, A Goldberg, S Sands, BE Podolsky, DK AF Ooi, CJ Willett, CG Zeitman, A Goldberg, S Sands, BE Podolsky, DK TI Acute and late toxicities in patients with inflammatory bowel disease (IBD) treated with radiation therapy (RT) for abdominal and pelvic neoplasms SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3456 BP A797 EP A797 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403457 ER PT J AU Ooi, CJ Sriram, V Sands, BE AF Ooi, CJ Sriram, V Sands, BE TI Variation in administration of the Crohn's disease activity index (CDAI): A survey of researchers SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, CSIBD, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3421 BP A788 EP A789 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403422 ER PT J AU Patterson, MM Schrenzel, MD Feng, Y Xu, S Delano, ML Dewhirst, FE Fox, JG AF Patterson, MM Schrenzel, MD Feng, Y Xu, S Delano, ML Dewhirst, FE Fox, JG TI Novel Helicobacter species isolated from Syrian hamsters with chronic gastritis and intestinal metaplasia SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Univ Massachusetts, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G1216 BP A277 EP A277 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401217 ER PT J AU Perez, AR Moncure, AC Rattner, DW AF Perez, AR Moncure, AC Rattner, DW TI Obesity is a major cause of failure for both transabdominal and transthoracic antireflux operations SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 14 Z9 14 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 APR PY 1999 VL 116 IS 4 MA S0210 BP A1343 EP A1343 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405818 ER PT J AU Plath, T Hocker, M Wang, TC Wiedenmann, B Rosewicz, S AF Plath, T Hocker, M Wang, TC Wiedenmann, B Rosewicz, S TI INTERFERON-alpha inhibits chromogranin a promoter activity in pancreatic neuroendocrine cancer cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Free Univ Berlin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany. Massachusetts Gen Hosp, Boston, MA USA. Univ Clinum Charite, Berlin, Germany. NR 0 TC 0 Z9 0 U1 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1852 BP A423 EP A423 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401853 ER PT J AU Qamar, A Warny, M Michetti, P Pothoulakis, C LaMont, JT Kelly, CP AF Qamar, A Warny, M Michetti, P Pothoulakis, C LaMont, JT Kelly, CP TI Saccharomyces boulardii stimulates an intestinal IgA immune response to Clostridium difficile toxin A in mice SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. BIDMC, DANA 601, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3887 BP A894 EP A894 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403888 ER PT J AU Qiu, BS Mashimo, H Blennerhassett, PA Collins, SM AF Qiu, BS Mashimo, H Blennerhassett, PA Collins, SM TI The critical role of nitric oxide in the maintenance of colonic goblet cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 McMaster Univ, GI Div, Hamilton, ON, Canada. McMaster Univ, IDRP, Hamilton, ON, Canada. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G3789 BP A871 EP A871 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403790 ER PT J AU Rattner, DW AF Rattner, DW TI Improvement of psychological well being and gastrointestinal symptoms by laparoscopic Nissen fundoplication SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA S0209 BP A1343 EP A1343 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405817 ER PT J AU Raychowdhury, R Wang, TC AF Raychowdhury, R Wang, TC TI Cloning of a novel transcription factor which mediates gastrin responsiveness by the human histidine decarbxylase (HDC) promoter SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2785 BP A638 EP A638 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402786 ER PT J AU Sands, BE Winston, B Salzberg, B Barish, C Safdi, M Wruble, L Varilek, G Singleton, J Katz, S Miner, PB Shapiro, M Schwertschlag, US AF Sands, BE Winston, B Salzberg, B Barish, C Safdi, M Wruble, L Varilek, G Singleton, J Katz, S Miner, PB Shapiro, M Schwertschlag, US TI A randomized, double-masked, placebo-controlled study of recombinant human interleukin eleven (rhIL-11) in Crohn's disease subjects not receiving prednisone SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. N Houston Med Res Ctr, Houston, TX USA. Wake Res Assoc, Raleigh, NC USA. Consultants Clin Res, Cincinnati, OH USA. Mid S Clin Res Instute, Memphis, TN USA. Univ Kentucky, Lexington, KY USA. Univ Colorado, Denver, CO 80202 USA. Nassau Gastroenterol Assoc, Great Neck, NY USA. Oklahoma Fdn Digest Res, Oklahoma City, OK USA. Genet Inst, Cambridge, MA 02140 USA. NR 0 TC 7 Z9 7 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 APR PY 1999 VL 116 IS 4 MA G3518 BP A811 EP A811 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403519 ER PT J AU Schulz, RJ Hoepffner, N Koyasu, S Reinherz, EL Wiedenmann, B AF Schulz, RJ Hoepffner, N Koyasu, S Reinherz, EL Wiedenmann, B TI Generation of intestinal epithelial lymphocytes (IEL) through m. tuberculosis in Fcr gamma chain deficient mice from gut residing progenitors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Humboldt Univ, Berlin, Germany. Keio Univ, Sch Med, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4034 BP A928 EP A928 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404035 ER PT J AU Shito, M Balis, UJ Thompkins, RG Yarmush, ML Toner, M AF Shito, M Balis, UJ Thompkins, RG Yarmush, ML Toner, M TI Survival and blood chemistry of fulminant hepatic failure model in the rat: Involvement of interleukin-1 beta and tumor necrosis factor-alpha. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Shriners Res Ctr, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2817 BP A646 EP A646 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402818 ER PT J AU Snapper, SB Liu, CH Mizoguchi, E Stockton, B Von Andrian, U Bhan, AK Rosen, FS Alt, FW AF Snapper, SB Liu, CH Mizoguchi, E Stockton, B Von Andrian, U Bhan, AK Rosen, FS Alt, FW TI Wiskott-Aldrich syndrome protein (WASP) deficient mice have lymphoid homing abnormalities and develop chronic colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MA Gen Hosp, Boston, MA USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3566 BP A822 EP A822 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403567 ER PT J AU Syngal, S Schrag, D Davis, K Falchuk, M Tung, N Farraye, F Miller, G Garber, JE AF Syngal, S Schrag, D Davis, K Falchuk, M Tung, N Farraye, F Miller, G Garber, JE TI Prevalence of the APC gene I1307K variant and associated clinical characteristics in Ashkenazi Jews with adenomatous polyps SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2251 BP A513 EP A513 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402252 ER PT J AU Taupin, DR Kinoshita, K Podolsky, DK AF Taupin, DR Kinoshita, K Podolsky, DK TI The trefoil peptide ITF regulates colonic epithelial apoptosis and tumor cell resistance to chemotherapy SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G2269 BP A517 EP A517 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402270 ER PT J AU Tsuzuki, Y Fukumura, D Gohongi, T Jain, RK AF Tsuzuki, Y Fukumura, D Gohongi, T Jain, RK TI High vascular permeability and low angiogenesis in an orthotopic model of pancreatic adenocarcinoma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G5073 BP A1170 EP A1170 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405074 ER PT J AU Vasiliauskas, E Targan, S Sands, B Hanauer, S Mayer, L Present, D Braakman, T DeWoody, K Schaible, T Rutgeerts, P AF Vasiliauskas, E Targan, S Sands, B Hanauer, S Mayer, L Present, D Braakman, T DeWoody, K Schaible, T Rutgeerts, P TI Consistency of treatment benefit with infliximab in patients with moderate-to-severe active Crohn's disease SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Chicago, IL 60637 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Centocor Inc, Malvern, PA 19355 USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. NR 0 TC 7 Z9 7 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3636 BP A837 EP A837 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403637 ER PT J AU Wang, TC Dangler, CA Chen, D Goldenring, JR Koh, TJ Raychowdhury, R Coffey, RJ Ito, S Varro, A Dockray, GJ Fox, JG AF Wang, TC Dangler, CA Chen, D Goldenring, JR Koh, TJ Raychowdhury, R Coffey, RJ Ito, S Varro, A Dockray, GJ Fox, JG TI Hypergastrinemia leads to atrophy and invasive gastric cancer in transgenic mice SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lund, Lund, Sweden. Med Coll Georgia, Augusta, GA 30912 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 9 Z9 9 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 APR PY 1999 VL 116 IS 4 MA G2314 BP A527 EP A527 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402315 ER PT J AU Wang, YH Ennes, HS Tache, Y Wei, JY Mayer, EA AF Wang, YH Ennes, HS Tache, Y Wei, JY Mayer, EA TI Vagal afferent response to gastric distension in c-kit mutant mice and their wild-type siblings: An in vitro study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. 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 APR PY 1999 VL 116 IS 4 MA G4768 BP A1099 EP A1099 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404769 ER PT J AU Warny, M Keates, AC Keates, S Qamar, A Castagliuolo, I Pothoulakis, C Kelly, CP AF Warny, M Keates, AC Keates, S Qamar, A Castagliuolo, I Pothoulakis, C Kelly, CP TI Clostridium difficile toxin A-induced map kinase activation mediates IL-8 production and cell necrosis in human monocytes SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. BIDMC, DANA 601, Boston, MA USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G3242 BP A746 EP A747 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403243 ER PT J AU Wershil, BK Vergara, P Lu, L AF Wershil, BK Vergara, P Lu, L TI Neuropeptides alter IgE-dependent mast cell mediator release: A possible role for modulation of allergic responses by the nervous system in the gut SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fac Vet, Barcelona, Spain. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 116 IS 4 MA G3671 BP A845 EP A845 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403672 ER PT J AU Wershil, BK Teitelbaum, JE AF Wershil, BK Teitelbaum, JE TI Human mast cell tryptase induces proliferation and IL-8 production in intestinal myofibroblasts SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G3670 BP A844 EP A845 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403671 ER PT J AU Z'graggen, K Werner, J Jimenez, RE Graeme-Cook, F Rivera, JA Warshaw, AL Castillo, CF AF Z'graggen, K Werner, J Jimenez, RE Graeme-Cook, F Rivera, JA Warshaw, AL Castillo, CF TI A high fat, high-protein diet promotes carcinogenesis in a rat model of ductal pancreatic adenocarcinoma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA S0333 BP A1372 EP A1372 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405941 ER PT J AU Zaninovic, V Gukovskaya, AS Bostandzhyan, E Eysselein, VE Pandol, SJ AF Zaninovic, V Gukovskaya, AS Bostandzhyan, E Eysselein, VE Pandol, SJ TI Effect of overexpression of transforming growth factor alpha on necrotizing cerulein pancreatitis in mice SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Harbor UCLA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 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 APR PY 1999 VL 116 IS 4 MA G5107 BP A1179 EP A1179 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405108 ER PT J AU Nishioka, NS Schomacker, KT AF Nishioka, NS Schomacker, KT TI Mucosal exposure to light during routine endoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID LASER-INDUCED FLUORESCENCE; CYTO-TOXICITY; SPECTROSCOPY; ULTRAVIOLET; ADENOMAS; TISSUE AB Background: The spectral irradiance delivered by a variety of gastrointestinal endoscopes was measured as a function of wavelength and used to estimate the amount of light delivered to the mucosal surface during routine endoscopic procedures. Methods: Spectral irradiances from seven different endoscopes were measured using a commercial spectroradiometer calibrated against a National Institute of Standards and Technology traceable source. Results: The largest maximum irradiance was 8.0 W/cm(2) obtained from an endoscope used in transillumination mode. In the typical viewing mode, the largest maximum irradiance measured was 1.6 W/cm(2). The majority of the light energy delivered by these gastrointestinal endoscopes was in the visible wavelength region (400 to 700 nm), Discussion: The measurements revealed surprisingly high light exposures in the visible wavelength range. In fact, the estimated tissue exposures can exceed by 40-fold the standards established for skin exposure to light set forth by the American National Standards Institute. Because gastrointestinal endoscopy is widely viewed to be safe, it is probable that the gastrointestinal tract has significant tolerance to light exposure. C1 Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Med Serv, Bartlett Hall 708,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 BP 456 EP 461 DI 10.1016/S0016-5107(99)70042-8 PN 1 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LC UT WOS:000079847600007 PM 10202058 ER PT J AU Bouma, BE Tearney, GJ Compton, CC Nishioka, NS AF Bouma, BE Tearney, GJ Compton, CC Nishioka, NS TI Endoscopic optical coherence tomography of the gastrointestinal tract SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 390 BP AB152 EP AB152 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100389 ER PT J AU Brandwein, SL Farrell, JJ Centeno, BA Brugge, WR AF Brandwein, SL Farrell, JJ Centeno, BA Brugge, WR TI EUS-guided FNA detects malignancy in IPMT SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 148 BP AB87 EP AB87 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100149 ER PT J AU Cass, OW Korman, LY Brugge, W Baerg, RD Roberts, IM Harford, WV AF Cass, OW Korman, LY Brugge, W Baerg, RD Roberts, IM Harford, WV TI Esophageal findings in patients whose reason for esophagogastroduodenoscopy (EGD) is dysphagia SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. VAMC, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tacoma Endoscopy Ctr, Tacoma, WA USA. Bridgeport Hosp, Bridgeport, CT USA. Univ Texas, SW Med Ctr, Dallas VA Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 342 BP AB139 EP AB139 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100341 ER PT J AU Farrell, JJ Graeme-Cook, F Kelsey, PB AF Farrell, JJ Graeme-Cook, F Kelsey, PB TI Endoscopic band ligation of bleeding colonic diverticula: An ex vivo and in vivo study SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 329 BP AB136 EP AB136 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100330 ER PT J AU Farrell, JJ Kelsey, PB AF Farrell, JJ Kelsey, PB TI Interventions and outcomes in significant diverticular bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 328 BP AB136 EP AB136 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100329 ER PT J AU Farrell, JJ Kelsey, PB AF Farrell, JJ Kelsey, PB TI Prophylactic endoscopic band ligation for high risk polypectomy SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 105 BP AB75 EP AB75 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100106 ER PT J AU Goldberg-Arnold, RJ Atif, Z Pettit, KG Karniecki, DJ Benner, K Zacker, C DiCesare, J Helfand, M AF Goldberg-Arnold, RJ Atif, Z Pettit, KG Karniecki, DJ Benner, K Zacker, C DiCesare, J Helfand, M TI Cost of treating an episode of variceal bleeding in a VA setting SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Arnold Pharmacol Int Inc, New York, NY USA. Portland VA Med Ctr, Portland, OR USA. Novartis Pharms Corp, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 581 BP AB203 EP AB203 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100580 ER PT J AU Kelsey, PB Rosenberg, PM Brugge, WR Schapiro, RH AF Kelsey, PB Rosenberg, PM Brugge, WR Schapiro, RH TI Improved survival in unresectable hilar cholangiocarcinoma with bilateral biliary drainage SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 686 BP AB233 EP AB233 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100685 ER PT J AU Kelsey, PB AF Kelsey, PB TI Duodenoscope-assisted cholangiopancreatoscopy (DACP) improves the effectiveness of interventional ERCP SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 291 BP AB126 EP AB126 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100292 ER PT J AU Nishioka, NS Wang, KK Allen, JI Stoltenberg, PH Cass, OW Kelsey, PB Nourbakhsh, A Jessurun, J Hawkins, DM Schomacker, KT AF Nishioka, NS Wang, KK Allen, JI Stoltenberg, PH Cass, OW Kelsey, PB Nourbakhsh, A Jessurun, J Hawkins, DM Schomacker, KT TI Distinguishing neoplastic from non-neoplastic colonic polyps using laser-induced fluorescence: Results of a prospective, multicenter trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Minnesota Gastroenterol, Minneapolis, MN USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 412 BP AB158 EP AB158 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100411 ER PT J AU Rosenberg, PM Brugge, WR Schapiro, RH Kelsey, PB AF Rosenberg, PM Brugge, WR Schapiro, RH Kelsey, PB TI Comparison of three different stents (plastic and metal) for malignant biliary obstruction SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 697 BP AB236 EP AB236 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100696 ER PT J AU Sica, GT Schreyer, A Hahn, P Miller, F Vu, T Gilbert, R Kikinis, R AF Sica, GT Schreyer, A Hahn, P Miller, F Vu, T Gilbert, R Kikinis, R TI Three dimensional reconstruction of the pelvis in patients with rectal tumors using endorectal MR imaging: Utility in pre-operative planning SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. St Elizabeths Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 416 BP AB159 EP AB159 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100415 ER PT J AU Wang, ML Belmonte, S Kim, U Dolan, M Morris, JW Goodman, HM AF Wang, ML Belmonte, S Kim, U Dolan, M Morris, JW Goodman, HM TI A cluster of ABA-regulated genes on Arabidopsis thaliana BAC TO7MO7 SO GENOME RESEARCH LA English DT Article ID PROTEIN PHOSPHATASE 2C; ACID SIGNAL-TRANSDUCTION; ABSCISIC-ACID; EXPRESSION; DNA; CONSTRUCTION; GENOME; PLANTS; ABI1; PATHWAYS AB Arabidopsis thaliana BAC T07M07 encoding the abscisic acid-insensitive 4 (ABI4) locus has been sequenced completely. It contains a 95,713-bp insert and 24 predicted genes. Most putative genes were confirmed by gel-based RNA profiling and a cluster of ABA-regulated genes was identified. One of the 24 genes, designated PP2C5, encodes a putative protein phosphatase 2C. The encoded protein was expressed in Escherichia coli, and its enzyme activity in vitro was confirmed. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Goodman, HM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM Howard.Goodman@molbio.mgh.harvard.edu NR 40 TC 12 Z9 35 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD APR PY 1999 VL 9 IS 4 BP 325 EP 333 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 189KU UT WOS:000079904300002 PM 10207155 ER PT J AU Sarkar, S Hobson, A Woolf, CJ Thompson, DG Aziz, Q AF Sarkar, S Hobson, A Woolf, CJ Thompson, DG Aziz, Q TI Oesophageal cortical evoked potentials are potentiated following acid induced hypersensitivity SO GUT LA English DT Meeting Abstract C1 Hope Hosp, Dept Med, Salford M6 8HD, Lancs, England. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Inst Psychiat, London, England. NR 1 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 1999 VL 44 SU 1 MA TH441 BP A111 EP A111 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 181NA UT WOS:000079446300441 ER PT J AU Sarkar, S Aziz, Q Woolf, CJ Hobson, A Thompson, DG AF Sarkar, S Aziz, Q Woolf, CJ Hobson, A Thompson, DG TI Referred somatic hypersensitivity following acid induced injury of the human esophagus SO GUT LA English DT Meeting Abstract C1 Hope Hosp, Dept Med, Salford M6 8HD, Lancs, England. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 1999 VL 44 SU 1 MA TH443 BP A111 EP A111 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 181NA UT WOS:000079446300443 ER PT J AU Lane, AH Lee, MM Fuller, AF Kehas, DJ Donahoe, PK MacLaughlin, DT AF Lane, AH Lee, MM Fuller, AF Kehas, DJ Donahoe, PK MacLaughlin, DT TI Diagnostic utility of Mullerian inhibiting substance determination in patients with primary and recurrent granulosa cell tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article ID BLEOMYCIN COMBINATION CHEMOTHERAPY; PROGNOSTIC FACTORS; OVARY; HORMONE; MARKER; VINBLASTINE; MANAGEMENT; CISPLATIN AB Objectives. In this study we evaluated changes in serum Mullerian inhibiting substance (MIS) concentration in a large number of patients with granulosa cell tumors (GCT) to determine whether MIS is elevated at the time of presentation and whether MIS is an index of successful surgical resection and management of recurrences, Methods. We retrospectively reviewed MIS levels from 17 subjects prior to tumor resection and studied serial MIS samples from 56 subjects following initial tumor resection, Clinical follow-up information was available for 36 of those with postoperative MIS values, Serum MIS was measured by an ELISA. MIS values were compared to a combination of normative values previously established in our laboratory and from more recently obtained samples from older pre- and postmenopausal women, using this assay. Results. Serum MIS was elevated pre-operatively in 6 of 8 (75%) subjects with juvenile GCTs and in 7 of 9 (78%) of those with adult GCTs relative to age-matched controls (76% for both types combined), Post-operative clinical correlation was available for 36 patients. There was no clinical recurrence in 21 subjects with normal or undetectable postoperative values, and incompletely resectable tumor or recurrence was identified in 6 of 15 patients with elevated postoperative values. Conclusions, The results of this study demonstrate that postoperative serum MIS concentrations may be used to evaluate the completeness of tumor removal following initial surgery and that serial MIS determinations may allow the detection of recurrences. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Lane, AH (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. OI Lee, Mary/0000-0002-7204-4884 FU NICHD NIH HHS [1F32HD08135-01] NR 29 TC 48 Z9 50 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 1999 VL 73 IS 1 BP 51 EP 55 DI 10.1006/gyno.1998.5290 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 188KT UT WOS:000079846200010 PM 10094880 ER PT J AU Todd, R Wong, DTW AF Todd, R Wong, DTW TI Epidermal growth factor receptor (EGFR) biology and human oral cancer SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE growth factor receptor; squamous cell carcinoma; oral; biomarker ID SQUAMOUS-CELL CARCINOMA; TYROSINE KINASE-ACTIVITY; HUMAN-BREAST-CANCER; ATP-BINDING-SITE; FACTOR-ALPHA; SIGNAL TRANSDUCTION; PROTEIN-KINASE; NECK-CANCER; AUTOPHOSPHORYLATION SITES; GENE AMPLIFICATION AB Dysregulation of the epidermal growth factor receptor (EGFR) is one of the most frequently studied molecular events leading to oral carcinogenesis. Overexpression of EGFR is a common event in many human solid tumors. Elevated levels of EGFR mRNA in human cancer occur with and without gene rearrangement. Structural alterations in the receptor can also result in the dysregulation of the EGFR pathway. EGFR overexpression without gene re-arrangement is frequently observed in human oral cancers. However, little is known whether structural alterations in the receptor or perturbations in the EGFR pathway contribute to oral carcinogenesis. Several preliminary studies suggest that EGFR-targeted therapeutic approaches might be successful in controlling oral cancer. C1 Harvard Univ, Sch Dent Med, Div Oral Pathol, Lab Mol Pathol,Dept Oral Med & Oral Diag, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Div Oral Pathol, Lab Mol Pathol,Dept Oral Med & Oral Diag, 188 Longwood Ave, Boston, MA 02115 USA. EM David_Wong@hms.harvard.edu FU NIDCR NIH HHS [R01 DE08680] NR 107 TC 51 Z9 54 U1 2 U2 3 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD APR PY 1999 VL 14 IS 2 BP 491 EP 500 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 182HD UT WOS:000079492400018 PM 10212811 ER PT J AU Glasow, A Bornstein, SR Chrousos, GP Brown, JW Scherbaum, WA AF Glasow, A Bornstein, SR Chrousos, GP Brown, JW Scherbaum, WA TI Detection of Ob-receptor in human adrenal neoplasms and effect of leptin on adrenal cell proliferation SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE immunostaining; leptin receptor; adrenal pathologies ID ACTIVATED PROTEIN-KINASE; EXPRESSION; SECRETION; LINE AB Leptin, a hormone mainly secreted from adipose tissue, communicates a metabolic signal to the adrenal gland. Ob-Receptor (Ob-R) expression was reported in rat, mice and human adrenal glands. This study intended to investigate possible differences in the Ob-R expression acid distribution of Ob-R protein in human adrenal tumors as compared to normal adrenal tissue. Proliferative effects of leptin were analyzed in the human adrenocortical carcinoma cell line (NCl-H295). The full length Ob-R mRNA and the isoforms B219.1 and B219.3 could be demonstrated by RT-PCR in all adrenal tumors (n=8), the tumor cell line (NCl-H295) and normal tissue. In contrast the Ob-R isoform B219.2 was absent in the carcinoma cell line and in most of the adrenal tumors (n = 5), whereas it was present in normal adrenals. The Ob-R protein could be demonstrated in benign and malignant adrenocortical tumors. Pheochromocytomas showed only a weak immunostaining with the human Ob-R antibody. Human leptin did not affect the proliferation or variability of adrenal tumor cells as demonstrated by [H-3]-thymidine assay and WST-1 test. In conclusion, although functional leptin receptors are expressed in human adrenal tumors, leptin does not regulate tumor cell proliferation. C1 Univ Leipzig, Med Klin & Poliklin 3, Dept Internal Med 3, D-04103 Leipzig, Germany. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. US Dept Vet Affairs, Ctr Med, Miami, FL USA. Univ Dusseldorf, Diabet Res Inst, D-4000 Dusseldorf, Germany. RP Glasow, A (reprint author), Univ Leipzig, Med Klin & Poliklin 3, Dept Internal Med 3, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. NR 21 TC 32 Z9 33 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD APR PY 1999 VL 31 IS 4 BP 247 EP 251 DI 10.1055/s-2007-978726 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 190ZA UT WOS:000079994400001 PM 10333078 ER PT J AU Giri, D Ittmann, M AF Giri, D Ittmann, M TI Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma SO HUMAN PATHOLOGY LA English DT Article DE prostate carcinoma; PTEN; thrombospondin-1; angiogenesis ID CANCER; MUTATIONS; ADENOCARCINOMAS; PTEN/MMAC1; INHIBITION; FREQUENT AB The PTEN tumor suppressor gene encodes a dual-specificity protein phosphatase that may play a key role in modulating integrin-mediated signals. Inactivation of the PTEN gene has been detected in a small percentage of clinically localized prostate cancers but is common in metastatic disease. It has been shown in glioblastoma cell lines that loss of chromosome 10q, where the PTEN gem is located, is associated with increased angiogenic activity in the conditioned medium attributable to downregulation of thrombospondin-l, a negative regulator of angiogenesis. Therefore, we wished to determine whether inactivation of PTEN might be associated with increased angiogenesis in prostate cancers, because increased angiogenesis in localized cancers is associated with development of metastatic disease. Angiogenesis was assessed by counting microvessels in areas of maximal neovascularization after immunostaining with anti-factor VIII-related antigen antibodies in eight cases with proven homozygous deletion of the PTEN gene and 24 control cases. There was: a statistically significant correlation between PTEN inactivation and increased microvessel counts. The microvessel density was higher at all Gleason scores in the cases with PTEN inactivation compared with control cases with the same score. To determine whether the increased angiogenesis in cases with PTEN inactivation was caused by downregulation of expression of the angiogenesis inhibitor thrombospondin-l, we analyzed a subset of the cases by immunostaining with anti-thrombospondin-1 antibody. Approximately 25% of cases showed decreased staining of prostate cancer cells, but there was no correlation with PTEN inactivation. Thus, PTEN inactivation is associated with increased angiogenesis, but the increased, angiogenesis is not attributable to downregulation of thrombospondin-1 expression. Copyright (C) 1999 by W.B. Saunders Company. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Ittmann, M (reprint author), Houston VAMC, Res Serv 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 20 TC 73 Z9 79 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1999 VL 30 IS 4 BP 419 EP 424 DI 10.1016/S0046-8177(99)90117-X PG 6 WC Pathology SC Pathology GA 184NY UT WOS:000079619300010 PM 10208463 ER PT J AU George, MS Stallings, LE Speer, AM Nahas, Z Spicer, KM Vincent, DJ Bohning, DE Cheng, KT Molloy, M Teneback, CC Risch, SC AF George, MS Stallings, LE Speer, AM Nahas, Z Spicer, KM Vincent, DJ Bohning, DE Cheng, KT Molloy, M Teneback, CC Risch, SC TI Prefrontal repetitive transcranial magnetic stimulation (rTMS) changes relative perfusion locally and remotely SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE transcranial magnetic stimulation; prefrontal cortex; cingulate; SPECT; blood flow; imaging ID POSITRON EMISSION TOMOGRAPHY; SIMPLE REACTION-TIME; MAJOR DEPRESSION; GLUCOSE-METABOLISM; SLEEP-DEPRIVATION; MOOD DISORDERS; IMPROVES MOOD; BLOOD-FLOW; CORTEX; TMS AB Although transcranial magnetic stimulation has been used as a stand-alone brain mapping tool, relatively few studies have attempted to couple TMS with functional brain imaging to understand the neurobiological effects of TMS. Technical problems of placing a TMS coil in a PET or MRI scanner have hampered previous efforts at imaging the immediate effects of TMS. Perfusion SPECT offers the advantage of tracer injection away from the camera, with later image development. We wondered if perfusion SPECT could be used to visualize brain changes during rTMS over the left prefrontal cortex - a region where rTMS has been shown to cause changes in mood or working memory. Eight healthy adult subjects were scanned with brain SPECT scintigraphy using 30 mCi (1110 MBq) Neurolite(R) (DuPont Pharma) on a triple-headed Picker camera. Each subject had three scans: (1) baseline, (2) bolus tracer injection during seconds 10-20 of a train of 2 min of left prefrontal rTMS 10 Hz; 60% motor threshold (MT); 10 s on/off, 600 stimuli) (2MIN), and (3) exactly as in the 2MIN, but immediately after subjects had received 18 min of high frequency stimulation (20 Hz; 80% MT; 2 s on/28 s off, 1440 + 600 = 2040 total stimuli) (20MIN). Scans were linearly transformed into Talairach space using SPM96b and compared across conditions (p < 0.05 for display). Contrary to our prestudy hypothesis, there was no relative increase at the coil site during the 2 min or the 20 min scan compared to baseline. In fact, at the 20 min comparison perfusion was relatively decreased in the right prefrontal cortex, bilateral anterior cingulate, and anterior temporal cortex. Also, relative perfusion was significantly increased in the orbitofrontal cortex (L > R) and hypothalamus at 20 min and at 2 min, with thalamic increases occurring at the 20 min scan compared to baseline. There was an apparent TMS dose effect with twice as many decreases at 20 min than 2 min. Directly comparing the 20 min to the 2 min scans demonstrated opposite hemisphere decreases and relative increases in the ipsilateral (left) hemisphere as a function of more TMS stimuli. Full interpretation of these results is hampered by incomplete knowledge of the effect of the relative amount of stimulation to rest during tracer uptake, pharmacokinetics of tracer uptake, and depth and intensity of the magnetic field. Nevertheless, coupling rTMS with split-dose perfusion SPECT appears to be a promising method for understanding the brain changes associated with rTMS, and for directly visualizing neural circuits. We have demonstrated that prefrontal rTMS at high frequencies has both local and remote effects. These imaging results may help explain the cognitive and behavioural effects demonstrated in other prefrontal rTMS studies involving mood and working memory. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC 29425 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. NR 50 TC 61 Z9 61 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD APR PY 1999 VL 14 IS 3 BP 161 EP + DI 10.1002/(SICI)1099-1077(199904)14:3<161::AID-HUP73>3.0.CO;2-2 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 198LU UT WOS:000080426300002 ER PT J AU Ma, Q Jones, D Springer, TA AF Ma, Q Jones, D Springer, TA TI The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment SO IMMUNITY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; LYMPHOCYTE CHEMOATTRACTANT; LYMPHOPOIESIS; SDF-1; HIV-1; MYELOPOIESIS; LESTR/FUSIN; ASSOCIATION; MOLECULES; CYTOKINES AB We report that the chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within fetal liver and bone marrow microenvironment, in CXCR4-deficient embryos, pro-B cells are present in blood but hardly detectable in liver; myeloid cells are elevated in blood and reduced in liver compared to wild-type embryos. Mice reconstituted with CXCR4-deficient fetal liver cells have reduced donor-derived mature B lymphocytes in blood and lymphoid organs. The numbers of pro-B and pre-B cells are reduced in bone marrow and abnormally high in blood. Granulocytic cells are reduced in bone marrow but elevated and less mature in the blood. B lineage and granulocytic precursors are released into the periphery in absence of CXCR4. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Jones, Daniel/I-7399-2015 FU NHLBI NIH HHS [HL-48675] NR 32 TC 458 Z9 468 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1999 VL 10 IS 4 BP 463 EP 471 DI 10.1016/S1074-7613(00)80046-1 PG 9 WC Immunology SC Immunology GA 190XB UT WOS:000079989600007 PM 10229189 ER PT J AU Ryan, ET Crean, TI John, M Butterton, JR Clements, JD Calderwood, SB AF Ryan, ET Crean, TI John, M Butterton, JR Clements, JD Calderwood, SB TI In vivo expression and immunoadjuvancy of a mutant of heat-labile enterotoxin of Escherichia coli in vaccine and vector strains of Vibrio cholerae SO INFECTION AND IMMUNITY LA English DT Article ID ORAL IMMUNIZATION; ATTENUATED VACCINE; PROTECTIVE IMMUNITY; NUCLEOTIDE-SEQUENCE; ANTIBODY-RESPONSES; TOXIN; LIVE; INFECTION; ANTIGENS; ADJUVANT AB Vibrio cholerae secretes cholera toxin (CT) and the closely related heat-labile enterotoxin (LT) of Escherichia coli, the latter when expressed in V. cholerae. Both toxins are also patent immunoadjuvants. Mutant LT molecules that retain immunoadjuvant properties while possessing markedly diminished enterotoxic activities when expressed by E. coli have been developed. One such mutant LT molecule has the substitution of a glycine residue for arginine-192 [LT(R192G)]. Live attenuated strains of V. cholerae that have been used both as V. cholerae vaccines and as vectors for inducing mucosal and systemic immune responses directed against expressed heterologous antigens have been developed. In order to ascertain whether LT(R192G) can act as an immunoadjuvant when expressed in vivo by V. cholerae, we introduced a plasmid (pCS95) expressing this molecule into three vaccine strains of V. cholerae, Peru2, ETR3, and JRB14; the latter two strains contain genes encoding different heterologous antigens in the chromosome of the vaccine vectors. We found that LT(R192G) was expressed from pCS95 in vitro by both E. coli and V. cholerae strains but that LT(R192G) was detectable in the supernatant fraction of V. cholerae cultures only In order to assess potential immunoadjuvanticity, groups of germfree mice were inoculated with the three V. cholerae vaccine strains alone and compared to groups inoculated with the V. cholerae vaccine strains supplemented with purified CT as an oral immunoadjuvant or V. cholerae vaccine strains expressing LT(R192G) from pCS95. We found that mice continued to pass stool containing V. cholerae strains with pCS95 for at least 4 days after oral inoculation, the last day evaluated. We found that inoculation with V. cholerae vaccine strains containing pCS95 resulted in anti-LT(R192G) immune responses, confirming in vivo expression, me were unable to detect immune responses directed against the heterologous antigens expressed at low levels in any group of animals, including animals that received purified CT as an immunoadjuvant. We were, however, able to measure increased vibriocidal immune responses against vaccine strains in animals that received V. cholerae vaccine strains expressing LT(R192G) from pCS95 compared to the responses in animals that received V. cholerae vaccine strains alone. These results demonstrate that mutant LT molecules can be expressed in vivo by attenuated vaccine strains of V. cholerae and that such expression can result in an immunoadjuvant effect. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Tulane Univ, Med Ctr, Dept Microbiol & Immunol, New Orleans, LA 70112 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM scalderwood@partners.org FU NIAID NIH HHS [K08AI01386, AI28835, R01 AI040725, K08AI01332] NR 42 TC 37 Z9 39 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1999 VL 67 IS 4 BP 1694 EP 1701 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700023 PM 10085006 ER PT J AU Kirikae, T Nitta, T Kirikae, F Suda, Y Kusumoto, S Qureshi, N Nakano, M AF Kirikae, T Nitta, T Kirikae, F Suda, Y Kusumoto, S Qureshi, N Nakano, M TI Lipopolysaccharides (LPS) of oral black-pigmented bacteria induce tumor necrosis factor production by LPS-refractory C3H/HeJ macrophages in a way different from that of Salmonella LPS SO INFECTION AND IMMUNITY LA English DT Article ID DIPHOSPHORYL-LIPID-A; PORPHYROMONAS BACTEROIDES GINGIVALIS; RHODOPSEUDOMONAS-SPHAEROIDES; C3H-HEJ MICE; CHEMICAL-STRUCTURE; ENDOTOXIN PROTEIN; SPLEEN-CELLS; GAMMA; TAXOL; 2-KETO-3-DEOXYOCTONATE AB Some lipopolysaccharide (LPS) preparations from S- or R-form members of the family Enterobacteriaceae and oral black-pigmented bacteria (Porphyromonas gingivalis and Prevotella intermedia) are known to activate LPS-refractory C3H/HeJ macrophages, When contaminating proteins are removed from R-form LPS of Enterobacteriaceae by repurification, however, this ability is lost. In the present study, we investigated the capacity of LPS from P. gingivalis, P. intermedia, Salmonella minnesota, and Salmonella abortusequi to induce production of tumor necrosis factor (TNF) in gamma interferon-primed C3H/HeJ macrophages before and after repurification. P. abortusequi S-LPS was fractionated by centrifugal partition chromatography into bo LPS forms: SL-LPS, having homologous long O-polysaccharide chains, and SS-LPS having short oligosaccharide chains. Prior to repurification, all LPS forms except SL-LPS induced TNF production in both C3H/HeJ and C3H/HeN macrophages, Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that repurification removed contaminating protein from the preparations, and repurified SS-LPS and S. minnesota Ra-LPS no longer stimulated TNF production in C3H/HeJ macrophages, although C3H/HeN macrophages remained responsive. In contrast, repurified oral bacterial LPS retained the capacity to induce TNF production in C3H/HeJ macrophages. Oral bacterial LPS preparations also were not antagonized by excess inactive, repurified SL-LPS; Ra-LPS; Rhodobacter sphaeroides lipid A, a competitive LPS antagonist, or paclitaxel, an LPS agonist, and they were comparatively resistant to polymyxin B treatment. Nevertheless, oral bacterial LPS was less toxic to D-galactosamine-treated C3H/HeN mice than was LPS from Salmonella. These findings indicate that the active molecule(s) and mode of action of LPS from P. gingivalis and P. intermedia are quite different from those of LPS from Salmonella. C1 Jichi Med Sch, Dept Microbiol, Minami Kawachi, Tochigi 3290498, Japan. Ohu Univ, Sch Dent, Dept Bacteriol, Koriyama, Fukushima 9638611, Japan. Osaka Univ, Fac Sci, Toyonaka, Osaka 5600043, Japan. William S Middleton Mem Vet Adm Med Ctr, Mycobacterial Res Lab, Madison, WI 53706 USA. RP Kirikae, T (reprint author), Jichi Med Sch, Dept Microbiol, 3311-1 Yakushiji, Minami Kawachi, Tochigi 3290498, Japan. EM tkirikae@jichi.ac.jp NR 41 TC 77 Z9 83 U1 0 U2 4 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 APR PY 1999 VL 67 IS 4 BP 1736 EP 1742 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700029 PM 10085012 ER PT J AU Fox, JG Gorelick, PL Kullberg, MC Ge, ZM Dewhirst, FE Ward, JM AF Fox, JG Gorelick, PL Kullberg, MC Ge, ZM Dewhirst, FE Ward, JM TI Novel urease-negative Helicobacter species associated with colitis and typhlitis in IL-10-deficient mice SO INFECTION AND IMMUNITY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; SP-NOV; INTERLEUKIN-10-DEFICIENT MICE; BACTERIAL-INFECTION; HEPATICUS; ENTEROCOLITIS; LIVERS; PYLORI AB A spiral-shaped bacterium with bipolar, single-sheathed flagella was isolated from the intestines of IL-10 (interleukin-10) deficient (IL-10(-/-)) mice with inflammatory bowel disease. The organism aas microaerobic, grew at 37 and 42 degrees C, and was oxidase and catalase positive but urease negative. On the basis of 16S rRNA gene sequence analysis and biochemical and phenotypic criteria, the organism is classified as a novel helicobacter. Cesarean section-rederived IL-10(-/-) mice without helicobacter infection did not have histological evidence of intestinal inflammation. However, helicobacter-free IL-10(-/-), SCID/NCr, and A/JNCr mice experimentally inoculated with the novel urease-negative Helicobacter sp. developed variable degrees of inflammation in the lower intestine, and in immunocompetent mice, the experimental infection was accompanied by a corresponding elevated immunoglobulin G antibody response to the novel Helicobacter sp. antigen. These data support other recent studies which demonstrate that multiple Helicobacter spp. in both naturally and experimentally infected mice can induce inflammatory bowel disease. The mouse model of helicobacter-associated intestinal inflammation should prove valuable in understanding how specific microbial antigens influence a complex disease process. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. NCI, Anim Hlth Diagnost Lab, Lab Anim Sci Program, FCRDC,Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Off Lab Anim Resources,Div Basic Sci, Frederick, MD 21702 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCI NIH HHS [P01 CA026731, P01CA26731, R01 CA067529, R01CA67529]; NCRR NIH HHS [RR010146]; NIDDK NIH HHS [R01 DK052413] NR 29 TC 86 Z9 88 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1999 VL 67 IS 4 BP 1757 EP 1762 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700032 PM 10085015 ER PT J AU Iezzoni, LI Davis, RB Palmer, RH Cahalane, M Hamel, MB Mukamal, K Phillips, RS Banks, NJ Davies, DT AF Iezzoni, LI Davis, RB Palmer, RH Cahalane, M Hamel, MB Mukamal, K Phillips, RS Banks, NJ Davies, DT TI Does the Complications Screening Program flag cases with process of care problems? Using explicit criteria to judge processes SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE administrative data; discharge abstracts; hospital complications; processes of care; quality measurement ID PROSPECTIVE-PAYMENT SYSTEM; HOSPITAL DEATH RATES; ADVERSE DRUG EVENTS; ADMINISTRATIVE DATA; PERFORMANCE REPORTS; MEDICARE CLAIMS; SOUNDING BOARD; QUALITY; MORTALITY; OUTCOMES AB Background. The Complications Screening Program (CSP) aims to identify 28 potentially preventable complications of hospital care using computerized discharge abstracts, including demographic information, diagnosis and procedure codes. Objective. To validate the CSF as a quality indicator by using explicit process of care criteria to determine whether hospital discharges flagged by the CSP experienced more process problems than unflagged discharges. Methods. The CSP was applied to computerized hospital discharge abstracts from Medicare beneficiaries greater than or equal to 65 years old admitted in 1994 to hospitals in California and Connecticut for major surgery or medical treatment. Of 28 CSP complications, 17 occurred sufficiently frequently to study. Discharges flagged (cases) and unflagged (controls) by the CSP were sampled and photocopied medical records were obtained. Physicians specified detailed, objective, explicit criteria, itemizing 'key steps' in processes of care that could potentially have prevented or caused complications. Trained nurses abstracted medical records using these explicit criteria. Process problem rates between cases and controls were compared. Results. The final sample included 740 surgical and 416 medical discharges. Rates of process problems were high, ranging from 24.4 to 82.5% across CSP screens for surgical cases. Problems were lower for medical cases, ranging from 2.0 to 69.1% across CSP screens. Problem rates were 45.7% for surgical and 5.0% for medical controls. Rates of problems did not differ significantly across flagged and unflagged discharges. Conclusions. The CSP did not flag discharges with significantly higher rates of explicit process problems than unflagged discharges. Various initiatives throughout the USA use techniques similar to the CSP to identify complications of care. Based on these CSP findings, such approaches should be evaluated cautiously. C1 Harvard Univ, Beth Deaconess Med Ctr, Sch Med, Dept Med,Div Gen Med & Primary Care, Boston, MA 02215 USA. Charles A Dana Res Inst, Boston, MA 02215 USA. Harvard Thorndike Lab, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. RP Iezzoni, LI (reprint author), Harvard Univ, Beth Deaconess Med Ctr, Sch Med, Dept Med,Div Gen Med & Primary Care, E Campus,330 Brookline Ave,LY-326, Boston, MA 02215 USA. FU AHRQ HHS [R01 HS09099] NR 50 TC 36 Z9 36 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD APR PY 1999 VL 11 IS 2 BP 107 EP 118 DI 10.1093/intqhc/11.2.107 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 188ME UT WOS:000079850200005 PM 10442841 ER PT J AU Saluzzi-Oefner, J Duerinckx, A AF Saluzzi-Oefner, J Duerinckx, A TI NASCI editorial SO INTERNATIONAL JOURNAL OF CARDIAC IMAGING LA English DT Editorial Material C1 NASCI, San Francisco, CA 94080 USA. W Los Angeles Vet Affairs Med Ctr, MRI Clin, Serv Radiol, Los Angeles, CA 90073 USA. RP Saluzzi-Oefner, J (reprint author), NASCI, 156 S Spruce Ave,Suite 207A, San Francisco, CA 94080 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-9899 J9 INT J CARDIAC IMAG JI Int. J. Card. Imaging PD APR PY 1999 VL 15 IS 2 BP 95 EP 96 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 222UR UT WOS:000081804100001 ER PT J AU Marks, LB Hardenbergh, PH Winer, ET Prosnitz, LR AF Marks, LB Hardenbergh, PH Winer, ET Prosnitz, LR TI Assessing the cost-effectiveness of postmastectomy radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 18-23, 1997 CL ORLANDO, FLORIDA SP Amer Soc Therapeut Radiol & Oncol DE cost; charges; effectiveness; benefit; utility; postmastectomy; radiation therapy; breast cancer ID EARLY BREAST-CANCER; ISOLATED LOCOREGIONAL RECURRENCE; LOCAL-REGIONAL RECURRENCE; ADJUVANT SYSTEMIC THERAPY; TERM FOLLOW-UP; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED TRIAL; PREMENOPAUSAL WOMEN; CHEMOTHERAPY; MASTECTOMY AB Purpose: To assess the cost-effectiveness of postmastectomy local-regional radiation therapy (RT) for patients with breast cancer with regard to local-regional relapse (LRR) and quality-adjusted life years (QALY), Methods and Materials: Data from the literature are used to estimate the risk of LRR, and the impact of RT on the risk of LRR and survival. The risk of LRR is related linearly to the number of positive axillary nodes [% rate of LRR = 10 + (4 x number of positive nodes)], RT reduces the risk of LRR by 67%, LRRs are treated with excision or biopsy followed by RT; half being controlled locally and half receiving additional salvage surgery and chemotherapy, Absolute improvements in 10-year overall survival due to RT are assumed to vary between 1 and 12%; and accrue linearly during the initial 10-year follow-up period. Professional and technical charges are used as a surrogate for costs. Money spent and benefits recognized in future years are discounted to 1997 values using a 3% annual rate. Quality factors are used to adjust for treatment, disease, and toxicity status. Results: The cost per LRR prevented with the addition of routine postmastectomy RT is highly dependent upon the number of positive axillary nodes and ranges from $100,000-$200,000 for patients with 0-2 nodes, and $25,000-$75,000 for greater than or equal to 4 nodes. The cost per QALY gained at 10 years is $10,000-$110,000 for survival benefits greater than or equal to 3%, Conclusions: The cost per LRR prevented decreases with increasing numbers of positive axillary nodes. There is not a sharp cutoff at the less than or equal to 3 vs. greater than or equal to 4 lymph node number, suggesting that using this cutoff for recommending or not recommending RT following mastectomy is not economically logical. The cost per QALY of $10,000-$100,000 compares favorably to that of other accepted medical procedures. Modest changes in the quantitative assumptions do not qualitatively alter the results. Concerns regarding costs should not generally preclude the use of postmastectomy RT, (C) 1999 Elsevier Science Inc. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. RP Marks, LB (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3085, Durham, NC 27710 USA. NR 61 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 1999 VL 44 IS 1 BP 91 EP 98 DI 10.1016/S0360-3016(98)00520-3 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 187JQ UT WOS:000079783800012 PM 10219800 ER PT J AU Wade, WG Downes, J Dymock, D Hiom, SJ Weightman, AJ Dewhirst, FE Paster, BJ Tzellas, N Coleman, B AF Wade, WG Downes, J Dymock, D Hiom, SJ Weightman, AJ Dewhirst, FE Paster, BJ Tzellas, N Coleman, B TI The family Coriobacteriaceae: reclassification of Eubacterium exiguum (Poco et al. 1996) and Peptostreptococcus heliotrinreducens (Lanigan 1976) as Slackia exigua gen. nov., comb. nov. and Slackia heliotrinireducens gen. nov., comb. nov., and Eubacterium lentum (Prevot 1938) as Eggerthella lenta gen. nov., comb. nov. SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article DE Coriobacteriaceae; Eubacterium; Peptostreptococcus; Slackia; Eggerthella ID ORAL ASACCHAROLYTIC EUBACTERIUM; IDENTIFICATION; PHYLOGENY AB 16S rRNA gene sequences were determined for Eubacterium exiguum and Peptostreptococcus heliotrinreducens. These species were found to be closely related and, together with Eubacterium lentum, to constitute a branch of the Coriobacteriaceae. Two new genera are proposed on the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons: Slackia to include the bile-sensitive species Eubacterium exiguum and P. heliotrinreducens, and Eggerthella to include the bile-resistant Eubacterium lentum. It is proposed that Eukacterium exiguum and Peptostreptococcus heliotrinreducens are transferred to the genus Slackia gen. nov. as Slackia exigua gen. nov., comb. nov. (type strain ATCC 700122(T)) and Slackia heliotrinireducens gen. nov., comb. nov. (type strain NTCC 11029(T)), respectively, and Eubacterium lentum is transferred to the genus Eggerthella gen. nov. as Eggerthella lenta gen, nov., comb, nov. with Eggerthella lenta as the type species. C1 Univ London Kings Coll, Guys Hosp, Dept Oral Med & Pathol, London SE1 9RT, England. Univ Bristol, Dept Oral & Dent Sci, Bristol BS1 2LY, Avon, England. Univ Wales, Sch Pure & Appl Biol, Cardiff CF1 3TL, S Glam, Wales. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. RP Wade, WG (reprint author), Univ London Kings Coll, Guys Hosp, Dept Oral Med & Pathol, London SE1 9RT, England. RI Weightman, Andrew/A-2970-2010 OI Weightman, Andrew/0000-0002-6671-2209 FU NIDCR NIH HHS [DE-10374, DE-11443] NR 30 TC 89 Z9 89 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1999 VL 49 BP 595 EP 600 PN 2 PG 6 WC Microbiology SC Microbiology GA 191LU UT WOS:000080024500030 PM 10319481 ER PT J AU Morimura, H Berson, EL Dryja, TP AF Morimura, H Berson, EL Dryja, TP TI Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PIGMENTOSA; RHODOPSIN; CLONING AB PURPOSE. To determine the frequency and spectrum of mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein (CRALBP) in patients with hereditary retinal degeneration. METHODS. The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen the coding exons of this gene (exons 2-8) for mutations in 324 unrelated patients with recessive or isolate retinitis pigmentosa, retinitis punctata albescens, Leber congenital amaurosis, or a related disease. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered the coding region or intron splice sites were evaluated further through segregation analysis in the families of the index cases. RESULTS. Four novel mutations were identified in this gene among three unrelated patients with recessively inherited retinitis punctata albescens. Two of the mutations were missense: one was a frameshift, and one affected a canonical splice donor site. CONCLUSIONS,us. Recessive mutations in the RLBP1 gene are an uncommon cause of retinal degeneration in humans. The phenotype produced by RLBP1 mutations seems to be a form of retinitis punctata albescens. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683] NR 15 TC 84 Z9 86 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1999 VL 40 IS 5 BP 1000 EP 1004 PG 5 WC Ophthalmology SC Ophthalmology GA 180DZ UT WOS:000079371500023 PM 10102299 ER PT J AU Kradin, R AF Kradin, R TI Generosity: a psychological and interpersonal motivational factor of therapeutic relevance SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Article DE analytic training; evolution; generosity; motivation; myth; psychotherapy; procreation AB This paper examines the role of generosity in analysis. Generosity represents a complex constellation of cognitions and affects that is antithetical to those states of super-ego harshness that characterize many forms of human psychopathology. In develop ment, generosity is evoked by idealization, and a dynamic axis of idealization-generosity promotes relational proximity between the child and its caretakers, and eventually fosters separation and individuation. Generosity is highly sensitive to adverse conditions, and requires environmental conditions that are conducive to psychosomatic well-being. The imaginal basis of generosity is rooted in the myth of the 'hero and the return', which is the mythic foundation of the analyst's role as psychopomp. It is argued that the generosity of the analyst is a cardinal therapeutic factor in treatment. C1 Massachusetts Gen Hosp, Dept Pulm Med Pathol & Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Pulm Med Pathol & Psychiat, Cox 5 Bldg, Boston, MA 02114 USA. NR 41 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD APR PY 1999 VL 44 IS 2 BP 221 EP 236 DI 10.1111/1465-5922.00085 PG 16 WC Psychology, Psychoanalysis SC Psychology GA 191DQ UT WOS:000080006800005 PM 10355370 ER PT J AU Kradin, R AF Kradin, R TI Response to Richard Kradin's 'Generosity: a psychological and interpersonal motivational factor of therapeutic relevance' Reply to Ann Casement SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pulm Med Pathol & Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Pulm Med Pathol & Psychiat, Cox 5 Bldg, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD APR PY 1999 VL 44 IS 2 BP 245 EP 248 DI 10.1111/1465-5922.00087 PG 4 WC Psychology, Psychoanalysis SC Psychology GA 191DQ UT WOS:000080006800007 ER PT J AU Lamb, DC Tribble, J Doukas, AG Flotte, TJ Ossoff, RH Reinisch, L AF Lamb, DC Tribble, J Doukas, AG Flotte, TJ Ossoff, RH Reinisch, L TI Custom designed acoustic pulses SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photoacoustic liquids; free electron lasers; biological acoustics; stress waves; computer simulations ID SHOCK-WAVES; IN-VITRO; LASER; MEMBRANE; CELL; WATER AB We have used a tunable, infrared, free-electron laser with a Pockels cell controlled pulse duration to generate photoacoustic pulses with separate variable rise times (from 15 to 100 ns), durations (100-400 ns), and amplitudes (0.005-0.1 M.Pa). The tunability of the free-electron laser across water absorption bands allows the rise time of the thermal-elastically generated acoustical pulsed to be varied, while a Pockels cell controls the duration and cross polarizers control the pressure amplitude. The mechanical effects of pressure transients on biological tissue can have dramatic consequences. In addition to cell necrosis, carefully controled pressure transients can also be used for therapeutic applications, such as drug delivery and gene therapy; This technique permits systemic probing of how biological tissue is affected by stress transients. (C) 1999 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(99)00302-0]. C1 Vanderbilt Univ, Med Ctr, Dept Otolaryngol, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Reinisch, L (reprint author), Vanderbilt Univ, Med Ctr, Dept Otolaryngol, Nashville, TN 37232 USA. RI Lamb, Don/G-9501-2014 OI Lamb, Don/0000-0002-0232-1903 NR 20 TC 5 Z9 5 U1 0 U2 1 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 1999 VL 4 IS 2 BP 217 EP 223 DI 10.1117/1.429912 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 229FZ UT WOS:000082184000004 PM 23015207 ER PT J AU Dearborn, JT Harris, WH AF Dearborn, JT Harris, WH TI High placement of an acetabular component inserted without cement in a revision total hip arthroplasty - Results after a mean of ten years SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REINFORCEMENT RING; RECONSTRUCTION; BONE AB Background Revision of an acetabular component in a patient who has severe periacetabular bone loss is a complex problem, particularly when there is not enough bone stock to allow placement of an acetabular component near the normal anatomical hip center. A valuable option for revision in such a situation is placement of a hemispherical shell, fixed with screws and without cement, against the superior margin of the acetabular defect. The resulting hip center is more proximal than that seen following a typical primary total hip replacement. Methods: Forty-six hips in forty-four patients were treated consecutively, between July 1984 and February 1988, with a revision in which a hemispherical acetabular component was fixed,vith screws and without cement. All shells but one were placed,vith a so-called line-to-line fit. The procedures resulted in a so-called high hip center - that is, the center of rotation of the revised hip was located at least thirty-five millimeters proximal to the interteardrop line. The mean age of the patients at the time of the index procedure was fifty-two years (range, twenty-five to eighty-one years). The most common diagnosis for which the original arthroplasty was performed was osteoarthritis secondary to congenital hip dysplasia or dislocation (twenty-two hips). Thirty-four hips had had a high hip center before the index revision, and most patients had had a substantial limb-length discrepancy, with a mean of 1.6 centimeters of shortening on the side of the operation. In thirty-three hips, the femoral component was replaced as well,,vith a long-neck or calcar-replacement stem used when necessary to maintain or increase the length of the limb. Results: Six patients (six hips) died before the minimum eight-year follow-up interval; none had had another revision or loosening of the revised acetabular component. Of the remaining patients, four (four hips) had the implant removed. One of them had a resection arthroplasty and one of them had a hip disarticulation because of infection after a subsequent femoral reoperation. Another had a hip disarticulation because of late infection. The fourth implant was removed because it had displaced into the pelvis at approximately six years; this was the only reoperation for aseptic loosening in the series. The remaining thirty-six hips (thirty-four patients) were followed for a mean of 10.4 years (range, 8.5 to 12.7 years). One acetabular component migrated medially and was scheduled for revision. No other acetabular component was loose or had been revised. The mean Harris hip score was 81 points (range, 56 to 100 points) at the time of the most recent follow-up. Despite the use of a high hip center, the prevalence of a positive Trendelenburg sign was reduced from 98 percent (forty-five of forty-six hips) preoperatively to 44 percent (sixteen of thirty-six hips) at the time of the most recent follow-up. The short limbs were lengthened a mean of seven millimeters (range, five millimeters of shortening to forty millimeters of lengthening). Conclusions: Tn this study of acetabular revisions with use of a high hip center in patients who had major periacetabular bone loss, mechanical failure occurred in 4 percent (two) of the forty-six hips in the entire series and in 6 percent (two) of the thirty-six hips in patients who were alive and still had the implant in place after a mean of 10.4 years of follow-up. The use of a high hip center did not adversely affect function of the abductor muscles, and the mean limb-length discrepancy was reduced by the femoral reconstruction. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hip & Implant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Dearborn, JT (reprint author), Fremont Orthopaed Med Grp, 38690 Stivers St, Fremont, CA 94536 USA. NR 44 TC 80 Z9 91 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 APR PY 1999 VL 81A IS 4 BP 469 EP 480 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 188FB UT WOS:000079835200004 PM 10225792 ER PT J AU Li, YP Chen, W AF Li, YP Chen, W TI Characterization of mouse cathepsin K gene, the gene promoter, and the gene expression SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MOLECULAR-CLONING; TISSUE DISTRIBUTION; HUMAN OSTEOCLASTS; GELATINASE-B; PYCNODYSOSTOSIS; CDNA; BONE; OSTEOPETROSIS; LOCALIZATION; SEQUENCE AB Cathepsin K, a lysosomal cysteine protease, is abundantly and selectively expressed in osteoclasts and has a specialized role in osteoclast-mediated bone resorption, In contrast to function studies, transcription regulation of cathepsin Ii remains largely unknown. In this study, the gene encoding mouse cathepsin K and the promoter have been isolated and completely sequenced. In addition, the temporal and spatial expressions of cathepsin K have been characterized. Intrachromosomal mapping studies revealed that the gene contains eight exons and seven introns spanning -10.6 kb of genomic DNA, a genomic organization that was highly conserved with respect to its human homology. Analysis of the 9 kb 5' flanking region indicates that this gene lacks canonical TATA and CAAT boxes and contains multiple putative transcription regulatory elements which are also present in the comparable position of 5' flanking region of human cathepsin K gene. Mouse cathepsin K was found to be a single-copy gene. Northern blot analysis of RNAs from a number of mouse tissues revealed that cathepsin K mRNA is selectively expressed in osteoclast. The selective expression of cathepsin K was confirmed by anticathepsin K immunohistochemical staining. The sequence of cathepsin K expression was linked to osteoclast differentiation in vivo and in vitro by a tartrate-resistant acid phosphatase-anticathepsin K dual imnunostaining technique. Cathepsin K is initially expressed at the preosteoclast stage and throughout the mature osteoclast stage. The primer extension assay indicated a major transcription start site 58 bp upstream of the initiator Met codon. The characterization of the cathepsin K gene, its promoter, and the temporal and spatial expression may provide valuable insights into its osteoclast-specific expression and the molecular mechanisms responsible for osteoclast activation. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 104 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10887] NR 30 TC 47 Z9 49 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1999 VL 14 IS 4 BP 487 EP 499 DI 10.1359/jbmr.1999.14.4.487 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178LL UT WOS:000079267100003 PM 10234569 ER PT J AU Zhou, L Keane, D Reed, G Ruskin, J AF Zhou, L Keane, D Reed, G Ruskin, J TI Thromboembolic complications of cardiac radiofrequency catheter ablation: A review of the reported incidence, pathogenesis and current research directions SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Review DE thrombosis; embolism; thromboembolism; catheter ablation; arrhythmia ID PARKINSON-WHITE SYNDROME; ACCESSORY ATRIOVENTRICULAR PATHWAYS; ATRIAL-FIBRILLATION; EMBOLIC COMPLICATIONS; MAZE PROCEDURE; TACHYARRHYTHMIAS; EXPERIENCE; TACHYCARDIA; TICLOPIDINE; DIAGNOSIS AB Thromboembolic Complications of Cardiac RF Catheter Ablation. introduction: Radiofrequency catheter ablation (RFCA) has become established as an effective therapy for the treatment of many cardiac tachyarrhythmias, The principle limitation of conventional RFCA continues to be the risk of thromboembolism. This risk is of particular concern for the ongoing development of the catheter maze procedure for the treatment of atrial fibrillation, which currently involves the creation of extensive linear lesions in the left atrium, Methods and Results: A Medline search of the literature over the last ten years was performed. Focused review of the reported thromboembolic complications of RFCA indicates an overall incidence of 0.6%. However, the risk is increased when ablation is performed in the left heart (1.8% to 2%) and for ventricular tachycardia (2.8%). It is of concern that intravenous heparin and the use of temperature feedback; to control radiofrequency current do not eliminate the risk of thromboembolic events. Conclusion: The thromboembolic complications of RFCA are not eliminated by the treatment of intravenous herapin and mode of temperature control during ablation. Potential approaches to further reduce the risk of thromboembolism include the adjunctive administration of specific inhibitors of platelet activation and aggregation, intraprocedural intracardiac echocardiography, irrigated radiofrequency ablation, and cryoablation catheter systems. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA USA. RP Keane, D (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 48 TC 120 Z9 131 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 1999 VL 10 IS 4 BP 611 EP 620 DI 10.1111/j.1540-8167.1999.tb00719.x PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 190TG UT WOS:000079980500015 PM 10355704 ER PT J AU Fiskum, G Murphy, AN Beal, MF AF Fiskum, G Murphy, AN Beal, MF TI Mitochondria in neurodegeneration: Acute ischemia and chronic neurodegenerative diseases SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE Alzheimer's disease; Parkinson's disease; Huntington's disease; amyotrophic lateral sclerosis; cerebral ischemia; stroke; apoptosis; mitochondrial membrane permeability transition ID AMYOTROPHIC-LATERAL-SCLEROSIS; NITRIC-OXIDE SYNTHASE; TRANSIENT FOREBRAIN ISCHEMIA; AMYLOID PRECURSOR PROTEIN; CYTOCHROME-C-OXIDASE; MOTOR-NEURON DISEASE; ACETYL-L-CARNITINE; MAGNETIC-RESONANCE SPECTROSCOPY; KETOGLUTARATE DEHYDROGENASE COMPLEX; IDIOPATHIC PARKINSONS-DISEASE C1 Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. MitoKor, San Diego, CA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Fiskum, G (reprint author), Univ Maryland, Sch Med, Dept Anesthesiol, 685 W Baltimore St,MSTF 534, Baltimore, MD 21201 USA. OI Murphy, Anne N/0000-0002-5222-9902 FU NINDS NIH HHS [NS16367, NS34152, NS34154] NR 274 TC 263 Z9 277 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 1999 VL 19 IS 4 BP 351 EP 369 PG 19 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 263FP UT WOS:000084115000001 PM 10197505 ER PT J AU Allen, DN Goldstein, G Mariano, E AF Allen, DN Goldstein, G Mariano, E TI Is the Halstead Category Test a multidimensional instrument? SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID INTELLIGENCE AB Factor structure of the Halstead Category Test was evaluated in patients with schizophrenia, heterogeneous forms of brain damage, and patient controls using confirmatory factor analysis. Analyses were performed including and excluding subtests 1 and 2. In the first analysis, a three-factor model was optimal, with subtests 1 and 2 loading on one factor (Counting), 3, 4, and 7 loading on a second factor (Spatial Positional Reasoning), and subtests 5 and 6 loading on a third factor (Proportional Reasoning). Excluding subtests 1 and 2, a two-factor solution was optimal consisting of the Spatial Positional (subtests 3 and 4) and Proportional Reasoning (subtests 5 and 6) factors, with subtest 7 loading on both factors. Optimal factor structures for the three groups were identical. Correlations between factor scores were similar among groups. Factor scores also correlated significantly (p < .01) with all of the other cognitive measures. It was concluded that the Category Test is a multidimensional procedure with factors associated in a general way with other cognitive abilities. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Allen, DN (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 24 TC 11 Z9 11 U1 1 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD APR PY 1999 VL 21 IS 2 BP 237 EP 244 DI 10.1076/jcen.21.2.237.926 PG 8 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 226CL UT WOS:000082002700008 PM 10425520 ER PT J AU Finkelstein, JS Arnold, AL AF Finkelstein, JS Arnold, AL TI Increases in bone mineral density after discontinuation of daily human parathyroid hormone and gonadotropin-releasing hormone analog administration in women with endometriosis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-RAY ABSORPTIOMETRY; OVARIECTOMIZED RATS; ESTROGEN-DEFICIENCY; POSTMENOPAUSAL WOMEN; PRIMARY HYPERPARATHYROIDISM; PREMENOPAUSAL WOMEN; REPLACEMENT THERAPY; CONTROLLED-TRIAL; MASS; OSTEOPOROSIS AB Intermittent PTH administration increases spinal bone mineral density (BMD) and prevents bone loss from the hip and total body in young women treated with a long acting GnRH analog for endometriosis. To establish whether these beneficial effects on BMD persist after PTH administration is discontinued, we remeasured BMD and biochemical markers of bone turnover in 38 women with endometriosis who had been treated with a GnRH analog alone (nafarelin acetate; 200 mu g, intranasally, twice daily; n = 23; group I) or who had received nafarelin plus human PTH-(1-34) (40 mu g/day, sc; n = 15; group 2) for 6-12 months 1 yr after therapy was completed. Cyclic menstrual function returned promptly after nafarelin therapy was discontinued. In group 1, BMD increased significantly at all sites [P < 0.001 for the anterior-posterior (API and lateral spine; P = 0.014 for the femoral neck; P = 0.004 for the trochanter], except the proximal radius (P = 0.065) and total body bone density (P = 0.069 after nafarelin therapy was stopped. In group 2, BMD increased significantly at the AP spine (P < 0.001), lateral spine (P = 0.012), femoral neck (P = 0.002), and trochanter (P = 0.029) after nafarelin therapy was stopped. BMD of the spine in the AP projection increased more in group 2 and than in group 1 after therapy was stopped (P = 0.045). Despite these increases after discontinuation of nafarelin therapy, BR;ID was still significantly below baseline values at the AP spine (P < 0.001) and femoral neck (P = 0.006) and tended to be lower than baseline values at the trochanter (P = 0.057) and total body (P = 0.101) at the end of the 1-yr follow-up period in group 1, In contrast, BMD was significantly above baseline values at the AP and lateral spine (P < 0.001) sites and was similar to baseline values at the other skeletal Bites at the end of the 1-yr follow-up period in group 2, Bone turnover returned to baseline values in both groups when therapy was stopped. We conclude that the beneficial effects of PTH on bone persist in women who regain cyclic menstrual function. Although part of the increases in BMD are probably due to restoration of ovarian function, additional increases in BMD most likely represent a further anabolic effect of PTH on bone that is not detected until after PTH administration is stopped. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM finkelstein@helix.mgh.harvard.edu FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [R29-DK-43341] NR 42 TC 27 Z9 27 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1999 VL 84 IS 4 BP 1214 EP 1219 DI 10.1210/jc.84.4.1214 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 183RN UT WOS:000079567400010 PM 10199756 ER PT J AU Deutsch, JC Sandhu, IS Lawrence, SP AF Deutsch, JC Sandhu, IS Lawrence, SP TI Splenosis presenting as an ulcerated gastric mass - Endoscopic and endoscopic ultrasonographic imaging SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE splenosis; endoscopic ultrasonography ID LEFT RENAL MASS; THORACIC SPLENOSIS; MIMICKING AB A case of an ulcerated gastric wall mass ultimately found to be splenosis is presented in which the index patient had endoscopic and endoscopic ultrasonographic evaluation prior to resection. Although no visual features identified this mass as a splenic implant preoperatively, the lesion appeared to be atypical for leiomyoma, which led to surgical intervention. The role of endoscopic ultrasonography in assessing isolated gastric masses is discussed. C1 Denver Vet Affairs Hosp, Div Gastroenterol, Denver, CO 80220 USA. Denver Vet Affairs Hosp, Div Hematol, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. RP Deutsch, JC (reprint author), Denver Vet Affairs Hosp, Div Gastroenterol, 4200 E 9th Ave,Campus Box B-170, Denver, CO 80220 USA. NR 15 TC 5 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD APR PY 1999 VL 28 IS 3 BP 266 EP 267 DI 10.1097/00004836-199904000-00020 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 178XH UT WOS:000079294100020 PM 10192620 ER PT J AU Virkamaki, A Ueki, K Kahn, CR AF Virkamaki, A Ueki, K Kahn, CR TI Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR TYROSINE KINASES; GUANINE-NUCLEOTIDE EXCHANGE; MEMBRANE GLYCOPROTEIN PC-1; AMINO-ACID POLYMORPHISM; SRC HOMOLOGY-2 DOMAINS; SKELETAL-MUSCLE; IN-VIVO C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM kahnr@joslab.harvard.edu FU NIDDK NIH HHS [DK-31036, DK-33201, DK-45935, R01 DK031036, R01 DK033201, R01 DK045935, R37 DK031036] NR 168 TC 577 Z9 598 U1 0 U2 20 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 1999 VL 103 IS 7 BP 931 EP 943 DI 10.1172/JCI6609 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 184VA UT WOS:000079633400002 PM 10194465 ER PT J AU Spergel, JM Mizoguchi, E Oettgen, H Bhan, AK Geha, R AF Spergel, JM Mizoguchi, E Oettgen, H Bhan, AK Geha, R TI Roles of T(H)1 and T(H)2 cytokines in a murine model of allergic dermatitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ATOPIC-DERMATITIS; INTERFERON-GAMMA; IFN-GAMMA; T-CELLS; EOSINOPHILIC INFLAMMATION; BRONCHIAL HYPERREACTIVITY; AIRWAYS HYPERREACTIVITY; KNOCKOUT MICE; LUNG DAMAGE; EXPRESSION AB Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-gamma. The role of these cytokines in the pathogenesis of AD is nor known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-gamma cytokine genes to assess the role of these cytokines in this model. OVA-sensitized skin from IL-5(-/-) mice had no detectable eosinophils and exhibited decreased epidermal and dermal thickening. Sensitized skin from IL-4(-/-) mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells. These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1 beta, and RANTES. Sensitized skin from IFN-gamma(-/-) mice was characterized by reduced dermal thickening. These results suggest that both the T(H)2 cytokines IL-4 and IL-5 and the T(H)1 cytokine IFN-gamma play important roles in the inflammation and hypertrophy of the skin in AD. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Dept Immunopathol, Boston, MA 02101 USA. RP Geha, R (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Enders 8,300 Longwood Ave, Boston, MA 02115 USA. OI Spergel, Jonathan/0000-0002-4658-5353 FU NIAID NIH HHS [P01 AI031541, R01 AI031136, U19 AI031541, T32 AI007512]; NICHD NIH HHS [P30HD27805]; NIDDK NIH HHS [DK-43551, R01 DK047677, DK-47677] NR 49 TC 243 Z9 252 U1 1 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 1999 VL 103 IS 8 BP 1103 EP 1111 DI 10.1172/JCI5669 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 189ED UT WOS:000079890400001 PM 10207161 ER PT J AU Koh, TJ Dockray, GJ Varro, A Cahill, RJ Dangler, CA Fox, JG Wang, TC AF Koh, TJ Dockray, GJ Varro, A Cahill, RJ Dangler, CA Fox, JG Wang, TC TI Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL-PROLIFERATION; RECEPTOR ANTAGONISTS; COLORECTAL-CARCINOMA; BINDING PROTEIN; GROWTH-FACTOR; PROGASTRIN; EXPRESSION; CANCER; CHOLECYSTOKININ; MUCOSA AB Gastrin is a peptide hormone involved in the growth of both normal and malignant gastrointestinal tissue. Recent studies suggest that the glycine-extended biosynthetic intermediates mediate many of these trophic effects, but the in vivo relevance of glycine-extended gastrin (G-Gly) has not been tested. We have generated mice (MTI/G-GLY) that overexpress progastrin truncated at glycine-72 to evaluate the trophic effects of G-Gly in an in vivo model. MTI/G-GLY mice have elevated serum and colonic mucosal levels of G-Gly compared with wild-type mice. MTI/G-GLY mice had a 43% increase in colonic mucosal thickness and a 41% increase in the percentage of goblet cells per crypt. MTI/G-GLY mice exhibited increased colonic proliferation compared with wild-type controls, with an expansion of the proliferative zone into the upper third of the colonic crypts. Continuous infusion of G-Gly into gastrin-deficient mice for two weeks also resulted in elevated G-Gly levels, a 10% increase in colonic mucosal thickness, and an 81% increase in colonic proliferation when compared with gastrin-deficient mice that received saline alone. To our knowledge, these studies demonstrate for the first time that G-Gly's contribute to colonic mucosal proliferation in vivo. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NIDDK NIH HHS [K08 DK02545-01, R01 DK-52778, R01 DK052778]; Wellcome Trust NR 39 TC 119 Z9 121 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 1999 VL 103 IS 8 BP 1119 EP 1126 DI 10.1172/JCI4910 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 189ED UT WOS:000079890400003 PM 10207163 ER PT J AU Richter, S Cormican, MG Pfaller, MA Lee, CK Gingrich, R Rinaldi, MG Sutton, DA AF Richter, S Cormican, MG Pfaller, MA Lee, CK Gingrich, R Rinaldi, MG Sutton, DA TI Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow transplant patient: Species identification and review of the literature SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; SECTION LONGIBRACHIATUM; GENUS TRICHODERMA; RISK-FACTORS; EPIDEMIOLOGY; RECIPIENT; REVISION; PERITONITIS; MANAGEMENT; TRENDS AB Trichoderma longibrachiatum was recovered from stool surveillance cultures and a perirectal ulcer biopsy specimen from a 29-year-old male who had received an allogeneic bone marrow transplant for acute lymphoblastic leukemia. The amphotericin B (2.0 mu g/ml) and itraconazole (1.0 mu g/ml) MICs for the organism were elevated. Therapy with these agents was unsuccessful, and the patient died on day 58 posttransplantation, At autopsy, histologic sections from the lungs, liver, brain, and intestinal wall showed infiltration by branching septate hyphae, Cultures were positive for Trichoderma longibrachiatum. While Trichoderma species have been recognized to be pathogenic in profoundly immunosuppressed hosts with increasing frequency, this is the first report of probable acquisition through the gastrointestinal tract. Salient features regarding the identification of molds in the Trichoderma longibrachiatum species aggregate are presented. C1 Univ Iowa, Coll Med, Dept Pathol, Div Med Microbiol, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Med, Iowa City, IA 52242 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Pfaller, MA (reprint author), Univ Iowa, Coll Med, Dept Pathol, Div Med Microbiol, C606 GH, Iowa City, IA 52242 USA. NR 37 TC 48 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1999 VL 37 IS 4 BP 1154 EP 1160 PG 7 WC Microbiology SC Microbiology GA 175QF UT WOS:000079105500046 PM 10074541 ER PT J AU Cox, JD Gallagher, MJ Hammond, EH Kaplan, RS Schellhammer, PF Crook, JM Leibel, SA Forman, JD Grimm, PD Zietman, AL Hudson, MA Schild, SA Beyer, DC Hussey, DH Thames, H Shipley, WU AF Cox, JD Gallagher, MJ Hammond, EH Kaplan, RS Schellhammer, PF Crook, JM Leibel, SA Forman, JD Grimm, PD Zietman, AL Hudson, MA Schild, SA Beyer, DC Hussey, DH Thames, H Shipley, WU CA Amer Soc Therapeutic Radiol & Oncol Consensus P TI Consensus statements on radiation therapy of prostate cancer: Guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT American-Society-for-Therapeutic-Radiology-and-Oncology Consensus Conference for Prostate Cancer CY SEP 06, 1997 CL ATLANTA, GEORGIA SP Amer Soc Therapeut Radiol & Oncol ID INTERSTITIAL BRACHYTHERAPY; DOSE-ESCALATION; RADIOTHERAPY; ADJUVANT; IRRADIATION AB Purpose: To develop evidence-based guidelines for (1) prostate re-biopsy after radiation and (2) radiation therapy with rising prostate-specific antigen (PSA) levels after radical prostatectomy in the management of patients with localized prostatic cancer. Design: The American Society of Therapeutic Radiology and Oncology (ASTRO) challenged a multidisciplinary consensus panel to address consensus on specific issues in each of the two topics. Four well-analyzed patient data sets were presented for review and questioning by the panel. The panel sought criteria that would be valid for patients in standard clinical practice as well as for patients enrolled in clinical trials. Subsequent to an executive session that followed these presentations, the panel presented its consensus guidelines. Results and Conclusions: Based on the data presented, the prostate re-biopsy negative rates ranged from 62% to 80% for patients with stage T1-2 tumors. The panel judged that prostate re-biopsy is not necessary as standard follow-up care and that the absence of a rising PSA level after radiation therapy is the most rigorous end paint of total tumor eradication. Further, the panel judged that re-biopsy may be an important research tool. Based on the data presented, the longterm (5 years or more) PSA remission rate after salvage radiation therapy ranges from 27% to 45%. The panel requested results from prospective randomized trials to evaluate optimally this information. The panel judged that the total dose of radiation should be 64 Gy or slightly higher and that, in patients with or without radiation therapy, there is no standard role for androgen suppressant therapy for rising PSA values after prostatectomy. (C) 1999 by American Society of Clinical Oncology. C1 MD Anderson Cancer Ctr, Houston, TX USA. Upper Delaware Valley Canc Ctr, Milford, PA USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD USA. Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 17 TC 244 Z9 250 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1155 EP 1163 PG 9 WC Oncology SC Oncology GA 182JR UT WOS:000079496300010 PM 10561174 ER PT J AU Elias, A Ibrahim, J Skarin, AT Wheeler, C McCauley, M Ayash, L Richardson, P Schnipper, L Antman, KH Frei, E AF Elias, A Ibrahim, J Skarin, AT Wheeler, C McCauley, M Ayash, L Richardson, P Schnipper, L Antman, KH Frei, E TI Dose-intensive therapy for limited-stage small-cell lung cancer: Long-term outcome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC PROGENITOR CELLS; DISEASE-FREE SURVIVAL; PERIPHERAL-BLOOD; BRONCHOGENIC-CARCINOMA; MONOCLONAL-ANTIBODIES; RADIATION-THERAPY; CHEMOTHERAPY; METASTASES; RELAPSE AB Purpose: To determine progression-free survival (PFS) and overall long-term survival for limited-stage small-cell lung cancer (SCLC) patients aged 60 years or younger who respond to first-line chemotherapy followed by high-dose combination alkylating agents (cyclophosphamide 5,625 mg/m(2), cisplatin 165 mg/m(2), and carmustine 480 mg/m(2)) with hematologic stem-cell support and chest and prophylactic cranial radiotherapy. patients and Methods: Patients were selected on the basis of their continued response to first-line therapy, their relative lack of significant comorbidity, and their ability to obtain financial clearance. Results: Of 36 patients with stage III SCLC, nine patients (25%) had achieved a complete response (CR), 20 had achieved a near-CR, and seven had achieved a partial response before undergoing high-dose therapy. Toxicity included three deaths (8%). For all patients, the median PFS was 21 months. The 2- and 5-year survival rates after dose intensification were 53% (95% confidence interval [CI], 39% to 72%), and 41%(95% CI, 28% to 61%). Of the 29 patients who were in or near CR before undergoing high-dose therapy, 14 remain continuously progression-free a median of 61 months (range, 40 to 139 months) after high-dose therapy. Actuarial 2- and 5-year PFS rates were 57% (95% CI, 41% to 79%) and 53% (95% CI, 38% to 76%). By multivariate analysis, short intensive induction chemotherapy wets associated with favorable outcome (P < .05). Conclusion: Use of high-dose systemic therapy with intensive local-regional radiotherapy was associated with manageable treatment-related morbidity and mortality. Patients who were in or near CR before intensification are enjoying an unmaintained 5-year PFS rate of 53%. Late complications were infrequent, and most patients returned to full-time work and activity. A randomised comparison of this approach and conventional-dose therapy should define the use of dose intensification with hematopoietic support in patients with responding limited-stage SCLC. (C) 1999 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Dept Med, Boston, MA 02115 USA. RP Elias, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Div Biostat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA13849] NR 45 TC 43 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1175 EP 1184 PG 10 WC Oncology SC Oncology GA 182JR UT WOS:000079496300012 PM 10561176 ER PT J AU Porter, DL Connors, JM Van Deerlin, VMD Duffy, KM McGarigle, C Saidman, SL Leonard, DGB Antin, JH AF Porter, DL Connors, JM Van Deerlin, VMD Duffy, KM McGarigle, C Saidman, SL Leonard, DGB Antin, JH TI Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; MONONUCLEAR CELL INFUSIONS; CHRONIC MYELOID-LEUKEMIA; HOST-DISEASE; IMMUNOTHERAPY; RELAPSE; PHASE; IMMUNOSUPPRESSION; DISCONTINUATION; TRANSFUSIONS AB purpose: Histocompatible allogeneic donor leukocyte infusions (DLIs) were administered as primary cancer therapy in a phase I trial to determine (1) whether mixed chimerism could be detected without a prior allogeneic transplantation, (2) the toxicity of primary DLI, and (3) whether a graft-versus-tumor (GVT) reaction could be observed. Patients and Methods: Eighteen patients were studied, Patients received interferon alfa-ab for a minimum of 4 weeks, followed by DLI (level 1). Patients with no toxicity or engraftment were eligible to receive cytarabine or cyclophosphamide followed by another course of DLI (level 2). Engraftment was determined using polymerase chain reaction amplification of donor and host-specific DNA polymorphisms. Results: Donor cells were detected in the blood in 14 of 16 assessable patients within 1 hour of DLI. Chimerism detectable 4 weeks after DLI was observed in four patients, and five patients were not assessable. Prior autologous transplantation was associated with late chimerism (P =.0014). Acute graft-versus-host disease (GVHD) occurred in four of 16 assessable patients (grade 1, two patients; grade 2, one patient; grade 4, one patient). One patient with grade 4 acute GVHD developed pancytopenia. Only the four patients treated after prior autologous transplantation developed acute GVHD (P =.0005). Three of four patients with acute GVHD and late chimerism responded to primary DLI, and one patient was not assessable for response. Conclusion: Allogeneic adoptive immunotherapy resulted in sustained chimerism, acute GVHD, and a GVT response in heavily pretreated patients, This indicates that it may be possible to generate a direct GVT response for patients with malignancies without the need for intensive conditioning therapy immediately before DLI. Immunosuppression may be required for sustained donor cell engraftment. (C) 1999 by American Society of Clinical Oncology. C1 Univ Penn, Med Ctr, Div Hematol Oncol, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Mol Diagnost Core Facil, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Partners Canc Care, Dept Adult Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Porter, DL (reprint author), Univ Penn, Med Ctr, Div Hematol Oncol, Dept Med, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM dlporter@mail.med.upenn.edu NR 34 TC 89 Z9 94 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1234 EP 1243 PG 10 WC Oncology SC Oncology GA 182JR UT WOS:000079496300020 PM 10561184 ER PT J AU Cheson, BD Horning, SJ Coiffier, B Shipp, MA Fisher, RI Connors, JM Lister, TA Vose, J Grillo-Lopez, A Hagenbeek, A Cabanillas, F Klippensten, D Hiddemann, W Castellino, R Harris, NL Armitage, JO Carter, W Hoppe, R Canellos, GP AF Cheson, BD Horning, SJ Coiffier, B Shipp, MA Fisher, RI Connors, JM Lister, TA Vose, J Grillo-Lopez, A Hagenbeek, A Cabanillas, F Klippensten, D Hiddemann, W Castellino, R Harris, NL Armitage, JO Carter, W Hoppe, R Canellos, GP TI Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW INVOLVEMENT; POSITRON-EMISSION-TOMOGRAPHY; CHRONIC LYMPHOCYTIC-LEUKEMIA; SPONSORED-WORKING-GROUP; LARGE-CELL LYMPHOMA; CORE-NEEDLE BIOPSY; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; MALIGNANT-LYMPHOMA; COMBINATION CHEMOTHERAPY AB Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy bur with a residual mass, to include patients - especially those with large cell NHL - who may not have residual disease, Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response Kites may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients, We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Bethesda, MD 20892 USA. Stanford Univ, Palo Alto, CA 94304 USA. Ctr Hosp Lyon Sud, Lyon, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Loyola Univ, Maywood, IL 60153 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. St Bartholomews Hosp, London, England. Univ Nebraska, Omaha, NE 68182 USA. Idec Pharmaceut Corp, San Diego, CA USA. Univ Utrecht, Utrecht, Netherlands. MD Anderson Cancer Ctr, Houston, TX 77030 USA. Roswell Pk Canc Inst, Buffalo, NY USA. Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA 90034 USA. RP Cheson, BD (reprint author), NCI, Execut Plaza N,Rm 741, Bethesda, MD 20892 USA. EM chesonb@ctep.nci.nih.gov NR 51 TC 2362 Z9 2469 U1 1 U2 82 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1244 EP 1253 PG 10 WC Oncology SC Oncology GA 182JR UT WOS:000079496300021 PM 10561185 ER PT J AU Nichols, KE Levitz, S Shannon, KE Wahrer, DCR Bell, DW Chang, G Hegde, S Neuberg, D Shafman, T Tarbell, NJ Mauch, P Ishioka, C Haber, DA Diller, L AF Nichols, KE Levitz, S Shannon, KE Wahrer, DCR Bell, DW Chang, G Hegde, S Neuberg, D Shafman, T Tarbell, NJ Mauch, P Ishioka, C Haber, DA Diller, L TI Heterozygous germline ATM mutations do not contribute to radiation-associated malignancies after Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; ATAXIA-TELANGIECTASIA GENE; LI-FRAUMENI-SYNDROME; BREAST-CANCER; IONIZING-RADIATION; BOMB SURVIVORS; EARLY-ONSET; A-T; FAMILIES; P53 AB Purpose: The successful treatment of Hodgkin's disease has been associated with an increased incidence of secondary malignancies. To investigate whether genetic factors contribute to the development of secondary tumors, we collected family cancer histories and performed mutational analysis of the ataxia-telangiectasia (AT) gene, ATM, in a cohort of Hodgkin's disease survivors with secondary malignancies. ATM was chosen for evaluation because of the increased radiosensitivity of cells derived from AT patients and obligate heterozygotes and the epidemiologic observation that AT carriers are at increased risk for radiation-induced breast cancer. Patients and Methods: Fifty-two patients who developed one or more neoplasms after treatment for Hodgkin's disease participated in this study. Personal and family histories of cancer were obtained through patient interviews and review of medical records. ATM mutational analysis war performed using a yeast-based protein truncation assay. Results: Seventy-six secondary neoplasms were ob-served in this cohort of 52 Hodgkin's disease survivors, with 18 patients (35%) developing more than one secondary neoplasm, Positive family histories of cancer were present in 11 (21%) of 52 patients, compared with three (4%) of 68 Hodgkin's disease patients in a comparison cohort who did not develop secondary neoplasms (P =.008; Fisher's exact test). No germline ATM mutations were identified, resulting in an estimated AT carrier frequency in this population of 0% (90% confidence interval, 0% to 4%), Conclusion: Analysis of the number of tumors per individual and the family history of cancer in our cohort suggests that generic factors may contribute to development of secondary neoplasms in a subset of Hodgkin's disease survivors, Mutational analysis, however, does not support a significant role for heterozygous truncating ATM mutations. Future studies evaluating other genes involved in DNA damage response pathways are warranted, (C) 1999 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Genet Lab, Ctr Canc Risk Anal, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Tohoku Univ, Sendai, Miyagi 980, Japan. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Genet Lab, Ctr Canc Risk Anal, Bldg 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU NIAID NIH HHS [IH K11-AI01331-04] NR 58 TC 40 Z9 41 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1259 EP 1266 PG 8 WC Oncology SC Oncology GA 182JR UT WOS:000079496300023 PM 10561187 ER PT J AU Wolfe, J Fairclough, DL Clarridge, BR Daniels, ER Emanuel, EJ AF Wolfe, J Fairclough, DL Clarridge, BR Daniels, ER Emanuel, EJ TI Stability of attitudes regarding physician-assisted suicide and euthanasia among oncology patients, physicians, and the general public SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LIFE-SUSTAINING TREATMENTS; WASHINGTON-STATE; RECOMMENDATIONS; TERMINATION; REQUESTS; CHOICES AB Purpose: Attitudes regarding the ethics of physician-assisted suicide (PAS) and euthanasia have been examined in many cross-sectional studies. Stability of these attitudes has not been studied, and this is important in informing the dialog on PAS in this country. We evaluated the stability of attitudes regarding euthanasia and PAS among three cohorts. Methods: Subjects included 593 respondents: 111 oncology patients, 324 oncologists, and 158 members of the general public. We conducted initial and follow-vp interviews separated by 6 to 12 months by telephone, regarding acceptance of PAS and euthanasia in four different clinical vignettes. Results: The proportion of respondents with stable responses to vignettes ranged from 69.2% to 94.8%. In comparison to patients and the general public, physicians had less stable responses concerning the PAS pain vignette (69.1% v 80.8%; P = .001) and more stable responses for all euthanasia vignettes (P < .001)except for pain. Over time, physicians were significantly more likely to change toward opposing PAS and euthanasia in all vignettes (P < .05). Characteristics previously associated with attitudes regarding PAS and euthanasia, such as Roman Catholic religion, were not predictive of stability. Conclusion: Up to one third of participants changed their attitudes regarding the ethical acceptability of PAS and euthanasia in their follow-up interview. This lack of consistency mandates careful interpretation of referendums and requests for physician-assisted suicide. Furthermore, in this study, we found that physicians are becoming increasingly opposed to PAS and euthanasia. The growing disparity between physicians and patients regarding the role of these practices is large enough to suggest possible conflicts in the delivery of end-of-life care. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Amer Med Ctr, Canc Res Ctr, Denver, CO USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM joanne_wolfe@dfci.harvard.edu FU AHRQ HHS [5 T32 HS00063] NR 28 TC 35 Z9 36 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1274 EP 1279 PG 6 WC Oncology SC Oncology GA 182JR UT WOS:000079496300025 PM 10561189 ER PT J AU Nierenberg, AA Keefe, BR Leslie, VC Alpert, JE Pava, JA Worthington, JJ Rosenbaum, JF Fava, M AF Nierenberg, AA Keefe, BR Leslie, VC Alpert, JE Pava, JA Worthington, JJ Rosenbaum, JF Fava, M TI Residual symptoms in depressed patients who respond acutely to fluoxetine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID MAJOR DEPRESSION; DISORDER; REMISSION; RELAPSE AB Background: Antidepressants have unequivocal efficacy as compared with placebo, but many patients have residual symptoms despite a robust response to antidepressant therapy. The purpose of this study is to assess residual symptoms in outpatients who respond acutely to fluoxetine. Method: Two hundred and fifteen outpatients with major depressive disorder as assessed with the Structured Clinical Interview for DSM-III-R (SCID-P) were treated openly with fluoxetine 20 mg/day for 8 weeks. One hundred and eight (50.2%) were considered full responders (final 17-item Hamilton Rating Scale for Depression [HAM-D] score less than or equal to 7). Percentages of full responders who continued to have subthreshold or full major depressive disorder symptoms were calculated. The relationship beta een residual symptoms and Axis I and Axis II (assessed with SCID-II for personality disorders) comorbidity was assessed. Results: Of the 108 responders, 19 (17.6%) had no subthreshold or threshold SCID-P major depressive disorder symptoms, while 28 (25.9%) had 1 symptom, and 61 (56.5%) had 2 or more symptoms. No statistically significant relationships were found between number of residual symptoms and selected Axis I comorbid conditions or total number of Axis II disorders. Conclusion: Less than 20% of full responders to fluoxetine by HAM-D criteria were free of all SCID-P subthreshold and threshold major depressive disorder symptoms after 8 weeks of treatment. While depressed patients benefit from antidepressants, most continue to have some symptoms of depression. The high prevalence of residual symptoms among antidepressant responders suggests the need for further study including whether residual symptoms abate with longer treatment or increased dose of fluoxetine. Other strategies, such as cognitive behavioral therapy, may be needed to address residual symptoms. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Clin Psychopharmacol Unit, Outpatient Psychiat Div, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Clin Psychopharmacol Unit, Outpatient Psychiat Div, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01MH48483-01] NR 15 TC 274 Z9 280 U1 1 U2 7 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 APR PY 1999 VL 60 IS 4 BP 221 EP 225 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 189TB UT WOS:000079921300003 PM 10221281 ER PT J AU Kleiner, J Altshuler, L Hendrick, V Hershman, JM AF Kleiner, J Altshuler, L Hendrick, V Hershman, JM TI Lithium-induced subclinical hypothyroidism: Review of the literature and guidelines for treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID BIPOLAR AFFECTIVE-DISORDER; SYMPTOMLESS AUTOIMMUNE-THYROIDITIS; MANIC-DEPRESSIVE PATIENTS; L-THYROXINE TREATMENT; LONG-TERM; BONE LOSS; ANTITHYROID ANTIBODIES; REFRACTORY DEPRESSION; NATURAL COURSE; DOUBLE-BLIND AB Background: This review addresses the definition, prevalence, etiology, and clinical significance of lithium-associated subclinical hypothyroidism and offers guidelines for evaluation and treatment of this condition. Data Sources: MEDLINE was used to search all articles written in English from 1964-present that included the words lithium and thyroid; lithium and subclinical hypothyroidism; mood and thyroid function; and bipolar illness and thyroid function. Study Findings: Lithium interferes with thyroid metabolism and increases the incidence of overt and subclinical hypothyroidism. Subclinical hypothyroidism may be associated with the presence of somatic and neuropsychiatric symptoms and interfere with treatment responsiveness. Conclusion: A careful assessment of thyroid function is recommended prior to initiating lithium treatment and during maintenance treatment. Recommendations regarding the threshold for initiation of thyroxine supplementation in patients with lithium-associated subclinical hypothyroidism are discussed in relationship to the degree of detrimental effects potentially associated with thyroid dysfunction. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, UCLA Mood Disorders Res Program, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Altshuler, L (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, UCLA Mood Disorders Res Program, 300 Med Plaza,Suite 1544, Los Angeles, CA 90095 USA. NR 96 TC 62 Z9 66 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 APR PY 1999 VL 60 IS 4 BP 249 EP 255 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 189TB UT WOS:000079921300009 PM 10221287 ER PT J AU Glynn, SM Eth, S Randolph, ET Foy, DW Urbaitis, M Boxer, L Paz, GG Leong, GB Firman, G Salk, JD Katzman, JW Crothers, J AF Glynn, SM Eth, S Randolph, ET Foy, DW Urbaitis, M Boxer, L Paz, GG Leong, GB Firman, G Salk, JD Katzman, JW Crothers, J TI A test of behavioral family therapy to augment exposure for combat-related posttraumatic stress disorder SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID PSYCHOTHERAPY OUTCOME RESEARCH; FLOODING THERAPY; SOCIAL ADJUSTMENT; VIETNAM VETERANS; SELF-REPORT; PTSD; MANAGEMENT; SCHIZOPHRENIA; SCALE; DEPRESSION AB This study tested a family-based skills-building intervention in veterans with chronic combat-related posttraumatic stress disorder (PTSD). Veterans and a family member were randomly assigned to 1 of 3 conditions: (a) waiting list, (b) 18 sessions of twice-weekly exposure therapy, or (c) 18 sessions of twice-weekly exposure therapy followed by 16 sessions of behavioral family therapy (BFT). Participation in exposure therapy reduced PTSD positive symptoms (e.g., reexperiencing and hyperarousal) but not PTSD negative symptoms. Positive symptom gains were maintained at 6-month follow-up. However, participation in BFT had no additional impact on PTSD symptoms. C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Pepperdine Univ, Grad Sch Educ & Psychol, Malibu, CA 90265 USA. RP Glynn, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 65 TC 103 Z9 103 U1 4 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 1999 VL 67 IS 2 BP 243 EP 251 DI 10.1037/0022-006X.67.2.243 PG 9 WC Psychology, Clinical SC Psychology GA 186MK UT WOS:000079733400010 PM 10224735 ER PT J AU Gonzalez, S Rajadhyaksha, M Gonzalez-Serva, A White, WM Anderson, RR AF Gonzalez, S Rajadhyaksha, M Gonzalez-Serva, A White, WM Anderson, RR TI Confocal reflectance imaging of folliculitis in vivo: correlation with routine histology SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID IN-VIVO; MICROSCOPY AB Near-infrared confocal reflectance microscopy (CM) is a high-resolution non-invasive imaging technique with promising future in dermatology. A pustular lesion from a 35-year-old male with a known history of folliculitis was non-invasively viewed with CM and later biopsied, Optical sections were correlated with routine histology. This optical technique allows us to view non-invasively transverse skin sections to a controlled depth in real time, In the CM images, tissue can be visualized with cellular and subcellular detail as shown by imaging infiltrating neutrophils (PMNs) within the subcorneal pustule of a superficial folliculitis in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Lucid Inc, Henrietta, NY USA. Pathol Serv Inc, Boston, MA USA. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, BHX-630,55 Blossom St, Boston, MA 02114 USA. NR 9 TC 55 Z9 62 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 1999 VL 26 IS 4 BP 201 EP 205 DI 10.1111/j.1600-0560.1999.tb01829.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 188YE UT WOS:000079876300006 PM 10335898 ER PT J AU Chiovato, L Rocchi, R Fiore, E AF Chiovato, L Rocchi, R Fiore, E TI Radioiodine is an effective, inexpensive, and safe treatment for Graves' hyperthyroidism, but its immunological effects must be taken into account SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Editorial Material DE Graves' disease; thyroid associated ophthalmopathy; I-131 therapy; thyroid stimulating antibody; TSH-blocking antibody; thyroid ultrasound volume ID THERAPY; ANTIBODIES; DISEASE; DAMAGE C1 Univ Pisa, Dipartimento Endocrinol, I-56124 Pisa, Italy. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. RP Chiovato, L (reprint author), Univ Pisa, Dipartimento Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. NR 11 TC 4 Z9 4 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD APR PY 1999 VL 22 IS 4 BP 310 EP 312 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192UT UT WOS:000080098500012 PM 10342367 ER PT J AU Blumenthal, D Causino, N Chang, YC Culpepper, L Marder, W Saglam, D Stafford, R Starfield, B AF Blumenthal, D Causino, N Chang, YC Culpepper, L Marder, W Saglam, D Stafford, R Starfield, B TI The duration of ambulatory visits to physicians SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE office visits; efficiency; physician-patient relations ID PRIMARY-CARE; PRODUCTIVITY AB BACKGROUND. The objective of our study was to determine the typical length of ambulatory visits to a nationally representative sample of primary care physicians, and the patient, physician, practice, and visit characteristics affecting duration of visit. METHODS. We used an analysis of cross-sectional survey data to determine duration of visit and the characteristics associated with it. The data sources were a random sample of the 19,192 visits by adults to 686 primary care physicians contained in the 1991-1992 National Ambulatory Medical Care Survey, and the results of the Physician Induction Interview conducted by the National Center for Health Statistics. Duration of visit was defined as the total time spent in face-to-face contact with the physician. RESULTS. Mean duration of visit was 16.3 minutes (standard deviation = 9.7). Multivariate analysis allowed the calculation of the independent effect on visit length of a variety of characteristics of patients, physicians, organizational/practice setting, geographic location, and visit content. Certain patient characteristics (increasing age and the presence of psychosocial problems) were associated with increased duration of visit, Visit content was also associated with increased duration, including ordering or performing 4 or more diagnostic tests (71% increase), Papanicolaou smears (34%), ambulatory surgical procedures (34%), patient admission to the hospital (32%), and 3 preventive screening tests (25%). Reduced duration of visit was associated with availability of nonphysician support personnel and health maintenance organization and Medicaid insurance. CONCLUSIONS. Multiple factors affect duration of visit. Clinicians, policymakers, and health system managers should take these considerations into account in managing physician resources during daily ambulatory practice. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Partners HealthCare Syst Inc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Boston Univ, Sch Med, Dept Family Med, Boston, MA 02215 USA. Medstat Grp, Cambridge, MA USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Blumenthal, D (reprint author), Hlth Policy Res & Dev Unit, 50 Staniford St, Boston, MA 02114 USA. OI Marder, William/0000-0002-7198-6933 FU AHRQ HHS [R01HSO7892-01A2] NR 21 TC 92 Z9 94 U1 1 U2 2 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 1999 VL 48 IS 4 BP 264 EP 271 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 314UR UT WOS:000087076400003 PM 10229250 ER PT J AU Weissman, JS AF Weissman, JS TI The future US healthcare system: Who will care for the poor and uninsured? SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Book Review C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weissman, JS (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD APR PY 1999 VL 24 IS 2 BP 383 EP 388 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 188HM UT WOS:000079840800007 ER PT J AU Barnes, JL Mitchell, RJ Kanalas, JJ Barnes, VL AF Barnes, JL Mitchell, RJ Kanalas, JJ Barnes, VL TI Differential expression of thrombospondin and cellular fibronectin during remodeling in proliferative glomerulonephritis SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE thrombospondin; alternatively spliced fibronectin; mesangial cell; migration; proliferation; extracellular matrix ID GROWTH-FACTOR-BETA; HABU SNAKE-VENOM; EXTRACELLULAR-MATRIX; MESANGIAL CELLS; MOUSE EMBRYO; ENDOTHELIAL-CELLS; WOUND REPAIR; MIGRATION; MACROPHAGES; PROTEINS AB Thrombospondin-l (TSP-1) and an alternatively spliced fibronectin (Fn)-EIIIA isoform are adhesive proteins associated with embryogenesis and tissue remodeling. We compared, by immunohistochemistry and in situ hybridization, the course of TSP-1 and Fn-EIIIA expression in a model of glomerulonephritis induced by Habu snake venom (HV) and characterized by mesangial cell migration, proliferation, and extracellular matrix (ECM) synthesis. At 24 hr after HV, TSP-1 and Fn-EIIIA proteins localized in the central aspects of lesions associated with platelets and macrophages and at the margins of lesions coinciding with mesangial cell migration (determined by Thy-1 staining). Mesangial cells at this time expressed TSP-1 but not Fn-EIIIA mRNA. TSP-1 protein and mRNA peaked in lesions at 48 hr and were associated with cell proliferation (determined by PCNA, alpha-smooth muscle actin phenotype, and expression of beta-PDCF receptor mRNA). TSP-1 expression declined at 72 hr when expression of ECM synthesis peaked, as determined by increased expression of collagen Type IV, laminin, and TGF-beta(1) protein and mRNA. Mesangial cell expression of Fn-EIIIA was first observed at 48 hr and was most abundant at 72 hr after HV. Therefore, platelet- and macrophage-derived Fn-EIIIA and TSP-1 in early lesions are associated with mesangial cell migration. Mesangial cell upregulation of TSP-1 is associated with migration and proliferation but not maximal ECM accumulation, whereas mesangial cell expression of Fn-EIIIA is associated with proliferation and ECM accumulation. These results suggest distinctive temporal and spatial roles for TSP-1 and Fn-EIIIA in remodeling during glomerular disease. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Med Res Serv, San Antonio, TX 78284 USA. Thomas Jefferson Univ, Dept Med, Div Nephrol, Philadelphia, PA 19107 USA. RP Barnes, JL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDDK NIH HHS [DK38758] NR 68 TC 16 Z9 16 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD APR PY 1999 VL 47 IS 4 BP 533 EP 543 PG 11 WC Cell Biology SC Cell Biology GA 181RZ UT WOS:000079457300012 PM 10082755 ER PT J AU Murphy, RL Gulick, RM DeGruttola, V D'Aquila, RT Eron, JJ Sommadossi, JP Currier, JS Smeaton, L Frank, I Caliendo, AM Gerber, JG Tung, R Kuritzkes, DR AF Murphy, RL Gulick, RM DeGruttola, V D'Aquila, RT Eron, JJ Sommadossi, JP Currier, JS Smeaton, L Frank, I Caliendo, AM Gerber, JG Tung, R Kuritzkes, DR CA AIDS Clin Trials Grp 347 Study Team TI Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Infectious Diseases CY FEB 01-05, 1998 CL CHICAGO, ILLINOIS ID DYNAMICS IN-VIVO; PROTEASE INHIBITORS; ALPHA(1)-ACID GLYCOPROTEIN; VIRAL INFECTIVITY; CONTROLLED TRIAL; VX-478; THERAPY; INDINAVIR; ANALOGS; BINDING AB Amprenavir is a human immunodeficiency virus (HIV) protease inhibitor with a favorable; pharmacokinetic profile and good in vitro activity. Ninety-two lamivudine- and protease inhibitor-naive individuals with greater than or equal to 50 CD4 cells/mm(3) and greater than or equal to 5000 HN RNA copies/mL were assigned amprenavir (1200 mg) alone or with zidovudine (300 mg) plus lamivudine (150 mg), all given every 12 h. After a median follow-up of ss days, the findings of a planned interim review resulted in termination of the amprenavir monotherapy arm. Among 85 subjects with confirmed plasma HIV RNA determination, 15 pf 42 monotherapy versus 1 of 43 triple-therapy subjects had an HIV RNA increase above basline or 1 log(10) above nadir (P=.0001). For subjects taking triple therapy at 24 weeks, the median decrease in HIV RNA was 2.04 log(10) copies/mL, and 17 (63%) of 27 evaluable subjects had <500 HIV RNA copies/mL;. Treatment: with amprenavir, zidovudine, and lamivudine together reduced he levels of HIV RNA significantly more than did amprenavir monotherapy. C1 Northwestern Univ, Comprehens AIDS Ctr, Sch Med, Chicago, IL 60611 USA. Cornell Univ, Coll Med, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Univ Alabama, Birmingham, AL USA. Univ So Calif, Los Angeles, CA 90089 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Penn, Philadelphia, PA 19104 USA. Vertex Pharmaceut, Cambridge, MA 02138 USA. RP Murphy, RL (reprint author), Northwestern Univ, Comprehens AIDS Ctr, Sch Med, 303 E Super St,Room 828, Chicago, IL 60611 USA. OI Murphy, Robert/0000-0003-3936-2052 FU NCRR NIH HHS [RR-00051, RR-00046]; NIAID NIH HHS [AI-38858] NR 36 TC 67 Z9 67 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 808 EP 816 DI 10.1086/314668 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800007 PM 10068575 ER PT J AU Maytin, EV Lin, JC Krishnamurthy, R Batchvarova, N Ron, D Mitchell, PJ Habener, JF AF Maytin, EV Lin, JC Krishnamurthy, R Batchvarova, N Ron, D Mitchell, PJ Habener, JF TI Direct and indirect roles for transcription factors C/EBP and AP-2 in the regulation of keratin k10 gene expression in mammalian epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Dermatol, Mol Endocrinol Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA. Univ Zurich, Inst Pharmacol, CH-8006 Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 046 BP 530 EP 530 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800070 ER PT J AU Rheinwald, JG Dickson, MA Hahn, WC Weinberg, RA Ronfard, V Li, FP Wu, JY AF Rheinwald, JG Dickson, MA Hahn, WC Weinberg, RA Ronfard, V Li, FP Wu, JY TI Properties of immortal cell liner arising from human epidermal keratinocytes and mesothelial cells stably transfected to express hTERT (human telomerase catalytic subunit) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Organogenesis Inc, Canton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 049 BP 531 EP 531 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800072 ER PT J AU Hamoen, K Morgan, J AF Hamoen, K Morgan, J TI Genetically modified human keratinocytes overexpressing hepatocyte growth factor form a hyperproliferative epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 106 BP 540 EP 540 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800130 ER PT J AU Frank, J Pignata, C Panteleyev, AA Prowse, DM Baden, H Weiner, L Gaetaniello, L Ahmad, W Pozzi, N Cserhalmi-Friedman, PB Gordon, D Ott, J Brissette, JL Christiano, AM AF Frank, J Pignata, C Panteleyev, AA Prowse, DM Baden, H Weiner, L Gaetaniello, L Ahmad, W Pozzi, N Cserhalmi-Friedman, PB Gordon, D Ott, J Brissette, JL Christiano, AM TI The human nude phenotype: Congenital alopecia and severe T-cell immunodeficiency associated with a nonsense mutation in the whn gene SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Columbia Univ, Dept Dermatol, New York, NY 10027 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. Univ Naples Federico II, Dept Pediat, Naples, Italy. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. RI Pignata, Claudio/O-2466-2013; Ahmad, Wasim/E-9713-2015 OI Pignata, Claudio/0000-0003-1568-9843; NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 152 BP 548 EP 548 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800177 ER PT J AU Streit, M Velasco, P Brown, LF Skobe, M Richards, L Lawler, J Detmar, M AF Streit, M Velasco, P Brown, LF Skobe, M Richards, L Lawler, J Detmar, M TI Overexpression of the endogenous angiogenesis inhibitor TSP-1 inhibits tumor growth and angiogenesis in human squamous carcinoma cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 203 BP 556 EP 556 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800224 ER PT J AU Lerner, L Qureshi, A Reddy, V Lerner, E AF Lerner, L Qureshi, A Reddy, V Lerner, E TI Nitric oxide in Stevens Johnson/toxic epidermal necrolysis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 219 BP 559 EP 559 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800241 ER PT J AU Riccardi, L Streit, M Velasco, P Brown, L Lawler, J Detmar, M AF Riccardi, L Streit, M Velasco, P Brown, L Lawler, J Detmar, M TI The endogenous angiogenesis inhibitor thrombospondin-2 is expressed in basal keratinocyte of normal epidermis in vivo and in epidermal keratinocytes in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 227 BP 560 EP 560 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800248 ER PT J AU Morgan, J Hamoen, K AF Morgan, J Hamoen, K TI Engineering a new autocrine loop by genetic modification of human melanocytes: Hepatocyte growth factor expression stimulates proliferation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 411 BP 591 EP 591 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800433 ER PT J AU Fairhurst, D Mitchnick, M Kollias, N Gillies, R Pinnell, S AF Fairhurst, D Mitchnick, M Kollias, N Gillies, R Pinnell, S TI Microfine zinc oxide (Z-cote) and microfine titanium dioxide - A critical comparison of their use as physical sunscreen actives SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 SunSmart Inc, Wainscott, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 537 BP 612 EP 612 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800559 ER PT J AU Torres, R Gonzalez, S Maytin, E AF Torres, R Gonzalez, S Maytin, E TI Loss and induction of transcription factors C/EBP01 beta and CHOP (gadd153) in murine epidermis following exposure to UVB light SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 539 BP 612 EP 612 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800560 ER PT J AU Bykowski, J Zonios, G Gillies, R LaMuraglia, G Kollias, N AF Bykowski, J Zonios, G Gillies, R LaMuraglia, G Kollias, N TI Diffuse reflectance spectroscopy (400-800 nm) of skin indicates arterial insufficiency SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 542 BP 613 EP 613 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800567 ER PT J AU Skobe, M Brown, L Tognazzi, K Groupman, J Alitalo, K Detmar, M AF Skobe, M Brown, L Tognazzi, K Groupman, J Alitalo, K Detmar, M TI Vascular endothelial growth factor-C (VEGF-C) and its receptors VEGFR-2 and VEGFR-3 are expressed in AIDS-associated Kaposi's sarcoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Beth Israel Hosp, Dept Pathol, Boston, MA 02215 USA. Beth Israel Hosp, Dept Internal Med, Boston, MA 02215 USA. Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 573 BP 618 EP 618 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800595 ER EF