FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Richardson, P Anderson, K AF Richardson, P Anderson, K TI Thalidomide and dexamethasone: A new standard of care for initial therapy in multiple myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID NEWLY-DIAGNOSED MYELOMA; HIGH-DOSE CHEMOTHERAPY; COMBINATION THERAPY; PLUS DEXAMETHASONE; DRUG-RESISTANCE; CC-5013; CELLS; MM; TRANSPLANTATION; DOXORUBICIN C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Neoplasa, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Neoplasa, Boston, MA 02115 USA. NR 26 TC 33 Z9 36 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 334 EP 336 DI 10.1200/JCO.2005.03.8851 PG 3 WC Oncology SC Oncology GA 004TX UT WOS:000234776300006 PM 16365174 ER PT J AU Buchholz, TA Theriault, RL Niland, JC Hughes, ME Ottesen, R Edge, SB Bookman, MA Weeks, JC AF Buchholz, TA Theriault, RL Niland, JC Hughes, ME Ottesen, R Edge, SB Bookman, MA Weeks, JC TI The use of radiation as a component of breast conservation therapy in national comprehensive cancer network centers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL Colorado Springs, CO ID CARCINOMA IN-SITU; CONSERVING SURGERY; OLDER WOMEN; STAGE; TRIAL; RADIOTHERAPY; PREVENTION; LUMPECTOMY; TAMOXIFEN; SURVIVAL AB Purpose Benchmark data regarding quality measures of breast cancer management are needed. We investigated rates of radiation use after breast conservation therapy (BCT) for patients treated for ductal carcinoma-in-situ (DCIS) or invasive breast cancer at National Comprehensive Cancer Network (NCCN) centers. Patients and Methods We studied 3,333 consecutive patients treated between 1997 and 2002 with BCT for DCIS (n = 587) or for stage I or II breast cancer (n = 2,746) in eight NCCN centers. Results The overall rate of radiation therapy use was 91%, with a lower frequency of radiation use in DCIS versus invasive breast cancers (82% v 94%, odds ratio [OR] = 0.31, P < .0001). In a multivariable analysis of the patients with DCIS, the only factor significantly associated with lower rates of radiation use was low/intermediate grade (OR = 0.19; P = .0003). For patients with invasive breast cancer, significant factors were presence of comorbidity (OR = 0.53; P = .0005), tubular histology (OR = 0.39; P = .02), type of health insurance (P = .0072), and the NCCN institution (P = .0005). The model also showed lower rates of radiation use in patients with stage 11 disease who did not receive systemic therapy (OR = 0.01; P = .0001), younger patients who did not receive systemic therapy (P = .003); and older patients with stage I disease (P < .0001). Conclusion Radiation use as a component of BCT was high for patients seen at NCCN centers; however, there was variability in practice patterns noted across institutions. Radiation was most commonly omitted in patients with favorable disease characteristics, patients with comorbidities, and patients who also did not receive guideline-recommended systemic treatment. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol & Med Oncol, Houston, TX 77030 USA. City Hope Hosp, Dept Oncol, Los Angeles, CA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Roswell Pk Canc Inst, Dept Breast & Soft Tissue Surg, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Dept Oncol, Philadelphia, PA 19111 USA. RP Buchholz, TA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM tbuchhol@mdanderson.org FU NCI NIH HHS [P50CA89393] NR 26 TC 55 Z9 55 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 361 EP 369 DI 10.1200/JCO.2005.02.3127 PG 9 WC Oncology SC Oncology GA 004TX UT WOS:000234776300010 PM 16421417 ER PT J AU Kulke, MH Stuart, K Enzinger, PC Ryan, DP Clark, JW Muzikansky, A Vincitore, M Michelini, A Fuchs, CS AF Kulke, MH Stuart, K Enzinger, PC Ryan, DP Clark, JW Muzikansky, A Vincitore, M Michelini, A Fuchs, CS TI Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 20th Chemotherapy-Foundation Symposium CY NOV 12-15, 2003 CL New York, NY SP Chemotherapy Fdn ID ISLET-CELL-CARCINOMA; SOUTHWEST-ONCOLOGY-GROUP; ANTITUMOR-ACTIVITY; ENDOCRINE TUMORS; STREPTOZOCIN; DOXORUBICIN; DACARBAZINE; FLUOROURACIL; TRIAL; COMBINATION AB Purpose Standard, intravenous chemotherapy regimens for neuroendocrine tumors have been associated with limited response rates and significant toxicity. We evaluated the efficacy of an oral regimen of temozolomide and thalidomide in patients with metastatic carcinoid, pheochromocytoma, or pancreatic neuroenclocrine tumors. Patients and Methods Twenty-nine patients were treated with a combination of temozolomide, administered at a dose of 150 mg/m(2) for 7 days, every other week, and thalidomide at doses of 50 to 400 mg daily. Patients were followed for evidence of toxicity, biochemical response, radiologic response, and survival. Results Treatment with temozolomide and thalidomide was associated with an objective biochemical (chromogranin A) response rate of 40%, and a radiologic response rate of 25% (45% among pancreatic endocrine tumors, 33% among pheochromocytomas, and 7% among carcinoid tumors). The median duration of response was 13.5 months, 1-year survival was 79%, and 2-year survival was 61%. The median administered dose of temozolomide was 150 mg/m(2), and the median administered dose of thalidomide was 100 mg daily. Grade 3-4 toxicities were uncommon, with the exception of grade 3-4 lymphopenia, which developed in 69% of the patient population. Opportunistic infections occurred in three patients (10%) during the time of lymphopenia, and included single cases of Pneumocystis carinii pneumonia, disseminated varicella zoster virus, and herpes simplex virus. Conclusion Orally administered temozolomide and thalidomide seems to be an active regimen for the treatment of neuroenclocrine tumors, In this 29-patient study, this regimen appeared more active in pancreatic endocrine tumors than in carcinoid tumors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 24 TC 288 Z9 297 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 401 EP 406 DI 10.1200/JJCO.2005.03.6046 PG 6 WC Oncology SC Oncology GA 004TX UT WOS:000234776300015 PM 16421420 ER PT J AU Blackstock, AW Herndon, JE Paskett, ED Miller, AA Lathan, C Niell, HB Socinski, MA Vokes, EE Green, MR AF Blackstock, AW Herndon, JE Paskett, ED Miller, AA Lathan, C Niell, HB Socinski, MA Vokes, EE Green, MR TI Similar outcomes between African American and non-African American patients with extensive-stage small-cell lung carcinoma: Report from the Cancer and Leukemia Group B SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; 2 RURAL STATES; PROGNOSTIC-FACTORS; SPECIAL SECTION; CHEMOTHERAPY; SURVIVAL; RACE; STATISTICS; PATTERNS; NATION AB Purpose Among patients with small-cell lung carcinoma, African Americans have lower survival rates than non-African Americans. We investigated whether the disparity in survival would persist when patients were treated with similar therapies (ie, phase II/III Cancer and Leukemia Group B [CALGB] trials). Patients and Methods We assessed 995 patients (928 non-African American and 67 African American) receiving chemotherapy in CALGB studies for extensive-stage small-cell lung cancer (ES-SCLC). Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. The Cox proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two sided. Results The unadjusted survival distribution of African American patients was not significantly different from that of non-African American patients; median survival was 11.5 months (95% CI, 9.4 to 13.4 months) for African American patients versus 9.9 months (95% CI, 9.6 to 10.3 months) for non-African American patients. Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the outcome for African American patients. Survival was similar even though African American patients were more likely to have a poorer performance status, present with significant weight loss, and be Medicaid recipients (20% v 6%), which is an indicator of lower socioeconomic status. Conclusion African American patients tended to present with prognostic features associated with a worse survival. However, when offered equivalent therapy, the outcome for African American patients was the same as that observed for non-African American patients. C1 Wake Forest Univ, Sch Med, Dept Radiat Oncol, Winston Salem, NC 27157 USA. Univ N Carolina, Chapel Hill, NC USA. Duke Univ, Ctr Stat, Leukemia Grp B, Durham, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Chicago, Chicago, IL 60637 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Wake Forest Univ, Sch Med, Dept Radiat Oncol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM ablackst@wfubmc.edu FU NCI NIH HHS [CA31946] NR 39 TC 27 Z9 27 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 407 EP 412 DI 10.1200/JCO.2005.02.1436 PG 6 WC Oncology SC Oncology GA 004TX UT WOS:000234776300016 PM 16365181 ER PT J AU Lathan, CS Neville, BA Earle, CC AF Lathan, CS Neville, BA Earle, CC TI The effect of race on invasive staging and surgery in non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID POSITRON-EMISSION-TOMOGRAPHY; RACIAL-DIFFERENCES; CHEMOTHERAPY; POPULATION; VALIDATION; CARCINOMA AB Purpose Black patients with early-stage non-small-cell lung cancer (NSCLC) have worse overall survival than white patients. Decreased likelihood of resection has been implicated. To isolate the effect of decision making from access to care, we used receipt of surgical staging as a proxy for access and willingness to undergo invasive procedures, and examined treatments and outcomes by race. Patients and Methods We examined registry and claims data of Medicare-eligible patients with nonmetastatic NSCLC in areas monitored by the Surveillance, Epidemiology, and End Results program from 1991 to 2001. Patients who obtained invasive staging, defined as bronchoscopy, mediastinoscopy, or thoracoscopy, were included. Logistic regression and Cox modeling calculated the odds of having staging and surgery, and survival outcomes. Results A total of 14,224 patients underwent staging, and 6,972 had surgery for lung cancer. Black patients were less likely to undergo staging (odds ratio [OR] = 0.75; 95% CI, 0.67 to 0.83), and once staged, were still less likely to have surgery than whites (OR = 0.55; 95% CI, 0.47 to 0.64). Survival for blacks and whites was equivalent after resection (hazard ratio = 1.02; P = .06). Staged black patients were less likely to receive a recommendation for surgery when it was not clearly contraindicated (67.0% v 71.4%; P < .05), and were more likely to decline surgery (3.4% v 2.0%; P < .05). Conclusion Black patients obtain surgery for lung cancer less often than whites, even after access to care has been demonstrated. They are more likely not to have surgery recommended, and more likely to refuse surgery. Additional research should focus on the physician-patient encounter as a potential source of racial disparities. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu NR 26 TC 119 Z9 119 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 413 EP 418 DI 10.1200/JCO.2005.02.1758 PG 6 WC Oncology SC Oncology GA 004TX UT WOS:000234776300017 PM 16365180 ER PT J AU Rajkumar, SV Blood, E Vesole, D Fonseca, R Greipp, PR AF Rajkumar, SV Blood, E Vesole, D Fonseca, R Greipp, PR TI Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: A clinical trial coordinated by the eastern cooperative oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; DEEP-VEIN THROMBOSIS; RECEIVING THALIDOMIDE; THERAPY; SURVIVAL; DOXORUBICIN; RISK; VAD AB Purpose To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma. Patients and Methods Patients were randomly assigned to receive thalidomide plus dexamethasone or dexamethasone alone. Patients in arm A received thalidomide 200 mg orally for 4 weeks; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4, 9 to 12, and 17 to 20. Cycles were repeated every 4 weeks. Patients in arm B received dexamethasone alone at the same schedule as in arm A. Results Two hundred seven patients were enrolled: 103 were randomly assigned to thalidomide plus dexamethasone and 104 were randomly assigned to dexamethasone alone; eight patients were ineligible, The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone (63% v 41 %, respectively; P = .0017). The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72% v 50%, respectively. The incidence rates of grade 3 or higher deep vein thrombosis (DVT), rash, bradycardia, neuropathy, and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone (45% v 21 %, respectively; P < .001). DVT was more frequent in arm A than in arm B (17% v 3%); grade 3 or higher peripheral neuropathy was also more frequent (7% v 4%, respectively). Conclusion Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone. However, this must be balanced against the greater toxicity seen with the combination. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA 02115 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Mayo Clin, Scottsdale, AZ USA. RP Rajkumar, SV (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM rajks@mayo.edu OI Fonseca, Rafael/0000-0002-5938-3769; Rajkumar, S. Vincent/0000-0002-5862-1833 FU NCI NIH HHS [CA21115, CA13650, CA23318, CA66636, CA93842] NR 28 TC 546 Z9 588 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 431 EP 436 DI 10.1200/JCO.2005.03.0221 PG 6 WC Oncology SC Oncology GA 004TX UT WOS:000234776300019 PM 16365178 ER PT J AU Byrd, JC Gribben, JG Peterson, BL Grever, MR Lozanski, G Lucas, DM Lampson, B Larson, RA Caligiuri, MA Heerema, NA AF Byrd, JC Gribben, JG Peterson, BL Grever, MR Lozanski, G Lucas, DM Lampson, B Larson, RA Caligiuri, MA Heerema, NA TI Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: Justification for risk-adapted therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID VARIABLE-REGION MUTATIONS; DISEASE PROGRESSION; CD38 EXPRESSION; SURVIVAL; CYCLOPHOSPHAMIDE; PHASE-2; CAP AB Purpose Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutaled Ig V-H mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy. Methods We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase 11 study, Cancer and Leukemia Group B (CALGB) 9712. Results Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig V, mutational status to classify risk, there was no association between complete response rate with either unmutated Ig V-H mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig V-H unmutated patients as compared with the Ig V, mutated patients. Using the hierarchical classification of Dohner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk. Conclusion These data demonstrate that high-risk CLL patients characterized by Ig V-H unmutated (>= 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig V. mutational status and interphase cytogenetics on treatment outcome. C1 Ohio State Univ, Div Hematol Oncol, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CALGB, Ctr Stat, Durham, NC USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Byrd, JC (reprint author), Ohio State Univ, Div Hematol Oncol, Starling Loving Hall,Room 302, Columbus, OH 43210 USA. EM john.byrd@osumc.edu RI Lucas, David/E-3555-2011; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA31946, R21CA101332, UO1CA101140] NR 27 TC 162 Z9 163 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2006 VL 24 IS 3 BP 437 EP 443 DI 10.1200/JCO.2005.03.1021 PG 7 WC Oncology SC Oncology GA 004TX UT WOS:000234776300020 PM 16344317 ER PT J AU Lou, ZK Minter-Dykhouse, K Franco, S Gostissa, M Rivera, MA Celeste, A Manis, JP van Deursen, J Nussenzweig, A Paull, TT Alt, FW Chen, JJ AF Lou, ZK Minter-Dykhouse, K Franco, S Gostissa, M Rivera, MA Celeste, A Manis, JP van Deursen, J Nussenzweig, A Paull, TT Alt, FW Chen, JJ TI MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; CLASS-SWITCH RECOMBINATION; IONIZING-RADIATION; ATAXIA-TELANGIECTASIA; RESPONSE PATHWAYS; DEFICIENT MICE; REPAIR FACTORS; ACTIVATION; 53BP1 AB MDC1 functions in checkpoint activation and DNA repair following DNA damage. To address the physiological role of MDC1, we disrupted the MDC1 gene in mice. MDC1(-/-) mice recapitulated many phenotypes of H2AX(-/-) mice, including growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects, and radiation sensitivity. At the molecular level, H2AX, MDC1, and ATM form a positive feedback loop, with MDC1 directly mediating the interaction between H2AX and ATM. MDC1 binds phosphorylated H2AX through its BRCT domain and ATM through its FHA domain. Through these interactions, MDC1 accumulates activated ATM flanking the sites of DNA damage, facilitating further ATM-dependent phosphorylation of H2AX and the amplification of DNA damage signals. In the absence of MDC1, many downstream ATM signaling events are defective. These results suggest that MDC1, as a signal amplifier of the ATM pathway, is vital in controlling proper DNA damage response and maintaining genomic stability. C1 Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Texas, Dept Mol Genet & Microbiol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Chen, JJ (reprint author), Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. EM chen.junjie@mayo.edu RI Minter Dykhouse, Katherine/L-4573-2013 OI Minter Dykhouse, Katherine/0000-0003-4363-5826 FU NCI NIH HHS [CA92312, R01 CA89239] NR 44 TC 350 Z9 374 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 20 PY 2006 VL 21 IS 2 BP 187 EP 200 DI 10.1016/j.molcel.2005.11.025 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 007BR UT WOS:000234943000008 PM 16427009 ER PT J AU Franco, S Gostissa, M Zha, S Lombard, DB Murphy, MM Zarrin, AA Yan, C Tepsuporn, S Morales, JC Adams, MM Lou, ZK Bassing, CH Manis, JP Chen, JJ Carpenter, PB Alt, FW AF Franco, S Gostissa, M Zha, S Lombard, DB Murphy, MM Zarrin, AA Yan, C Tepsuporn, S Morales, JC Adams, MM Lou, ZK Bassing, CH Manis, JP Chen, JJ Carpenter, PB Alt, FW TI H2AX prevents DNA breaks from progressing to chromosome breaks and translocations SO MOLECULAR CELL LA English DT Article ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; INDUCED CYTIDINE DEAMINASE; PHOSPHORYLATED HISTONE H2AX; GENOMIC INSTABILITY; PROTEIN 53BP1; REGION RECOMBINATION; V(D)J RECOMBINATION; IONIZING-RADIATION; DAMAGE CHECKPOINT AB Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires activation-induced cytidine deaminase (AID) and involves joining of DSB intermediates by end joining. We find that AID-dependent IgH locus chromosome breaks occur at high frequency in primary H2AX-deficient B cells activated for CSR and that a substantial proportion of these breaks participate in chromosomal translocations. Moreover, activated B cells deficient for ATM, 53BP1, or MDC1, which interact with H2AX during the DSB response, show similarly increased IgH locus breaks and translocations. Thus, our findings implicate a general role for these factors in promoting end joining and thereby preventing DSBs from progressing into chromosomal breaks and translocations. As cellular p53 status does not markedly influence the frequency of such events, our results also have implications for how p53 and the DSB response machinery cooperate to suppress generation of lymphomas with oncogenic translocations. C1 Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem & Mol Biol, Houston, TX 77225 USA. Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Childrens Hosp, Joint Program Transfus Med,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Lab Med,Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NCI NIH HHS [CA92312, P01CA092625-05, R01 CA89239]; NIAID NIH HHS [2PO1AI031541-15]; NIGMS NIH HHS [GM65812] NR 57 TC 191 Z9 191 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 20 PY 2006 VL 21 IS 2 BP 201 EP 214 DI 10.1016/j.molcel.2006.01.005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 007BR UT WOS:000234943000009 PM 16427010 ER PT J AU Wei, XL Xu, H Kufe, D AF Wei, XL Xu, H Kufe, D TI MUC1 oncoprotein stabilizes and activates estrogen receptor alpha SO MOLECULAR CELL LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODY DF3; BETA-CATENIN; BREAST-CANCER; GENE-TRANSCRIPTION; NUCLEAR RECEPTORS; PROTEIN-KINASE; MAMMARY-GLAND; C-SRC AB The MUC1 protein is aberrantly overexpressed by most human breast carcinomas. We report that the MUC1 C-terminal subunit associates with estrogen receptor alpha (ER alpha) and that this interaction is stimulated by 17 beta-estradiol (E2). MUC1 binds directly to the ER alpha DNA binding domain and stabilizes ER alpha by blocking its ubiquitination and degradation. Chromatin immunoprecipitation assays further demonstrate that MUC1 (1) associates with ER alpha complexes on estrogen-responsive promoters, (2) enhances ER alpha promoter occupancy, and (3) increases recruitment of the p160 coactivators SRC-1 and GRIP1. In concert with these results, we show that MUC1 stimulates ER alpha-mediated transcription and contributes to E2-mediated growth and survival of breast cancer cells. These findings provide evidence that MUC1 stabilizes ER alpha and that this oncoprotein is of importance to the activation of ER alpha function. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA097098] NR 52 TC 108 Z9 119 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 20 PY 2006 VL 21 IS 2 BP 295 EP 305 DI 10.1016/j.molcel.2005.11.030 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 007BR UT WOS:000234943000017 PM 16427018 ER PT J AU Ancuta, P Kuntsman, KJ Autissier, P Zaman, T Stone, D Wolinsky, SM Gabuzda, D AF Ancuta, P Kuntsman, KJ Autissier, P Zaman, T Stone, D Wolinsky, SM Gabuzda, D TI CD16(+) monocytes exposed to HIV promote highly efficient viral replication upon differentiation into macrophages and interaction with T cells SO VIROLOGY LA English DT Article DE HIV; CD16(+) monocytes; T cells; conjugates ID DENDRITIC CELLS; INFECTION; FRACTALKINE; SUBSET; BLOOD; HETEROGENEITY; LYMPHOCYTES; EXPRESSION; RECEPTORS; DEMENTIA AB The CD16(+) subset of monocytes is dramatically expanded in peripheral blood during progression to AIDS, but its contribution to HIV pathogenesis is unknown. Here, we demonstrate that CD16(+) but not CD16(-) monocytes promote high levels of HIV replication upon differentiation into macrophages and interaction with T cells. Conjugates formed between CD16(+) monocyte-derived macrophages and T cells are major sites of viral replication. Furthermore, similar monocyte-T cell conjugates detected in peripheral blood of HIV-infected patients harbor HIV DNA. Thus, expansion of CD16(+) monocytes during HIV infection and their subsequent recruitment into tissues such as lymph nodes, brain, and intestine may contribute to HIV dissemination and establishment of productive infection in T cells. (C) 2005 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Lemuel Shattuck Hosp, Jamaica Plain, MA 02130 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012 FU NIDA NIH HHS [DA016549] NR 20 TC 48 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 2006 VL 344 IS 2 BP 267 EP 276 DI 10.1016/j.virol.2005.10.027 PG 10 WC Virology SC Virology GA 004UD UT WOS:000234776900002 PM 16305804 ER PT J AU Bettinger, CJ Weinberg, EJ Kulig, KM Vacanti, JP Wang, YD Borenstein, JT Langer, R AF Bettinger, CJ Weinberg, EJ Kulig, KM Vacanti, JP Wang, YD Borenstein, JT Langer, R TI Three-dimensional microfluidic tissue-engineering scaffolds using a flexible biodegradable polymer SO ADVANCED MATERIALS LA English DT Article ID FLUID SHEAR-STRESS; VASCULAR ENDOTHELIAL-CELLS; PDMS POLYDIMETHYLSILOXANE; POLY(GLYCEROL SEBACATE); FABRICATION; CULTURE; BIOCOMPATIBILITY; HEPATOCYTES; BIOREACTOR; ELASTOMER AB Three-dimensional microfluidic networks using a flexible biodegradable polymer have been fabricated using modified microfabrication processes tailored specifically for poly(glycerol-co-sebacate). A model hepatocyte cell line (HepG(2)) is seeded and pet-fused in the microfluidic networks to demonstrate cell viability and function, which is maintained in long-term perfusion culture (see Figure; scale bar is 50 mu m). The seeded, fully degradable device can potentially be integrated into a patient's existing vasculature in order to restore organ function. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Charles Stark Draper Lab Inc, MEMS Technol Grp, Cambridge, MA 02139 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rlanger@mit.edu RI Bettinger, Christopher/A-3895-2009; OI Wang, Yadong/0000-0003-2067-382X FU NHLBI NIH HHS [R01 HL060435-08, R01 HL060435, R01 HL060435-09]; NIDCR NIH HHS [R01 DE013023, R01 DE013023-08, R01 DE013023-09] NR 36 TC 173 Z9 178 U1 6 U2 82 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0935-9648 J9 ADV MATER JI Adv. Mater. PD JAN 19 PY 2006 VL 18 IS 2 BP 165 EP + DI 10.1002/adma.200500438 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 007TV UT WOS:000234993700002 PM 19759845 ER PT J AU Munhall, AC Johnson, SW AF Munhall, AC Johnson, SW TI Dopamine-mediated actions of ephedrine in the rat substantia nigra SO BRAIN RESEARCH LA English DT Article DE ephedrine; substantia nigra; dopamine; brain slice; neurophysiology; microelectrode ID VENTRAL TEGMENTAL AREA; POTASSIUM CONDUCTANCE; ZONA COMPACTA; D2 RECEPTORS; IN-VITRO; NEURONS; AMPHETAMINE; RELEASE; TRANSMISSION; SEROTONIN AB Although ephedrine is a centrally active stimulant, its effect on midbrain dopamine neurons is not known. To study the effect of ephedrine on dopamine-containing cells, current-clamp microelectrode recordings were made from substantia nigra pars compacta (SNC) neurons in horizontal brain slice preparations. Ephedrine (100-1000 mu M) slowed spontaneous firing and produced a modest concentration-dependent hyperpolarization of membrane potential (EC50 279 mu M), with a concomitant net decrease in membrane resistance. These effects were blocked by the D-2-like dopamine antagonist sulpiride (1 mu M). Electrically evoked inhibitory synaptic potentials mediated by GABA(B) receptors were reduced 28% by ephedrine. However, ephedrine did not reduce fast synaptic potentials mediated by GABA(A) or ionotropic glutamate receptors. Inhibition of the GABA(B) response appeared to be mediated by a postsynaptic mechanism because ephedrine also reduced baclofen-induced hyperpolarization by 28%. Both ephedrine-induced hyperpolarization and inhibition of baclofen-induced hyperpolarization were abolished when slices were superfused with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Despite perfusion with AMPT, the ability of ephedrine to cause hyperpolarization was restored after perfusing the slice with dopamine (30 mu M). Taken together, these results suggest that ephedrine causes hyperpolarization and suppresses GABAB receptor-mediated effects by releasing endogenous dopamine. However, the high concentrations required to observe these effects in vitro suggest that biologically relevant central effects of ephedrine are more likely to be mediated either by non-dopamine systems, such as those involving noradrenaline, or by dopamine systems outside the SNC. (c) 2005 Elsevier B.V. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NIMH NIH HHS [MH40416] NR 34 TC 9 Z9 9 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 19 PY 2006 VL 1069 IS 1 BP 96 EP 103 DI 10.1016/j.brainres.2005.11.044 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 018IZ UT WOS:000235759000011 PM 16386715 ER PT J AU Solit, DB Garraway, LA Pratilas, CA Sawai, A Getz, G Basso, A Ye, Q Lobo, JM She, YH Osman, I Golub, TR Sebolt-Leopold, J Sellers, WR Rosen, N AF Solit, DB Garraway, LA Pratilas, CA Sawai, A Getz, G Basso, A Ye, Q Lobo, JM She, YH Osman, I Golub, TR Sebolt-Leopold, J Sellers, WR Rosen, N TI BRAF mutation predicts sensitivity to MEK inhibition SO NATURE LA English DT Article ID CYCLIN D1; PROTEIN-KINASE; RAS MUTATIONS; IN-VIVO; MELANOMA; CANCER; EXPRESSION; PATHWAY; GENE; PROTEOLYSIS AB The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members(1). Using small-molecule inhibitors of MEK and an integrated genetic and pharmacologic analysis, we find that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition when compared to either 'wild-type' cells or cells harbouring a RAS mutation. This MEK dependency was observed in BRAF mutant cells regardless of tissue lineage, and correlated with both downregulation of cyclin D1 protein expression and the induction of G1 arrest. Pharmacological MEK inhibition completely abrogated tumour growth in BRAF mutant xenografts, whereas RAS mutant tumours were only partially inhibited. These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. NYU Med Ctr, Dept Med, New York, NY 10016 USA. NYU Med Ctr, Dept Urol, New York, NY 10016 USA. Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA. RP Rosen, N (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM rosenn@mskcc.org RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [P01 CA094060, P01 CA094060-01A1, T32 CA009172] NR 28 TC 829 Z9 853 U1 0 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 19 PY 2006 VL 439 IS 7074 BP 358 EP 362 DI 10.1038/nature04304 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 003LA UT WOS:000234682100050 PM 16273091 ER PT J AU Davis, BT Thiim, M Zukerberg, LR AF Davis, BT Thiim, M Zukerberg, LR TI A 31-year-old, HIV-positive man with rectal pain - Lymphogranuloma venereum proctitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHLAMYDIA-TRACHOMATIS; MEN; SEX C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Davis, BT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. NR 10 TC 8 Z9 8 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 JAN 19 PY 2006 VL 354 IS 3 BP 284 EP 289 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 003DF UT WOS:000234661100010 PM 16421370 ER PT J AU Cheng, I Stram, DO Penney, KL Pike, M Le Marchand, L Kolonel, LN Hirschhorn, J Altshuler, D Henderson, BE Freedman, ML AF Cheng, I Stram, DO Penney, KL Pike, M Le Marchand, L Kolonel, LN Hirschhorn, J Altshuler, D Henderson, BE Freedman, ML TI Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR-I; BINDING PROTEIN-3; BREAST-CANCER; POPULATION STRATIFICATION; COMPLEX TRAITS; ASSOCIATION; MEN; PREDICTORS; IGFBP-3; POLYMORPHISMS AB Background. Insulin-like growth factor I (IGF-I) appears to play a role in prostate development and careinogenesis. We investigated whether genetic variation at the IGF1 locus is associated with prostate cancer risk. Methods: We sequenced IGF1 exons in germline DNA from 95 men with advanced prostate cancer to identify missense variants. IGF1 linkage disequilibrium patterns and common haplotypes were characterized by genotyping 64 single-nucleotide polymorphisms (SNPs) spanning 156 kilobases in 349 control subjects. Associations between IGF1 haplotypes and genotypes were investigated among 2320 patients with prostate cancer and 2290 control subjects from the Multiethnic Cohort. Odds ratios (ORs) and 95% confidence intervals (Cis) were estimated by unconditional logistic regression to determine the association between prostate cancer and IGF1 haplotypes and. genotypes. We used permutation testing to correct for multiple hypothesis testing. All statistical tests were two-sided. Results: No IGF1 missense variants were observed. We identified four blocks of strong linkage disequilibrium and selected a subset of 29 tagging SNPs that could accurately predict both the common IGF1 haplotypes and the remaining SNPs. Haplotype analysis revealed nominally statistically significant associations with prostate cancer risk in each of the four haplotype blocks: haplotype 1B (OR = 1.21, 95% CI = 1.04 to 1.40), haplotype 2C (OR = 1.24, 95% CI = 1.06 to 1.44), haplotype 3C (OR = 1.25, 95% CI = 1.03 to 1.50), and haplotype 4D (OR = 1.19, 95% CI = 1.02 to 1.39). Two SNPs-rs7978742 (P-trend =.002) and rs7965399 (P-trend =.002)-were perfectly correlated (correlation coefficient = 1.0) with one another and also associated with prostate cancer risk. These two SNPs were strong proxies for haplotypes 1B, 2C, 3C, and 4D and could account for the haplotype findings. Permutation testing revealed that a similarly strong result would be observed by chance only 5.6% of the time. Conclusion: Inherited variation in IGF1 may play a role in the risk of prostate cancer. C1 Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Univ Hawaii, Canc Res Ctr Hawaii, Canc Etiol Program, Honolulu, HI 96813 USA. Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. Dept Pediat, Boston, MA USA. RP Freedman, ML (reprint author), Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. EM freedman@broad.mit.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA 54281, CA 63464] NR 50 TC 75 Z9 78 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 2006 VL 98 IS 2 BP 123 EP 134 DI 10.1093/jnci/djj013 PG 12 WC Oncology SC Oncology GA 008JH UT WOS:000235036100011 PM 16418515 ER PT J AU Larson, EB Wang, L Bowen, JD McCormick, WC Teri, L Crane, P Kukull, W AF Larson, EB Wang, L Bowen, JD McCormick, WC Teri, L Crane, P Kukull, W TI Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY; ALZHEIMERS-DISEASE; COGNITIVE PERFORMANCE; APOLIPOPROTEIN-E; AEROBIC FITNESS; HEALTH; PEOPLE; ADULTS; RECOMMENDATION; IMPAIRMENT AB Background: Alzheimer disease and other dementing disorders are major sources of morbidity and mortality in aging societies. Proven strategies to delay onset or reduce risk for dementing disorders would be greatly beneficial. Objective: To determine whether regular exercise is associated with a reduced risk for dementia and Alzheimer disease. Design: Prospective cohort study. Setting: Group Health Cooperative, Seattle, Washington. Participants: 1740 persons older than age 65 years without cognitive impairment who scored above the 25th percentile on the Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought study and who were followed biennially to identify incident dementia. Measurements: Baseline measurements, including exercise frequency, cognitive function, physical function, depression, health conditions, lifestyle characteristics, and other potential risk factors for dementia (for example, apolipoprotein E EURO4); biennial assessment for dementia. Results: During a mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107 developed Alzheimer disease). The incidence rate of dementia was 13.0 per 1000 person-years for participants who exercised 3 or more times per week compared with 19.7 per 1000 person-years for those who exercised fewer than 3 times per week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% Cl, 0.44 to 0.86; P = 0.004). The interaction between exercise and performance-based physical function was statistically significant (P = 0.013). The risk reduction associated with exercise was greater in those with lower performance levels. Similar results were observed in analyses restricted to participants with incident Alzheimer disease. Limitations: Exercise was measured by self-reported frequency. The study population had a relatively high proportion of regular exercisers at baseline. Conclusion: These results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer disease, further supporting its value for elderly persons. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. RP Larson, EB (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM larson.e@ghc.org RI Crane, Paul/C-8623-2014; OI Kukull, Walter/0000-0001-8761-9014; Crane, Paul/0000-0003-4278-7465 FU NIA NIH HHS [AG06781] NR 44 TC 539 Z9 568 U1 14 U2 121 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 17 PY 2006 VL 144 IS 2 BP 73 EP 81 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 004AX UT WOS:000234725500003 PM 16418406 ER PT J AU Rumsfeld, JS Epstein, AJ AF Rumsfeld, JS Epstein, AJ TI Racial disparities in cardiovascular procedure outcomes - Turn down the volume SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID BYPASS GRAFT-SURGERY; QUALITY; MORTALITY; PATIENT; CARE; RACE C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Sect Cardiol,Div Cardiol, Denver, CO 80220 USA. Yale Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT USA. RP Rumsfeld, JS (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Sect Cardiol,Div Cardiol, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM John.Rumsfeld@med.va.gov NR 17 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 17 PY 2006 VL 47 IS 2 BP 425 EP 426 DI 10.1016/j.jacc.2005.10.025 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 003FM UT WOS:000234667100026 PM 16412872 ER PT J AU Namiki, Y Zou, L AF Namiki, Y Zou, L TI ATRIP associates with replication protein A-coated ssDNA through multiple interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ATR; cell cycle; checkpoint; DNA damage; genomic stability ID SINGLE-STRANDED-DNA; MEC1 SIGNALING PATHWAY; IN-VIVO; SACCHAROMYCES-CEREVISIAE; CHECKPOINT; DAMAGE; COMPLEX; ACTIVATION; SITES; ATM AB The ATR (ATM- and rad3-related)-mediated checkpoint pathway has a crucial role in regulating the cellular responses to DNA damage and DNA-replication stress. ATRIP (ATR-interacting protein), the regulatory partner of ATR, binds directly to replication protein A (RPA)-coated ssDNA and enables the ATR-ATRIP complex to recognize this DNA damage-induced structure. Here, we show that ATRIP associates with RPA-ssDNA through multiple interactions. Two major RPA-ssDNA-interacting domains of ATRIP were mapped to the regions flanking the conserved coiled-coil domain. In contrast to a recent article, we found that ATRIP mutants lacking the N terminus retained the ability to bind to RPA-ssDNA, suggesting that the multiple interactions between ATRIP and RPA-ssDNA may function redundantly in the recruitment of ATR-ATRIP. Unexpectedly, one internal region of ATRIP exhibited affinity to ssDNA, suggesting that ATRIP may interact with ssDNA in the ATRIP-RPA-ssDNA complex. Also, the N terminus of ATRIP associated with RPA-ssDNA in two distinct ways, indicating a dynamic and regulated association between ATRIP and RPA-ssDNA. C1 Massachusetts Gen Hosp, Canc Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Massachusetts Gen Hosp, Canc Ctr, 7th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu NR 32 TC 64 Z9 64 U1 0 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 JAN 17 PY 2006 VL 103 IS 3 BP 580 EP 585 DI 10.1073/pnas.0510223103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 004BU UT WOS:000234727800016 PM 16407120 ER PT J AU Norris, AW Kahn, CR AF Norris, AW Kahn, CR TI Analysis of gene expression in pathophysiological states: Balancing false discovery and false negative rates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE metabolic disease; microarray analysis; multiple hypothesis testing; statistics ID INSULIN-RESISTANCE; MICROARRAY; MICE; PREDICTION; METABOLISM; MUSCLE AB Nucleotide-microarray technology, which allows the simultaneous measurement of the expression of tens of thousands of genes, has become an important tool in the study of disease. In disorders such as malignancy, gene expression often undergoes broad changes of sizable magnitude, whereas in many common multifactorial diseases, such as diabetes, obesity, and atherosclerosis, the changes in gene expression are modest. In the latter circumstance, it is therefore challenging to distinguish the truly changing from nonchanging genes, especially because statistical significance must be considered in the context of multiple hypothesis testing. Here, we present a balanced probability analysis (BPA), which provides the biologist with an approach to interpret results in the context of the total number of genes truly differentially expressed and false discovery and false negative rates for the list of genes reaching any significance threshold. In situations where the changes are of modest magnitude, sole consideration of the false discovery rate can result in poor power to detect genes truly differentially expressed. Concomitant analysis of the rate of truly differentially expressed genes not identified, i.e., the false negative rate, allows balancing of the two error rates and a more thorough insight into the data. To this end, we have developed a unique, model-based procedure for the estimation of false negative rates, which allows application of BPA to real data in which changes are modest. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Norris, Andrew/0000-0001-8396-9543 FU NIDDK NIH HHS [K08-DK064906, K08 DK064906, R01-DK060837, R01 DK060837] NR 22 TC 28 Z9 30 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 JAN 17 PY 2006 VL 103 IS 3 BP 649 EP 653 DI 10.1073/PNAS.0510115103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 004BU UT WOS:000234727800028 PM 16407153 ER PT J AU Kepe, V Barrio, JR Huang, SC Ercoli, L Siddarth, P Shoghi-Jadid, K Cole, GM Satyamurthy, N Cummings, JL Small, GW Phelps, ME AF Kepe, V Barrio, JR Huang, SC Ercoli, L Siddarth, P Shoghi-Jadid, K Cole, GM Satyamurthy, N Cummings, JL Small, GW Phelps, ME TI Serotonin 1A receptors in the living brain of Alzheimer's disease patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE [F-18]MPPF; brain 5-HT1A receptors; neuronal loss; positron emission tomography ID MILD COGNITIVE IMPAIRMENT; NEUROFIBRILLARY TANGLES; 5-HT1A RECEPTOR; NEURONAL LOSS; HIPPOCAMPAL-FORMATION; ENTORHINAL CORTEX; PYRAMIDAL NEURONS; PET; TOMOGRAPHY; PLAQUES AB 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide, a selective serotonin 1A (5-HT1A) molecular imaging probe, was used in conjunction with positron emission tomography (PET) for quantification of 5-HT1A receptor densities in the living brains of Alzheimer's disease patients (ADs) (n = 8), subjects with mild cognitive impairment (n = 6), and controls (n = 5). ADs had receptor densities significantly decreased in both hippocampi (binding potential: controls 1.62 +/- 0.07; ADs 1.18 +/- 0.26) and also in raphe nuclei (controls 0.63 +/- 0.09; ADs 0.37 +/- 0.20). When volume losses are included, 5-HT1A losses are even more severe (i.e., average mean decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong correlation of 5-HT1A receptor decreases in hippocampus with worsening of clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these decreases in 5-HT1A receptor measures correlate with decreased glucose utilization as measured with 2-deoxy-2-[F-18]fluoro-D-glucose PET in the brains of ADs (standardized uptake values; globally: controls 0.89 +/- 0.04, ADs 0.72 +/- 0.04; posterior cingulate gyrus: controls 1.05 +/- 0.09, ADs 0.79 +/- 0.11). They also inversely correlate with increased neuropathological loads measured with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile PET in several neocortical regions in the same subjects. The in vivo observations were confirmed independently by in vitro digital autoradiography with 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl)benz-amide and 2-(1-(6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile on brain tissue specimens from two ADs and three nondemented subjects. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst & Geriatr, North Hills, CA 91343 USA. RP Barrio, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. EM jbarrio@mednet.ucla.edu; mphelps@mednet.ucla.edu RI Shoghi, Kooresh/H-7398-2014 OI Shoghi, Kooresh/0000-0003-3204-457X FU NIA NIH HHS [AG05142, P50 AG005142] NR 45 TC 135 Z9 138 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 17 PY 2006 VL 103 IS 3 BP 702 EP 707 DI 10.1073/pnas.0510237103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 004BU UT WOS:000234727800037 PM 16407119 ER PT J AU Kim, HJ Ryu, H Hong, SH Woo, HR Lim, PO Lee, IC Sheen, J Nam, HG Hwang, I AF Kim, HJ Ryu, H Hong, SH Woo, HR Lim, PO Lee, IC Sheen, J Nam, HG Hwang, I TI Cytokinin-mediated control of leaf longevity by AHK3 through phosphorylation of ARR2 in Arabidopsis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histidine kinase 3; cytokinin; leaf senescence ID SIGNAL-TRANSDUCTION; RESPONSE REGULATORS; SENESCENCE; THALIANA; FAMILY; GENE; IDENTIFICATION; CAROTENOIDS; INHIBITION; PERCEPTION AB Cytokinins are plant hormones with profound roles in growth and development, including control of leaf longevity. Although the cytokinin signal is known to be perceived by histidine kinase receptors, the underlying molecular mechanism and specificity of the receptors leading to delayed leaf senescence have not yet been elucidated. Here, we found that AHK3, one of the three cytokinin receptors in Arabidopsis, plays a major role in controlling cytokinin-mediated leaf longevity through a specific phosphorylation of a response regulator, ARR2. This result was obtained through identification of a gain-of-function Arabidopsis mutant that shows delayed leaf senescence because of a missense mutation in the extracellular domain of AHK3. A loss-of-function mutation in AHK3, but not of the other cytokinin receptors, conferred a reduced sensitivity to cytokinin in cytokinin-dependent delay of leaf senescence and abolished cytokinin-dependent phosphorylation of ARR2. Consistently, transgenic overexpression of wild-type, but not an unphosphorylatable mutant ARR2, led to delayed senescence of leaves. C1 Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang 790784, South Korea. Pohang Univ Sci & Technol, Natl Core Res Ctr Biodynam, Pohang 790784, South Korea. Pohang Univ Sci & Technol, IBIO Grad Program, Pohang 790784, South Korea. Cheju Natl Univ, Dept Sci Educ, Cheju 690756, South Korea. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Nam, HG (reprint author), Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang 790784, South Korea. EM nam@bric.postech.ac.kr; ihwang@postech.ac.kr NR 32 TC 195 Z9 214 U1 5 U2 50 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 JAN 17 PY 2006 VL 103 IS 3 BP 814 EP 819 DI 10.1073/pnas.0505150103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 004BU UT WOS:000234727800056 PM 16407152 ER PT J AU Aharon, I Becerraa, L Chabris, CF Borsooka, D AF Aharon, I Becerraa, L Chabris, CF Borsooka, D TI Noxious heat induces fMRI activation in two anatomically distinct clusters within the nucleus accumbens SO NEUROSCIENCE LETTERS LA English DT Article DE nucleus accumbens; pain; aversion; fMRI ID HUMAN BRAIN; SEEKING BEHAVIOR; SHELL; CORE; DOPAMINE; COCAINE; RECEPTORS; RESPONSES; STRIATUM; STIMULI AB Using functional magnetic resonance imaging (fMRI) we found that a noxious thermal stimulus (46 degrees C) to the hand activates the nucleus accumbens (NAc) in humans, while a non-noxious warm stimulus (41 degrees C) does not. Following the noxious stimulus, two distinct foci of decreased activation were observed showing distinct time course profiles. One focus was anterior, superior, and lateral and the second that was more posterior, inferior, and medial. The anatomical segregation may correlate with the functional components of the NAc, i.e., shell and core. The results support heterogeneity of function within the NAc and have implications for the understanding the contribution of NAc function to processing of pain and analgesia. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 McLean Hosp, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Athinoula Martinos NMR Ctr Med Imaging, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Borsooka, D (reprint author), McLean Hosp, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02478 USA. EM dborsook@mclean.harvard.edu FU PHS HHS [012581, 13650] NR 28 TC 19 Z9 21 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 16 PY 2006 VL 392 IS 3 BP 159 EP 164 DI 10.1016/j.neulet.2005.09.054 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 999OV UT WOS:000234400100001 PM 16257488 ER PT J AU Olendzki, B Speed, C Domino, FJ AF Olendzki, B Speed, C Domino, FJ TI Nutritional assessment and counseling for prevention and treatment of cardiovascular disease SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; FATTY-ACIDS; LIPOPROTEIN CHOLESTEROL; WHOLE GRAINS; US MEN; RISK; WOMEN; CONSUMPTION; DIET AB Physicians face several barriers to counseling their patients about nutrition, including conflicting evidence of the benefit of counseling, limited training and understanding of the topic, and imperfect and varied guidelines to follow. Because cardiovascular disease remains the leading cause of death in industrialized nations, family physicians should provide more than pharmacologic interventions. They must identify the patient's dietary habits and attitudes and provide appropriate counseling. Tools are available to help, and a seven-step approach to nutritional therapy for the dyslipidemic patient maybe useful. These steps include recommending increased intake of plant proteins; increased intake of omega-3 fatty acids; modification of the types of oils used in food preparation; decreased intake of saturated and trans-fatty acids; increased intake of whole grains and dietary fiber (especially soluble fiber) and decreased intake of refined grains; modification of alcohol intake, if needed; and regular exercise. Recommendations should be accompanied by patient information handouts presenting acceptable substitutions for currently identified detrimental food choices. C1 Univ Massachusetts, Sch Med, Dept Prevent & Behav Med, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Mem Med Ctr, Worcester, MA 01655 USA. RP Olendzki, B (reprint author), Univ Massachusetts, Sch Med, Dept Prevent & Behav Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM Barbara.Olendzki@umassmed.edu OI Olendzki, Barbara/0000-0003-4307-5187 NR 37 TC 11 Z9 12 U1 1 U2 3 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JAN 15 PY 2006 VL 73 IS 2 BP 257 EP 264 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 003NT UT WOS:000234689600006 PM 16445271 ER PT J AU Chen, AA Palacios, IF Mela, T Yoerger, DM Picard, MH Vlahakes, G Lowry, PA Fifer, MA AF Chen, AA Palacios, IF Mela, T Yoerger, DM Picard, MH Vlahakes, G Lowry, PA Fifer, MA TI Acute predictors of subacute complete heart block after alcohol septal ablation for obstructive hypertrophic cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID REDUCTION THERAPY AB Acute and subacute complete heart block (CHB) are sequelae of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy. Temporary pacemakers are routinely placed at the time of ASA, but there are no widely accepted guidelines for their management. This study examined acute predictors of subacute CHB in 52 consecutive ASA procedures in 48 patients without preexisting permanent pacemakers. Acute CHB occurred during 32 ASA procedures (62%), with the return of atrioventricular conduction on the day of ASA in all cases. New intraventricular conduction defects (IVCDs) were noted after 32 procedures (62%); in 9 of these, there was new first-degree atrioventricular block as well. CHB recurred subacutely 36 22 hours after 13 ASA procedures (25%). In 5 of these cases, there was absent or inconsistent ventricular escape rhythm. Subacute CHB did not occur in 9 cases without acute CHB during ASA or new IVCDs after ASA. Acute CHB during ASA, new IVCDs after ASA, and new first-degree atrioventricular block after ASA incrementally increased the risk for subacute CHB. In conclusion, patients with acute CHB during ASA or new IVCDs after ASA are at high risk for developing subacute CHB, sometimes without a reliable escape rhythm; these patients should therefore have temporary pacing support for >= 48 hours after ASA or the last occurrence of CHB. Patients without acute CHB during ASA or new IVCDs after ASA are at low risk for subacute CHB. (C) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM mfifer@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 13 TC 28 Z9 30 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2006 VL 97 IS 2 BP 264 EP 269 DI 10.1016/j.amjcard.2005.08.032 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 005VC UT WOS:000234851100023 PM 16442376 ER PT J AU Cheng, CA Chen, JS Patel, RP AF Cheng, CA Chen, JS Patel, RP TI Unlabeled uses of botulinum toxins: A review, part 1 SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE botulinum toxin A; botulinum toxins; drugs; mechanism of action; skeletal; muscle relaxants; toxicity ID TENSION-TYPE HEADACHE; RANDOMIZED CONTROLLED-TRIAL; ESSENTIAL HAND TREMOR; DOUBLE-BLIND; ESOPHAGEAL ACHALASIA; PALMAR HYPERHIDROSIS; PNEUMATIC DILATATION; FOCAL HYPERHIDROSIS; BALLOON DILATION; PLACEBO AB Purpose. Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. Summary. More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. Conclusion. Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications. C1 Univ Calif San Francisco, Drug Informat & Anal Serv, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Blue Shield Calif, San Francisco, CA USA. RP Cheng, CA (reprint author), Univ Calif San Francisco, Drug Informat & Anal Serv, 521 Parnassus Ave,C-152,Box 0622, San Francisco, CA 94143 USA. EM chengc@pharmacy.ucsf.edu NR 42 TC 24 Z9 24 U1 0 U2 4 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JAN 15 PY 2006 VL 63 IS 2 BP 145 EP 152 DI 10.2146/ajhp050137 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 006MN UT WOS:000234901700007 PM 16390928 ER PT J AU Deckersbach, T Dougherty, DD Savage, C McMurrich, S Fischman, AJ Nierenberg, A Sachs, G Rauch, SL AF Deckersbach, T Dougherty, DD Savage, C McMurrich, S Fischman, AJ Nierenberg, A Sachs, G Rauch, SL TI Impaired recruitment of the dorsolateral prefrontal cortex and hippocampus during encoding in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat DE bipolar disorder; episodic memory; working memory; PET ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; EPISODIC MEMORY IMPAIRMENT; WORKING-MEMORY; LEARNING-STRATEGIES; EXPLICIT MEMORY; MOOD DISORDERS; RATING-SCALE; PET; SCHIZOPHRENIA AB Background: The aim of the present study was to examine the functional neuroanatomy of episodic memory impairment in euthymic subjects with bipolar I disorder. There is evidence that individuals with bipolar disorder have cognitive impairments not only during mood episodes but also when they are euthymic. The most consistently reported cognitive difficulty in euthymic subjects with bipolar disorder is impairment in verbal episodic memory (i.e., the ability to learn new verbal information). Methods: The current study examined verbal learning in eight euthymic, remitted subjects with bipolar I disorder (BP-I; seven nonmedicated) and eight control subjects matched for age, gender, education, and intelligence. Subjects underwent O-15-CO2 positron emission tomography scanning while completing a verbal learning paradigm that consisted of encoding (learning) several lists of words. Results: The BP-I subjects had more difficulties learning the lists of words compared with the control subjects. Compared with control subjects, BP-I subjects exhibited blunted regional cerebral blood flow (rCBF) increases in the left dorsolateral prefrontal cortex (Brodmann's area 9/46) during encoding. Conclusions: Consistent with previous studies, subjects with BP-I were impaired in learning new verbal information. This was associated with rCBF abnormalities in brain regions involved in learning and episodic memory. C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Psychiat Neurosci Program, 149-2611,Bldg 149,13th St,2nd Floor, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org NR 56 TC 41 Z9 43 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2006 VL 59 IS 2 BP 138 EP 146 DI 10.1016/j.biopsych.2005.06.030 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 006CB UT WOS:000234871600006 PM 16169530 ER PT J AU Jones, GB Crasto, CF Mathews, JE Xie, LF Mitchell, MO El-Shafey, A D'Amico, AV Bubley, GJ AF Jones, GB Crasto, CF Mathews, JE Xie, LF Mitchell, MO El-Shafey, A D'Amico, AV Bubley, GJ TI An image contrast agent selectively activated by prostate specific antigen SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE enzyme substrates; PSA; linker; imaging agents; chemical synthesis; prodrugs; coumarin; hexapeptides ID PRODRUG; CANCER AB A family of image contrast agent conjugates designed to undergo enzymatic activation has been synthesized. The agents underwent activation both with enzymatically active prostate specific antigen (PSA) and a-chymotrypsin, releasing free fluorophore via cleavage of a three-component system. A hexapeptide derivative showed exclusive activation by PSA and constitutes a method for tracking PSA activity in vitro. (c) 2005 Elsevier Ltd. All rights reserved. C1 Northeastern Univ, Bioorgan & Med Chem Labs, Dept Chem & Chem Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Jones, GB (reprint author), Northeastern Univ, Bioorgan & Med Chem Labs, Dept Chem & Chem Biol, Boston, MA 02115 USA. EM gr.jones@neu.edu NR 14 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2006 VL 14 IS 2 BP 418 EP 425 DI 10.1016/j.bmc.2005.08.015 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 995HN UT WOS:000234091500012 PM 16185875 ER PT J AU Islam, SA Thomas, SY Hess, C Medoff, BD Means, TK Brander, C Lilly, CM Tager, AM Luster, AD AF Islam, SA Thomas, SY Hess, C Medoff, BD Means, TK Brander, C Lilly, CM Tager, AM Luster, AD TI The leukotriene B-4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in humans SO BLOOD LA English DT Article ID DENDRITIC CELLS; CHEMOKINE PRODUCTION; DEPENDENT MIGRATION; NKT CELLS; G-PROTEIN; IN-VIVO; MEMORY; EXPRESSION; EFFECTOR; TRAFFICKING AB We have recently shown that the leukotriene B-4 (LTB4)-BLT1 pathway is important in early effector T-cell recruitment in mouse models of inflammation. Here we characterize the phenotype and function of human peripheral blood BLT1(+) T cells in health and illustrate their involvement in asthma and acute infection. In healthy individuals, BLT1(+) T cells are a rare peripheral blood T-cell population enriched for the activation markers CD38 and HLA-DR. Compared with BLT1(-)T cells, a larger proportion of peripheral blood BLT1(+) T cells express the effector cytokines IFN gamma and IL-4 and inflammatory chemokine receptors, CCR1, CCR2, CCR6, and CXCR1. Consequently, in healthy individuals peripheral blood BLT1(+) T cells are a rare antigen-primed T-cell subset with unique phenotypic, migratory, and functional properties. BLT1 expression on T cells is tightly regulated by inflammation and only transiently expressed after naive T-cell activation by dendritic cells. Although rare in the peripheral blood of healthy individuals, BLT1(+) T cells are markedly increased in frequency in the peripheral blood in response to acute Epstein-Barr virus (EBV) infection and moderately increased in the airways of asymptomatic allergic asthmatics. Our studies provide novel insights into the LTB4-BLT1 lipid chemoattractant pathway in human T-cell responses, and how it may link innate and adaptive immunity. C1 Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Partners AIDS Res, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu OI Brander, Christian/0000-0002-0548-5778; Thomas, Seddon/0000-0003-0075-0744 FU NIAID NIH HHS [KO8 AI055663, K08 AI055663, R01 AI050892] NR 64 TC 42 Z9 45 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2006 VL 107 IS 2 BP 444 EP 453 DI 10.1182/blood-2005-06-2362 PG 10 WC Hematology SC Hematology GA 001PR UT WOS:000234549300014 PM 16179368 ER PT J AU Kamath, AF Chauhan, AK Kisucka, J Dole, VS Loscalzo, J Handy, DE Wagner, DD AF Kamath, AF Chauhan, AK Kisucka, J Dole, VS Loscalzo, J Handy, DE Wagner, DD TI Elevated levels of homocysteine compromise blood-brain barrier integrity in mice SO BLOOD LA English DT Article ID CYSTATHIONINE BETA-SYNTHASE; CEREBRAL VASCULAR DYSFUNCTION; NITRIC-OXIDE; ACCELERATES ATHEROSCLEROSIS; ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; HYPERHOMOCYSTEINEMIA; DEFICIENT; INFLAMMATION; METAANALYSIS AB Elevated levels of plasma homocysteine (Hcy) correlate with increased risk of cardiovascular and Alzheimer diseases. We studied the effect of elevated Hcy on the blood-brain barrier (BBB) to explore the possibility of a vascular link between the 2 diseases. On a hyperhomocysteinemic diet, cystathionine beta-synthase (Cbs)-heterozygous mice develop hyperhomo-cysteinemia. Intravital microscopy analysis of the mesenteric venules showed that leukocyte rolling velocity was markedly decreased and numbers of adherent cells were increased in the mutant mice. This was due at least in part to increased expression of P-selectin. BBB permeability was measured by Evans blue dye permeation and was found to be 25% greater in the Cbs(+/-) cortex compared with wild-type controls. Our study suggests an important toxic effect of elevated Hcy on brain microvessels and implicates Hcy in the disruption of the BBB. C1 CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Dept Med,Med Sch, Boston, MA 02115 USA. RP Wagner, DD (reprint author), CBR, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [HL58976, R01 HL041002, R37 HL41002] NR 32 TC 88 Z9 92 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2006 VL 107 IS 2 BP 591 EP 593 DI 10.1182/blood-2005-06-2506 PG 3 WC Hematology SC Hematology GA 001PR UT WOS:000234549300034 PM 16189268 ER PT J AU O'Neil, J Calvo, J McKenna, K Krishnamoorthy, V Aster, JC Bassing, CH Alt, FW Kelliher, M Look, AT AF O'Neil, J Calvo, J McKenna, K Krishnamoorthy, V Aster, JC Bassing, CH Alt, FW Kelliher, M Look, AT TI Activating Notch1 mutations in mouse models of T-ALL SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSGENIC MICE; HISTONE H2AX; GENOMIC INSTABILITY; EXPRESSION; THYMOCYTES; MUTANT; TUMORS AB Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also acquired in mouse models of T-ALL. We sequenced the heterodimerization domain and the PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors harbor activating mutations in Notch1. Cell lines derived from these tumors undergo G(0)/G(1) arrest and apoptosis when treated with a gamma-secretase inhibitor. In addition, we found activating Notch1 mutations in 31% of thymic lymphomas that occur in mice deficient for various combinations of the H2AX, Tp53, and Rag2 genes. Thus, Notch1 mutations are often acquired as a part of the molecular pathogenesis of T-ALLs that develop in mice with known predisposing genetic alterations. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer Bldg,Rm 630,44 Binney St, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu FU NCI NIH HHS [R01 CA096899] NR 24 TC 161 Z9 162 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2006 VL 107 IS 2 BP 781 EP 785 DI 10.1182/blood-2005-06-2553 PG 5 WC Hematology SC Hematology GA 001PR UT WOS:000234549300058 PM 16166587 ER PT J AU Syngal, S Stoffel, E Chung, D Willett, C Schoetz, D Schroy, P Jagadeesh, D Morel, K Ross, M AF Syngal, S Stoffel, E Chung, D Willett, C Schoetz, D Schroy, P Jagadeesh, D Morel, K Ross, M TI Detection of stool DNA mutations before and after treatment of colorectal neoplasia SO CANCER LA English DT Article DE colorectal carcinoma; colorectal adenoma; fecal DNA; polymerase chain reaction (PCR) ID FECAL DNA; CANCER; TUMORIGENESIS; COLONOSCOPY AB BACKGROUND. Whether stool DNA abnormalities arise solely from colorectal neoplastic lesions or are due to more pervasive field effects is not known. In the current study, the authors conducted a prospective multicenter study to evaluate the performance of stool-based DNA testing in a large cohort and to examine whether the findings before treatment persist after surgical resection and/or adjuvant therapy. METHODS. Patients with newly diagnosed colorectal carcinoma or advanced adenomas (AA) provided stool samples before therapy, 1-3 months after Surgical resection, and 6-9 months postresection. Stool samples were analyzed using the multitarget DNA assay panel (MTAP) consisting of 23 markets: 21 Mutations in the p53, K-ras, and APC genes, a microsatellite instability market (BAT-26), and the DNA integrity assay (DIA), a market of loss of apoptosis. RESULTS. Overall, 49 of 91 individuals (54%) tested positive with the MTAP test. The sensitivity of the MTAP test was 63% for invasive tumors compared with 26% for AA. Individuals whose lesions had a more advanced TNM stage or were located distal to the splenic flexure were significantly more likely to have a positive MTAP test. Of the 79 samples collected at 1-3 months after Surgical resection of the neoplasm, 14 (18%) had a positive MTAP result, 12 of which were positive for DIA only. Of those collected at 6-9 months of follow-up, 5 of 72 (7%) tested positive oil the MTAP panel. CONCLUSIONS. Although many samples collected 1-3 months after Surgical resection of the colorectal neoplasm tested positive oil the MTAP, most were negative by 6-9 months, indicating that stool DNA abnormalities disappear after treatment of the neoplastic lesions. Surgery and chemoradiation appear to induce transient DIA abnormalities that may be independent of the presence of neoplasia. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Lahey Clin Fdn, Dept Colon & Rectal Surg, Burlington, MA 01805 USA. Boston Med Ctr, Gastroenterol Sect, Boston, MA USA. EXACT Sci Corp, Marlborough, MA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org NR 15 TC 34 Z9 36 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 2006 VL 106 IS 2 BP 277 EP 283 DI 10.1002/cncr.21558 PG 7 WC Oncology SC Oncology GA 002CJ UT WOS:000234588700005 PM 16342248 ER PT J AU Yamanaka, K Clark, R Dowgiert, R Hurwitz, D Shibata, M Rich, BE Hirahara, K Jones, DA Eapen, S Mizutani, H Kupper, TS AF Yamanaka, K Clark, R Dowgiert, R Hurwitz, D Shibata, M Rich, BE Hirahara, K Jones, DA Eapen, S Mizutani, H Kupper, TS TI Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphorna SO CLINICAL CANCER RESEARCH LA English DT Article ID IFN-GAMMA PRODUCTION; ATOPIC-DERMATITIS; HUMAN KERATINOCYTES; MYCOSIS-FUNGOIDES; INTERFERON-GAMMA; SEZARY-SYNDROME; IL-18 RECEPTOR; MESSENGER-RNA; HUMAN SKIN; CYTOKINE AB Purpose: Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing Th2 T cells. Clonal T cells and CTCL skin lesions typically express Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-10, but fail to produce Th1 cytokines. However, the reason for Th2 bias is unknown. IL-18 is a pleiotropic proinflammatory cytokine produced by monocytes/macrophages lineage as well as epithelial cells, such as human keratinocytes. In the absence of IL-12, IL-18 leads to increased immunoglobulin E production from B cells and enhanced production of IL-4 and IL-13 by basophils, mast cells, and CD4(+) T cells. We have analyzed cytokines in CTCL patients, which may bias the immune response around the Th1/Th2 axis. Experimental Design: We examined plasma of 95 CTCL patients and skin of 20 CTCL patients for IL-18, caspase-1, IL-12, and other cytokines. To identify the presence or absence of these cytokine proteins in CTCL and normal skin, we cultured explants from skin biopsies on three-dimensional matrices. Results: Plasma levels of IL-18 and its converting enzyme, caspase-1, were significantly elevated in CTCL. mRNA levels for these factors were also elevated in CTCL skin lesions. Matrices populated with CTCL lesional skin produced significant amounts of IL-18 and caspase-1; however, production of IL-12 protein was barely detectable. Conclusions: We propose that the high levels of IL-18 expression in lesional CTCL skin contribute to increased plasma levels of IL-18 and that this, in the face of significantly lower levels of IL-12, may contribute to the Th2 bias seen in this disease. C1 Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Biostat Core Facil, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Mie Univ, Fac Med, Dept Dermatol, Tsu, Mie 514, Japan. RP Kupper, TS (reprint author), Harvard Inst Med, Harvard Skin Dis Res Ctr, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM tskupper@rics.bwh.harvard.edu NR 51 TC 27 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2006 VL 12 IS 2 BP 376 EP 382 DI 10.1158/1078-0432.CCR-05-1777 PG 7 WC Oncology SC Oncology GA 004ZL UT WOS:000234791300009 PM 16428475 ER PT J AU Ye, B Skates, S Mok, SC Horick, NK Rosenberg, HF Vitonis, A Edwards, D Sluss, P Han, WK Berkowitz, RS Cramer, DW AF Ye, B Skates, S Mok, SC Horick, NK Rosenberg, HF Vitonis, A Edwards, D Sluss, P Han, WK Berkowitz, RS Cramer, DW TI Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine SO CLINICAL CANCER RESEARCH LA English DT Article ID MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; NONSECRETORY RIBONUCLEASE; PREGNANT-WOMEN; PROTEINS; CARCINOMA; INFLAMMATION; BIOMARKER; PLASMA; BLOOD AB Purpose: The objective was to identify and characterize low molecular weight proteins/peptides in urine and their posttranslational modifications that might be used as a screening tool for ovarian cancer. Experimental Design: Urine samples collected preoperatively from postmenopausal women with ovarian cancer and benign conditions and from nonsurgical controls were analyzed by surface-enhanced laser desorption/ionization mass spectrometry and two-dimensional gel electrophoresis. Selected proteins from mass profiles were purified by chromatography and followed by liquid chromatography-tandem mass spectrometry sequence analysis. Specific antibodies were generated for further characterization, including immunoprecipitation and glycosylation. Quantitative and semiquantitative ELISAs were developed for preliminary validation in patients of 128 ovarian cancer, 52 benign conditions, 44 other cancers, and 188 healthy controls. Results: A protein (m/z similar to 17,400) with higher peak intensities in cancer patients than in benign conditions and controls was identified and subsequently defined as eosinophil-derived neurotoxin (EDN). A glycosylated form of EDN was specifically elevated in ovarian cancer patients. A cluster of COOH-terminal osteopontin was identified from two-dimensional gels of urine from cancer patients. Modified forms EDN and osteopontin fragments were elevated in early-stage ovarian cancers and a combination of both resulted to 93% specificity and 72% sensitivity. Conclusions: Specific elevated posttranslationally modified urinary EDN and osteopontin COOH-terminal fragments in ovarian cancer might lead to potential noninvasive screening tests for early diagnosis. Urine with less complexity than serum and relatively high thermodynamic stability of peptides or metabolites is a promising study medium for discovery of the novel biomarkers which may present in many nonurinary tract neoplastic diseases. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Ctr,Lab Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Ctr, Renal & Pathol Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit Lab, Boston, MA 02114 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Ye, B (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Ctr,Lab Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, 221 Longwood Ave,LMRC 610B, Boston, MA 02115 USA. EM Bye@partners.org FU NCI NIH HHS [1P50 CA 105009, R21 CA 111949-01, U01 CA 86381] NR 48 TC 97 Z9 108 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2006 VL 12 IS 2 BP 432 EP 441 DI 10.1158/1078-0432.CCR-05-0461 PG 10 WC Oncology SC Oncology GA 004ZL UT WOS:000234791300017 PM 16428483 ER PT J AU Ino, Y Saeki, Y Fukuhara, H Todo, T AF Ino, Y Saeki, Y Fukuhara, H Todo, T TI Triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble B7-1 results in enhanced antitumor efficacy SO CLINICAL CANCER RESEARCH LA English DT Article ID GAMMA-INDUCING FACTOR; BACTERIAL ARTIFICIAL CHROMOSOME; SQUAMOUS-CELL CARCINOMA; IFN-GAMMA; GENE-TRANSFER; BRAIN-TUMOR; CLASS-I; THERAPY; IL-12; REPLICATION AB Conditionally replicating herpes simplex virus-1 (HSV-1) vectors are promising therapeutic agents for cancer. Insertion of therapeutic transgenes into the viral genome should confer desired anticancer functions in addition to oncolytic activities. Herein, using bacterial artificial chromosome and two recombinase-mediated recombinations, we simultaneously created four "armed- oncolytic HSV-1, designated vHsv-B7.1-1g, vHsv-interleukin (IL)-12, vHsv-IL-18, and vHsv-null, which express murine soluble 137.1 (B7.1-Ig), murine IL-12, murine IL-18, and no transgene, respectively. These vHsv vectors possess deletions in the),34.5 genes and contain the green fluorescent protein gene as a histochemical marker and the immunostimulatory transgene inserted in the deleted ICP6 locus. The vHsv showed similar replicative capabilities in vitro. The in vivo efficacy was tested in A/J mice harboring s.c. tumors of syngeneic and poorly immunogenic Neuro2a neuroblastoma. The triple combination of vHsv-B7.1-Ig, vHsv-IL-12, and vHsv-IL-18 exhibited the highest efficacy among all single vHsv or combinations of two viruses. Combining 1 X 105 plaque-forming units each of the three armed viruses showed stronger antitumor activities than any single armed virus at 3 x 105 plaque-forming units in inoculated tumors as well as in noninoculated remote tumors. Studies using athymic mice indicated that this enhancement of antitumor efficacy was likely mediated by T-cell immune responses. The combined use of multiple oncolytic HSV-1 armed with different immunostimulatory genes may be a useful strategy for cancer therapy. C1 Univ Tokyo, Dept Neurosurg, Bunkyo Ku, Tokyo 1138655, Japan. Univ Tokyo, Dept Neurooncol & Mol Therapeut, Tokyo 1138655, Japan. Univ Tokyo, Dept Urol, Tokyo 1138655, Japan. Harvard Univ, Sch Med, Mol Neurosurg Lab, Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Mol Neurooncol Lab, Massachusetts Gen Hosp, Charlestown, MA USA. RP Todo, T (reprint author), Univ Tokyo, Dept Neurosurg, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM toudou-nsu@umin.ac.jp NR 49 TC 58 Z9 64 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2006 VL 12 IS 2 BP 643 EP 652 DI 10.1158/1078-0432.CCR-05-1494 PG 10 WC Oncology SC Oncology GA 004ZL UT WOS:000234791300045 PM 16428511 ER PT J AU Hadano, S Benn, SC Kakuta, S Otomo, A Sudo, K Kunita, R Suzuki-Utsunomiya, K Mizumura, H Shefner, JM Cox, GA Iwakura, Y Brown, RH Ikeda, JE AF Hadano, S Benn, SC Kakuta, S Otomo, A Sudo, K Kunita, R Suzuki-Utsunomiya, K Mizumura, H Shefner, JM Cox, GA Iwakura, Y Brown, RH Ikeda, JE TI Mice deficient in the Rab5 guanine nucleotide exchange factor ALS2/alsin exhibit age-dependent neurological deficits and altered endosome trafficking SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; HEREDITARY SPASTIC PARAPLEGIA; UNIT NUMBER ESTIMATION; SMALL GTPASE RAB5; ALS2 GENE; AXONAL-TRANSPORT; INFANTILE-ONSET; BULBAR INVOLVEMENT; MUTATION AB ALS2/alsin is a member of guanine nucleotide exchange factors for the small GTPase Rab5 (Rab5GEFs), which act as modulators in endocytic pathway. Loss-of-function mutations in human ALS2 account for a number of juvenile recessive motor neuron diseases (MNDs). However, the normal physiological role of ALS2 in vivo and the molecular mechanisms underlying motor dysfunction are still unknown. To address these issues, we have generated mice homozygous for disruption of the Als2 gene. The Als2-null mice observed through 21 months of age demonstrated no obvious developmental, reproductive or motor abnormalities. However, immunohistochemical and electrophysiological analyses identified an age-dependent, slowly progressive loss of cerebellar Purkinje cells and disturbance of spinal motor neurons associated with astrocytosis and microglial cell activation, indicating a subclinical dysfunction of motor system in Als2-null mice. Further, quantitative epidermal growth factor (EGF)-uptake analysis identified significantly smaller-sized EGF-positive endosomes in Als2-null fibroblasts, suggesting an alteration of endosome/vesicle trafficking in the cells. Collectively, while loss of ALS2 does not produce a severe disease phenotype in mice, these Als2-null animals should provide a useful model with which to understand the interplay between endosomal dynamics and the long-term viability of large neurons such as Purkinje cells and spinal motor neurons. C1 Tokai Univ, Sch Med, Inst Med Sci, Dept Mol Neurosci, Kanagawa 2591193, Japan. Tokai Univ, Sch Med, Dept Mol Life Sci, Kanagawa 2591193, Japan. Japan Sci & Technol Agcy, Solut Oriented Res Sci & Technol, Kawaguchi, Saitama 3320012, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan. SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13104 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Ottawa, Fac Med, Dept Paediat, Ottawa, ON K1H 8M5, Canada. RP Ikeda, JE (reprint author), Tokai Univ, Sch Med, Inst Med Sci, Dept Mol Neurosci, Kanagawa 2591193, Japan. EM joh-e@nga.med.u-tokai.ac.jp RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 56 TC 83 Z9 86 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2006 VL 15 IS 2 BP 233 EP 250 DI 10.1093/hmg/ddi440 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 002RZ UT WOS:000234630400006 PM 16321985 ER PT J AU Apostol, BL Illes, K Pallos, J Bodai, L Wu, J Strand, A Schweitzer, ES Olson, JM Kazantsev, A Marsh, JL Thompson, LM AF Apostol, BL Illes, K Pallos, J Bodai, L Wu, J Strand, A Schweitzer, ES Olson, JM Kazantsev, A Marsh, JL Thompson, LM TI Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity SO HUMAN MOLECULAR GENETICS LA English DT Article ID POLYGLUTAMINE-EXPANDED HUNTINGTIN; ANDROGEN RECEPTOR PROTEIN; GENE-EXPRESSION CHANGES; N-TERMINAL KINASE; MOUSE MODEL; CHAPERONE SUPPRESSION; CELLULAR TOXICITY; STRESS-RESPONSE; DISEASE; APOPTOSIS AB Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract within the huntingtin protein (Htt). Identifying the pathways that are altered in response to the mutant protein is crucial for understanding the cellular processes impacted by the disease as well as for the rational development of effective pharmacological interventions. Here, expression profiling of a cellular HD model identifies genes that implicate altered mitogen-activated protein kinase (MAPK) signaling. Targeted biochemical studies and pharmacological modulation of these MAPK pathways suggest that mutant Htt affects signaling at upstream points such that both ERK and JNK are activated. Modulation of the ERK pathway suggests that this pathway is associated with cell survival, whereas inhibition of JNK was found to effectively suppress pathogenesis. These studies suggest that pharmacological intervention in MAPK pathways, particularly at the level of ERK activation, may be an appropriate approach to HD therapy. C1 Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Hematol Oncol, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol Chem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Ctr Aging & Neurodegenerat, Charlestown, MA 02129 USA. RP Thompson, LM (reprint author), Univ Calif Irvine, Dept Psychiat & Human Behav, Gillespie 2121, Irvine, CA 92697 USA. EM lmthompson@uci.edu RI Bodai, Laszlo/A-9764-2012 OI Bodai, Laszlo/0000-0001-8411-626X FU NICHD NIH HHS [HD36081]; NINDS NIH HHS [NS045283, NS42157-04] NR 64 TC 85 Z9 85 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2006 VL 15 IS 2 BP 273 EP 285 DI 10.1093/hmg/ddi443 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 002RZ UT WOS:000234630400009 PM 16330479 ER PT J AU Niemi, SM AF Niemi, SM TI Making comparative medicine more so SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material ID GENOME; DOG C1 Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Niemi, SM (reprint author), Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA 02129 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JAN 15 PY 2006 VL 228 IS 2 BP 199 EP 200 DI 10.2460/javma.228.2.199 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 004RZ UT WOS:000234771200013 PM 16426183 ER PT J AU Mizoguchi, A Bhan, AK AF Mizoguchi, A Bhan, AK TI A case for regulatory B cells SO JOURNAL OF IMMUNOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; ALPHA MUTANT MICE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NONOBESE DIABETIC MICE; CD4(+) T-CELLS; MARGINAL ZONE; AUTOIMMUNE-DISEASE; EXPERIMENTAL COLITIS; CYTOKINE PRODUCTION; ULCERATIVE-COLITIS AB B cells are typically characterized by their ability to produce Abs, including autoantibodies. However, B cells possess additional immune functions, including the production of cytokines and the ability to function as a secondary APC As with T cells, the B cell population contains functionally distinct subsets capable of performing both pathogenic and regulatory functions. Recent studies indicate that regulatory B cells develop in several murine models of chronic inflammation, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The regulatory function may be directly accomplished by the production of regulatory cytokines IL-10 and TGF-beta and/or by the ability of B cells to interact with pathogenic T cells to dampen harmful immune responses. In this review, we make a case for the existence of regulatory B cells and discuss the possible developmental pathways and functional mechanisms of these B cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Immunopathol Unit, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, 55 Fruit St, Boston, MA 02114 USA. EM abhan@partners.org FU NIDDK NIH HHS [DK064531, DK47677] NR 104 TC 336 Z9 383 U1 2 U2 24 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2006 VL 176 IS 2 BP 705 EP 710 PG 6 WC Immunology SC Immunology GA 001RK UT WOS:000234553800004 PM 16393950 ER PT J AU Delgado, JC Baena, A Thim, S Goldfeld, AE AF Delgado, JC Baena, A Thim, S Goldfeld, AE TI Aspartic acid homozygosity at codon 57 of HLA-DQ beta is associated with susceptibility to pulmonary tuberculosis in Cambodia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; T-CELL RESPONSES; SINGLE NUCLEOTIDE POLYMORPHISMS; NECROSIS-FACTOR-ALPHA; CLASS-II ALLELES; MYCOBACTERIUM-TUBERCULOSIS; OLIGONUCLEOTIDE HYBRIDIZATION; FALCIPARUM MALARIA; CRYSTAL-STRUCTURE; INTERFERON-GAMMA AB After infection with Mycobacterium tuberculosis, clinical disease usually remains latent, contained by the host immune response. Although polymorphisms of HLA loci have been hypothesized to play a major role in the breakdown of latency, a functional link has not been established. Molecular-based HLA-typing methods were used to test the association of sets of HLA alleles encoding an aspartic acid at codon 57 of the HLA-DQ beta-chain (HLA-DQ beta 57-Asp) with susceptibility to tuberculosis in a cohort of 436 pulmonary tuberculosis patients and 107 healthy controls from Cambodia. HLA class II null cells were transduced with HLA-DQ beta 57-Asp or HLA-DQ beta 57-Ala and evaluated for their ability to bind peptides from two immunogenic M. tuberculosis specific proteins, ESAT-6 and CFP-10. In this study, we report a highly significant association between progressive pulmonary tuberculosis and homozygosity for HLA-DQ 1357-Asp alleles. The presence of HLA-DQ 1357-Asp resulted in a significantly reduced ability to bind a peptide from the central region of the ESAT-6 protein. Furthermore, when this peptide was presented by an HLA-DQ beta 57-Asp allele, Ag-specific IFN-gamma production from CD4(+) T cells from tuberculosis patients was significantly less than when this peptide was presented by an HLA-DQ-beta allele encoding an alanine at codon 57. Multiple genetic loci and ethnic-specific factors are likely involved in the human immune response to tuberculosis. The data presented here provide a functional explanation for a highly significant association between an HLA polymorphism and tuberculosis in a highly characterized group of patients with susceptibility to progressive tuberculosis infection in Cambodia. C1 Harvard Univ, CBR Inst Biomed Res, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Cambodian Hlth Comm, Phnom Penh, Cambodia. RP Goldfeld, AE (reprint author), Harvard Univ, CBR Inst Biomed Res, Sch Med, 800 Huntington Ave, Boston, MA 02115 USA. EM goldfeld@cbrinstitute.org FU NHLBI NIH HHS [HL59838, HL67471] NR 55 TC 36 Z9 39 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 JAN 15 PY 2006 VL 176 IS 2 BP 1090 EP 1097 PG 8 WC Immunology SC Immunology GA 001RK UT WOS:000234553800051 PM 16393997 ER PT J AU Chen, ZQ Mikulec, AA McKenna, MJ Sewell, WF Kujawa, SG AF Chen, ZQ Mikulec, AA McKenna, MJ Sewell, WF Kujawa, SG TI A method for intracochlear drug delivery in the mouse SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE mouse; inner ear; CNQX; salicylate; cochlea; drug delivery; cochleostomy ID INNER-EAR; OTOACOUSTIC EMISSIONS; SURGICAL APPROACH; STAPEDIAL ARTERY; GENE-THERAPY; HAIR-CELLS; RECEPTOR; MICE; TRANSMISSION; SOUND AB The confluence of two rapidly emerging research arenas - development of mouse models of human deafness and inner ear drug therapy for treatment and prevention of hearing loss - provides an opportunity for unprecedented approaches to study and treat deafness. Toward such goals, we have developed a method for intracochlear drug delivery in the mouse. The bulla was exposed using a ventral approach and the stapedial artery cauterized. An opening made into the inferior-medial aspect of the bulla, where the basal cochlear wall fuses with tympanic bulla, provided direct access to the scala tympani without separately opening the bulla or elevating auditory response thresholds. Cochlear responses, assayed by frequency-specific effects on ABRs and DPOAEs, were stable with infusion (1 mu l/h) of an artificial perilymph solution (80 min). The glutamate receptor antagonist, CNQX (100 mu M; 175 min), reduced ABR responses without affecting DPOAEs. Salicylate (5 mM; 165 min) altered both. Both drugs had greatest effects at high frequencies, but distributed throughout the cochlea and were reversible. The safe delivery of drugs into the cochlea by this approach has immediate application in the study and treatment of various forms of human hearing loss that can be modeled in the mouse. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Kujawa, SG (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. EM zhiqiang_chen@meei.harvard.edu; mikuleca@slu.edu; michael_mckenna@meei.harvard.edu; william_sewell@epl.meei.harvard.edu; sharon_kujawa@meei.harvard.edu FU NIDCD NIH HHS [R01 DC03401-07, R21 DC04983, P30 DC0052009, R01 DC00767]; PHS HHS [DLH-543157] NR 21 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2006 VL 150 IS 1 BP 67 EP 73 DI 10.1016/j.jeumeth.2005.05.017 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 004ST UT WOS:000234773200008 PM 16043228 ER PT J AU Huppert, TJ Hoge, RD Diamond, SG Franceschini, MA Boas, DA AF Huppert, TJ Hoge, RD Diamond, SG Franceschini, MA Boas, DA TI A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans SO NEUROIMAGE LA English DT Article DE near-infrared spectroscopy; BOLD; ASL; multimodality comparison ID NEAR-INFRARED SPECTROSCOPY; HUMAN BRAIN ACTIVITY; BLOOD OXYGENATION; BALLOON MODEL; IN-VIVO; DEOXYHEMOGLOBIN CONCENTRATION; SENSORY STIMULATION; EXPERIMENTAL-DESIGN; INTRINSIC SIGNAL; FUNCTIONAL MRI AB In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98; P < 10(-20)) than with deoxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging." Med. Phys. 28 (4) 521-527; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans." NeuroImage 20 1246-1252; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Grad Program Biophys, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Huppert, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Grad Program Biophys, Charlestown, MA 02129 USA. EM thuppert@nmr.mgh.harvard.edu OI Diamond, Solomon/0000-0002-7589-2942 FU NCRR NIH HHS [P41 RR014075-106006, P41 RR014075, P41 RR014075-086776, P41 RR014075-098612, P41-RR14075]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-05, R01 EB002482, R01 EB002482-02, R01 EB002482-03, R01-EB001954, R01-EB002482] NR 51 TC 333 Z9 336 U1 3 U2 34 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2006 VL 29 IS 2 BP 368 EP 382 DI 10.1016/j.neuroimage.2005.08.065 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 005RJ UT WOS:000234841200003 PM 16303317 ER PT J AU Nobori, S Samelson-Jones, E Shimizu, A Hisashi, Y Yamamoto, S Kamano, C Teranishi, K Vagefi, PA Nuhn, M Okumi, M Wong, B Houser, S Sachs, DH Yamada, K AF Nobori, S Samelson-Jones, E Shimizu, A Hisashi, Y Yamamoto, S Kamano, C Teranishi, K Vagefi, PA Nuhn, M Okumi, M Wong, B Houser, S Sachs, DH Yamada, K TI Long-term acceptance of fully allogeneic cardiac grafts by cotransplantation of vascularized thymus in miniature swine SO TRANSPLANTATION LA English DT Article DE tolerance; thymus transplantation; heart transplantation; miniature swine ID MISMATCHED RENAL-ALLOGRAFTS; REGULATORY T-CELLS; CLASS-I; TRANSPLANTATION TOLERANCE; COMPOSITE THYMOKIDNEYS; LOBE TRANSPLANTATION; STABLE INDUCTION; ADULT THYMUS; PIG; MHC AB Background. We have previously reported the ability of both thymokidney and vascularized thymic lobe (VTL) allografts to induce transplantation tolerance to renal allografts across a full major histocompatibility complex (MHC) mismatch in thymectomized miniature swine. However, whether vascularized thymus is capable of inducing tolerance to less tolerogeneic organs when it is transplanted simultaneously is not yet known. The present study investigates cardiac allograft survival and the mechanism of long-term acceptance in recipient swine following cotransplantation of VTL and cardiac grafts from fully MHC-mismatched donors. Methods. Animals received a heart graft, a heart graft and a VTL, or a heart graft and a donor thymocyte infusion. Immunosuppressive regimens consisted of 12 or 28 days of tacrolimus. Results. All animals that received a VTL maintained their grafts significantly longer than their counterparts that received only a heart graft, and those receiving 28 days of tacrolimus maintained their heart grafts long-term. Recipients of a donor thymocyte infusion demonstrated slightly prolonged cardiac graft survival but all rejected their grafts, highlighting the importance of thymic stroma. Cytotoxic T-lymphocyte responses against third-party antigens by cells from tolerant animals showed restriction by both self and donor MHC, whereas responses of controls were restricted to self MHC only. The presence of donor dendritic cells in the VTL grafts and results of co-culture assays suggest that both central and regulatory mechanisms were involved in achieving long-term acceptance. Conclusion. This is the first demonstration of the long-term acceptance of fully MHC-mismatched cardiac allografts in large animals. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,13th St,CNY-149,9019, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIAID NIH HHS [5P01-AI45897] NR 31 TC 25 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2006 VL 81 IS 1 BP 26 EP 35 DI 10.1097/01.tp.0000200368.03991.e0 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 004WU UT WOS:000234784100007 PM 16421473 ER PT J AU Shimizu, I Smith, NR Zhao, GL Medof, E Sykes, M AF Shimizu, I Smith, NR Zhao, GL Medof, E Sykes, M TI Decay-accelerating factor prevents acute humoral rejection induced by low levels of anti-alpha Gal natural antibodies SO TRANSPLANTATION LA English DT Article DE humoral rejection; antibodies; alpha Gal; decay-accelerating factor ID INCOMPATIBLE KIDNEY-TRANSPLANTATION; DELAYED XENOGRAFT REJECTION; TO-PRIMATE MODEL; HYPERACUTE REJECTION; HEART-TRANSPLANTATION; COMPLEMENT ACTIVATION; ENDOTHELIAL-CELLS; MIXED CHIMERISM; RENAL-TRANSPLANTATION; TRANSGENIC PIGS AB Background. Hyperacute and delayed vascular rejection due to natural antibodies (NAb) present major obstacles in pig-to-primate xenotransplantation. Although "supraphysiologic" expression of human complement regulatory proteins (CRPs) can prevent hyperacute rejection in discordant xenogenic recipients, their physiologic role in the homologous setting is undefined. We have evaluated the effect of the absence of decay-accelerating factor (DAF) on cardiac allograft rejection in the presence of different levels of antidonor antibodies (Ab). Methods. DAF1-deficient (DAF KO; B6129F2 H-2(b)) mice were used as heart graft donors to alpha 1,3-galactosyltransferase deficient (GalT KO; B6, H-2(b)) recipients. Heterotopic heart grafting was performed with or without presensitization. Graft survival, histology, and anti-alpha Gal Ab levels were monitored. Results. DAF knockout (KO) but not wild-type (WT) grafts showed hyperacute or acute humoral rejection in nonsensitized GAT KO mice with low levels of anti-alpha Gal I-M NAb. However, humoral rejection of both DAF KO and DAF WT donor grafts occurred in presensitized GAT KO recipients. Conclusions. The expression of DAF prevents hyperacute rejection in mice with low titers of anti-alpha Gal antibody. These studies demonstrate the physiologic role of DAF in preventing humoral rejection in the presence of low levels of NAb and have implications for transplantation of discordant vascularized xenografts. C1 Harvard Univ, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Med Sch, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. RP Sykes, M (reprint author), Harvard Univ, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Med Sch, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL 18646] NR 55 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2006 VL 81 IS 1 BP 95 EP 100 DI 10.1097/01.tp.0000188176.18666368 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 004WU UT WOS:000234784100017 PM 16421483 ER PT J AU Trivedi, MA Schmitz, TW Ries, ML Torgerson, BM Sager, MA Hermann, BP Asthana, S Johnson, SC AF Trivedi, Mehul A. Schmitz, Taylor W. Ries, Michele L. Torgerson, Britta M. Sager, Mark A. Hermann, Bruce P. Asthana, Sanjay Johnson, Sterling C. TI Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study SO BMC MEDICINE LA English DT Review ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E GENOTYPE; E EPSILON-4 ALLELE; CEREBRAL GLUCOSE-METABOLISM; VOXEL-BASED MORPHOMETRY; E TYPE-4 ALLELE; BRAIN ACTIVATION; MEMORY PERFORMANCE; NOVELTY DETECTION; ELDERLY SUBJECTS AB Background: The presence of the apolipoprotein E ( APOE) epsilon 4 allele is a major risk factor for the development of Alzheimer's disease ( AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI ( fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the epsilon 4 allele on hippocampal activation has not been firmly established. Methods: The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe ( MTL) during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged ( mean = 54 years) individuals who had at least one parent with AD. Results: We found that epsilon 3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to epsilon 3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in epsilon 3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the epsilon 3/3 homozygotes, but not in the epsilon 3/4 heterozygotes. Conclusion: Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE epsilon 4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline. C1 William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Neurol, Madison, WI 53706 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM mt2@medicine.wisc.edu; tws@medicine.wisc.edu; mlr@medicine.wisc.edu; bmt@medicine.wisc.edu; masager@facstaff.wisc.edu; hermann@neurology.wisc.edu; sa@medicine.wisc.edu; scj@medicine.wisc.edu FU NIA NIH HHS [AG021155, R01 AG021155] NR 103 TC 72 Z9 73 U1 4 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD JAN 13 PY 2006 VL 4 AR 1 DI 10.1186/1741-7015-4-1 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 145KH UT WOS:000244863200001 PM 16412236 ER PT J AU Wang, XZ Khaleque, MA Zhao, MJ Zhong, R Gaestel, M Calderwood, SK AF Wang, XZ Khaleque, MA Zhao, MJ Zhong, R Gaestel, M Calderwood, SK TI Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK FACTOR; TUMOR-NECROSIS-FACTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; DNA-BINDING; PROTEIN-KINASE; FACTOR-I; SUBSTRATE-SPECIFICITY; MOLECULAR CHAPERONES; GENE-TRANSCRIPTION AB Heat shock transcription factor 1 (HSF1) monitors the structural integrity of intracellular proteins and its regulation is essential for the health and longevity of eukaryotic organisms. HSF1 also plays a role in the acute inflammatory response in the negative regulation of cytokine gene transcription. Here we show, for the first time, that HSF1 is regulated by the proinflammatory protein kinase MAPKAP kinase 2 (MK2). We have shown that MK2 directly phosphorylates HSF1 and inhibits activity by decreasing its ability to bind the heat shock elements (HSE) found in the promoters of target genes encoding the HSP molecular chaperones and cytokine genes. We show that activation of HSF1 to bind HSE in hsp promoters is inhibited through the phosphorylation of a specific residue, serine 121 by MK2. A potential mechanism for MK2- induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1. Dephosphorylation of serine 121 in cells exposed to non-steroidal anti-inflammatory drugs leads to HSP90 dissociation from HSF1, which then forms active DNA binding trimers. These experiments indicate a novel mechanism for the regulation of HSF1 by proinflammatory signaling and may permit HSF1 to respond rapidly to extracellular events, permitting optimal physiological regulation. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. Hannover Med Sch, Inst Biochem, D-30625 Hannover, Germany. RP Calderwood, SK (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, 21-27 Burlington Ave,Room 553B, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu OI Gaestel, Matthias/0000-0002-4944-4652 FU NCI NIH HHS [CA31303, CA47407, CA50642] NR 59 TC 69 Z9 77 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 13 PY 2006 VL 281 IS 2 BP 782 EP 791 DI 10.1074/jbc.M505822200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 000FV UT WOS:000234447200015 PM 16278218 ER PT J AU Park, S Dong, XC Fisher, TL Dunn, S Omer, AK Weir, G White, MF AF Park, S Dong, XC Fisher, TL Dunn, S Omer, AK Weir, G White, MF TI Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; INSULIN-RECEPTOR SUBSTRATE-2; PROTEIN-KINASE; DIABETES-MELLITUS; EXENATIDE EXENDIN-4; GLYCEMIC CONTROL; KNOCKOUT MICE; GLP-1 ACTION; TYPE-2; APOPTOSIS AB The insulin receptor substrate 2 (Irs2) branch of the insulin/insulin-like growth factor-signaling cascade prevents diabetes in mice because it promotes beta cell replication, function, and survival, especially during metabolic stress. Because exendin-4 (Ex4), a long acting glucagon-like peptide 1 receptor agonist, has similar effects upon beta cells in rodents and humans, we investigated whether Irs2 signaling was required for Ex4 action in isolated beta cells and in Irs2(-/-) mice. Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation. In wild type mice Ex4 administered continuously for 28 days increased beta cell mass 2-fold. By contrast, Ex4 failed to arrest the progressive beta cell loss in Irs2(-/-) mice, which culminated in fatal diabetes; however, Ex4 delayed the progression of diabetes by 3 weeks by promoting insulin secretion from the remaining islets. We conclude that some short term therapeutic effects of glucagon-like peptide 1 receptor agonists can be independent of Irs2, but its long term effects upon beta cell growth and survival are mediated by the Irs2 branch of the insulin/insulin-like growth factor signaling cascade. C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Howard Hughes Med Inst,Div Endocrinol,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Howard Hughes Med Inst,Div Endocrinol,Dept Med, Karp Res Bldg,300 Longwood Ave, Boston, MA 02115 USA. EM morris.white@childrens.harvard.edu FU NIDDK NIH HHS [DK55326] NR 65 TC 131 Z9 135 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 13 PY 2006 VL 281 IS 2 BP 1159 EP 1168 DI 10.1074/jbc.M508307200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 000FV UT WOS:000234447200058 PM 16272563 ER PT J AU Rubin, RH Gilman, MD Kradin, RL Harris, NL Ginns, L AF Rubin, RH Gilman, MD Kradin, RL Harris, NL Ginns, L TI A 64-year-old male lung-transplant recipient with fever, cough, hemoptysis, and abdominal pain - Cytomegalovirus colitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. RP Rubin, RH (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 3 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 JAN 12 PY 2006 VL 354 IS 2 BP 180 EP 187 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 001JE UT WOS:000234528600012 PM 16407514 ER PT J AU Jackson, LA Nelson, JC Whitney, CG Neuzil, KM Benson, P Malais, D Baggs, J Mullooly, J Black, S Shay, DK AF Jackson, LA Nelson, JC Whitney, CG Neuzil, KM Benson, P Malais, D Baggs, J Mullooly, J Black, S Shay, DK TI Assessment of the safety of a third dose of pneumococcal polysaccharide vaccine in the Vaccine Safety Datalink population SO VACCINE LA English DT Article DE pneumococcal vaccine; pneumococcal polysaccharide vaccine; vaccine safety AB There is little information on the safety of administration of a third dose of pneumococcal polysaccharide vaccine (PPV). The authors conducted a retrospective assessment of 316,995 adult members of three health maintenance organizations who had received one, two, or three PPV doses. Medical encounters associated with diagnosis codes potentially indicative of an injection site reaction in the week following a first, second, or third PPV dose were identified. These presumptive events occurred in 0.3% (911/279504) of the first PPV group, 0.7% (257/36888) of the second PPV group, and 0.5% (3/603) of the third PPV group (p > 0.5 for both comparisons with the third PPV group). These findings do not suggest that a third PPV dose is associated with an increased risk of medically attended injection site reactions compared with a first or second PPV dose. (c) 2005 Elsevier Ltd. All rights reserved. C1 Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Kaiser Permanente NW Ctr Hlth Res, Portland, OR USA. Kaiser Permanente, Vaccine Study Ctr, Oakland, CA USA. RP Jackson, LA (reprint author), Ctr Hlth Studies, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. EM jackson.1@ghc.org OI Shay, David/0000-0001-9619-4820; Baggs, James/0000-0003-0757-4683 NR 5 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 12 PY 2006 VL 24 IS 2 BP 151 EP 156 DI 10.1016/j.vaccine.2005.07.066 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 004UM UT WOS:000234777800006 PM 16122845 ER PT J AU Robbins, EM Betensky, RA Domnitz, SB Purcell, SM Garcia-Alloza, M Greenberg, C Rebeck, GW Hyman, BT Greenberg, SM Frosch, MP Bacskai, BJ AF Robbins, EM Betensky, RA Domnitz, SB Purcell, SM Garcia-Alloza, M Greenberg, C Rebeck, GW Hyman, BT Greenberg, SM Frosch, MP Bacskai, BJ TI Kinetics of cerebral amyloid angiopathy progression in a transgenic mouse model of Alzheimer disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloid-beta; Alzheimer; vascular; angiopathy; mouse; transgenic ID VASCULAR COGNITIVE IMPAIRMENT; VIVO MULTIPHOTON MICROSCOPY; PRECURSOR PROTEIN; NEURONAL LOSS; HUMAN BRAIN; BETA; MICE; HEMORRHAGE; PLAQUES; MUTANT AB Cerebral amyloid angiopathy (CAA), the deposition of cerebrovascular beta-amyloid (A beta) in the walls of arterial vessels, has been implicated in hemorrhagic stroke and is present in most cases of Alzheimer disease. Previous studies of the progression of CAA in humans and animal models have been limited to the comparison of pathological tissue from different brains at single time points. Our objective was to visualize in real time the initiation and progression of CAA in Tg2576 mice by multiphoton microscopy through cranial windows. Affected vessels were labeled by methoxy-X04, a fluorescent dye that selectively binds cerebrovascular beta-amyloid and plaques. With serial imaging sessions spaced at weekly intervals, we were able to observe the earliest appearance of CAA in leptomeningeal arteries as multifocal deposits of band-like A beta. Over subsequent imaging sessions, we were able to identify growth of these deposits ( propagation), as well as appearance of new bands ( additional initiation events). Statistical modeling of the data suggested that as the extent of CAA progressed in this vascular bed, there was increased prevalence of propagation over initiation. During the early phases of CAA development, the overall pathology burden progressed at a rate of 0.35% of total available vessel area per day (95% confidence interval, 0.3 - 0.4%). The consistent rate of disease progression implies that this model is amenable to investigations of therapeutic interventions. C1 Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Frosch, MP (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, B114-2700,114 16th St, Charlestown, MA 02129 USA. EM matthewfrosch@hms.harvard.edu OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG020570, AG08487, AG021084]; NIBIB NIH HHS [EB000768] NR 43 TC 49 Z9 49 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 11 PY 2006 VL 26 IS 2 BP 365 EP 371 DI 10.1523/JNEUROSCI.3854-05.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 001SI UT WOS:000234556200002 PM 16407531 ER PT J AU Kong, J Gollub, RL Rosman, IS Webb, JM Vangel, MG Kirsch, I Kaptchuk, TJ AF Kong, J Gollub, RL Rosman, IS Webb, JM Vangel, MG Kirsch, I Kaptchuk, TJ TI Brain activity associated with expectancy-enhanced placebo analgesia as measured by functional magnetic resonance Imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE placebo; placebo analgesia; expectancy; expectancy manipulation; pain; placebo acupuncture needle; Steitberger needle ID ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; VERBAL PAIN DESCRIPTORS; OPIOID SYSTEMS; CUTANEOUS HEAT; RATIO SCALES; ACUPUNCTURE; RESPONSES; AWARENESS; NEEDLE AB In this study, a well established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle, to investigate the brain network involved in placebo analgesia. Sixteen subjects completed the experiment. We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo-treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the functional magnetic resonance imaging ( fMRI) signal difference between post-treatment and pretreatment during pain application on placebo side from the same difference on control side [e.g., placebo (post - pre) - control (post - pre)], significant differences were observed in the bilateral rostral anterior cingulate cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal gyrus, and left inferior parietal lobule. The simple regression ( correlation) analysis between each subject's fMRI signal difference of post-treatment and pretreatment difference on placebo and control side and the corresponding subjective pain rating difference showed that significant negative correlation was observed in the bilateral lateral/ orbital prefrontal cortex, rACC, cerebellum, right fusiform, parahippocampus, and pons. These results are different from a previous study that found decreased activity in pain-sensitive regions such as the thalamus, insula, and ACC when comparing the response to noxious stimuli applied to control and placebo cream-treated areas of the skin. Our results suggest that placebo analgesia may be configured through multiple brain pathways and mechanisms. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. MGH Gen Clin Res Ctr Biomed Imaging Core, Charlestown, MA 02129 USA. Univ Plymouth, Sch Appl Psychosocial Studies, Plymouth PL4 8AA, Devon, England. Harvard Univ, Sch Med, Osher Inst, Boston, MA 02215 USA. RP Kong, J (reprint author), 149 13th St,Room 2661, Charlestown, MA 02129 USA. EM kongj@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NCCIH NIH HHS [P01-AT002048, R21 AT002860, R21 AT00949] NR 56 TC 204 Z9 217 U1 9 U2 35 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 11 PY 2006 VL 26 IS 2 BP 381 EP 388 DI 10.1523/JNEUROSCI.3556-05.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 001SI UT WOS:000234556200004 PM 16407533 ER PT J AU Spoelgen, R von Arnim, CAF Thomas, AV Peltan, ID Koker, M Deng, A Irizarry, MC Andersen, OM Willnow, TE Hyman, BT AF Spoelgen, R von Arnim, CAF Thomas, AV Peltan, ID Koker, M Deng, A Irizarry, MC Andersen, OM Willnow, TE Hyman, BT TI Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sorLA; Alzheimer's disease; amyloid-beta; BACE; amyloid precursor protein; LR11 ID RECEPTOR-RELATED PROTEIN; LIFETIME IMAGING MICROSCOPY; RESONANCE ENERGY-TRANSFER; ALZHEIMERS-DISEASE; CYTOPLASMIC DOMAIN; ASPARTYL PROTEASE; FAMILY-MEMBER; NT2N CELLS; COMPARTMENT; CLEAVAGE AB sorLA is a recently identified neuronal receptor for amyloid precursor protein (APP) that is known to interact with APP and affect its intracellular transport and processing. Decreased levels of sorLA in the brain of Alzheimer's disease ( AD) patients and elevated levels of amyloid-beta peptide (A beta) in sorLA-deficient mice point to the importance of the receptor in this neurodegenerative disorder. We analyzed APP cleavage in an APP-shedding assay and found that both sorLA and, surprisingly, a sorLA tail construct inhibited APP cleavage in a beta-site APP-cleaving enzyme (BACE)-dependent manner. In line with this finding, sorLA and the sorLA tail significantly reduced secreted A beta levels when BACE was overexpressed, suggesting that sorLA influences beta-cleavage. To understand the effect of sorLA on APP cleavage by BACE, we analyzed whether sorLA interacts with APP and/or BACE. Because both full-length sorLA and sorLA C-terminal tail constructs were functionally relevant for APP processing, we analyzed sorLA - APP for a potential cytoplasmatic interaction domain. sorLA and C99 coimmunoprecipitated, pointing toward the existence of a new cytoplasmatic interaction site between sorLA and APP. Moreover, sorLA and BACE also coimmunoprecipitate. Thus, sorLA interacts both with BACE and APP and might therefore directly affect BACE - APP complex formation. To test whether sorLA impacts BACE - APP interactions, we used a fluorescence resonance energy transfer assay to evaluate BACE - APP interactions in cells. We discovered that sorLA significantly reduced BACE - APP interactions in Golgi. We postulate that sorLA acts as a trafficking receptor that prevents BACE - APP interactions and hence BACE cleavage of APP. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Unit, Alzheimers Dis Res Lab,Sch Med,, Charlestown, MA 02129 USA. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Unit, Alzheimers Dis Res Lab,Sch Med,, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Peltan, Ithan/0000-0003-1730-234X FU NIA NIH HHS [AG 12406] NR 43 TC 112 Z9 116 U1 2 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 11 PY 2006 VL 26 IS 2 BP 418 EP 428 DI 10.1523/JNEUROSCI.3882-05.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 001SI UT WOS:000234556200009 PM 16407538 ER PT J AU Xu, K Xu, YH Brown-Jermyn, D Chen, JF Ascherio, A Dluzen, DE Schwarzschild, MA AF Xu, K Xu, YH Brown-Jermyn, D Chen, JF Ascherio, A Dluzen, DE Schwarzschild, MA TI Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adenosine A(2A) receptor; dopamine; gender; methylxanthine; ovariectomy; striatum ID MPTP-INDUCED NEUROTOXICITY; COFFEE CONSUMPTION; STRIATAL DOPAMINE; CYTOCHROMES P450; C57BL/6 MICE; ESTRADIOL; ADENOSINE; GENDER; TWINS; RISK AB Epidemiological studies have strongly linked caffeine consumption with a reduced risk of developing Parkinson's disease (PD) in men. Interestingly, in women, this inverse association is present only in those who have not taken postmenopausal estrogens, suggesting an interaction between the influences of estrogen and caffeine use on the risk of PD. To explore a possible biological basis for this interaction, we systematically investigated how the neuroprotective effect of caffeine is influenced by gender, ovariectomy (OVX), and then exogenous estrogen in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. (1) Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal dopamine loss in both young and retired breeder (RB) male, but not female, mice. (2) In female mice (both young and RB), caffeine was less potent or altogether ineffective as a neuroprotectant after sham surgery compared to OVX or after OVX plus estrogen replacement compared to OVX plus placebo treatment. (3) Estrogen treatment also prevented the protection of caffeine against dopamine loss in young male mice. (4) Consistent with the putative protective effect of estrogen, female and OVX plus estrogen mice were relatively resistant to MPTP toxicity compared to male and OVX plus placebo mice, respectively. (5) There was no overall difference in brain levels of caffeine and its metabolites between OVX plus placebo and OVX plus estrogen mice. Together, these results suggest that estrogen can occlude and thereby prevent the neuroprotective effect of caffeine in a model of PD neurodegeneration, supporting a biological basis for the interaction between estrogen and caffeine in modifying the risk of PD. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Mol Neurobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Northeastern Ohio Univ Coll Med & Pharm, Dept Anat, Rootstown, OH 44272 USA. RP Xu, K (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Mol Neurobiol Lab, 114 16th St,Room 2925, Charlestown, MA 02129 USA. EM xu@helix.mgh.harvard.edu FU NIDA NIH HHS [DA013508]; NIEHS NIH HHS [ES10804] NR 40 TC 66 Z9 70 U1 3 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 11 PY 2006 VL 26 IS 2 BP 535 EP 541 DI 10.1523/JNEUROSCI.3008-05.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 001SI UT WOS:000234556200022 PM 16407551 ER PT J AU Gurol, ME Irizarry, MC Smith, EE Raju, S Diaz-Arrastia, R Bottiglieri, T Rosand, J Growdon, JH Greenberg, SM AF Gurol, ME Irizarry, MC Smith, EE Raju, S Diaz-Arrastia, R Bottiglieri, T Rosand, J Growdon, JH Greenberg, SM TI Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID LOBAR INTRACEREBRAL HEMORRHAGE; APOLIPOPROTEIN-E EPSILON-2; MILD COGNITIVE IMPAIRMENT; TOTAL HOMOCYSTEINE LEVELS; SILENT BRAIN INFARCTS; ALZHEIMERS-DISEASE; CARDIOVASCULAR HEALTH; FUNCTIONAL HYPEREMIA; CLINICAL-DIAGNOSIS; OXIDATIVE STRESS AB Background: Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating beta-amyloid peptide in microvascular dysfunction and white matter disease. Methods: The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of beta-amyloid (A beta 40 and A beta 42) detected by specific enzyme-linked immunosorbent assays. Results: Plasma A beta 40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p <= 0.005). Plasma A beta 40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased A beta 40 in both groups. nWMH was greater in CAA (19.8 cm(3)) than AD (11.1 cm(3)) or MCI (10.0 cm(3); p < 0.05 for both comparisons). Conclusions: Plasma beta-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly. C1 Massachusetts Gen Hosp, Dept Neurol, Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Memory Disorders Unit, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75230 USA. Baylor Inst Metab Dis, Dallas, TX USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Clin Trials Unit, Wang ACC 836,55 Fruit St, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Gurol, Edip/J-2279-2014 OI Smith, Eric/0000-0003-3956-1668; Gurol, Edip/0000-0002-2169-4457 FU NIA NIH HHS [P50 AG05134]; NINDS NIH HHS [T32 NS048005, R01 NS04140] NR 42 TC 177 Z9 185 U1 1 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 10 PY 2006 VL 66 IS 1 BP 23 EP 29 DI 10.1212/01.wnl.0000191403.95453.6a PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 000VI UT WOS:000234490100007 PM 16401840 ER PT J AU Bar, M Kassam, KS Ghuman, AS Boshyan, J Schmidt, AM Dale, AM Hamalainen, MS Marinkovic, K Schacter, DL Rosen, BR Halgren, E AF Bar, M Kassam, KS Ghuman, AS Boshyan, J Schmidt, AM Dale, AM Hamalainen, MS Marinkovic, K Schacter, DL Rosen, BR Halgren, E TI Top-down facilitation of visual recognition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE feedback; object recognition; orbitofrontal cortex; visual cortex; low spatial frequency ID OBJECT RECOGNITION; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; SPATIAL-FREQUENCY; TEMPORAL CORTICES; DECISION-MAKING; MEMORY; CONNECTIONS; MECHANISMS; ATTENTION AB Cortical analysis related to visual object recognition is traditionally thought to propagate serially along a bottom-up hierarchy of ventral areas. Recent proposals gradually promote the role of top-down processing in recognition, but how such facilitation is triggered remains a puzzle. We tested a specific model, proposing that low spatial frequencies facilitate visual object recognition by initiating top-down processes projected from orbitofrontal to visual cortex. The present study combined magnetoencephalography, which has superior temporal resolution, functional magnetic resonance imaging, and a behavioral task that yields successful recognition with stimulus repetitions. Object recognition elicited differential activity that developed in the left orbitofrontal cortex 50 ms earlier than it did in recognition-related areas in the temporal cortex. This early orbitofrontal activity was directly modulated by the presence of low spatial frequencies in the image. Taken together, the dynamics we revealed provide strong support for the proposal of how top-down facilitation of object recognition is initiated, and our observations are used to derive predictions for future research. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, Biophys Program, Charlestown, MA 02138 USA. Harvard Univ, Dept Psychol, Charlestown, MA 02138 USA. RP Bar, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, 149 13th St, Charlestown, MA 02129 USA. EM bar@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Hamalainen, Matti/C-8507-2013; OI Schacter, Daniel/0000-0002-2460-6061 FU NCRR NIH HHS [5P41RR014075, P41 RR014075]; NINDS NIH HHS [NS18741, NS44319, NS50615, R01 NS018741, R01 NS044319, R01 NS050615] NR 56 TC 684 Z9 703 U1 12 U2 75 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 JAN 10 PY 2006 VL 103 IS 2 BP 449 EP 454 DI 10.1073/pnas.0507062103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 002PR UT WOS:000234624100036 PM 16407167 ER PT J AU Lazar, G Goodman, HM AF Lazar, G Goodman, HM TI MAX1, a regulator of the flavonoid pathway, controls vegetative axillary bud outgrowth in Arabidopsis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE branching; apical dominance ID AUXIN TRANSPORT; APICAL DOMINANCE; MERISTEM DEVELOPMENT; PEA; HORMONE; AMINOPEPTIDASES; SEEDLINGS; THALIANA; MUTANTS; FAMILY AB We show that MAX1, a specific repressor of vegetative axillary bud outgrowth in Arabidopsis, acts a positive regulator of the flavonoid pathway, including 11 structural genes and the transcription factor An2. Repression of bud outgrowth requires MAX1-dependent flavonoid gene expression. As the flavonoidless state leads to lateral outgrowth in Arabidopsis, our data suggest that a flavonoid-based mechanism regulates axillary bud outgrowth and that this mechanism is under the control of MAX1. Flavonoid gene expression results in the diminished expression of auxin transporters in the bud and stem, and this, in turn, decreases the rate of polar auxin transport. We speculate that MAX1 could repress axillary bud outgrowth via regulating flavonoid-dependent auxin retention in the bud and underlying stem. Because MAX1 is implicated in synthesis of the carotenoid-derived branch regulator(s) from the root, it likely links long-distance signaling with local control of bud outgrowth. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lazar, G (reprint author), Harvard Univ, Sch Med, Dept Genet, 185 Cambridge St, Boston, MA 02114 USA. EM lazar@molbio.mgh.harvard.edu NR 28 TC 89 Z9 94 U1 2 U2 19 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 JAN 10 PY 2006 VL 103 IS 2 BP 472 EP 476 DI 10.1073/pnas.0509463102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 002PR UT WOS:000234624100040 PM 16387852 ER PT J AU Barry, MJ AF Barry, MJ TI The PSA conundrum SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID PROSTATE-CANCER MORTALITY; ANTIGEN C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St, Boston, MA 02114 USA. EM mbarry@partners.org NR 12 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 9 PY 2006 VL 166 IS 1 BP 7 EP 8 DI 10.1001/archinte.166.1.7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 001OD UT WOS:000234545300001 PM 16401804 ER PT J AU Broom, WJ Russ, C Sapp, PC McKenna-Yasek, D Hosler, BA Andersen, PM Brown, RH AF Broom, WJ Russ, C Sapp, PC McKenna-Yasek, D Hosler, BA Andersen, PM Brown, RH TI Variants in candidate ALS modifier genes linked to Cu/Zn superoxide dismutase do not explain divergent survival phenotypes SO NEUROSCIENCE LETTERS LA English DT Article DE amyotrophic lateral sclerosis; superoxide dismutase 1; single nucleotide polymorphism ID AMYOTROPHIC-LATERAL-SCLEROSIS; SOD1 MUTATION; SUPEROXIDE-DISMUTASE-1; HOMOZYGOSITY; HAPLOTYPE; FAMILIES; MUTANTS AB Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; approximately 25% are due to mutations in the Cu/Zn superoxide dismutase gene (SOD1). In North America, SOD1(A4V) is the most common SOD I mutation. A4V ALS cases typically have a very short survival (1-1.5 years versus 3-5 years for other dominant SOD1 mutations). A recent study of A4V carriers identified a common haplotype around the SOD I locus, suggesting the hypothesis that genetic variations within the haplotypic region might accelerate the course of A4V cases. By contrast, SOD1(D90A/D90A) ALS cases have a very slow progression (>10 years), raising the reciprocal hypothesis that modifier genes linked to SOD1 ameliorate the phenotype of recessively inherited SOD1(D90A/D90A) mutations. In the present study, DNA sequencing of four genes within the haplotypic region shared in A4V and D90A ALS patients revealed 15 novel variants, but none result in changes in amino acid sequences specifically associated with SOD1(D90A/D90A) or SOD1(A4V) ALS. We conclude that mutations within coding regions of genes around the SOD1 locus are not responsible for the more aggressive and more benign natures of the SOD1(A4V) and SOD1(D90A/D90A) mutations, respectively. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. MIT, Howard Hughes Med Inst, Cambridge, MA USA. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, 114 16th St,Navy Yard, Charlestown, MA 02129 USA. EM wbroom@partners.org; rhbrown@partners.org NR 32 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 9 PY 2006 VL 392 IS 1-2 BP 52 EP 57 DI 10.1016/j.neulet.2005.08.058 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 997SP UT WOS:000234268400011 PM 16174551 ER PT J AU Mansury, Y Diggory, M Deisboeck, TS AF Mansury, Y Diggory, M Deisboeck, TS TI Evolutionary game theory in an agent-based brain tumor model: Exploring the 'Genotype-Phenotype' link SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE gliomas; game theory; agent based; tumor modeling ID INTERCELLULAR COMMUNICATION; CELL MOTILITY; GLIOMA-CELLS; PROLIFERATION; ORGANIZATION; DYNAMICS; BIOLOGY; CANCER AB To investigate the genotype-phenotype link in a polyclonal cancer cell population, here we introduce evolutionary game theory into our previously developed agent-based brain tumor model. We model the heterogeneous cell population as a mixture of two distinct genotypes: the more proliferative Type A and the more migratory Type B. Our agent-based simulations reveal a phase transition in the tumor's velocity of spatial expansion linking the tumor fitness to genotypic composition. Specifically, velocity initially falls as rising payoffs reward the interactions among the more stationary Type A cells, but unexpectedly accelerates again when these A-A payoffs increase even further. At this latter accelerating stage, fewer migratory Type B cells appear to confer a competitive advantage in terms of the tumor's spatial aggression over the overall numerically dominating Type A cells, which in turn leads to an acceleration of the overall tumor dynamics while its surface roughness declines. We discuss potential implications of our findings for cancer research. (c) 2005 Elsevier Ltd. All rights reserved. C1 MIT, HST Biomed Engn Ctr, Complex Biosyst Modeling Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Harvard MIT HST, Charlestown, MA 02129 USA. Harvard Univ, Ctr Data, MIT, Cambridge, MA 02138 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp E, Complex Biosyst Modeling Lab, Harvard MIT HST, Athinoula A Martinos Ctr Biomed Imaging, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU NCI NIH HHS [CA 085139, CA 09502, CA113004] NR 30 TC 57 Z9 60 U1 1 U2 13 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD JAN 7 PY 2006 VL 238 IS 1 BP 146 EP 156 DI 10.1016/j.jtbi.2005.05.027 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 996DI UT WOS:000234154200012 PM 16081108 ER PT J AU Kiehl, TR Nechiporuk, A Figueroa, KP Keating, MT Huynh, DP Pulst, SM AF Kiehl, TR Nechiporuk, A Figueroa, KP Keating, MT Huynh, DP Pulst, SM TI Generation and characterization of Sca2 (ataxin-2) knockout mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Spinocerebellar Ataxia Type 2; SCA2; ataxin-2; A2BP1; Fox-1; knockout; obesity; rotarod; segregation distortion ID PABC DOMAIN; GENE; EXPRESSION; PROTEIN; IDENTIFICATION; CLONING; REPEAT; TYPE-2; MOUSE; CHROMOSOME-16 AB Ataxin-2, the gene product ofthe Spinocerebellar Ataxia Type 2 (SCA2) gene, is a protein of unknown function with abundant expression in embryonic and adult tissues. Its interaction with A2BP1/Fox-1, a protein with an RNA recognition motif, suggests involvement of ataxin-2 in mRNA translation or transport. To study the effects of in vivo ataxin-2 function, we generated an ataxin-2 deficient mouse strain. Ataxin-2 deficient mice were viable. Genotypic analysis of litters from mating of heterozygous mice showed segregation distortion with a significant reduction in the birth of Sca(-/-) females. Detailed macroscopic and microscopic analysis of surviving nullizygous Sca2 knockout mice showed no major histological abnormalities. On a fat-enriched diet, ataxin-2 deficient animals had increased weight gain. Out-results demonstrate that ataxin-2, although widely expressed, is not essential in development or during adult Survival in the mouse, but leads to adult-onset obesity. (c) 2005 Elsevier Inc. All rights reserved. C1 Cedars Sinai Med Ctr, Burns & Allen Res Inst, Rose Moss Lab Parkinson & Neurodegenerat Dis, Los Angeles, CA 90048 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Div Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. RP Pulst, SM (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN2, Boston, MA 02114 USA. EM pulst@cshs.org FU NINDS NIH HHS [R01-NS33123] NR 30 TC 46 Z9 49 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 JAN 6 PY 2006 VL 339 IS 1 BP 17 EP 24 DI 10.1016/j.bbrc.2005.10.186 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 993HF UT WOS:000233944500003 PM 16293225 ER PT J AU Ceccarelli, DFJ Song, HK Poy, F Schaller, MD Eck, MJ AF Ceccarelli, DFJ Song, HK Poy, F Schaller, MD Eck, MJ TI Crystal structure of the FERM domain of focal adhesion kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-TERMINAL DOMAIN; CELL-MIGRATION; ERM PROTEINS; PHOSPHATIDYLINOSITOL 3-KINASE; NEUROFIBROMATOSIS TYPE-2; CATALYTIC-ACTIVITY; TYROSINE KINASES; BINDING-SITE; MEMBRANE; SRC AB Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Eck, MJ (reprint author), SM 1036,44 Binney St, Boston, MA 02215 USA. EM eck@red.dfci.harvard.edu RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 FU NCI NIH HHS [CA080942]; NHLBI NIH HHS [HL48675] NR 63 TC 67 Z9 70 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 6 PY 2006 VL 281 IS 1 BP 252 EP 259 DI 10.1074/jbc.M509188200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 998GS UT WOS:000234307200033 PM 16221668 ER PT J AU Tinaz, S Schendan, HE Schon, K Stern, CE AF Tinaz, S Schendan, HE Schon, K Stern, CE TI Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: An MRI study SO BRAIN RESEARCH LA English DT Article DE dorsolateral prefrontal cortex; globus pallidus; planning; selective updating ID NIGRA PARS RETICULATA; DORSOLATERAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; SPATIAL WORKING-MEMORY; FUNCTIONAL-ANATOMY; FRONTAL-CORTEX; OCULOMOTOR FUNCTIONS; PARKINSONS-DISEASE; EFFECTIVE CONNECTIVITY; HIPPOCAMPAL-FORMATION AB Semantic event sequencing is the ability to plan ahead and order meaningful events chronologically. To investigate the neural systems supporting this ability, an fMRI picture sequencing task was developed. Participants sequenced a series of four pictures presented in random order based on the temporal relationship among them. A control object discrimination task was designed to be comparable to the sequencing task regarding semantic, visuospatial, and motor processing requirements but without sequencing demands. fMRI revealed significant activation in the dorsolateral prefrontal cortex and globus pallidus internal part in the picture sequencing task compared with the control task. The findings suggest that circuits involving the frontal lobe and basal ganglia output nuclei are important for picture sequencing and more generally for the sequential ordering of events. This is consistent with the idea that the basal ganglia output nuclei are critical not only for motor but also for high-level cognitive function, including behaviors involving meaningful information. We suggest that the interaction between the frontal lobes and basal ganglia output nuclei in semantic event sequencing can be generalized to include the sequential ordering of behaviors in which the selective updating of neural representations is the key computation. (c) 2005 Elsevier B.V. All rights reserved. C1 Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. Boston Univ, Program Neurosci, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Tinaz, S (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St,Room 109, Boston, MA 02215 USA. EM atinaz@bu.edu FU NIMH NIH HHS [R21 MH066213] NR 93 TC 19 Z9 20 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 5 PY 2006 VL 1067 IS 1 BP 239 EP 249 DI 10.1016/j.brainres.2005.10.057 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 012RI UT WOS:000235356500029 PM 16360121 ER PT J AU Busuttil, RA Rubio, M Dolle, MET Campisi, J Vijg, J AF Busuttil, RA Rubio, M Dolle, MET Campisi, J Vijg, J TI Mutant frequencies and spectra depend on growth state and passage number in cells cultured from transgenic lacZ-plasmid reporter mice SO DNA REPAIR LA English DT Article DE lacZ-plasmid mouse embryonic fibroblasts; ultraviolet (UV); mutation; quiescence; proliferation ID IN-VIVO MUTATIONS; SOMATIC MUTATIONS; MURINE CELLS; MOUSE MODEL; REPAIR; FIBROBLASTS; IMMORTALIZATION; ACCUMULATION; REPLICATION; EXPRESSION AB Transgenic mice harboring the lacZ gene within a plasmid that can be recovered and amplified in Escherichia coli, to establish mutant frequencies and spectra, have provided crucial insights into the relationships between mutations, cancer and aging in vivo. Here, we use embryonic fibroblasts from transgenic lacZ-plasmid reporter mice to determine the relationship between cell proliferation in culture and mutations induced by ultraviolet (UV) light. A single dose of 2.5 J/m(2) of UVC to actively proliferating cells caused an approximately eightfold increase in mutant frequency 24 h after irradiation. Identically treated quiescent cells showed a two-fold increase in mutant frequency. Thus, whereas proliferation facilitated the acquisition of mutations, it was not an absolute requirement. Characterization of the UV-induced mutations indicated that the lower mutant frequency in quiescent cells was due mainly to a reduction in point mutations; size-change mutations, indicative of translocations or deletions, were relatively unaffected by the growth state of the cells. To investigate long-term genomic stability after UVC-induced damage, we monitored the lacZ locus in irradiated cells passaged for many generations in culture. The results indicated the emergence of jackpot mutations of rapidly changing frequency, most likely reflecting the successive emergence and decline of dominant cell clones during long-term culture. These findings show that the lacZ-plasmid locus is a valid reporter for studying induced mutations in short-term cultures of both quiescent and proliferating fibroblasts. In long-term cultures, the locus is less suitable for studying induced mutations owing to the instability of the cell population. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Buck Inst Age Res, Novato, CA USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Inst Longev & Aging Studies, STCBM Bldg,Suite 2-200,15355 Lambda, San Antonio, TX 78245 USA. EM vijg@uthscsa.edu FU NIA NIH HHS [AG17242, AG20438] NR 24 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JAN 5 PY 2006 VL 5 IS 1 BP 52 EP 60 DI 10.1016/j.dnarep.2005.07.006 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 004VG UT WOS:000234780000006 PM 16126462 ER PT J AU Palliser, D Chowdhury, D Wang, QY Lee, SJ Bronson, RT Knipe, DM Lieberman, J AF Palliser, D Chowdhury, D Wang, QY Lee, SJ Bronson, RT Knipe, DM Lieberman, J TI An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SHORT INTERFERING RNA; REPLICATION-DEFECTIVE MUTANT; DNA-BINDING PROTEIN; HERPES; INHIBITION; ESCAPE; CHALLENGE; CELLS AB Herpes simplex virus 2 (HSV-2) infection causes significant morbidity(1) and is an important cofactor for the transmission of HIV infection(2). A microbicide to prevent sexual transmission of HSV-2 would contribute substantially to controlling the spread of HIV and other infections(3,4). Because RNA interference (RNAi) provides effective antiviral defence in plants and other organisms, several studies have focused on harnessing RNAi to inhibit viral infection(5). Here we show that vaginal instillation of small interfering RNAs (siRNAs) targeting HSV-2 protects mice from lethal infection. siRNAs mixed with lipid are efficiently taken up by epithelial and lamina propria cells and silence gene expression in the mouse vagina and ectocervix for at least nine days. Intravaginal application of siRNAs targeting the HSV-2 UL27 and UL29 genes ( which encode an envelope glycoprotein and a DNA binding protein(6), respectively) was well tolerated, did not induce interferon-responsive genes or cause inflammation, and protected mice when administered before and/or after lethal HSV-2 challenge. These results suggest that siRNAs are attractive candidates for the active component of a microbicide designed to prevent viral infection or transmission. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 NR 29 TC 273 Z9 301 U1 4 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 5 PY 2006 VL 439 IS 7072 BP 89 EP 94 DI 10.1038/nature04263 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 999HA UT WOS:000234378700040 PM 16306938 ER PT J AU Polu, KR Wolf, M AF Polu, KR Wolf, M TI Needle in a haystack SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ATHEROEMBOLIC RENAL-DISEASE; FAILURE; PATIENT C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. RP Wolf, M (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 55 Fruit St,Bartlett 917, Boston, MA 02114 USA. EM mswolf@partners.org NR 11 TC 7 Z9 7 U1 0 U2 1 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 JAN 5 PY 2006 VL 354 IS 1 BP 68 EP 73 DI 10.1056/NEJMcps051939 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 998ZO UT WOS:000234358600011 PM 16394304 ER PT J AU Travis, LB Rabkin, CS Brown, LM Allan, JM Alter, BP Ambrosone, CB Begg, CB Caporaso, N Chanock, S DeMichele, A Figg, WD Gospodarowicz, MK Hall, EJ Hisada, M Inskip, P Kleinerman, R Little, JB Malkin, D Ng, AK Offit, K Pui, CH Robison, LL Rothman, N Shields, PG Strong, L Taniguchi, T Tucker, MA Greene, MH AF Travis, LB Rabkin, CS Brown, LM Allan, JM Alter, BP Ambrosone, CB Begg, CB Caporaso, N Chanock, S DeMichele, A Figg, WD Gospodarowicz, MK Hall, EJ Hisada, M Inskip, P Kleinerman, R Little, JB Malkin, D Ng, AK Offit, K Pui, CH Robison, LL Rothman, N Shields, PG Strong, L Taniguchi, T Tucker, MA Greene, MH TI Cancer survivorship - Genetic susceptibility and second primary cancers: Research strategies and recommendations SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LI-FRAUMENI-SYNDROME; ACUTE LYMPHOBLASTIC-LEUKEMIA; INDUCED GENOMIC INSTABILITY; TISSUE-SPECIFIC EXPRESSION; HEREDITARY BREAST-CANCER; CHECKPOINT CONTROL GENE; SECONDARY BRAIN-TUMORS; ACUTE MYELOID-LEUKEMIA; CELL LUNG-CANCER; HODGKINS-DISEASE AB Cancer survivors constitute 3.5% of the United States population, but second primary malignancies among this high-risk group now account for 16% of all cancer incidence. Although few data currently exist regarding the molecular mechanisms for second primary cancers and other late outcomes after cancer treatment, the careful measurement and documentation of potentially carcinogenic treatments (chemotherapy and radiotherapy) provide a unique platform for in vivo research on gene-environment interactions in human carcinogenesis. We review research priorities identified during a National Cancer Institute (NCI)-sponsored workshop entitled '' Cancer Survivorship-Genetic Susceptibility and Second Primary Cancers.'' These priorities include 1) development of a national research infrastructure for studies of cancer survivorship; 2) creation of a coordinated system for biospecimen collection; 3) development of new technology, bioinformatics, and biomarkers; 4) design of new epidemiologic methods; and 5) development of evidence-based clinical practice guidelines. Many of the infrastructure resources and design strategies that would facilitate research in this area also provide a foundation for the study of other important nonneoplastic late effects of treatment and psychosocial concerns among cancer survivors. These research areas warrant high priority to promote NCI's goal of eliminating pain and suffering related to cancer. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ York, York YO10 5DD, N Yorkshire, England. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Harvard Univ, Sch Publ Hlth, Radiobiol Lab, Boston, MA 02115 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Minnesota, Minneapolis, MN USA. Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Travis, LB (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7086,MSC 7238, Bethesda, MD 20892 USA. EM travisl@mail.nih.gov RI Allan, James/B-4448-2009; Tucker, Margaret/B-4297-2015; Figg Sr, William/M-2411-2016; OI Kleinerman, Ruth/0000-0001-7415-2478 FU Intramural NIH HHS; NCI NIH HHS [CA-21765] NR 143 TC 138 Z9 141 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 4 PY 2006 VL 98 IS 1 BP 15 EP 25 DI 10.1093/jnci/djj001 PG 11 WC Oncology SC Oncology GA 003XK UT WOS:000234715800007 PM 16391368 ER PT J AU Aghi, M Rabkin, S Martuza, RL AF Aghi, M Rabkin, S Martuza, RL TI Effect of chemotherapy-induced DNA repair on oncolytic herpes simplex viral replication SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN TUMOR-CELLS; RIBONUCLEOTIDE REDUCTASE; MALIGNANT GLIOMA; ALKYLATING-AGENTS; MISMATCH REPAIR; GENE; TEMOZOLOMIDE; VIRUS; CANCER; MUTANT AB Background. Gliomas treated with the alkylating agent temozolomide have incomplete responses in part because of tumoral repair of chemotherapy-induced DNA damage. Data from phase I trials suggest that G207, an oncolytic herpes simplex virus (HSV) with mutated ribonucleotide reductase (RR) and gamma 34.5 genes, is safe but needs greater viral oncolysis to be effective. We hypothesized that temozolomide and G207 treatment limitations could be jointly addressed using temozolomide-induced tumor-protective DNA repair pathways to enhance viral replication. Methods: Human glioblastoma cells (U87, T98, and U373) and U87 cells transfected with the gene for the DNA repair enzyme O-6-methylguanine DNA methyltransferase (MGMT) were treated with G207 and/or temozolomide. Drug interactions, expression of the growth arrest DNA damage 34 (GADD34) and RR transcripts before and after their knockdown with short interfering RNAs, DNA strand breaks, and apoptosis were measured using Chou-Talalay analysis, real-time reverse transcription-polymerase chain reaction, the comet assay, and flow cytometry, respectively. Survival of mice (groups of ten) with intracranial U87 xenograft tumors treated with temozolomide and/or G207 was analyzed using Kaplan-Meier analysis. Results: Temozolomide exhibited strong synergy with G207 in both MGMT-negative and the MGMT inhibitor O-6-benzylguanine-treated MGMT-expressing gliomas (Chou-Talalay combination indices = 0.005 to 0.39) and induced GADD34 expression primarily in nonapoptotic MGMT-negative U87 glioma cells (fold difference = 16, 95% confidence interval [CI] = 12.6 to 20.4, compared with untreated cells). MGMT-expressing T98 and U87/MGMT cells treated with temozolomide plus O-6 -benzylguanine had higher RR expression than untreated cells (fold difference = 14.9, 95% CI = 10.1 to 22.0 [T98]; 9.9, 95% CI = 7.0 to 13.8 [U87/MGMT]). GADD34 and RR knockdown increased temozolomide-induced DNA damage and inhibited the synergy of G207 and temozolomide in U87 and O-6-benzylguanine-treated U87/MGMT cells. Mice bearing intracranial U87 tumors survived longer after combination therapy (100% survival at 90 days) than after single-agent therapy (median survival = 46 and 48 days with G207 and temozolomide treatment, respectively). Conclusions: Temozolomide-induced DNA repair pathways vary with MGMT expression and enhance HSV-mediated oncolysis in glioma cells. These findings unveil the potential of HSV to target cells surviving temozolomide treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Res Ctr, Boston, MA 02114 USA. RP Aghi, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Res Ctr, Simches Res Bldg,185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. EM maghi@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NINDS NIH HHS [NS32677, P30 NS045776] NR 38 TC 98 Z9 100 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 4 PY 2006 VL 98 IS 1 BP 38 EP 50 DI 10.1093/jnci/djj003 PG 13 WC Oncology SC Oncology GA 003XK UT WOS:000234715800009 PM 16391370 ER PT J AU Kathiresan, S Otvos, JD Sullivan, LM Keyes, MJ Schaefer, EJ Wilson, PWF D'Agostino, RB Vasan, RS Robins, SJ AF Kathiresan, S Otvos, JD Sullivan, LM Keyes, MJ Schaefer, EJ Wilson, PWF D'Agostino, RB Vasan, RS Robins, SJ TI Increased small low-density lipoprotein particle number - A prominent feature of the metabolic syndrome in the Framingham Heart Study SO CIRCULATION LA English DT Article DE cholesterol; lipids; lipoproteins; metabolic syndrome X; risk factors ID NUCLEAR-MAGNETIC-RESONANCE; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; APOLIPOPROTEIN-B; SUBFRACTION DISTRIBUTION; RISK-FACTORS; SIZE; SPECTROSCOPY; CHOLESTEROL; LDL AB Background-Levels of LDL cholesterol (LDL-C) are frequently not elevated in individuals with the metabolic syndrome (MetSyn). However, the atherogenic potential of LDL may depend on the number and size of LDL particles in addition to the cholesterol content of LDL. Methods and Results-We examined the sex-specific cross-sectional relations of small LDL particle number ( determined by nuclear magnetic resonance spectroscopy) to the presence of MetSyn and its components in 2993 Framingham Heart Study participants ( mean age, 51 years; 53% women) without cardiovascular disease (CVD) and the relations of small LDL particle number to CVD incidence in people with MetSyn. The MetSyn (>= 3 of 5 traits as defined by the National Cholesterol Education Adult Treatment Panel III) was present in 27% of men and 17% of women. In both sexes, small LDL particle number increased from 0 to 5 MetSyn traits, a pattern partly accounted for by strong correlations between small LDL particle number and serum triglycerides (r=0.61, P < 0.0001) and HDL-C (r=-0.55, P < 0.0001). Compared with participants without the MetSyn, those with the MetSyn had a higher CVD event rate. However, among participants with the MetSyn, CVD rates were similar for groups with an elevated versus a lower number of small LDL particles ( defined by the sex-specific median). Conclusions-Small LDL particle number is elevated in the MetSyn, increases with the number of MetSyn components, and most prominently is correlated with triglycerides and HDL-C. Whereas increased small LDL particle number identified the MetSyn with high sensitivity, a higher small LDL particle number was not associated with greater CVD event rates in people with the MetSyn. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA USA. LipoSci Inc, Raleigh, NC USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Stat & Consulting Unit, Boston, MA 02215 USA. Tufts Univ, Sch Med, Lipid Res Lab, Boston, MA 02111 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Robins, SJ (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM sjrobins@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24 HL04334, N01-HC-25195] NR 44 TC 158 Z9 164 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 3 PY 2006 VL 113 IS 1 BP 20 EP 29 DI 10.1161/CIRCULATINAHA.105.567107 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 998VC UT WOS:000234347000005 PM 16380547 ER PT J AU Anwaruddin, S Lloyd-Jones, DM Baggish, A Chen, A Krauser, D Tung, R Chae, C Januzzi, JL AF Anwaruddin, S Lloyd-Jones, DM Baggish, A Chen, A Krauser, D Tung, R Chae, C Januzzi, JL TI Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement - Results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NT-PROBNP; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; RISK-FACTORS; DIAGNOSIS; INSUFFICIENCY; BNP; DYSFUNCTION; DIALYSIS; CARE AB OBJECTIVES We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels. BACKGROUND The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis. METHODS A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration. RESULTS Glomerular filtration rates ranged from 15 ml/min/1.73m(2) to 252 ml/min/1.73m(2). Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of >450 pg/ml for patients ages <50 years and >900 pg/ml for patients >= 50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR >= 60 ml/min/1.73m(2). Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73m(2), we found sensitivity and specificity, to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m 2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006). CONCLUSIONS The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org RI Lloyd-Jones, Donald/C-5899-2009 NR 31 TC 192 Z9 205 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 3 PY 2006 VL 47 IS 1 BP 91 EP 97 DI 10.1016/j.jacc.2005.08.051 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000UQ UT WOS:000234488300014 PM 16386670 ER PT J AU Safran, M Kim, WY O'Connell, F Flippin, L Gunzler, V Horner, JW DePinho, RA Kaelin, WG AF Safran, M Kim, WY O'Connell, F Flippin, L Gunzler, V Horner, JW DePinho, RA Kaelin, WG TI Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: Assessment of an oral agent that stimulates erythropoietin production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bioluminescence; imaging; von Hippel-Lindau ID HYPOXIA-INDUCIBLE FACTOR; UBIQUITIN-PROTEASOME PATHWAY; LINDAU TUMOR-SUPPRESSOR; PROLINE HYDROXYLATION; GENE-EXPRESSION; FACTOR 1-ALPHA; RENAL MEDULLA; IN-VIVO; COMPLEX; CANCER AB Many human diseases are characterized by the development of tissue hypoxia. Inadequate oxygenation can cause cellular dysfunction and death. Tissues use many strategies, including induction of angiogenesis and alterations in metabolism, to survive under hypoxic conditions. The heterodimeric transcription factor hypoxia-inducible factor (HIF) is a master regulator of genes that promote adaptation to hypoxia. HIF activity is linked to oxygen availability because members of the EGLIN family hydroxylate HIF alpha subunits on specific prolyl residues when oxygen is present, which marks them for ubiquitination and proteasomal degradation. We created a mouse that ubiquitously expresses a bioluminescent reporter consisting of firefly luciferase fused to a region of HIF that is sufficient for oxygen-dependent degradation. Our validation studies suggest that this mouse will be useful for monitoring hypoxic tissues and evaluating therapeutic agents that stabilize HIF. One such agent, the HIF prolyl hydroxylase inhibitor FG-4383, was active in the liver and kidney after systemic administration as determined by bioluminescence imaging, transcription profiling, and production of erythropoietin, indicating that the HIF transcriptional program can be manipulated in vivo with orally active organic small molecules. C1 Harvard Univ, Dept Med Oncol, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. FibroGen Inc, San Francisco, CA 94080 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Harvard Univ, Dept Med Oncol, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 34 TC 163 Z9 169 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 JAN 3 PY 2006 VL 103 IS 1 BP 105 EP 110 DI 10.1073/pnas.0509459103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 003JL UT WOS:000234677800020 PM 16373502 ER PT S AU Yu, P Han, X Segonne, F Liu, AK Poldrack, RA Golland, P Fischll, B AF Yu, Peng Han, Xiao Segonne, Florent Liu, Arthur K. Poldrack, Russell A. Golland, Polina Fischll, Bruce BE Tang, YY Wang, SP Lorette, G Yeung, DS Yan, H TI Shape-based discrimination and classification of cortical surfaces SO 18TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION, VOL 3, PROCEEDINGS SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 18th International Conference on Pattern Recognition (ICPR 2006) CY AUG 20-24, 2006 CL Hong Kong, PEOPLES R CHINA SP IAPR, CAA, Hong Kong Baptist Univ ID SEGMENTATION AB Advances in medical imaging technique make it possible to study shape variations of neuroanatomical structures in vivo, which has been proved useful in the study of neuropathology and neurodevelopment. In this paper, we propose the use of spherical wavelet transformation to extract shape features, as it can characterize the underlying functions in a local fashion in both space and frequency, in contrast to spherical harmonics that have a noncompact basis set. The extracted shape features can be used to statistically detect and visualize group shape differences from a coarse to fine resolution, and facilitate shape-based classification. A procedure is developed to apply this method to cortical surface models, and promising results are acquired on synthetic and real data. C1 [Yu, Peng; Fischll, Bruce] MIT, Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Han, Xiao] CMS Inc, St Louis, MO 63132 USA. [Segonne, Florent; Golland, Polina; Fischll, Bruce] MIT, AI Lab, Cambridge, MA 02139 USA. [Liu, Arthur K.; Fischll, Bruce] MGH, Radiol, Charlestown, MA 02129 USA. [Poldrack, Russell A.] Univ Calif Los Angeles, Inst Brain Res, Dept Psychol, Los Angeles, CA 90095 USA. [Fischll, Bruce] Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Yu, P (reprint author), MIT, Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Yu, Peng/A-2877-2010 NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1051-4651 BN 0-7695-2521-0 J9 INT C PATT RECOG PY 2006 BP 445 EP + PG 2 WC Computer Science, Artificial Intelligence SC Computer Science GA BFB29 UT WOS:000240705600106 ER PT S AU Srinivasan, L Brown, EN AF Srinivasan, Lakshminarayan Brown, Emery N. GP IEEE TI Dynamic-goal state equations for tracking reaching movements using neural signals SO 2006 1ST IEEE RAS-EMBS INTERNATIONAL CONFERENCE ON BIOMEDICAL ROBOTICS AND BIOMECHATRONICS, VOLS 1-3 SE Proceedings of the IEEE RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics LA English DT Proceedings Paper CT 1st IEEE RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics (BioRob 2006) CY FEB 20-22, 2006 CL Pisa, ITALY SP IEEE, RAS, EMBS, Scuola Superiore Sant Anna, Int Soc Gerontechnol, SIRI, AURION, ONDI, ERA Endoscopy, KTeam, ROBOTECH srl, Carismi DE motor; neural prosthetics; goal-directed; estimation; state equation AB Motor prosthetic algorithms were recently proposed to combine target and path information to drive reaching arm movements to a static goal. In this paper, we extend two approaches to support goals that may themselves evolve over the duration of the reaching movement. The resulting probabilistic and control-based dynamic-goal reach state equations represent an intermediate level of user flexibility between static-goal reach state equations and unconstrained movement. C1 [Srinivasan, Lakshminarayan] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Srinivasan, Lakshminarayan; Brown, Emery N.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Srinivasan, Lakshminarayan; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Srinivasan, L (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM ls2@neurostat.mgh.harvard.edu FU NIH Medical Scientist Training Program [R01 DA015644] FX This work was supported in part by the NIH Medical Scientist Training Program Fellowship to LS and NIH grant R01 DA015644 to ENB. Correspondence can be addressed to ls2@neurostat.mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2155-1782 BN 978-1-4244-0039-3 J9 P IEEE RAS-EMBS INT PY 2006 BP 644 EP + PG 2 WC Engineering, Biomedical; Robotics SC Engineering; Robotics GA BFS90 UT WOS:000244445100109 ER PT B AU Barbieri, R Brown, EN AF Barbieri, Riccardo Brown, Emery N. GP IEEE TI Correction of erroneous and ectopic beats using a point process adaptive algorithm SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc ID HEART-RATE-VARIABILITY; TIMING SIGNAL AB We present a new R-R interval correction procedure based on a point process model of the human heart beat. The algorithm combines an adaptive point process filter with a set of conditions on the probability of having a beat according to the model. This framework allows for correction of ectopic and erroneously detected beats in an on-line fashion, simultaneous with computation of instantaneous estimates of heart rate and heart rate variability. Results demonstrate the efficacy of the method, and show new heart rate and heart rate variability dynamics corrected for artifacts introduced by incorrect and/or irregular R-R intervals. C1 [Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Mit Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Barbieri, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM barbieri@neurostat.mgh.harvard.edu; brown@neurostat.mgh.harvard.edu FU NIMH [MH59733, MH61637]; NLDA [DA015644]; NSF [EN-008 1458] FX Manuscript received April 3, 2006. Support was provided in part by NIMH grants MH59733, MH61637, NLDA grant DA015644 and NSF grant EN-008 1458. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 346 EP 349 PG 4 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284700085 ER PT B AU Shaltis, PA Reisner, A Asada, HH AF Shaltis, Phillip A. Reisner, Andrew Asada, H. Harry GP IEEE TI Wearable, cuff-less PIFIG-Based blood pressure monitor with novel height sensor SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc ID FINGER ARTERIES; PULSE AB A truly wearable non-invasive blood pressure (NIBP) sensor - light-weight, compact, unobstrusive, and essentially unnoticeable to the patient - could revolutionize healthcare delivered beyond the traditional walls of medical facilities, offering new ways to care for patients in their everyday surroundings. This paper presents results from our work towards the development of a self-contained, wearable blood pressure sensor. A PPG-based approach to blood pressure monitoring is presented. The design enables significant miniaturization of traditional oscillometric devices without the need for occlusive circumferential pressures. It will be shown how natural raising and lowering of the arm replaces the need for bulky actuators. Additionally, a dual-accelerometer height sensor that is tetherless is proposed and supported by experimental results. C1 [Shaltis, Phillip A.; Asada, H. Harry] MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Reisner, Andrew] Massachusetts Gen Hosp Boston, Boston, MA 02114 USA. RP Shaltis, PA (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM psbaltis@mit.edu; areisner@partners.org; asada@mit.edu FU Sharp Corporation FX This work was supported in part by the Sharp Corporation. NR 7 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 2390 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284702178 ER PT B AU Deng, ZD Poon, CS Arzeno, NM Katz, ES AF Deng, Zhi-De Poon, Chi-Sang Arzeno, Natalia M. Katz, Eliot S. GP IEEE TI Heart rate variability in pediatric obstructive sleep apnea SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc DE heart rate variability; nonlinear dynamics; obstructive sleep apnea; pediatric ID TIME-SERIES ANALYSIS; APPROXIMATE ENTROPY; SPECTRAL-ANALYSIS; STANDARDS; CHILDREN; CHAOS AB Obstructive sleep apnea syndrome (OSAS) is observed in approximately 2% of children. Heart rate variability (HRV) is a potentially simple, non-invasive diagnostic screening tool for OSAS. In this study, we investigated the diagnostic potential of HRV using power spectral analysis, numerical titration, sample entropy, and detrended fluctuation analysis. Effects of sleep stages (REM and NREM sleep) are evaluated. The results show that the heart rate chaos intensity, as measured by the noise limit in numerical fitration, is significantly higher during REM sleep than NREM sleep in all patient groups. By using the receiver-operating characteristic analysis, the detection of OSAS vielded a specificity of 72.2% and sensitivity of 81.3% using the numerical-titration technique. The findings suggest that sleep state and disordered breathing are important determinants of cardiac autonomic control. Nonlinear techniques such as numerical titration, when used in conjunction with spectral analysis of HRV could be all effective screening tool for pediatric OSAS. C1 [Deng, Zhi-De; Poon, Chi-Sang; Arzeno, Natalia M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Katz, Eliot S.] Massachusetts Gen Hosp, Dept Pediatr Pulmonol, Boston, MA 02114 USA. RP Deng, ZD (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM zzdeng@mit.edu; cpoon@mit.edu; natalia2@mit.edu FU National Institutes of Health [HL075014, HL079503] FX This work was supported by National Institutes of Health Grant HL075014 and HL079503. NR 25 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 2467 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284702198 ER PT B AU McCombie, DB Reisner, AT Asada, HH AF McCombie, Devin B. Reisner, Andrew T. Asada, H. Harry GP IEEE TI Adaptive blood pressure estimation from wearable PPG sensors using peripheral artery pulse wave velocity measurements and multi-channel blind identification of local arterial dynamics. SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc AB A method for estimating pulse wave velocity (PWV) using circulatory waveform signals derived from multiple photoplethysmograph (PPG) sensors is described. The method employs two wearable in-line PPG sensors placed at a known distance from one another at the ulnar and digital artery. A technique for calibrating the measured pulse wave velocity to arterial blood pressure using hydrostatic pressure variation is presented. Additionally, a framework is described for estimating local arterial dynamics using PPG waveforms and multi-channel blind system ID. Initial results implementing the method on data derived from a human subject at different arterial pressures is presented. Results show that the method is capable of measuring the changes in arterial PWV that result from fluctuations in mean arterial pressure. C1 [McCombie, Devin B.; Asada, H. Harry] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Boston, MA USA. RP McCombie, DB (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mccombie@mit.edu; areisner@partners.org; asada@mit.edu NR 9 TC 0 Z9 0 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 2824 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284703075 ER PT B AU Deliolanis, N Lasser, T Niedre, M Soubret, A Ntziachristos, V AF Deliolanis, Nikolaos Lasser, Tobias Niedre, Mark Soubret, Antoine Ntziachristos, Vasilis GP IEEE TI In-vivo lung cancer imaging in mice using 360 degrees free-space fluorescence molecular tomography SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc ID OPTICAL TOMOGRAPHY; TURBID MEDIA; RECONSTRUCTION AB We present the development and performance characteristics of a free-space fluorescence tomography system. The imaging system can capture complete angle projections of photons propagating through tissue in transillumination using a CCD camera. Experimental data on imaging lung cancer are presented. Overall, this imaging approach can offer unprecedented imaging performance in Fluorescence Molecular Tomography of small animals. C1 [Deliolanis, Nikolaos; Lasser, Tobias; Niedre, Mark; Soubret, Antoine; Ntziachristos, Vasilis] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bio Opt & Mol Imaging, CNY 149 13th Str 5209, Charlestown, MA 02129 USA. RP Deliolanis, N (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bio Opt & Mol Imaging, CNY 149 13th Str 5209, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.haryard.edu FU NIH [EB000750-1, R43-ES012360] FX The authors acknowledge support from NIH grant ROI EB000750-1 and R43-ES012360. NR 15 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 2828 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284703076 ER PT B AU Yun, SH AF Yun, S. H. GP IEEE TI Optical coherence tomography using rapidly swept lasers SO 2006 28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Sci ID FREQUENCY-DOMAIN REFLECTOMETRY; INTRAOCULAR DISTANCES; HUMAN RETINA; FIBER; OCT; INTERFEROMETRY; PRINCIPLES; COMPACT; NERVE; NM AB Optical coherence tomography (OCT) has proven to be a useful diagnostic tool in several medical areas. Am emerging second-generation OCT technology, termed optical frequency domain imaging, is expected to increase the clinical applications of OCT significantly. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St,BAR 818, Boston, MA 02114 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 6064 EP 6067 PG 4 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284707013 ER PT B AU Pratt, D Hahn, W Matthews Febbo, P Berger, R Duckworth, B Levy, J Segaran, T Sun, J Ladd, B Elliston, K AF Pratt, D. Hahn, W. Matthews Febbo, P. Berger, R. Duckworth, B. Levy, J. Segaran, T. Sun, J. Ladd, B. Elliston, K. GP IEEE TI Computational causal reasoning models of mechanisms of androgen stimulation in prostate cancer SO 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 LA English DT Proceedings Paper CT 28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 30-SEP 03, 2006 CL New York, NY SP IEEE Engn Med & Biol Soc C1 [Pratt, D.; Hahn, W.; Matthews; Levy, J.; Segaran, T.; Sun, J.; Ladd, B.; Elliston, K.] Genstruct Inc, Cambridge, MA 02140 USA. [Hahn, W.; Febbo, P.; Berger, R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pratt, D (reprint author), Genstruct Inc, Cambridge, MA 02140 USA. EM dpratt@genstruct.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-0032-4 PY 2006 BP 6236 EP 6236 PG 1 WC Engineering, Biomedical SC Engineering GA BGI19 UT WOS:000247284707059 ER PT B AU Cheyne, HA AF Cheyne, Harold A., II GP IEEE TI Estimating glottal voicing source characteristics by measuring and modeling the acceleration of the skin on the neck SO 2006 3RD IEEE/EMBS INTERNATIONAL SUMMER SCHOOL ON MEDICAL DEVICES AND BIOSENSORS LA English DT Proceedings Paper CT IEEE/EMBS International Summer School on Medical Devices and Biosensors CY SEP 04-06, 2006 CL Cambridge, MA SP IEEE, EMBS ID ACCUMULATOR; IMPEDANCE; SIGNALS; SPEECH; SYSTEM AB Quantifying vocal function is becoming increasingly important both for corroborating clinicians' subjective impressions during a voice evaluation and for assessing the effectiveness of surgery or voice therapy. Accelerometers offer significant potential for measuring voice use because they are immune to environmental noise, inexpensive, and suitable for ambulatory monitoring. This work investigates the extent to which measures of the acceleration of the skin on the neck (near the larynx) can be used to estimate important vocal function parameters. Simultaneous acceleration, acoustic, and airflow recordings from one male subject with a normal voice were made to initially examine relationships between the acceleration signal and the acoustic or airflow signals. A vocal system model is proposed to provide insights into these relationships. The model's acceleration-derived estimates of Maximum Flow Declination Rate (MFDR) and Sound Pressure Level (SPL) are compared to direct measures obtained from the airflow (MFDR) and acoustic (SPL) signals at the lips. Results show high correlations between the estimated and measured MFDR (r=0.86) and SPL (r=0.94) values, suggesting that clinically relevant parameters can be derived from accelerometer data using a vocal system model. C1 Massachusetts Gen Hosp, MGH Voice Ctr, Boston, MA 02114 USA. RP Cheyne, HA (reprint author), Massachusetts Gen Hosp, MGH Voice Ctr, Boston, MA 02114 USA. EM hcheyne@partners.org NR 28 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-0-7803-9786-6 PY 2006 BP 118 EP 121 DI 10.1109/ISSMDBS.2006.360113 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA BGP00 UT WOS:000249125500032 ER PT B AU Patel, S Hester, T Hughes, R Huggins, N Standaert, D Flaherty, A Bonato, P AF Patel, Shyamal Hester, Todd Hughes, Richard Huggins, Nancy Standaert, David Flaherty, Alice Bonato, Paolo GP IEEE TI Using wearable sensors to enhance DBS parameter adjustment for Parkinson's disease patients through measures of motor response SO 2006 3RD IEEE/EMBS INTERNATIONAL SUMMER SCHOOL ON MEDICAL DEVICES AND BIOSENSORS LA English DT Proceedings Paper CT IEEE/EMBS International Summer School on Medical Devices and Biosensors CY SEP 04-06, 2006 CL Cambridge, MA SP IEEE, EMBS ID STIMULATION AB Parkinson's disease is a common movement disorder and affects many older adults. The use of deep brain stimulation has been shown to have good results in symptom reduction, but quantitative methods for the adjustment of deep brain stimulator parameters are required. In this paper, we show that features derived from wearable sensors (accelerometers) are able to characterize changes in the severity of bradykinesia observed when turning the stimulator off and on as well as changes while the stimulator is off for a period of time. We also demonstrate results derived by means of predictors that accurately estimated the clinical scores associated with the motor activities performed during the experiments. These preliminary results are very encouraging and show the potential for the developed methodology to provide clinicians with assistance in adjusting deep brain stimulator parameters. C1 [Patel, Shyamal; Hester, Todd; Hughes, Richard; Bonato, Paolo] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Huggins, Nancy; Standaert, David; Flaherty, Alice] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA USA. RP Patel, S (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. EM spatell9@partners.org; todd.hester@gmail.com; rhughes1@partners.org; nhuggins@partners.org; dstandaert@partners.org; aflaherty@partners.org; pbonato@partners.org OI Standaert, David/0000-0003-2921-8348 FU brazilian fundation FAPESP; Harvard Center for Neurodegeneration Harvard Center for Neurodegeneration and Repair; Enhancing DBS Parameter Adjustment Through Measures of Motor Response FX This work was supported by the brazilian fundation FAPESP. This work was supported by the Harvard Center for Neurodegeneration and Repair under the grant entitled "Enhancing DBS Parameter Adjustment Through Measures of Motor Response". NR 6 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-0-7803-9786-6 PY 2006 BP 141 EP + DI 10.1109/ISSMDBS.2006.360119 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BGP00 UT WOS:000249125500038 ER PT S AU Tyrrell, JA Roysam, B di Tomaso, E Tong, R Brown, EB Jain, RK AF Tyrrell, James A. Roysam, Badrinath di Tomaso, Emmanuelle Tong, Ricky Brown, Edward B. Jain, Rakesh K. GP IEEE TI Robust 3-D modeling of tumor microvasculature using superellipsoids SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID MICROSCOPY AB This paper presents automated methods for robust modeling and analysis of 3-D tumor microvasculature. Our methodology uses a cylindroidal superellipsoid to model localized segments of vasculature. The proposed vessel model has an explicit, low-order parameterization, allowing for joint estimation of boundary and centerline information, thereby approximating the medial axis. Further, this explicit parameterization provides a geometric framework for traversing vessels in a directed manner. Topological information like branch point location and connectivity is provided as a side effect. The proposed methodology behaves quite well across scalespace, shows a high degree of insensitivity to adjacent structures and implicitly handles branching. Exemplar results are presented from a pre-clinical study of tumor microvasculature in mice. C1 [Tyrrell, James A.; Roysam, Badrinath] Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. [di Tomaso, Emmanuelle; Tong, Ricky; Brown, Edward B.; Jain, Rakesh K.] Massachusetts Gen Hosp, Harlem Med Sch, Boston, MA 02114 USA. RP Tyrrell, JA (reprint author), Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. RI Tyrrell, James/A-6359-2010 NR 8 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 185 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000047 ER PT S AU Sosnovik, DE Weissleder, R AF Sosnovik, David E. Weissleder, Ralph GP IEEE TI Cardiovascualr molecular MRI SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID MAGNETIC-RESONANCE; NANOPARTICLES; PEPTIDE; CELLS AB Recent advances in contrast agent design and imaging techniques now make it possible to image some molecular targets at the cellular and subcellular level by MRI. In this review we highlight the use of superparamagnetic iron-oxide nanoparticles for molecular imaging applications in the cardiovascular system. The potential roles of these nanoparticles in cell labeling, targeted imaging and as activatable contrast agents are discussed. C1 [Sosnovik, David E.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. FU CONICET, UNC FX This work is being supported by CONICET, UNC and Mincyt-Cordoba. The authors acknowledge to Prof. G. Montich and CIQUIBIC-CONICET for the access to infrastructure for the liposome suspension preparation. NR 16 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 363 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000092 ER PT S AU Brown, E Jain, RK AF Brown, Edward Jain, Rakesh K. GP IEEE TI Nonlinear microscopy of living tumors and their treatment SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID PERMEABILITY AB We will discuss the application of the multiphoton laser-scanning microscope (MPLSM) to the study of the tumor microenvironment. This will include its use in the quantification of angiogenic parameters and the study of tumor vessel permeability. We also will explore the use of an intrinsic contrast mechanism, second harmonic generation, to quantify modification of the tumor extracellular matrix, with the ultimate goal of improving therapeutic efficacy. C1 [Brown, Edward] Univ Rochester, Med Ctr, Dept Biomed Engn, 601 Elmwood Ave, Rochester, NY 14642 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, E L Steele Lab, Boston, MA 02114 USA. RP Brown, E (reprint author), Univ Rochester, Med Ctr, Dept Biomed Engn, 601 Elmwood Ave, Rochester, NY 14642 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 367 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000093 ER PT S AU Hyde, D Miller, E Brooks, D Ntziachristos, V AF Hyde, Damon Miller, Eric Brooks, Dana Ntziachristos, Vasilis GP IEEE TI A statistical method for inverting the born ratio SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID TOMOGRAPHY; RECONSTRUCTION AB We examine a statistical solution to the problem of Fluorescence Molecular Tomography (FMT) using the Born ratio. Experimentally verified noise models for the fluorescence and excitation signals are combined to generate a stochastic model for the Born ratio. This model is then utilized within a maximum likelihood (ML) framework to obtain a fixed point iteration about a linear least squares problem. Results for experimental data are shown, including phantoms implanted within a small animal, and in-vivo data using an exogenous probe. C1 [Hyde, Damon; Miller, Eric; Brooks, Dana] Northeastern Univ, Boston, MA 02115 USA. [Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Hyde, D (reprint author), Northeastern Univ, Boston, MA 02115 USA. RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 NR 9 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 598 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000151 ER PT S AU Karimi, R Chan, R Houser, S Bouma, BE Mofrad, MRK AF Karimi, Reza Chan, Raymond Houser, Stuart Bouma, Brett E. Mofrad, Mohammad R. Kaazempur GP IEEE TI A novel framework for elastography and modulus estimation: Integration of tissue mechanics with imaging SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID OPTICAL COHERENCE TOMOGRAPHY; STRAIN; ELASTICITY; PLAQUES AB The feasibility of optical coherence elastography is examined and the steps necessary for registration of optical coherence tomography (OCT) images are developed. We address the drawbacks of conventional techniques for solving the "image registration problem and inverse elasticity problem (IEP)" and then propose a new scheme for simultaneous solution of both problems. We have previously exploited the kinematics of incompressible tissue as a side-constraint term in OCT registration, and we now assess how the integration of FEM-derived mechanics directly within the registration process, improves the overall quality. The new technique estimates fewer unknowns and still it generates more realistic strain/modulus maps with less sensitivity to local minima. It is composed of a series of computationally-efficient and robust algorithms to create elastograms and elastic modulus maps and it does not need to utilize a multi resolution grid. Finally, we apply our scheme to a porcine aorta and demonstrate its ability in recovering lipid pools both in the strain map and in the elastic modulus image. C1 [Karimi, Reza; Chan, Raymond; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Karimi, Reza] MIT, Dept Mech Engn, Cambridge, MA USA. [Chan, Raymond; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA USA. [Houser, Stuart] Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Mofrad, Mohammad R. Kaazempur] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA USA. [Chan, Raymond] Philips Res N Amer, Briarcliff Manor, NY USA. RP Chan, R (reprint author), Philips Res N Amer, Briarcliff Manor, NY USA. FU NIH [R01 HL70039-01] FX NIH R01 HL70039-01 funding and help from A. Chau and S. Nadkarni were really appreciated. NR 16 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 602 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000152 ER PT S AU Desai, M Mangoubi, R Kennedy, D AF Desai, Mukund Mangoubi, Rami Kennedy, David GP IEEE TI Robust constrained nonGaussian fMRI detection SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE DE constraint; detector; robust; fMRI; Gaussian; non-Gaussian; prior; CFAR AB For fMRI detection, it is desirable to have sensitive detectors for enhanced performance in low SNR environment. This sensitivity, usually captured through learning of associated models, comes at the price of increased false alarms. In this paper, we address the issue of robustness to false alarm while maintaining sensitivity by providing the analytical framework for incorporating prior information in the form of constraints in Gaussian and non-Gaussian settings. We show that the impact on the decision statistic of incorporating constraints is simply captured through a simple modification of the unconstrained detector's statistic. The computational burden of the constrained and unconstrained detectors are thus similar. The performance of the new constrained detector is shown on fMRI data to provide superior performance when compared the conventional CFAR detector. C1 [Desai, Mukund; Mangoubi, Rami] Charles Stark Draper Lab Inc, Cambridge, MA USA. [Kennedy, David] Massachusetts Gen Hosp, Boston, MA USA. RP Desai, M (reprint author), Charles Stark Draper Lab Inc, Cambridge, MA USA. FU Draper Laboratory IRD fund; NIH [R01 NS34189-10]; National Institute of Neurological Disorders and Stroke FX Work supported by a Draper Laboratory IR&D fund, and by NIH Grant No.2 R01 NS34189-10 from the National Institute of Neurological Disorders and Stroke. NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 1076 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000272 ER PT S AU Hillman, EMC Devor, A Boas, DA AF Hillman, Elizabeth M. C. Devor, Anna Boas, David A. GP IEEE TI High-resolution functional optical imaging of living tissues SO 2006 3RD IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1-3 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE ID TURBID MEDIA AB Laminar Optical Tomography (LOT) is an optical imaging technique capable of imaging absorption and fluorescence contrast in-vivo to depths of > 2mm with 100-200 micron resolution. LOT has been used to image the living brain in experiments to investigate the hemodynamic response in rat cortex during forepaw stimulus. We show that using LOT, it is possible to resolve the contributions of each vascular compartment to the ensemble hemodynamic response. The LOT system will be described and its future application to other areas of medical imaging will be discussed. C1 [Hillman, Elizabeth M. C.; Devor, Anna; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. RP Hillman, EMC (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ehillman@nmr.mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-0-7803-9576-3 J9 I S BIOMED IMAGING PY 2006 BP 1192 EP + PG 2 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BFS91 UT WOS:000244446000301 ER PT S AU Hahn, JO Reisner, A Asada, HH AF Hahn, Jin-Oh Reisner, Andrew Asada, H. Harry GP IEEE TI A blind approach to reconstruction of aortic blood pressure waveform using gray-box identification of multiple pressure transfer channels SO 2006 AMERICAN CONTROL CONFERENCE, VOLS 1-12 SE Proceedings of the American Control Conference LA English DT Proceedings Paper CT American Control Conference 2006 CY JUN 14-16, 2006 CL Minneapolis, MN SP Amer Automat Control Council ID DERIVATION AB This paper presents a blind approach to the reconstruction of central aortic blood pressure waveform from multiple peripheral blood pressure measurements. The blind channel identification methodology is applied to the gray-box model of the arterial circulatory system to formulate the arterial system identification problem, which is solved using constrained optimization technique. The aortic blood pressure waveform is then reconstructed by de-convolution of the identified gray-box arterial system dynamics. In contrast to most of the previously developed methods for estimating aortic blood pressure waveform, the key merit of the proposed algorithm is its abitity to be individualized, i.e. the proposed method can be applied on a per-patient basis. Experimental results show the clinical potential of the proposed algorithm as well as its efficacy to accurately reconstruct the aortic blood pressure waveform. C1 [Hahn, Jin-Oh; Asada, H. Harry] MIT, Darbeloff Lab Informat Syst & Technol, Cambridge, MA 02139 USA. [Reisner, Andrew] Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. RP Hahn, JO (reprint author), MIT, Darbeloff Lab Informat Syst & Technol, Cambridge, MA 02139 USA. EM stardust@mit.edu; areisner@partners.org; asada@mit.edu FU National Science Foundation [0330280] FX This paper is based upon work supported by the National Science Foundation under Grant No. 0330280. NR 15 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0743-1619 BN 1-4244-0209-3 J9 P AMER CONTR CONF PY 2006 VL 1-12 BP 3415 EP 3420 PG 6 WC Automation & Control Systems SC Automation & Control Systems GA BFG14 UT WOS:000241666306061 ER PT S AU Laxminarayan, S Diamond, SG Miller, E Tadmor, G Boas, D Brooks, DH AF Laxminarayan, Srinivas Diamond, Solomon G. Miller, Eric Tadmor, Gilead Boas, David Brooks, Dana H. GP IEEE TI Controlling dimensionality in a systems approach to dynamic multimodal functional brain imaging SO 2006 FORTIETH ASILOMAR CONFERENCE ON SIGNALS, SYSTEMS AND COMPUTERS, VOLS 1-5 SE Conference Record of the Asilomar Conference on Signals Systems and Computers LA English DT Proceedings Paper CT 40th Asilomar Conference on Signals, Systems and Computers CY OCT 29-NOV 02, 2006 CL Pacific Grove, CA SP Naval Postgrad Sch, ATK Mission Res, IEEE Signal Proc Soc ID MODEL; ACTIVATION; FLOW AB The complementary spatial, temporal and specificity advantages of fMRI, EEG, MEG, PET and DOT for functional brain imaging motivate interest in multimodal functional brain imaging. State-variable dynamical systems modeling of neural activity and its relation to local hemodynamics, further coupled with autonomic physiology offers enhanced spatiotemporal resolution and insight into physiological signals and mechanisms. However, such a model also implies an explosion of state dimension. We discuss strategies for controlling this high dimensionality based on subspace approaches applied to the observed data and the model structure. C1 [Laxminarayan, Srinivas; Diamond, Solomon G.; Miller, Eric; Tadmor, Gilead; Brooks, Dana H.] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Boas, David] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Laxminarayan, S (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. OI Diamond, Solomon/0000-0002-7589-2942 FU Gordon Center for Subsurface Sensing and Imaging an NSF ERC [EEC-9986821]; MGH Functional NeuroImaging center; MIND Institute [NIH-T32CA09502, NCRR P41-RR14075] FX We thank Jorge J. Riera of Tohoku University, Japan for providing us with his neuronal code and his paper. Theodore J. Huppert of Martinos Center, for the 3 compartment windkessel model. Matti Hamalainen also of Martinos Center for the EEG/MEG data and the MNE analysis and visualization software, and Manu B. Jonny of Saint Louis University, for bringing the neuronal and hemodynamics models into state- space form, and implementing the local linearization method for state estimation. The authors acknowledge the support of Gordon Center for Subsurface Sensing and Imaging an NSF ERC (Grant number EEC-9986821),the MGH Functional NeuroImaging center, and the MIND Institute (Grant Numbers NIH-T32CA09502, NCRR P41-RR14075). NR 12 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1058-6393 BN 978-1-4244-0784-2 J9 CONF REC ASILOMAR C PY 2006 BP 166 EP + DI 10.1109/ACSSC.2006.356607 PG 2 WC Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Telecommunications SC Engineering; Imaging Science & Photographic Technology; Telecommunications GA BGH15 UT WOS:000246925200030 ER PT S AU Coleman, TP Yanike, M Suzuki, W Brown, EN AF Coleman, Todd P. Yanike, Marianna Suzuki, Wendy Brown, Emery N. GP IEEE TI A mixed filter algorithm for state estimation from simultaneously recorded continuous-valued, point process and binary observations SO 2006 FORTIETH ASILOMAR CONFERENCE ON SIGNALS, SYSTEMS AND COMPUTERS, VOLS 1-5 SE Conference Record of the Asilomar Conference on Signals Systems and Computers LA English DT Proceedings Paper CT 40th Asilomar Conference on Signals, Systems and Computers CY OCT 29-NOV 02, 2006 CL Pacific Grove, CA SP Naval Postgrad Sch, ATK Mission Res, IEEE Signal Proc Soc ID BEHAVIORAL-EXPERIMENTS; DYNAMIC-ANALYSIS C1 [Coleman, Todd P.] Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. [Yanike, Marianna; Suzuki, Wendy] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Brown, Emery N.] Massachusetts Gen Hosp, MIT, Harvard Med Sch, Neurosci Stat Res Lab, Boston, MA USA. RP Coleman, TP (reprint author), Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. EM colemant@uiuc.edu; yanike@cns.nyu.edu; wendy@cns.nyu.edu; brown@neurostat.mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1058-6393 BN 978-1-4244-0784-2 J9 CONF REC ASILOMAR C PY 2006 BP 1949 EP + DI 10.1109/ACSSC.2006.355104 PG 3 WC Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Telecommunications SC Engineering; Imaging Science & Photographic Technology; Telecommunications GA BGH15 UT WOS:000246925204020 ER PT S AU Unal, G Slabaugh, G Ess, A Yezzi, A Fang, T Tyan, J Requardtd, M Kriegd, R Seethainraju, R Harisinghani, M Weissleder, R AF Unal, G. Slabaugh, G. Ess, A. Yezzi, A. Fang, T. Tyan, J. Requardtd, M. Kriegd, R. Seethainraju, R. Harisinghani, M. Weissleder, R. GP IEEE TI Semi-automatic lymph node segmentation in LN-MRI SO 2006 IEEE INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, ICIP 2006, PROCEEDINGS SE IEEE International Conference on Image Processing ICIP LA English DT Proceedings Paper CT IEEE International Conference on Image Processing (ICIP 2006) CY OCT 08-11, 2006 CL Atlanta, GA SP IEEE DE biomedical image processing; image segmentation; biomedical magnetic resonance imaging; medical diagnosis AB Accurate staging of nodal cancer still relies on surgical exploration because many primary malignancies spread via lymphatic dissemination. The put-pose of this study was to utilize nanoparticle-enhanced lymphotropic magnetic resonance imaging (LN-MRI) to explore semi-automated noninvasive nodal cancer staging. We present a joint image segmentation and registration approach, which makes use of the problem specific information to increase the robustness of the algorithm to noise and weak contrast often observed in medical imaging applications. The effectiveness of the approach is demonstrated with a given lymph node segmentation problem in post-contrast pelvic MRI sequences. C1 [Unal, G.; Slabaugh, G.; Fang, T.; Tyan, J.] Siemens Corp Res, Intelligent Vis & Reasoning, Princeton, NJ 08540 USA. [Ess, A.] Swiss Fed Inst ETH, Dept Comp Sci, Zurich, Switzerland. [Yezzi, A.] Georgia Inst Technol, Sch ECE, Atlanta, GA USA. [Requardtd, M.; Kriegd, R.] Siemens Med MIR, Med Solut, Erlangen, Germany. [Requardtd, M.] Siemens Medical Solutions, Med MR, Malvern, PA 19355 USA. [Harisinghani, M.; Weissleder, R.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02138 USA. RP Ess, A (reprint author), Siemens Corp Res, Intelligent Vis & Reasoning, Princeton, NJ 08540 USA. OI Slabaugh, Greg/0000-0003-4060-5226 NR 18 TC 9 Z9 9 U1 2 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1522-4880 BN 978-1-4244-0481-0 J9 IEEE IMAGE PROC PY 2006 BP 77 EP + DI 10.1109/ICIP.2006.312366 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGA25 UT WOS:000245768500020 ER PT S AU Park, M Mahmood, A Zimmerman, RE Limpa-Amara, N Makrigiorgos, GM Moore, SC AF Park, M. Mahmood, A. Zimmerman, R. E. Limpa-Amara, N. Makrigiorgos, G. M. Moore, S. C. GP IEEE TI Assessment of the activity distribution of metal radionuclides in plastic phantoms using mu SPECT imaging and gamma counting SO 2006 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOL 1-6 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium CY OCT 29-NOV 04, 2006 CL San Diego, CA SP IEEE AB At neutral pH, metal radionuclides, e. g., In-111 and Y-90, precipitate and adhere to container walls, yielding nonuniform activity distributions in compartments of plastic phantoms used for dosimetry validation. For various concentrations of a chelator, EDTA, we evaluated the uniformity of activity distributions in phantoms, as well as the accuracy of a fluorescent liquid dosimeter, coumarin-3-carboxylic acid (CCA). Solutions of In-111 and Y-90 with activity concentrations of 10-25 mu Ci/cc containing increasing EDTA concentrations (0-25 mu M) were stored in polymethyl methacrylate (PMMA) phantoms for 24 h to accumulate dose. Activity in the solution was then measured in a gamma counter and/or by mu SPECT imaging. Phantoms containing 0.1mM CCA with EDTA were also irradiated either with a Cs-137 irradiator or with Y-90 to evaluate the effect of EDTA concentration on fluorescence intensity (FI). Activity measurements from images and gamma counting indicated that 40-50% of the activity of In-111 and Y-90 (25 mu Ci/cc) accumulated on phantom walls for EDTA concentration <2.5 mu M, whereas no adherence was observed for EDTA concentration >2.5 mu M. For a fixed absorbed dose, fluorescence intensity decreased by <15% when using 2.5 mu M EDTA. For all EDTA concentrations, a linear dose-FI relationship was observed up to similar to 15Gy. For phantom dose measurements using metal radionuclides, solutions should contain similar to 1,000 EDTA molecules for each radiolabeled atom to obtain a uniform activity distribution. C1 [Park, M.; Mahmood, A.; Zimmerman, R. E.; Limpa-Amara, N.; Moore, S. C.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Makrigiorgos, G. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Park, M.; Mahmood, A.; Zimmerman, R. E.; Limpa-Amara, N.; Makrigiorgos, G. M.; Moore, S. C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Park, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-0561-9 J9 IEEE NUCL SCI CONF R PY 2006 BP 3139 EP 3141 DI 10.1109/NSSMIC.2006.356540 PG 3 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BUC53 UT WOS:000288875603045 ER PT S AU Jarlskog, CZ Jiang, HY Paganetti, H AF Jarlskog, Christina Zacharatou Jiang, Hongyu Paganetti, Harald GP IEEE TI Proton Monte Carlo in the clinic SO 2006 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOL 1-6 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium CY OCT 29-NOV 04, 2006 CL San Diego, CA SP IEEE ID SIMULATIONS; GEANT4 AB Proton Monte Carlo dose calculation has been implemented clinically for use in parallel to a commercial treatment planning system at Massachusetts General Hospital, Boston, USA. Treatment heads were modeled in detail and a software link was created between the treatment machine control system and the Monte Carlo program to transfer information about the treatment head settings. To describe the patient anatomy, Hounsfield Units were converted into materials with explicit element composition and density. A link of the Monte Carlo program to the departmental patient database and the commercial planning system was established to import treatment information. This presentation gives a roadmap to clinical implementation of Monte Carlo dose calculation covering all relevant aspects. C1 [Jarlskog, Christina Zacharatou; Jiang, Hongyu; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jarlskog, CZ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM czacharatoujarlskog@partners.org; hjiang@partners.org; hpaganetti@partners.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-0561-9 J9 IEEE NUCL SCI CONF R PY 2006 BP 3891 EP 3893 PG 3 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BUC53 UT WOS:000288875603209 ER PT S AU Chen, Y Liu, B O'Connor, M Didier, CS Glick, SJ AF Chen, Yu Liu, Bob O'Connor, Michael Didier, Clay S. Glick, Stephen J. GP IEEE TI Comparison of Scatter/Primary Measurements with GATE Simulations for X-Ray Spectra in Cone Beam CT Mammography SO 2006 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOL 1-6 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT 15th International Workshop on Room-Temperature Semiconductor X- and Gamma-Ray Detectors/ 2006 IEEE Nuclear Science Symposium CY OCT 29-NOV 04, 2006 CL San Diego, CA SP IEEE ID COMPUTED-TOMOGRAPHY; BREAST CT; RADIATION; SCATTER; TOOLKIT AB It is commonly understood that scattered radiation in CT degrades the reconstructed image. Scatter correction relies on precise measurements or Monte Carlo simulation results in experimental conditions. Previous studies on both experimental measurements and Monte Carlo simulations have been reported in diagnostic radiology and conventional mammography. Rapidly developed cone beam CT mammography significantly differs from conventional mammography in breast shape, geometry, etc. aspects, which are amongst the most important factors that impact the scatter fraction. The Geant4 based Monte Carlo simulation package GATE has been successful in the application of PET and SPECT with its implemented precise modeling of various physics processes. However, there exist little reports in the literature about the GATE application in X-ray CT. We present some preliminary results on the experimental measurements of the scatter to primary ratios in cone beam CT mammography setting using the beam stop and aperture methods. The measurements were used to compare and validate the performance of the GATE simulations by choosing the low energy or standard physics models for electromagnetic processes including Compton and Rayleigh scatterings. Aided by precise GATE simulations, we discovered a significant scatter component from sources other than the studied object in scatter measurement using conventional methods. We developed a new strategy of measurement to subtract this background scatter. C1 [Chen, Yu; Glick, Stephen J.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Connor, Michael; Didier, Clay S.] Univ Massachusetts, Biomed Engn Program, Lowell, MA 01854 USA. RP Chen, Y (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. EM Yu.Chen@umassmed.edu FU National Cancer Institute (NCI); CA-78573 FX This work was supported in part by the National Cancer Institute (NCI) under Grant No. CA-78573. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI. NR 18 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-0561-9 J9 IEEE NUCL SCI CONF R PY 2006 BP 3909 EP 3914 DI 10.1109/NSSMIC.2006.353843 PG 6 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BUC53 UT WOS:000288875603213 ER PT J AU Boudreaux, ED Hunter, GC Bos, K Clark, S Camargo, CA AF Boudreaux, ED Hunter, GC Bos, K Clark, S Camargo, CA TI Predicting smoking stage of change among emergency department patients and visitors SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE smoking; stage of change; readiness to quit; emergency medicine; public health; prevention ID PREVENTIVE SERVICES; TRANSTHEORETICAL MODEL; SOCIOECONOMIC-STATUS; NICOTINE DEPENDENCE; DECISIONAL BALANCE; HEALTH-PROMOTION; CONTROLLED-TRIAL; REGULAR SOURCE; SELF-EFFICACY; PRIMARY-CARE AB Objectives: Little is known about whether emergency department (ED) patients or those who accompany them (visitors) are interested in smoking cessation. The authors hypothesized that several variables would be associated with stage of change, including nicotine dependence, self-efficacy, presence of a smoking-related illness, and anticipated cessation-related health improvement. Methods: For two 24-hour periods, consecutive patients and visitors aged 18 years and older presenting to four Boston EDs were interviewed. The authors assessed a range of smoking-related constructs. Exclusion criteria included severe illness, cognitive insufficiency, and acute distress. Results: One thousand ten subjects were screened (56% patients, 44% visitors). Two hundred thirty-seven (23%) subjects were current smokers, with 57% being in precontemplation, 31% in contemplation, and 12% in preparation stages. When ordinal regression was used, the variables most strongly associated with stage of change were as follows: self-efficacy (odds ratio [OR] = 5.1; p < 0.001), anticipated cessation-related health improvement (OR = 2.7, p = 0.02), and having a smoking-related health problem (OR = 1.9; P = 0.08). Conclusions: Because many disenfranchised Americans use the ED as a regular source of health care, increased attention to smoking in the ED setting holds tremendous public health potential. This study's results reinforce the validity of the stage-of-change model within the ED setting. Developers of ED-initiated interventions will have to consider the heterogeneity in stage of change when designing their treatments. C1 Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Boudreaux, ED (reprint author), Cooper Hosp Univ Med Ctr, 1 Cooper Plaza, Camden, NJ 08103 USA. EM boudreaux-edwin@cooperhealth.edu OI Boudreaux, Edwin/0000-0002-3223-6371 FU NHLBI NIH HHS [R01 HL-63841]; NIDA NIH HHS [K23 DA-016698-01]; NIEHS NIH HHS [T32 ES07069] NR 47 TC 17 Z9 17 U1 0 U2 3 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 JAN PY 2006 VL 13 IS 1 BP 39 EP 47 DI 10.1197/j.aem.2005.07.030 PG 9 WC Emergency Medicine SC Emergency Medicine GA 000PO UT WOS:000234474500007 PM 16365327 ER PT J AU Shetty, SK Resnik, CS AF Shetty, SK Resnik, CS TI Fellowship directors' perceptions of the 2005 NRMP Radiology Fellowship Match SO ACADEMIC RADIOLOGY LA English DT Article DE radiology education; fellowship training; fellowship match AB Rationale and Objectives. The aim of the study is to gauge radiology fellowship directors' experiences with the fellowship application process and perceptions of the National Resident Matching Program Radiology Fellowship Match, as well as compare these perceptions with those of senior residents. Methods and Materials. An electronic survey was sent to 291 members of the Association of Program Directors in Radiology. Responses were compared directly with an earlier survey of senior residents who participated in the same cycle of the Fellowship Match. Results. Sixty-seven respondents participated in the survey. Based on our estimates of the total number of US-based radiology subspecialty fellowship programs, this represents between 15.3% (67/438) and 24.2% (67/277) of all fellowship directors. Approximately three quarters (52/76 directors; 77.6%) participated in the Fellowship Match. Respondents believe that the match process makes the process fairer for all applicants (31/43 respondents; 70.5%) and primarily benefits residents (30/76 respondents; 60.0%), a significant difference compared with senior residents (P <.01). The majority of fellowship directors favor the current calendar and the ability to select internal candidates Outside the Match. The majority of respondents believe that programs generally are not abiding by the rules of the Match (22/43 respondents; 51.2%), and at least 15 instances of rule violations were reported. A majority of fellowship directors favor continuing the Match in some form (26/42 respondents; 61.9%). Conclusion. Although there are significant differences in perception of the Match process between fellowship directors and senior residents, the majority of fellowship directors favor continuing the Match in some form. Several potential solutions, including explicit declaration of the number of available positions and strict enforcement of Match rules, may help improve the process in the future. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Shetty, SK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 14 Fruit St,Yawkey 6th Floor, Boston, MA 02114 USA. EM sshetty@partners.org NR 7 TC 11 Z9 11 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2006 VL 13 IS 1 BP 121 EP 130 DI 10.1016/j.acra.2005.09.085 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 003CK UT WOS:000234659000014 PM 16399040 ER PT J AU Ball, AR Casadei, G Samosorn, S Bremner, JB Ausubel, FM Moy, TI Lewis, K AF Ball, Anthony R. Casadei, Gabriele Samosorn, Siritron Bremner, John B. Ausubel, Frederick M. Moy, Terence I. Lewis, Kim TI Conjugating berberine to a multidrug resistance pump inhibitor creates an effective antimicrobial SO ACS CHEMICAL BIOLOGY LA English DT Article ID MEDIATED DRUG-RESISTANCE; P-GLYCOPROTEIN GENE; STAPHYLOCOCCUS-AUREUS; EFFLUX PUMP; TRANSPORTERS; MULTIPLE; AGENTS; MODEL; NORA; IDENTIFICATION AB In bacteria, multidrug-resistance pumps (MDRs) confer resistance to chemically unrelated amphipathic toxins. A major challenge in developing efficacious antibiotics is identifying antimicrobial compounds that are not rapidly pumped out of bacterial cells. The plant antimicrobial berberine, the active component of the medicinal plants echinacea and golden seal, is a cation that is readily extruded by bacterial MDRs, thereby rendering it relatively ineffective as a therapeutic agent. However, inhibition of MDR efflux causes a substantial increase in berberine antimicrobial activity, suggesting that berberine and potentially many other compounds could be more efficacious if an effective MDR pump inhibitor could be identified. Here we show that covalently linking berberine to INF55, an inhibitor of Major Facilitator MDRs, results in a highly effective antimicrobial that readily accumulates in bacteria. The hybrid molecule showed good efficacy in a Caenorhabditis elegans model of enterococcal infection, curing worms of the pathogen. C1 Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Northeastern Univ, Antimicrobiol Discovery Ctr, Boston, MA 02115 USA. Univ Wollongong, Inst Biomol Sci, Wollongong, NSW 2522, Australia. Univ Wollongong, Dept Chem, Wollongong, NSW 2522, Australia. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Lewis, K (reprint author), Northeastern Univ, Dept Biol, Boston, MA 02115 USA. EM jbremner@uow.edu.au; k.lewis@neu.edu RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 FU NIAID NIH HHS [AI059483-01] NR 38 TC 56 Z9 61 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PY 2006 VL 1 IS 9 BP 594 EP 600 DI 10.1021/cb600238x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 131UD UT WOS:000243894700012 PM 17168555 ER PT S AU Ozcan, A Tewary, A Digonnet, MJF Kino, GS AF Ozcan, Aydogan Tewary, Anuranjita Digonnet, Michel J. F. Kino, Gordon S. BE Dutta, AK Ohishi, Y Dutta, NK Moerk, J TI Transmission properties of tapered air-core photonic bandgap fibers - art. no. 63890W SO Active and Passive Optical Components for Communications VI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Active and Passive Optical Components for Communication VI CY OCT 03-04, 2006 CL Boston, MA SP SPIE DE photonic bandgap fibers; microstructured fibers; air-core photonic band.-ap fibers; fiber tapers; fiber bi-tapers ID SINGLE-MODE FIBERS; OPTICAL-FIBER; CONVERSION; DEVICES AB Fiber tapers have found a wide range of important applications in communication and sensing, including narrow-band filters, mode-matching between waveguides, evanescent mode-coupling and fused couplers. Applying these taper-based technologies to air-core photonic bandgap fibers (PBFs) is very appealing because it would enable creating these same components directly in air-core fibers. Although there have been several studies of tapers in solid-core microstructured fibers, the transmission properties of tapered air-core photonic-bandgap fibers have not yet been studied. In this work, we report on the fabrication and testing of tapered air-core photonic-bandgap fibers. Our motivation in this work was to study the basic transmission properties of PBF bitapers in the bandgap region, and in particular, to see how the overall transmission was impacted by the taper, e.g., whether the taper induced resonant coupling to one or more cladding modes. Our experimental results indicate that air-core PBFs are highly sensitive to tapering, and unlike conventional single-mode telecommunication fibers, even a small tapering ratio results in significant modal interference in the transmission spectrum. Furthermore, we found out that the mechanical silica support surrounding the holey region of the PBF contributes as a lossy Fabry-Perot resonator to the observed transmission properties. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ozcan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6487-2 J9 P SOC PHOTO-OPT INS PY 2006 VL 6389 BP W3890 EP W3890 AR 63890W DI 10.1117/12.685420 PG 8 WC Optics; Telecommunications SC Optics; Telecommunications GA BFI52 UT WOS:000242037000026 ER PT S AU Ozcan, A AF Ozcan, Aydogan BE Dutta, AK Ohishi, Y Dutta, NK Moerk, J TI Second-order nonlinear thin film characterization using logarithmic Hilbert transform - art. no. 63890Y SO Active and Passive Optical Components for Communications VI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Active and Passive Optical Components for Communication VI CY OCT 03-04, 2006 CL Boston, MA SP SPIE DE second-order optical nonlinearity; poled glass; poled nonlinear materials; Maker fringe technique; minimum-phase functions; Fienup algorithm; error reduction algorithms; Hilbert transform; logarithmic Hilbert transform ID POLED FUSED-SILICA; GLASS AB A new technique based on logarithmic Hilbert transform processing of Maker-fringe (MF) curves to characterize second-order optical nonlinear depth profile of thin films is described. Such characterization methods are important for several fields, for example to characterize the nonlinear coefficient profile of poled glass samples, which hold an important potential for fiber based nonlinear devices in telecommunication links. In the classical MF measurement system, a laser beam is focused onto the nonlinear film and the generated second-harmonic power is recorded vs. the laser incidence angle. The resulting MF curve is proportional to the square of the magnitude of the Fourier transform of the spatial profile d(z) of the nonlinear coefficient, where z is perpendicular to the film surface. Our new analytical method requires only the measurement of the MF curve of the nonlinear sample alone. It is based on the computation of the logarithmic Hilbert transform of the measured MF curve of the sample. Being analytical, this approach provides speed advantage over its iterative alternative. This new technique is verified experimentally with two germanosilicate-Infrasil structures, thermally poled at similar to 5 kV and 280 degrees C in air. This choice of material was primarily made because germanosilicate films form excellent waveguides with a refractive index close to that of silica, which makes them compatible with fiber-optic technology. This is the first time that a Hilbert transform based analytical tool has been applied to uniquely characterize nonlinear thin films. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ozcan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6487-2 J9 P SOC PHOTO-OPT INS PY 2006 VL 6389 BP Y3890 EP Y3890 AR 63890Y DI 10.1117/12.685158 PG 7 WC Optics; Telecommunications SC Optics; Telecommunications GA BFI52 UT WOS:000242037000028 ER PT J AU Kilbourne, AM McGinnis, GF Belnap, BH Klinkman, M Thomas, M AF Kilbourne, AM McGinnis, GF Belnap, BH Klinkman, M Thomas, M TI The role of clinical information technology in depression care management SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article DE chronic diseases; depression; information systems; major depressive disorder; quality improvement ID RANDOMIZED CONTROLLED-TRIAL; ELECTRONIC MEDICAL-RECORD; QUALITY IMPROVEMENT; TRANSLATING EVIDENCE; CHRONIC ILLNESS; HEALTH-CARE; STRATEGIES; TELEPHONE; COMPUTER; SYMPTOMS AB We examine the literature on the growing application of clinical information technology in managing depression care and highlight lessons learned from Robert Wood Johnson Foundation's national program "Depression in Primary Care-Incentives Demonstrations." Several program sites are implementing depression care registries. Key issues discussed about implementing registries include using a simple yet functional format, designing registries to track multiple conditions versus depression alone (i.e., patient-centric versus disease-centric registries) and avoiding violations of patient privacy with the advent of more advanced information technologies (e.g., web-based formats). Finally, we discuss some implications of clinical information technology for healthcare practices and policy makers. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. Colorado Access, Denver, CO USA. Univ Colorado Hlth Sci Syst, Denver, CO USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Ctr Hlth Equ Res & Promot 151C, Univ Dr C, Pittsburgh, PA 15240 USA. EM Amy.Kilbourne@med.va.gov NR 36 TC 7 Z9 7 U1 2 U2 2 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JAN PY 2006 VL 33 IS 1 BP 54 EP 64 DI 10.1007/s10488-005-4236-0 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 043NB UT WOS:000237606800009 PM 16215661 ER PT J AU Williams, ME AF Williams, ME TI Internet organ solicitation, explained SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE organ donation; transplant; internet; solicitation ID DONATION; REGISTRY; DONORS AB The growth of internet-based communications and the increasing demand for living organ donors are resulting in more use of Web sites for organ solicitation. Web resources have the capacity to improve public awareness about both organ donations and transplant outcomes. Rules for organ donation and fair allocation must follow legal principles regarding organ solicitation. Categories of internet recipient/donor matching services include "clearing house," "membership," and "individual" sites. All these raise ethical concerns related to the individual recipient/donor relationship and to the current system of organ allocation. However, a lack of rules and regulations regarding internet solicitation exists. Several pragmatic steps are proposed. (c) 2006 by the National Kidney Foundation, Inc. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Williams, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 17 TC 2 Z9 2 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JAN PY 2006 VL 13 IS 1 BP 70 EP 75 DI 10.1053/j.ackd.2005.10.003 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 011JT UT WOS:000235265100011 PM 16412973 ER PT S AU Wu, CJ Ritz, J AF Wu, CJ Ritz, J BE Allison, JP Franoff, G TI Induction of tumor immunity following allogeneic stem cell transplantation SO ADVANCES IN IMMUNOLOGY, VOL 90: CANCER IMMUNOTHERAPY SE Advances in Immunology LA English DT Review; Book Chapter ID BONE-MARROW-TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGEN; VERSUS-HOST-DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LYMPHOCYTE INFUSION; CHRONIC MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; SINGLE-NUCLEOTIDE POLYMORPHISMS; ACUTE LYMPHOBLASTIC-LEUKEMIA; KIR LIGAND INCOMPATIBILITY AB The curative potential of allogeneic hematopoietic stein cell transplantation (allo-HSCT) for many hematologic malignancies derives in large pall from reconstitution, Of normal donor immunity and the development of a potent graft-versus-leukemia (GVL) immune response capable of rejecting tumor cell in vivo. Elucidation of the mechanisms of GVL by studies Of animal models and analysis of clinical data has yielded important insights into how clinically effective tumor immunity is generated following allo-HSCT These studies have identified NK cells and B cells as well as T cells as important mediators of the GVL response. A variety of antigenic targets of the GVL response have also been identified, and include tumor-associated antigens (is well (is minor histocompatibility antigens. The principles of effective GVL, can now be applied to the development Of novel therapies that enhance the therapeutic benefit of allogeneic HSCT while minimizing the toxicities associated with treatment. Moreover, many components of this approach that result in elimination of tumor cells following allogeneic HSCT can potentially be adapted to enhance the effectiveness of tumor immunity in the autologous setting. C1 Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Dept Med Oncol, Boston, MA 02115 USA. NR 182 TC 48 Z9 48 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022489-5 J9 ADV IMMUNOL JI Adv.Immunol. PY 2006 VL 90 BP 133 EP 173 DI 10.1016/S0065-2776(06)90004-2 PG 41 WC Immunology SC Immunology GA BEC59 UT WOS:000236802500004 PM 16730263 ER PT S AU Hodi, FS Dranoff, G AF Hodi, FS Dranoff, G BE Allison, JP Franoff, G TI Combinatorial cancer immunotherapy SO ADVANCES IN IMMUNOLOGY, VOL 90: CANCER IMMUNOTHERAPY SE Advances in Immunology LA English DT Review; Book Chapter ID COLONY-STIMULATING FACTOR; T-CELL RESPONSES; VACUOLAR H+-ATPASE; TUMOR-INFILTRATING LYMPHOCYTES; APOPTOSIS PROTEIN FAMILY; OPEN READING FRAME; MHC CLASS-I; POLYMORPHIC EPITHELIAL MUCIN; AUGMENTS ANTITUMOR IMMUNITY; MATURE DENDRITIC CELLS AB The formulation, of therapeutic strategies to enhance immune-mediated tumor destruction is a central goal of cancer immunology. Substantive progress toward delineating the mechanisms involved innate and adaptive tumor immunity has improved the prospects for crafting efficacious treatments. Schemes under active clinical evaluation include, cancer vaccines, monoclonal antibodies, recombinant cytokines, and adoptive cellular infusions. While these manipulations increase tumor immunity in many patients, the majority still. succumbs to progressive disease. Detailed analysis of subjects oil experimental protocols together with informative studies of murine tumor models have begun to clarify the parameters that determine therapeutic activity and resistance. These investigations have highlighted efficient dendritic cell activation and inhibition Of negative immune regulation, as central pathways for intervention. This review discusses the development of genetically modified whole tumor cell vaccines and antibody-blockade of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as immunotherapies targeting these key control points. Early-stage clinical testing raises the possibility that combinatorial approaches that augment dendritic cell-mediated tumor antigen presentation and antagonize negative immune regulation may accomplish significant tumor destruction without the induction of serious autoimmune disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 156 TC 25 Z9 26 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022489-5 J9 ADV IMMUNOL JI Adv.Immunol. PY 2006 VL 90 BP 341 EP 368 DI 10.1016/S0065-2776(06)90009-1 PG 28 WC Immunology SC Immunology GA BEC59 UT WOS:000236802500009 PM 16730268 ER PT J AU Mimiaga, MJ Safren, SA Benet, DJ Manseau, MW DeSousa, N Mayer, KH AF Mimiaga, MJ Safren, SA Benet, DJ Manseau, MW DeSousa, N Mayer, KH TI MSM in HIV-prevention trials are sexual partners with each other: An ancillary study to the EXPLORE intervention SO AIDS AND BEHAVIOR LA English DT Article DE HIV-prevention trials; MSM; sexual behavior ID BASE-LINE DATA; RISK BEHAVIORS; MEN; GAY AB The EXPLORE study evaluated a behavioral intervention to prevent HIV seroconversion among men who have sex with men (MSM). The present ancillary study enrolled 345 EXPLORE participants at one study site (Boston) and assessed high-risk sexual behavior with other EXPLORE participants. It also assessed sexual intentions across other EXPLORE participants, HIV-negative individuals, and unknown HIV serostatus partners. Thirty-one percent reported having sex with another EXPLORE participant: 27% unprotected receptive oral sex with ejaculation (UO), 30% unprotected insertive anal sex (UIA), and 34% reported unprotected receptive anal sex (URA). Significant relationships between intentions to engage in UO, UIA, and URA, and type of partner emerged with intentions to engage in UO, UIA, and URA higher in HIV-negative partners, other EXPLORE participants, and unknown-HIV serostatus partners. Future HIV-prevention studies recruiting MSM at increased sexual risk of HIV infection should address participants potentially becoming sexual partners with each other. C1 Fenway Community Hlth, Dept Res & Evaluat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. ABT Associates Inc, Boston, MA USA. Columbia Univ, Coll Phys & Surg, New York, NY 10025 USA. Brown Univ, Miriam Hosp, Providence, RI USA. RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Dept Res & Evaluat, 7 Haviland St, Boston, MA 02115 USA. EM mmimiaga@fenwayhealth.org OI Manseau, Marc/0000-0002-3433-3562 FU NIAID NIH HHS [N01 AI45200, N01 AI35176, 5 U01 AI46749, U01 AI48040] NR 13 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD JAN PY 2006 VL 10 IS 1 BP 27 EP 34 DI 10.1007/s10461-005-9025-y PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 027OY UT WOS:000236426100004 PM 16331532 ER PT J AU O'Cleirigh, C Safren, SA AF O'Cleirigh, C Safren, SA TI Domains of life satisfaction among patients living with HIV: A factor analytic study of the quality of life inventory SO AIDS AND BEHAVIOR LA English DT Article DE HIV; quality of life; life satisfaction; health related quality of life; factor analysis ID ACTIVE ANTIRETROVIRAL THERAPY; COGNITIVE-BEHAVIORAL THERAPY; INCREASE ADHERENCE; MEDICATIONS; INSTRUMENTS; DEPRESSION; SYMPTOMS AB This study sought to identify multidimensional factors of life satisfaction in individuals with HIV through a factor analysis of the Quality of Life Inventory (QOLI), and to examine the relationship of these factors to health-related quality of life, depression, and medication adherence. Four quality of life domains emerged: Achievement, Self-Expression, Environment, and Interpersonal Relationships. QOLI means were substantially lower than the normative means and were significantly related to the SF-12 mental (but not the physical) component summary. Multidimensional assessments of quality of life in HIV may help specify targets sensitive to psychosocial interventions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat Psychol, Boston, MA USA. Fenway Community Hlth, Res & Evaluat Dept, Boston, MA USA. Univ Miami, Dept Psychol, Miami, FL 33152 USA. RP Safren, SA (reprint author), MGH Psychiat, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM ssafren@partners.org FU NIMH NIH HHS [MH R21 66660] NR 14 TC 11 Z9 11 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD JAN PY 2006 VL 10 IS 1 BP 53 EP 58 DI 10.1007/s10461-005-9027-9 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 027OY UT WOS:000236426100007 PM 16400507 ER PT J AU Gulliver, SB Kamholz, BW Helstrom, AW AF Gulliver, Suzy Bird Kamholz, Barbara W. Helstrom, Amy W. TI Smoking cessation and alcohol abstinence: What do the data tell us? SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE alcohol and tobacco; alcohol, tobacco, and other drug (ATOD) use, abuse, and dependence; alcohol and other drug (AOD) craving; AOD use pattern; AOD abstinence; alcohol and tobacco; alcohol abuse; alcoholism; smoking; cigarette smoking; nicotine; treatment program; co-treatment; treatment outcome; AOD abstinence; cue reactivity; alcohol and other drug use disorders (AODD) relapse ID NICOTINE DEPENDENCE; SUBSTANCE USE; SMOKERS; TOBACCO; TRIAL; INTERVENTIONS; DRINKING; RECOVERY; URGES; INDIVIDUALS AB Cigarette smoking and nicotine dependence commonly co-occur with alcohol dependence. However, treatment for tobacco dependence is not routinely included in alcohol treatment programs, largely because of concerns that addressing both addictions concurrently would be too difficult for patients and would adversely affect recovery from alcoholism. To the contrary, research shows that smoking cessation does not disrupt alcohol abstinence and may actually enhance the likelihood of longer-term sobriety. Smokers in alcohol treatment or recovery face particular challenges regarding smoking cessation. Researchers and clinicians should take these circumstances into account when determining how best to treat these patients' tobacco dependence. C1 VA Boston Healthcare Syst, Brockton, MA USA. Boston Univ, Dept Psychiat & Psychol, Boston, MA 02215 USA. VA Boston Healthcare Syst Mood Disorders Clin, Jamaica Plain, MA USA. RP Gulliver, SB (reprint author), VA Boston Healthcare Syst, Brockton Campus, Brockton, MA USA. FU NIAAA NIH HHS [1R01-AA013727, 2R01-AA1164201A]; NIDA NIH HHS [DA016138] NR 43 TC 32 Z9 32 U1 0 U2 8 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2006 VL 29 IS 3 BP 208 EP 212 PG 5 WC Substance Abuse SC Substance Abuse GA 146NE UT WOS:000244940400009 PM 17373411 ER PT J AU Myers, MG Kelly, JF AF Myers, Mark G. Kelly, John F. TI Cigarette smoking among adolescents with alcohol and other drug use problems SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE alcohol and tobacco; alcohol; tobacco; and other drug (ATOD), use, abuse, and dependence; smoking; gateway drug; nicotine dependence; adolescent; youth; high-risk; youth; alcohol and other drug use (AODU) treatment method; smoking cessation treatment; co-treatment.intervention; brief intervention; motivational interviewing; peer relations; treatment outcome ID SUBSTANCE-ABUSING ADOLESCENTS; PSYCHIATRIC-DISORDERS; CESSATION; INTERVENTION; OUTCOMES; RECOMMENDATIONS; SMOKERS AB Cigarette and alcohol use often develop concurrently, and smoking is especially common among youth treated for alcohol and other drug (AOD) use disorders. Special considerations for adolescent smoking cessation treatment include peer influences, motivation, and nicotine dependence. Little research has addressed smoking cessation treatment for youth with AOD use disorders, but the few available studies suggest that tobacco cessation efforts are feasible and potentially effective for this population. Findings to date suggest that adolescents with AOD use disorders may benefit more from relatively intensive multicomponent programs rather than brief treatment for smoking cessation. Additional research is needed to further address the inclusion of tobacco-specific interventions for adolescents in AOD use disorder treatment programs. C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. Massachusetts Gen Hosp, Addict Res Program, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Myers, MG (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA. OI Myers, Mark/0000-0003-4044-2914 FU NIAAA NIH HHS [AA-11333, R01 AA015526, R01 AA015526-01A1]; NIDA NIH HHS [DA-017652, K02 DA017652, K02 DA017652-02] NR 23 TC 28 Z9 30 U1 4 U2 6 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2006 VL 29 IS 3 BP 221 EP 227 PG 7 WC Substance Abuse SC Substance Abuse GA 146NE UT WOS:000244940400011 PM 17373413 ER PT J AU Franco, RA AF Franco, RA TI Laryngopharyngeal reflux SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID LARYNGEAL EPITHELIAL DEFENSES; GASTROESOPHAGEAL-REFLUX; SUBGLOTTIC STENOSIS; CELL BIOLOGY; PROTON PUMP; DISEASE; ATPASE; ACID; MANIFESTATIONS; RELIABILITY AB Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents (acid and enzymes such as pepsin) into the laryngopharynx leading to symptoms referable to the larynx/hypopharynx. Typical LPR symptoms include dysphonia, globus pharyngeus, mild dysphagia, chronic cough, and nonproductive throat clearing. Most patients are relatively unaware of LPR with only 35% reporting heartburn. LPR has been associated with such disease entities as vocal fold granulomas and laryngospasm and is believed to play a role in the formation of subglottic stenosis. Although not yet substantiated, chronic laryngeal irritation may lead to the formation of laryngeal carcinoma in those patients without a history of alcohol consumption or tobacco smoking. Many issues with respect to the diagnosis and treatment of LPR are considered controversial, including the clinical diagnostic criteria and the studies necessary to establish a diagnosis. LPR, like other forms of extraesophageal manifestations of reflux, is treated with a combination of diet changes, behavior modifications, and a regimen of high-dose, twice-a-day proton pump inhibitors. Allergists, as physicians who treat patients with chronic cough, globus sensation, and atypical asthma not responsive to medications, need to be familiar with the diagnosis and proper treatment of LPR to deliver optimal care to these patients. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Div Laryngol, Boston, MA 02114 USA. RP Franco, RA (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Div Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Ramon_Franco@meei.harvard.edu NR 28 TC 10 Z9 12 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JAN-FEB PY 2006 VL 27 IS 1 BP 21 EP 25 PG 5 WC Allergy SC Allergy GA 021GB UT WOS:000235970600006 PM 16598989 ER PT S AU Hyman, BT AF Hyman, Bradley T. BE Jucker, M Beyreuther, K Haass, C Nitsch, RM Christen, Y TI Anatomical changes underlying dementia in Alzheimer's disease SO Alzheimer: 100 Years and Beyond SE RESEARCH AND PERSPECTIVES IN ALZHEIMERS DISEASE LA English DT Proceedings Paper CT Conference on Alzheimer - 100 Years and Beyond CY NOV 02-05, 2006 CL Univ Tubingen, Inst Psychiat, Tubingen, GERMANY HO Univ Tubingen, Inst Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat, 114 16th St, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 3-540-37651-8 J9 RES PER ALZ PY 2006 BP 89 EP 94 DI 10.1007/978-3-540-37652-1_7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA BFO03 UT WOS:000243382000007 ER PT S AU Tanzi, RE AF Tanzi, Rudolph E. BE Jucker, M Beyreuther, K Haass, C Nitsch, RM Christen, Y TI From the amyloid beta protein (A4) to isolation of the first Alzheimer's disease gene: amyloid beta (A4) precursor protein (APP) SO Alzheimer: 100 Years and Beyond SE RESEARCH AND PERSPECTIVES IN ALZHEIMERS DISEASE LA English DT Proceedings Paper CT Conference on Alzheimer - 100 Years and Beyond CY NOV 02-05, 2006 CL Univ Tubingen, Inst Psychiat, Tubingen, GERMANY HO Univ Tubingen, Inst Psychiat C1 Harvard Univ, Genet & Aging Res Unit, MassGen Inst Neurol, Massachusetts Gen Hosp,Med Sch, Cambridge, MA 02138 USA. RP Tanzi, RE (reprint author), Harvard Univ, Genet & Aging Res Unit, MassGen Inst Neurol, Massachusetts Gen Hosp,Med Sch, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 3-540-37651-8 J9 RES PER ALZ PY 2006 BP 163 EP 169 DI 10.1007/978-3-540-37652-1_17 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA BFO03 UT WOS:000243382000017 ER PT J AU Jarvik, LF Matsityatna, SS AF Jarvik, LF Matsityatna, SS TI Two decades of research in Alzheimer disease: Looking back to the first volume of ADAD SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Editorial Material DE Alzheimer disease; research progress; retrospective ID CHILDREN AB During the first two decades of the life of this Journal (ADAD) much progress has been made in our understanding of Alzheimer disease (AD). Advancing knowledge, however, has been accompanied by increasing appreciation of the complexity and heterogeneity of this disease. Prevention and cure continue to elude us as the number of afflicted and the cost of their care continues to increase. New techniques together with long-term prospective follow-up studies, as well as utilization of data accumulated in existing data bases, are needed to mode the field forward. We expect that during the next two decades, as new information accrues, reports published in ADAD will continue to contribute to the dissemination and elucidation of critical issues in Alzheimer research. C1 Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Jarvik, LF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza, Los Angeles, CA 90095 USA. EM ljarvik@ucla.edu NR 13 TC 2 Z9 2 U1 1 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 JAN-MAR PY 2006 VL 20 IS 1 BP 3 EP 5 DI 10.1097/01.wad.0000202412.54976.1e PG 3 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 020OX UT WOS:000235920300002 PM 16493229 ER PT J AU Skoch, J Hyman, BT Bacskai, BJ AF Skoch, Jesse Hyman, Bradley T. Bacskai, Brian J. BE Perry, G Avila, J Kinoshita, J Smith, MA TI Preclinical characterization of amyloid imaging probes with multiphoton microscopy SO ALZHEIMER'S DISEASE: A CENTURY OF SCIENTIFIC AND CLINICAL RESEARCH LA English DT Article; Book Chapter ID NEAR-INFRARED SPECTROSCOPY; IN-VIVO; ALZHEIMERS-DISEASE; TRANSGENIC MICE; BRAIN; PLAQUES; OXYGENATION; TOMOGRAPHY; ACTIVATION; CLEARANCE AB Multiphoton microscopy is an optical imaging technique that allows high resolution detection of fluorescence in thick, scattering tissues. The technique has been used for trans-cranial imaging of the brains of living transgenic mouse models of Alzheimer's disease. Direct detection of senile plaques in these mice has allowed the characterization of the natural history of individual senile plaques, the evaluation of plaque clearance during immunotherapy, and the characterization of the kinetics and biodistribution of the PET ligand, PIB. With the expanding repertoire of structural and functional fluorescent probes, and the preclinical characterization of new contrast agents for complementary imaging modalities like MRI, PET, SPECT, and NIRS, multiphoton microscopy will continue to be a powerful tool in understanding and combating Alzheimer's disease. C1 [Skoch, Jesse; Hyman, Bradley T.; Bacskai, Brian J.] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, MassGen Inst Neurodegenerat Dis, 114 16th St,2850, Charlestown, MA 02129 USA. EM bbacskai@partners.org NR 37 TC 2 Z9 2 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS BN 978-1-58603-619-5 PY 2006 BP 401 EP 407 PG 7 WC Biochemistry & Molecular Biology; Clinical Neurology; Neurosciences; Pathology SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pathology GA BMB04 UT WOS:000271716100045 ER PT J AU Gnanasekaran, SK Finkelstein, JA Lozano, P Farber, HJ Chi, FW Lieu, TA AF Gnanasekaran, SK Finkelstein, JA Lozano, P Farber, HJ Chi, FW Lieu, TA TI Influenza vaccination among children with asthma in Medicaid managed care SO AMBULATORY PEDIATRICS LA English DT Article DE asthma; influenza vaccination; managed care; Medicaid ID CHILDHOOD ASTHMA; HEALTH-SERVICES; CONTROLLER MEDICATIONS; RISK-FACTORS; UNDERIMMUNIZATION; ORGANIZATIONS; AMERICANS; POVERTY; QUALITY; STATES AB Objective.-To describe influenza vaccination rates and identify risk factors for missing vaccination among children with asthma in managed Medicaid. Methods.-As part of a longitudinal study of asthma care quality, parents of children aged 2-16 years with asthma enrolled in Medicaid managed care organizations in Massachusetts, Washington, and California were surveyed by telephone at baseline and 1 year. We evaluated influenza vaccination rates during the follow-up year. Results.-The study population included 1058 children with asthma. The influenza vaccination rate was 16% among all children with asthma and 21% among those with persistent asthma. Children with persistent asthma (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.36-0.79) and those who had been hospitalized during the follow-up year (OR 0.29, 95% CI 0.11-0.76) were less likely to miss vaccination. Children older than 9 years (OR 1.66, 95% CI 1.13-2.46) and children of parents with less than a high school education (OR 2.29, 95% Cl 1.05-5.03), compared with a college degree, were at risk for missing vaccination. Among children with persistent asthma, older children (OR 1.65, 95% CI 1.01-2.69) and children of parents with less than a high school education (OR 4.13, 95% Cl 1.43-11.90) were more likely to miss influenza vaccination. Conclusions.-Our findings suggest that interventions directed toward older children and families with lower educational levels may help improve influenza vaccination rates among this high-risk group. The low overall vaccination rate highlights the need for improvement in this important component of asthma care quality for all children with asthma. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Pediat Hlth Serv, Res Fellowship Program, Boston, MA 02115 USA. Harvard Univ, Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Ctr Child Hlth Care Studies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. Univ Washington, Ctr Hlth Studies, Grp Hlth Cooperat, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Inst Child Hlth, Dept Pediat, Seattle, WA 98195 USA. Kaiser Permanente, Dept Pediat, Vallejo, CA USA. Kaiser Permanente, Div Res, Oakland, CA USA. RP Gnanasekaran, SK (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM sgnanasekaran@partners.org FU AHRQ HHS [U01 HS09935]; NICHD NIH HHS [K24 HD047667]; PHS HHS [T32 HP 10018] NR 39 TC 19 Z9 20 U1 2 U2 3 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JAN-FEB PY 2006 VL 6 IS 1 BP 1 EP 7 DI 10.1016/j.ambp.2005.08.004 PG 7 WC Pediatrics SC Pediatrics GA 009JG UT WOS:000235107300001 PM 16443176 ER PT J AU Sabatine, MS Morrow, DA McCabe, CH Antman, EM Gibson, CM Cannon, CP AF Sabatine, MS Morrow, DA McCabe, CH Antman, EM Gibson, CM Cannon, CP TI Combination of quantitative ST deviation and troponin elevation provides independent prognostic and therapeutic information in unstable angina and non-ST-elevation myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; EARLY INVASIVE TREATMENT; ADMISSION ELECTROCARDIOGRAM; SEGMENT DEPRESSION; STRATIFICATION; TIROFIBAN; STRATEGY; BENEFIT; RISK; ECG AB Background ST deviation and troponin are indicators of risk in unstable angina/non-ST-elevation myocardial infarction with related but distinct pathophysiology. We hypothesized that a combination of the two would offer complementary information regarding the benefit of an invasive strategy. Methods and Results Electrocardiogram and troponin data were gathered in 1846 patients in TACTICS-TIMI 18. Adjusting for baseline characteristics, the independent odds ratio (OR) (95% CI) for death or myocardial infarction by 6 months was 1.29 (0.78-2.13) for 0.05 to 0.09 mV ST deviation, 1.83 (1.22-2.75) for >= 0.10 mV ST deviation, 1.69 (0.96-2.97) for troponin T 0.01 to 0.10 ng/mL, and 2.32 (1.52-3.53) for troponin T>0.10 ng/mL. There was a significant interaction between the magnitude of ST deviation and treatment strategy (P-interaction=.04). After adjusting for troponin and other baseline characteristics, an early invasive strategy was associated with a 27% greater reduction in the odds of death or myocardial infarction in those with 0.05 to 0.09 mV of ST deviation (ORinteraction 0.73, 95% CI 0.27-2.02) and a 64% greater reduction in those with >= 0.10 mV (ORinteraction 0.36, 95% CI 0.16-0.84) compared with in those without ST deviation. Conclusions The magnitude of ST deviation and degree of troponin elevation are graded independent predictors of outcome in unstable angina/non-ST-elevation myocardial infarction. ST deviation complements troponin elevation in selecting patients for early invasive management. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU NHLBI NIH HHS [R01 HL072872, R01 HL072879] NR 19 TC 13 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2006 VL 151 IS 1 BP 25 EP 31 DI 10.1016/j.ahj.2005.02.030 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000TK UT WOS:000234485100004 PM 16368287 ER PT J AU Rumsfeld, JS Magid, DJ Peterson, ED Plomondon, ME Petersen, LA Grunwald, GK Every, NR Sales, AE AF Rumsfeld, JS Magid, DJ Peterson, ED Plomondon, ME Petersen, LA Grunwald, GK Every, NR Sales, AE TI Outcomes after acute coronary syndrome admission to primary versus tertiary Veterans Affairs medical centers: The Veterans Affairs Access to Cardiology study SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; ARTERY-DISEASE; FUNCTIONAL STATUS; ELDERLY-PATIENTS; UNSTABLE ANGINA; UNITED-STATES; HOSPITALS; REVASCULARIZATION; CATHETERIZATION AB Background There is a concern that patients with acute coronary syndrome (ACS) admitted to primary care hospitals (without on-site cardiac procedures) may be at risk for worse outcomes compared with patients admitted to tertiary care hospitals. In addition to mortality, one way to assess patient outcomes is via health status and rehospitalization rates. We compared the health status and rehospitalization of patients with ACS admitted to primary versus tertiary care Veterans Affairs hospitals. Methods This was a cohort study of 2132 patients with ACS admitted to 21 Veterans Affairs hospitals (12 primary care and 9 tertiary care) from 1998 to 1999. Primary outcomes were 7-month health status as measured by the Seattle Angina Questionnaire and rehospitalization. Hierarchical multivariable regression was used to evaluate the association between admission to a primary (vs tertiary) care hospital and these outcomes. Discharge medications and 7-month cardiac procedure rates were also compared. Results There were no significant differences in discharge medication rates between primary and tertiary hospital patients. Forty-two percent of the patients admitted to a primary care hospital was transferred to a tertiary care hospital during index admission. Primary hospital patients had significantly lower 7-month rates of cardiac catheterization (36% vs 51%, P<.001) and percutaneous coronary intervention (11% vs 20%, P<.001), but there were no differences in coronary artery bypass graft surgery rates. After risk adjustment, there were no significant differences in 7-month angina frequency (odds ratio [OR] 0.98, 95% CI 0.78-1.22), physical limitation (OR 0.97, 95% CI 0.77-1.23), quality of life (OR 1.12, 95% CI 0.89-1.40), or rehospitalization (OR 1.07, 95% CI 0.54-2.14) between the 2 groups. Conclusions These results suggest that an integrated health care system can achieve similar intermediate-term health status and rehospitalization outcomes for patients with ACS irrespective of the site of admission despite the lower rates of cardiac procedures for the primary care hospital patients. C1 Denver VA Med Ctr, Cardiol & Hlth Serv Res, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Duke Clin Res Inst, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Houston VA Med Ctr, Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, Cardiol & Hlth Serv Res, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@med.va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 27 TC 1 Z9 1 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2006 VL 151 IS 1 BP 32 EP 38 DI 10.1016/j.ahj.2005.03.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000TK UT WOS:000234485100005 PM 16368288 ER PT J AU Baggish, AL Siebert, U Lainchbury, JG Cameron, R Anwaruddin, S Chen, A Krauser, DG Tung, R Brown, DF Richards, AM Januzzi, JL AF Baggish, AL Siebert, U Lainchbury, JG Cameron, R Anwaruddin, S Chen, A Krauser, DG Tung, R Brown, DF Richards, AM Januzzi, JL TI A validated clinical and biochemical score for the diagnosis of acute heart failure: The ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Acute Heart Failure Score SO AMERICAN HEART JOURNAL LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; RISK SCORE; MANAGEMENT AB Background No method integrating amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with clinical assessment for the evaluation of patients with suspected acute heart failure (HF) has been described. Methods Amino-terminal pro-brain natriuretic peptide results and clinical factors from 599 patients with dyspnea were analyzed. The beta coefficients of the 8 independent predictors of HF were used to assign a weighted integeric score for predictor. The sum of these integers provided a diagnostic HF "score" for each patient. Receiver operating characteristic curve analysis determined the optimal cut point for the diagnosis of acute HF. The performance of the score was evaluated in the development cohort and subsequently in a patient population from a separate clinical trial of patients with dyspnea conducted in Christchurch, New Zealand. Results Eight factors comprised the score: elevated NT-proBNP (4 points), interstitial edema on chest x-ray (2 points), orthopnea (2 points), absence of fever (2 points), loop diuretic use, age >75 years, rales, and absence of cough (all 1 point). Median scores in patients with acute HF were higher than those without acute HF (9 vs 3 points, P<.001). At a cut point of >= 6 points, the score had a sensitivity of 96% and a specificity of 84% for the diagnosis of acute HF (P<.001). The score improved diagnostic accuracy over NT-proBNP testing alone and retained discriminative capacity in patients in whom clinical uncertainty was present. Lastly, the accuracy of the score was validated in the external data set of patients with suspected acute HF, Conclusion We report a simple and accurate scoring system combining NT-proBNP testing and clinical assessment for the diagnosis or exclusion of acute HF in patients with dyspnea. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Christchurch Hosp, Dept Med, Christchurch, New Zealand. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Yawkey 5800,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 12 TC 32 Z9 37 U1 2 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2006 VL 151 IS 1 BP 48 EP 54 DI 10.1016/j.ahj.2005.02.031 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000TK UT WOS:000234485100008 PM 16368291 ER PT J AU Sanchez, PL Santos, JL Kaski, JC Cruz, I Arribas, A Villacorta, E Cascon, M Palacios, IF Martin-Luengo, C AF Sanchez, PL Santos, JL Kaski, JC Cruz, I Arribas, A Villacorta, E Cascon, M Palacios, IF Martin-Luengo, C CA Grupo AORTICA TI Relation of circulating C-reactive protein to progression of aortic valve stenosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LIPID-LOWERING THERAPY; ENDOTHELIAL-CELLS; ASSOCIATION; PREVENTION; PREDICTORS; TRIAL AB C-reactive protein (CRP) is a marker of inflammation and predicts outcome in apparently healthy subjects and patients with coronary artery disease. Systemic inflammation is present in patients with aortic valve stenosis.(AS). The aim of this prospective study was to assess whether CRP levels predict the progression of AS severity. Blood samples for high-sensitivity CRP measurements and echocardiographic data were obtained in 43 patients (70% men; mean age 73 +/- 8 years) with asymptomatic degenerative AS at study entry. On the basis of repeat echocardiographic assessment at 6 months, patients were grouped as (1) slow progressors (a decrease in aortic valve area [AVA] <0.05 cm(2) and/or an increase in aortic peak velocity <0.15 m/s) and (2) rapid progressors (a decrease in AVA >= 0.05 cm(2) and/or an increase in aortic peak velocity >= 0.15 m/s). Plasma CRP levels were significantly higher in rapid progressors than slow progressors (median 5.1 [range 2.3 to 11.3] vs 2.1 [range 1.0 to 3.1] mg/L, p = 0.007). In multivariate analysis, CRP levels >3 mg/L were independently associated with rapid AS progression (odds ratio 9.1, 95% confidence interval 2.2 to 37.3). In conclusion, CRP levels are higher in patients with degenerative AS who show rapid valve disease progression. These findings suggest that inflammation may have a pathogenic role in degenerative AS. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Valladolid, Hosp Clin, Inst Ciencias Corazon, Valladolid, Spain. Hosp Univ Salamanca, Cardiac Unit, Salamanca, Spain. Univ London St Georges Hosp, Sch Med, Dept Cardiac & Vasc Sci, London SW17 0RE, England. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Sanchez, PL (reprint author), Univ Valladolid, Hosp Clin, Inst Ciencias Corazon, Valladolid, Spain. EM pedrolsanchez@secardiologia.es OI Sanchez, Pedro L/0000-0002-4288-345X NR 17 TC 34 Z9 36 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2006 VL 97 IS 1 BP 90 EP 93 DI 10.1016/j.amjcard.2005.07.113 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002BU UT WOS:000234587200019 PM 16377290 ER PT J AU Legner, VJ Doerner, D McCormick, WC Reilly, DF AF Legner, VJ Doerner, D McCormick, WC Reilly, DF TI Clinician agreement with perioperative cardiovascular evaluation guidelines and clinical outcomes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MAJOR NONCARDIAC SURGERY; CARDIAC RISK; PREOPERATIVE ASSESSMENT; VASCULAR-SURGERY; AMERICAN-COLLEGE; AORTIC-SURGERY; COMPLICATIONS; MEDICINE; INDEX AB The American College of Cardiology/American Heart Association (ACC/AHA) published guidelines for preoperative cardiac risk stratification in 1996. Although clinician practice may differ from the guidelines, it remains unclear whether deviation from these guidelines affects clinical outcomes. This study sought to determine if discordance between clinician practice and the ACC/AHA guidelines affects perioperative cardiac outcomes. Eight hundred twenty-three patients who underwent 864 consecutive preoperative evaluations performed from 1995 to 1997 at a tertiary care academic medical center were prospectively followed. Clinician recommendations for preoperative cardiac testing were compared with ACC/AHA guideline recommendations. Frequencies of perioperative cardiac complications were compared between concordant and discordant testing recommendations. There were 33 perioperative cardiac complications (3.8%). Overall, there was no difference in the frequency of complications when there was discordance with the ACC/AHA guidelines compared with concordance (4.1% vs 3.7%, p = 0.81). The ACC/AHA guidelines recommended cardiac testing for 236 patients (27.3%). Clinicians ordered testing in half of those cases (n = 112). There was a lower frequency of cardiac complications when clinicians did not perform testing as recommended by the ACC/AHA guidelines (3.2% vs 10.7%, p = 0.02). Conversely, clinicians ordered cardiac testing in 45 patients (7%) when not recommended by the guidelines. Patients in this group had a trend toward more cardiac complications (6.7% vs 2.4%, p = 0.09). In conclusion, the failure of clinicians to follow the ACC/AHA guidelines when perioperative testing was recommended did not result in a higher frequency of cardiac complications. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Washington, Sch Med, Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Div Gerontol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Div Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. RP Legner, VJ (reprint author), Univ Washington, Sch Med, Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM legner@u.washington.edu NR 19 TC 6 Z9 6 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2006 VL 97 IS 1 BP 118 EP 122 DI 10.1016/j.amjcard.2005.07.115 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002BU UT WOS:000234587200024 PM 16377295 ER PT J AU Blanchard, MS Eisen, SA Alpern, R Karlinsky, J Toomey, R Reda, DJ Murphy, FM Jackson, LW Kang, HK AF Blanchard, MS Eisen, SA Alpern, R Karlinsky, J Toomey, R Reda, DJ Murphy, FM Jackson, LW Kang, HK TI Chronic multisymptom illness complex in Gulf War I veterans 10 years later SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Gulf War; metabolic syndrome X; Persian Gulf syndrome; quality of life; risk factors; stress; psychological; veterans ID MYCOPLASMA-FERMENTANS INFECTION; MIDDLE-AGED MEN; HEALTH-STATUS; NEUROMUSCULAR SYMPTOMS; RISK-FACTORS; ASSOCIATION; DISORDERS; SERVICE; STRESS; PREVALENCE AB Prior research has demonstrated that shortly after the 1991 Gulf War (Gulf War I), chronic multisymptom illness (CMI) was more common among deployed veterans than among nondeployed veterans. The aims of the current study were to determine the prevalence of CMI among deployed and nondeployed veterans 10 years after Gulf War I, compare the distribution of comorbid conditions, and identify prewar factors associated with CMI. Cross-sectional data collected from 1,061 deployed veterans and 1,128 nondeployed veterans examined between 1999 and 2001 were analyzed. CMI prevalence was 28.9% among deployed veterans and 15.8% among nondeployed veterans (odds ratio = 2.16, 95% confidence interval: 1.61, 2.90). Deployed and nondeployed veterans with CMI had similarly poorer quality-of-life measures and higher prevalences of symptom-based medical conditions, metabolic syndrome, and psychiatric disorders. Diagnoses of prewar anxiety disorders (not related to post-traumatic stress disorder) and depression were associated with CMI among both deployed and nondeployed veterans. Nicotine dependence and veteran-reported physician-diagnosed infectious mononucleosis were associated with CMI among deployed veterans, and migraine headaches and gastritis were associated with CMI among nondeployed veterans. CMI continues to be substantially more prevalent among deployed veterans than among nondeployed veterans 10 years after Gulf War I, but it manifests similarly in both groups. It is likely to be a common, persistent problem among veterans returning from the current Gulf War. C1 St Louis Vet Affairs Med Ctr, Med Serv, St Louis, MO 63106 USA. St Louis Vet Affairs Med Ctr, Res Serv, St Louis, MO 63106 USA. Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, W Roxbury, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dept Vet Affairs, Cent Off, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Dept Vet Affairs, Environm Epidemiol Serv, Washington, DC USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Blanchard, MS (reprint author), St Louis Vet Affairs Med Ctr, Med Serv, 111-JC,915 N Grand Ave, St Louis, MO 63106 USA. EM melvin.blanchard@med.va.gov NR 46 TC 54 Z9 56 U1 3 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2006 VL 163 IS 1 BP 66 EP 75 DI 10.1093/aje/kwj008 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 997CS UT WOS:000234223200008 PM 16293719 ER PT J AU Ioannou, GN Boyko, EJ Lee, SP AF Ioannou, GN Boyko, EJ Lee, SP TI The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999-2002 SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID OVERWEIGHT AB OBJECTIVES: The presence of elevated serum aminotransferase activity is a sign of possible underlying liver disease. We aimed to describe the prevalence and associations of elevated serum aminotransferase activity in a recent, nationally representative U.S. survey. METHODS: We described the prevalence and predictors of elevated alanine aminotransferase (ALT > 43 IU/L) or elevated aspartate aminotransferase (AST > 40 IU/L) activity among 6,823 participants of the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002. We compared our findings to the results already published based on the NHANES conducted between 1988 and 1994. RESULTS: In NHANES 1999-2002, the prevalences of elevated ALT, AST, or either ALT or AST were 8.9%, 4.9%, and 9.8%, respectively, in the entire population and 7.3%, 3.6%, and 8.1%, respectively, after excluding participants who tested positive for hepatitis C virus (HCV) antibody or reported excessive alcohol consumption. Strong predictors of elevated ALT activity included increasing waist circumference and body mass index, alcohol consumption, male sex, Mexican American ethnicity, decreasing age, and presence of HCV antibody. In NHANES 1988-1994, which employed a different assay methodology, the prevalences of elevated aminotransferases were approximately half of the prevalences we describe in NHANES 1999-2002, but the predictors of elevated ALT activity were similar. CONCLUSIONS: The current prevalence of elevated ALT activity in the United States (8.9%) is more than double that of previously available estimates. This prevalence is very high (7.3%) even among persons without viral hepatitis C or excessive alcohol consumption and is strongly associated with risk factors for nonalcoholic fatty liver disease. C1 VA Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. RP Ioannou, GN (reprint author), VA Puget Sound Hlth Care Syst, Res Enhancement Award Program, S-111-Gastro 1660 S Columbian Way, Seattle, WA 98108 USA. RI Lee, Sum Ping/C-4333-2009 NR 12 TC 143 Z9 148 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2006 VL 101 IS 1 BP 76 EP 82 DI 10.1111/j.1572-0241.2006.00341.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 999SY UT WOS:000234412000015 PM 16405537 ER PT J AU Dienstag, JL AF Dienstag, JL TI Looking to the future: New agents for chronic hepatitis B SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ADEFOVIR DIPIVOXIL; PEGINTERFERON ALPHA-2A; COMBINATION THERAPY; PHASE-III; LAMIVUDINE; TRIAL; ENTECAVIR; EFFICACY; INFECTION; DURATION AB New antiviral agents are currently being developed to treat patients with chronic hepatitis B. Both pegylated interferon alfa-2a and entecavir are now approved for the treatment of hepatitis B while telbivudine, tenofovir, emtricitabine, and pegylated interferon alfa-2b are in clinical development. Successive advances have resulted in more profound suppression of hepatitis B replication, a reduction in breakthrough resistance, and an increase in the frequency of attainment of virologic, serologic, biochemical, and histologic clinical endpoints. C1 Harvard Univ, GI Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Dienstag, JL (reprint author), Harvard Univ, GI Unit, Massachusetts Gen Hosp, Sch Med, GRJ 825,Blake 4,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 11 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2006 VL 101 SU 1 BP S19 EP S25 DI 10.1111/j.1572-0241.2006.00377.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 007RB UT WOS:000234986000004 PM 16448448 ER PT J AU Kennedy, RH Melchert, RB Joseph, J AF Kennedy, RH Melchert, RB Joseph, J TI Cardiovascular effects of hyperhomocysteinemia in conscious unrestrained rats SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; chronic hyperhomocysteinemia; heart rate; male rats; pulse pressure ID TOTAL PLASMA HOMOCYSTEINE; BLOOD-PRESSURE; HYPERTENSIVE RATS; ENDOTHELIAL DYSFUNCTION; RESISTANCE; CORONARY; LEADS AB Background: Experiments were designed to determine whether hyperhomocysteinemia (Hhe) affects cardiovascular function when monitored in conscious unrestrained animals. Methods: Adult, male Sprague-Dawley rats were fed a homocystine-supplemented diet for 6 months. Blood pressure (BP), heart rate, and pulse pressure were monitored continuously, 24 h a day, using biotelemetry techniques. Results: The resulting, intermediate level of Hhe was not associated with significant changes in heart rate, diastolic BP, systolic BP, or the circadian variation in heart rate. In spite of the lack of significant changes in systolic 4 and diastolic BP, there was a slight but statistically significant increase in pulse pressure after 4 months of treatment that returned toward control levels after 6 months. Conclusions: Current results indicate that Hhe alone does not have significant effects on BP. Furthermore, they suggest that the previously reported Hhe-induced adverse cardiac remodeling and diastolic dysfunction in this animal model are not the result of pressure overload. C1 Loyola Univ, Stritch Sch Med, Res Serv 120 400, Dept Pathol, Maywood, IL 60153 USA. Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR USA. VA Boston Healthcare Syst, Dept Internal Med, W Roxbury, MA USA. Boston Univ, Sch Med, W Roxbury, MA USA. RP Kennedy, RH (reprint author), Loyola Univ, Stritch Sch Med, Res Serv 120 400, Dept Pathol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM rkennedy@lumc.edu OI Melchert, Russell/0000-0003-4813-6911 NR 18 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2006 VL 19 IS 1 BP 94 EP 97 DI 10.1016/j.amhyper.2005.07.008 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 005VH UT WOS:000234851700018 PM 16461198 ER PT J AU Bian, J Dow, WH Matchar, DB AF Bian, J Dow, WH Matchar, DB TI Medicare HMO penetration and mortality outcomes of ischemic stroke SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATIONS; ACUTE MYOCARDIAL-INFARCTION; CARE MARKET SHARE; MANAGED CARE; SYSTEMS; SPECIALTIES; QUALITY; PLANS; RATES; COST AB objective: To examine associations between Medicare health maintenance organization (HMO) penetration and stroke mortality outcomes among older persons. Study Design: Panel analysis of nationally representative secondary data from 1993 to 1998. Methods: The first analysis sample included ischemic stroke hospitalizations among older persons in the Nationwide Inpatient Sample; the second included county-level ischemic stroke deaths in the National Vital Statistics System. The 2 samples were merged with the HMO enrollment data and the 2001 Area Resource File. The 2 outcomes were inhospital death status and county-level population ischemic stroke death rates among older persons; the 2 utilization variables were length of hospital stay for ischemic stroke and proportion of ischemic stroke deaths occurring in hospitals. The 3 key explanatory variables were county-level Medicare total, independent practice association, and nonindependent practice association HMO penetration. Ordinary least squares analysis with hospital or county fixed effects was used in estimation. Results: Medicare HMO penetration was not associated with the 2 ischemic stroke mortality outcomes (P > .05). Increases in Medicare total and independent practice association HMO penetration were associated with a significant shift in a higher proportion of stroke deaths from hospitals to nursing homes or residences (P < .05). Medicare HMO penetration was negatively associated with length of stay, although this was not statistically significant (P > .05). Conclusions: Increased Medicare HMO penetration was associated with a shift in ischemic stroke deaths from hospitals to nonhospital settings. The effect of Medicare HMO penetration on quality of stroke care needs further research. C1 Univ Alabama, Div Prevent Med, Birmingham, AL 35295 USA. Univ Calif Berkeley, Deep S Ctr Effectiveness, Birmingham VA Med Ctr, Berkeley, CA 94720 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Hlth Policy & Management, Berkeley, CA 94720 USA. Duke Univ, Duke Ctr Clin Hlth Policy Res, Durham, NC USA. RP Bian, J (reprint author), Univ Alabama, Div Prevent Med, MT 640,1530 3rd Ave S, Birmingham, AL 35295 USA. EM jbian@uab.edu OI Dow, William/0000-0002-4080-1668 FU AHRQ HHS [T32 HS00032] NR 33 TC 2 Z9 2 U1 0 U2 2 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2006 VL 12 IS 1 BP 58 EP 64 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 004WA UT WOS:000234782100006 PM 16402889 ER PT J AU Gripp, KW Lin, AE Stabley, DL Nicholson, L Scott, CI Doyle, D Aoki, Y Matsubara, Y Zackai, EH Lapunzina, P Gonzalez-Meneses, A Holbrook, J Agresta, CA Gonzalez, IL Sol-Church, K AF Gripp, KW Lin, AE Stabley, DL Nicholson, L Scott, CI Doyle, D Aoki, Y Matsubara, Y Zackai, EH Lapunzina, P Gonzalez-Meneses, A Holbrook, J Agresta, CA Gonzalez, IL Sol-Church, K TI HRAS mutation analysis in Costello syndrome: Genotype and phenotype correlation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE bladder cancer; gain-of-function; HRAS; overgrowth syndrome; rhabdomyosarcoma ID GROWTH-HORMONE DEFICIENCY; H-RAS; PATERNAL ORIGIN; RHABDOMYOSARCOMA; CARCINOMA; FGFR3; DNA AB Costello syndrome is a rare condition comprising mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy, and/or atrial tachycardia), tumor predisposition, and skin and musculoskeletal abnormalities. Recently mutations in HRAS were identified in 12 Japanese and Italian patients with clinical information available on 7 of the Japanese patients. To expand the molecular delineation of Costello syndrome, we performed mutation analysis in 34 North American and 6 European (total 40) patients with Costello syndrome, and detected missense mutations in HRAS in 33 (82.5%) patients. All mutations affected either codon 12 or 13 of the protein product, with G12S Occurring in 30 (90.9%) patients of the mutation-positive cases. In two patients, we found a mutation resulting in an alanine substitution in position 12 (G12A), and in one patient, we detected a novel mutation (G13C). Five different HRAS mutations have now been reported in Costello syndrome, however genotype- phenotype correlation remains incomplete. (c) 2005 Wiley-Liss, Inc. C1 AI DuPont Hosp Children, Div Med Genet, Wilmington, DE 19899 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Nemours Childrens Clin, Dept Biomed Res, Wilmington, DE USA. AI DuPont Hosp Children, Div Endocrinol, Wilmington, DE 19899 USA. Tohoku Univ, Sch Med, Dept Med Genet, Sendai, Miyagi 980, Japan. Childrens Hosp Philadelphia, Dept Human Genet, Philadelphia, PA 19104 USA. Hosp Univ La Paz, Dept Genet, Madrid, Spain. Hosp Univ Virgen Rocio, Serv Dysmorphol, Seville, Spain. RP Gripp, KW (reprint author), AI DuPont Hosp Children, Div Med Genet, POB 269, Wilmington, DE 19899 USA. EM kgripp@nemours.org FU NCRR NIH HHS [1P20 RR 020173-01] NR 30 TC 110 Z9 118 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN 1 PY 2006 VL 140A IS 1 BP 1 EP 7 DI 10.1002/ajmg.a.31047 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 000QK UT WOS:000234476900001 PM 16329078 ER PT J AU Kantarci, S Casavant, D Prada, C Russell, M Byrne, J Haug, LW Jennings, R Manning, S Boyd, TK Fryns, JP Holmes, LB Donahoe, PK Lee, C Kimonis, V Pober, BR AF Kantarci, S Casavant, D Prada, C Russell, M Byrne, J Haug, LW Jennings, R Manning, S Boyd, TK Fryns, JP Holmes, LB Donahoe, PK Lee, C Kimonis, V Pober, BR TI Findings from aCGH in patients with congenital diaphragmatic hernia (CDH): A possible locus for Fryns syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital diaphragmatic hernia; Fryns syndrome; chromosome 1q41-q42.12 deletion; array-based comparative genomic hybridization (aCGH); FISH ID COMPARATIVE GENOMIC HYBRIDIZATION; MCA SYNDROME; 2 SIBS; DEFECTS; OSTEOCHONDRODYSPLASIA; MALFORMATIONS; INHERITANCE; HYPOPLASIA; MOSAICISM; ANOMALIES AB Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect that can occur in isolation or as part of a malformation complex. Considerable progress is being made in the identification of genetic causes of CDH. We applied array-based comparative genomic hybridization (aCGH) of similar to 1Mb resolution to 29 CDH patients with prior normal karyotypes who had been recruited into Our multisite study. One patient, clinically diagnosed with Fryns syndrome, demonstrated a de novo 5Mb deletion at chromosome region 1q41-q42.12 that was confirmed by FISH. Given prior reports of CDH in association with cytogenetic abnormalities in this region, we propose that this represents a locus for Fryns syndrome, a Fryns syndrome phenocopy, or CDH. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Surg Res Labs, Boston, MA 02115 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Hosp Leuven, Dept Genet, Louvain, Belgium. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Pober, BR (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Genet, 300 Longwood Ave,Fegan 325, Boston, MA 02115 USA. EM Barbara.pober@childrens.harvard.edu FU NICHD NIH HHS [P01 HD039942, P01 HD 39942-03, R01 HD055150, R01 HD055150-02] NR 37 TC 49 Z9 49 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN 1 PY 2006 VL 140A IS 1 BP 17 EP 23 DI 10.1002/ajmg.a.31025 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 000QK UT WOS:000234476900003 PM 16333846 ER PT J AU Schaefer, PW Roccatagliata, L Ledezma, C Hoh, B Schwamm, LH Koroshetz, W Gonzalez, RG Lev, MH AF Schaefer, PW Roccatagliata, L Ledezma, C Hoh, B Schwamm, LH Koroshetz, W Gonzalez, RG Lev, MH TI First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MIDDLE CEREBRAL-ARTERY; ACUTE ISCHEMIC-STROKE; HYPERACUTE STROKE; COMPUTED-TOMOGRAPHY; MR DIFFUSION; THROMBOLYSIS; ANGIOGRAPHY; VIABILITY; BRAIN; TIME AB BACKGROUND AND PURPOSE: The purpose of this study was to determine whether, in acute stroke patients treated with intra-arterial (IA) recanalization therapy, CT perfusion (CTP) can distinguish ischemic brain tissue destined to infarct from that which will survive. METHODS: Dynamic CTP was obtained in 14 patients within 8 hours of stroke onset, before IA therapy. Initial quantitative cerebral blood volume (CBV) and flow (CBF) values were visually segmented and normalized in the "infarct core" (region 1: reduced CBV and CBF, infarction on follow-up), "penumbra that infarcts" (region 2: normal CBV, reduced CBF, infarction on follow-up), and "penumbra that recovers" (region 3: normal CBV, reduced CBF, normal on follow-up). Normalization was accomplished by dividing the ischemic region of interest value by that of a corresponding, contralateral, uninvolved region, which resulted in CBV and CBF "ratios." Separate CBV and CBF values were obtained in gray matter (GM) and white matter (WM). RESULTS: Mean CBF ratios for regions 1, 2, and 3 were 0.19 +/- 0.06, 0.34 +/- 0.06, and 0.46 +/- 0.09, respectively (all P <.001). Mean CBV ratios for regions 1, 2, and 3 were similarly distinct (all P <.05). Absolute CBV and CBF values for regions 2 and 3 were not significantly different. All regions with CBF ratio <0.32, CBV ratio <0.68, CBF < 12.7 mL/100 g/min, or CBV <2.2 mL/100 g infarcted. No region with CBF ratio >0.44 infarcted. GM versus WM CBF and CBV values were significantly different for region 2 compared with region 3 (P <.05). CONCLUSIONS: In acute stroke patients, quantitative CTP can distinguish ischemic tissue likely to infarct from that likely to survive. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 27 TC 113 Z9 135 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 JAN PY 2006 VL 27 IS 1 BP 20 EP 25 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 004VC UT WOS:000234779600016 PM 16418350 ER PT J AU Seddon, JM Gensler, G Klein, ML Milton, RC AF Seddon, JM Gensler, G Klein, ML Milton, RC TI Evaluation of plasma homocysteine and risk of age-related macular degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ASSOCIATION; DISEASE AB PURPOSE: To assess the relationship between plasma levels of homocysteine and age,related macular degeneration (AMD). DESIGN: Cross-sectional,case-control study. METHODS: Fasting plasma homocysteine levels were measured at two centers in 934 individuals who were participating in an ancillary study of the Age,Related Eye Disease Study. There were 547 cases and 387 control subjects, who were determined by fundus photography. Conditional logistic regression analyses were conducted to assess the association of homocysteine with AMD. RESULTS: Median values of homocysteine were higher among advanced AMD cases (9.51 mmol/l) compared with persons with no AMD (8.81 mmol/l; P = .01). Values of > 12 mmol/l vs <= 12 mmol/l were also associated with an increased risk of AMD (P = .023), when controlled for other covariates. CONCLUSION: Results are consistent with a possible small, independent association between higher homocysteine levels and AMD. Homocysteine may be a modifiable risk factor for AMD. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. Devers Eye Inst, Portland, OR USA. EMMES Corp, Rockville, MD USA. RP Seddon, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Johanna_Seddon@meei.harvard.edu FU NEI NIH HHS [R01 EY 13982, N01 EY 02126, N01 EY 02117] NR 7 TC 41 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 2006 VL 141 IS 1 BP 201 EP 203 DI 10.1016/j.ajo.2005.07.059 PG 3 WC Ophthalmology SC Ophthalmology GA 000FQ UT WOS:000234446700036 PM 16387004 ER PT J AU Emerick, K Cunningham, M Hartnick, C AF Emerick, K Cunningham, M Hartnick, C TI The potential impact of palivizumab on pediatric airway reconstruction SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; STAGE LARYNGOTRACHEAL RECONSTRUCTION; CONGENITAL HEART-DISEASE; HIGH-RISK INFANTS; TRANSPLANT RECIPIENTS; SUBGLOTTIC STENOSIS; INFECTION; PREVENTION; STRATEGIES; MANAGEMENT AB Purpose: To examine the role of palivizumab, a monoclonal antibody vaccine designed to prevent respiratory syncytial virus (RSV) infection, in the surgical setting, and to explore the feasibility, in terms of medical benefit and cost, of its use in pediatric airway reconstruction patients. Materials and methods: Literature review of MEDLINE database using the following indexing terms ("respiratory syncytial virus," "palivizurnab," "laryngotracheal reconstruction," and "cricotracheal reconstruction"), and. limited to following subcategories (English language, postoperative complication, and morbidity and mortality). All phase IV clinical trials reporting data regarding safety, efficacy, and application of palivizumab in the general pediatric population were selected, as well as all studies from any surgical specialty with data on postoperative outcome complicated by RSV infection. Results: The literature demonstrates significant postoperative morbidity and mortality attributable to RSV infection within several surgical specialties including otolaryngology. Meta-analysis of the data from phase IV clinical trials suggests potential benefit from the perioperative use of palivizumab. The cost of vaccination is the principal limiting factor preventing its more widespread application. Conclusion: Otolaryngologists need to be aware of the potential significant morbidity caused by perioperative RSV infection and should consider the prophylactic use of palivizumab in their pediatric airway reconstruction patients in high-risk seasons. A large multicenter study would be required to adequately perform a cost-benefit analysis of palivizumab use for this specific indication. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Hartnick, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 19 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JAN-FEB PY 2006 VL 27 IS 1 BP 9 EP 12 DI 10.1016/j.amjoto.2005.05.012 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 001OK UT WOS:000234546000003 PM 16360816 ER PT J AU Perry, GH Dominy, NJ Claw, KG Villanea, FA Iafrate, AJ Lee, C Stone, AC AF Perry, GH Dominy, NJ Claw, KG Villanea, FA Iafrate, AJ Lee, C Stone, AC TI Significance of amylase gene duplications in human and non-human primate evolution. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. Univ Calif Santa Cruz, Dept Anthropol, Santa Cruz, CA 95064 USA. Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. Univ Costa Rica, Escuela Biol, San Jose, Costa Rica. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Stone, Anne/B-5719-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2006 SU 42 BP 145 EP 146 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 016YQ UT WOS:000235661100373 ER PT J AU Canonne-Hergaux, F Donovan, A Delaby, C Wang, HJ Gros, P AF Canonne-Hergaux, F Donovan, A Delaby, C Wang, HJ Gros, P TI Comparative studies of duodenal and macrophage ferroportin proteins SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE expression; localization ID INTESTINAL IRON TRANSPORT; TRANSFERRIN RECEPTOR; PEPTIDE HEPCIDIN; DIETARY IRON; BRUSH-BORDER; ANEMIA MICE; METABOLISM; EXPRESSION; HEPHAESTIN; MEMBRANE AB Intestinal epithelial cells and reticuloendothelial macrophages are, respectively, involved in diet iron absorption and heme iron recycling from senescent erythrocytes, two critical processes of iron homeostasis. These cells appear to use the same transporter, ferroportin (Slc40a1), to export iron. The aim of this study was to compare the localization, expression, and regulation of ferroportin in both duodenal and macrophage cells. Using a high-affinity purified polyclonal antibody, we analyzed the localization and expression of ferroportin protein in the spleen, liver, and duodenum isolated from normal mice as well as from well-characterized mouse models of altered iron homeostasis. Ferroportin was found to be predominantly expressed in enterocytes of the duodenum, in splenic macrophages, and in liver Kupffer cells. Interestingly, the protein species detected in these cells migrated differently on SDS-PAGE. These differences in apparent molecular masses were partly explained by posttranslational complex N-linked glycosylations. In addition, in enterocytes, the transporter was mostly expressed at the basolateral membrane, whereas in bone marrow-derived macrophages, ferroportin was found predominantly localized in the intracellular vesicular compartment. However, some microdomains positive for ferroportin were also detected at the plasma membrane of macrophages. Despite these differences, we observed a parallel upregulation of ferroportin expression in tissue macrophages and enterocytes in response to iron-restricted erythropoiesis, suggesting that iron homeostasis is likely maintained through coordinate expression of the iron exporter in both intestinal and phagocytic cells. Our data also confirm a predominant regulation of ferroportin through systemic regulator(s) likely including hepcidin. C1 Univ Paris 07, INSERM, U656, F-75018 Paris, France. Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. McGill Univ, Dept Biochem, Montreal, PQ, Canada. RP Canonne-Hergaux, F (reprint author), Univ Paris 07, INSERM, U656, 16 Rue Henri Huchard, F-75018 Paris, France. EM fcanonne@bichat.inserm.fr FU NIDDK NIH HHS [K01-DK-64924-02] NR 41 TC 58 Z9 59 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 JAN PY 2006 VL 290 IS 1 BP G156 EP G163 DI 10.1152/ajpgi.00227.2005 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 993HE UT WOS:000233944400018 PM 16081760 ER PT J AU Palomeque, J Sapia, L Hajjar, RJ Mattiazzi, A Petroff, MNV AF Palomeque, J Sapia, L Hajjar, RJ Mattiazzi, A Petroff, MNV TI Angiotensin II-induced negative inotropy in rat ventricular myocytes: role of reactive oxygen species and p38 MAPK SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardium; calcium transients; mitogen-activated protein kinase ID PROTEIN-KINASE-C; CARDIAC TROPONIN-I; HEART-FAILURE; MYOCARDIAL-INFARCTION; SIGNAL-TRANSDUCTION; INTRACELLULAR CA2+; FORCE DEVELOPMENT; PHOSPHORYLATION; INHIBITION; CONTRACTILITY AB The octapeptide angiotensin II (ANG II) can modulate cardiac contractility and increased in heart failure, where contractile function is impaired. In rat cardiac myocytes, 1 mu M of ANG II produces a negative inotropic effect (NIE) (24.6 +/- 5% reduction). However, the subcellular signaling involved in this effect remains elusive. We examined the mechanisms and signaling events involved in the reduction in contractile function induced by the peptide in indo-1-loaded rat cardiomyocytes. The results showed that the NIE of ANG II was not associated with a parallel decrease in the intracellular Ca2+ transient, indicating that a decrease in myofilament responsiveness to Ca2+ underlies the reduction in contractility. We assessed the role of PKC, tyrosine kinases, reactive oxygen species (ROS), and mitogen- activated protein kinases (MAPKs) in the NIE of the peptide. Pretreatment of cells with the NAD(P) H oxidase inhibitor diphenyleneiodonium chloride or with the superoxide scavenger 4,5- dihydroxy- 1,3-benzene-disulfonic acid did not affect the ANG II-induced NIE. Moreover, ANG II-induced ROS production, after 20 min of incubation with the peptide, could not be detected with the use of either the fluorophore 5-(6)-chloromethyl-2', 7'-dichlorodihydrofluorecein diacetate or lucigenin- enhanced chemiluminescence. In contrast, the ANG II-induced NIE was abrogated by the inhibitors of PKC (calphostin C), tyrosine kinase (genistein), and p38 MAPK (SB-202190). Furthermore, the NIE was significantly exacerbated (60 +/- 10% reduction) by p38 MAPK overexpression. These results exclude the participation of ROS in the NIE of the peptide and point to PKC and tyrosine kinase as upstream mediators. Furthermore, they reveal p38 MAPK as the putative effector of the reduction in myofilament responsiveness to Ca2+ and the decrease in contractility induced by the peptide. C1 Univ Nacl La Plata, Ctr Invest Cardiovasc, Fac Ciencias Med, RA-1900 La Plata, Argentina. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. RP Petroff, MNV (reprint author), Univ Nacl La Plata, Ctr Invest Cardiovasc, Fac Ciencias Med, 60 & 120, RA-1900 La Plata, Argentina. EM mvila@atlas.med.unlp.edu.ar FU NHLBI NIH HHS [HL-57236, HL-078691, HL-71763] NR 41 TC 38 Z9 39 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2006 VL 290 IS 1 BP H96 EP H106 DI 10.1152/ajpheart.00324.2005 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 996BA UT WOS:000234148200013 PM 16055523 ER PT J AU Medoff, BD Tager, AM Jackobek, R Means, TK Wang, L Luster, AD AF Medoff, BD Tager, AM Jackobek, R Means, TK Wang, L Luster, AD TI Antibody-antigen interaction in the airway drives early granulocyte recruitment through BLT1 SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung inflammation; asthma; lipid mediator ID LEUKOTRIENE B-4 RECEPTOR; CD8(+) T-CELLS; MAST-CELLS; SEVERE ASTHMA; MURINE MODEL; ALVEOLAR MACROPHAGES; MOUSE MODEL; IN-VITRO; INFLAMMATION; MICE AB Antibodyantigen interactions in the airway initiate inflammation in acute asthma exacerbations. This inflammatory response is characterized by the recruitment of granulocytes into the airways. In murine models of asthma, granulocyte recruitment into the lung contributes to the development of airway hyperresponsiveness (AHR), mucus production, and airway remodeling. Leukotriene B-4 is a mediator released following antigen challenge that has chemotactic activity for granulocytes, mediated through its receptor, BLT1. We investigated the role of BLT1 in granulocyte recruitment following antigen challenge. Wild- type mice and BLT1(-/-) mice were sensitized and challenged with ovalbumin (OVA) to induce acute allergic airway inflammation. In addition, to explore the relevance to antibody-antigen interactions, we injected OVA bound to anti-OVA 1gG(1) or anti-OVA IgE intratracheally into naive wild-type and BLT1(-/-) mice. Cell composition of the lungs, cytokine levels, histology, and AHR were determined. After sensitization and challenge with ovalbumin, there was significantly reduced neutrophil and eosinophil recruitment into the airways of BLT1(-/-) mice compared with wild-type animals after one or two daily antigen challenges, but this difference was not seen after three or four daily antigen challenges. Mucus production and AHR were not affected. Intratracheal injection of OVA bound to 1gG1 or IgE induced neutrophil recruitment into the airways in wild-type mice but not in the BLT1(-/-) mice. We conclude that BLT1 mediates early recruitment of granulocytes into the airway in response to antigen-antibody interactions in a murine model of acute asthma. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammat Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Ctr Immunol & Inflammat Dis, Div Rheumatol Allergy & Immunol, CNY 8301,149 13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu FU NIAID NIH HHS [R01 AI-40618-08, F32-AI-50399, R01 AI-050892] NR 54 TC 23 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2006 VL 290 IS 1 BP L170 EP L178 DI 10.1152/ajplung.00212.2005 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 992QA UT WOS:000233897700021 PM 16126787 ER PT J AU Berfield, AK Chait, A Oram, JF Zager, RA Johnson, AC Abrass, CK AF Berfield, AK Chait, A Oram, JF Zager, RA Johnson, AC Abrass, CK TI IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE chronic kidney disease; cholesterol; peroxisome proliferator-activated receptor; foam cells ID LOW-DENSITY-LIPOPROTEIN; GROWTH-FACTOR-I; SMOOTH-MUSCLE-CELLS; PROLIFERATOR-ACTIVATED RECEPTORS; MACROPHAGE SCAVENGER RECEPTORS; CHOLESTEROL EFFLUX; RENAL-DISEASE; OXIDIZED LDL; LIPID-ACCUMULATION; ZUCKER RATS AB Rat glomerular mesangial cells ( MC) become lipid-laden foam cells when they are exposed to IGF-1. IGF-1 increased accumulation of triglyceride (TG) 2.5-fold in MC after 7 days. TG accumulation resulted from enhanced macropinocytosis and decreased efflux secondary to a 40-50% reduction in peroxisome proliferator-activated receptor ( PPAR)-delta (PPAR-delta). There was no evidence of primary or secondary changes in cholesterol or TG synthesis, increased uptake by LDL or scavenger receptors, or reduced efflux via ATP-binding cassette A-1. Although the lipid moiety taken up can be influenced by the concentration of cholesterol or TG in the medium, in standard medium MC preferentially accumulate TG. TG-rich MC foam cells fail to contract in response to angiotensin II (Berfield AK, Andress DL, and Abrass CK. Kidney Int 62: 1229 1237, 2002); however, their migratory response to IGF binding protein-5 is unaffected. This differs from cholesterol loading, which impairs both phagocytosis and migration. These findings have important implications for understanding the mechanisms that contribute to lipid accumulation in MC and the functional consequences of different forms of foam cells. These observations are relevant to understanding vascular disease and progressive renal diseases that are accelerated by abnormalities in lipid metabolism. C1 Univ Washington, Sch Med, Dept Med, Div Endocrinol & Metab, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Abrass, CK (reprint author), Univ Washington, Sch Med, Dept Med, Div Endocrinol & Metab, 1660 S Columbian Way, Seattle, WA 98108 USA. EM cabrass@u.washington.edu FU NIDDK NIH HHS [R01-DK-9771-05, DK-02456, R37-DK-38432] NR 81 TC 12 Z9 12 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 JAN PY 2006 VL 290 IS 1 BP F138 EP F147 DI 10.1152/ajprenal.00054.2005 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 991YJ UT WOS:000233850500016 PM 16077083 ER PT J AU Lee, DBN Huang, E Ward, HJ AF Lee, DBN Huang, E Ward, HJ TI Tight junction biology and kidney dysfunction SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE kidney disease; zonula occludens ID ACUTE-RENAL-FAILURE; TRANSCRIPTION FACTOR SNAIL; CELL-CELL ADHESION; EPITHELIAL-MESENCHYMAL TRANSITIONS; CHRONIC INTERSTITIAL NEPHRITIS; GLOMERULAR SLIT DIAPHRAGM; POLARITY PROTEIN PAR6; RHO-FAMILY GTPASES; E-CADHERIN; ATP DEPLETION AB Tight junction biology and kidney dysfunction. Am J Physiol Renal Physiol 290: F20-F34, 2006; doi:10.1152/ajprenal.00052.2005.- The epithelial tight junction (TJ) has three major functions. As a "gate," it serves as a regulatory barrier separating and maintaining biological fluid compartments of different composition. As a " fence," it generates and maintains the apicobasal polarity of cells that form the confluent epithelium. Finally, the TJ proteins form a trafficking and signaling platform that regulates cell growth, proliferation, differentiation, and dedifferentiation. Six examples are selected that illustrate the emerging link between TJ dysfunction and kidney disease. First, the glomerular slit diaphragm (GSD) is evolved, in part, from the TJ and, on maturation, exhibits all three functions of the TJ. GSD dysfunction leads to proteinuria and, in some instances, podocyte dedifferentiation and proliferation. Second, accumulating evidence supports epithelial-mesenchymal transformation (EMT) as a major player in renal fibrosis, the final common pathway that leads to end-stage renal failure. EMT is characterized by a loss of cell-cell contact and apicobasal polarity, which are hallmarks of TJ dysfunction. Third, in autosomal dominant polycystic kidney disease, mutations of the polycystins may disrupt their known interactions with the apical junction complex, of which the TJ is a major component. This can lead to disturbances in epithelial polarity regulation with consequent abnormal tubulogenesis and cyst formation. Fourth, evidence for epithelial barrier and polarity dysregulation in the pathogenesis of ischemic acute renal failure will be summarized. Fifth, the association between mutations of paracellin-1, the first TJ channel identified, and clinical disorders of magnesium and calcium wasting and bovine renal fibrosis will be used to highlight an integral TJ protein that can serve multiple TJ functions. Finally, the role of WNK4 protein kinase in shunting chloride across the TJ of the distal nephron will be addressed. C1 VA Med Ctr, Dept Med 111, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Ctr Med, Div Nephrol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Med, Vet Affairs Greater Los Angeles Healthcare Syst, VISN 22, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, King Drew Med Ctr, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90059 USA. RP Lee, DBN (reprint author), VA Med Ctr, Dept Med 111, 16111 Plummer St, Sepulveda, CA 91343 USA. EM dbnlee@ucla.edu FU NHLBI NIH HHS [T32-HL-07656]; NIDDK NIH HHS [T32-DK-07789, 1R01DK/HD-51948] NR 184 TC 95 Z9 98 U1 1 U2 8 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 JAN PY 2006 VL 290 IS 1 BP F20 EP F34 DI 10.1152/ajprenal.00052.2005 PG 15 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 991YJ UT WOS:000233850500004 PM 16339962 ER PT J AU Tian, W Fu, Y Wang, DH Cohen, DM AF Tian, W Fu, Y Wang, DH Cohen, DM TI Regulation of TRPV1 by a novel renally expressed rat TRPV1 splice variant SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE transient receptor potential channel ID VANILLOID RECEPTOR; CAPSAICIN RECEPTOR; CATION CHANNEL; VR1; ACTIVATION; MUTATIONS; SUGGESTS; MEDIATE; CLONING; RNAS AB Regulation of TRPV by a novel renally expressed rat TRPV1 splice variant. Am J Physiol Renal Physiol 290: F117-F126, 2006. First published August 9, 2005; doi:10.1152/ajprenal.00143.2005.- The capsaicin receptor and transient receptor potential channel TRPV1 senses heat, protons, and vanilloid agonists in peripheral sensory ganglia. Abundant data have suggested the presence of potentially novel splice variants in the kidney. We report a novel rat TRPV1 splice variant, TRPV1(VAR), cloned from kidney papilla. TRPV1VAR cDNA was identified in multiple kidney tissues. Its sequence was fully compatible with potential splice donor and acceptor sites in the rat TRPV1 gene. TRPV1VAR is predicted to encode a truncated form of TRPV1 consisting of the NH(2)-terminal 248 residues of TRPV1 ( all within the NH(2)-terminal intracellular domain) followed by five non-consensus amino acids (Arg-Glu-Ala-Met-Trp) and a stop codon. The variant utilizes the same consensus Kozak sequence as canonical TRPV1. A band of the appropriate molecular mass was identified in rat kidney papillary ( but not medullary) lysates immunoblotted with an antibody directed against the NH(2) terminus of TRPV1, whereas an antibody recognizing the TRPV1 COOH terminus failed to detect it. Upon heterologous expression in HEK 293 cells, TRPV1(VAR) potentiated the ability of cotransfected TRPV1 to confer calcium influx in response to resiniferatoxin. TRPV1(VAR) did not influence expression or cell surface localization of cotransfected TRPV1. TRPV1(VAR) protein product associated with the NH2 terminus of canonical TRPV1. Interestingly, when expressed in the COS-7 epithelial cell line, TRPV1(VAR) functioned in a dominant-negative acting capacity, partially blocking TRPV1-dependent resiniferatoxin responsiveness. We conclude that TRPV1(VAR) is one of perhaps several TRPV1 splice variants expressed in rat kidney and that it may serve to modulate TRPV1 responsiveness in some tissues. C1 Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Michigan State Univ, Dept Med Pharmacol & Toxicol, E Lansing, MI 48824 USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM cohend@ohsu.edu NR 35 TC 25 Z9 27 U1 0 U2 1 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 JAN PY 2006 VL 290 IS 1 BP F117 EP F126 DI 10.1152/ajprenal.00143.2005 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 991YJ UT WOS:000233850500014 PM 16091583 ER PT J AU Trivedi, MH Rush, AJ Wisniewski, SR Nierenberg, AA Warden, D Ritz, L Norquist, G Howland, RH Lebowitz, B McGrath, PJ Shores-Wilson, K Biggs, MM Balasubramani, GK Fava, M AF Trivedi, MH Rush, AJ Wisniewski, SR Nierenberg, AA Warden, D Ritz, L Norquist, G Howland, RH Lebowitz, B McGrath, PJ Shores-Wilson, K Biggs, MM Balasubramani, GK Fava, M CA STAR Study Team TI Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; ANTIDEPRESSANT EFFICACY TRIALS; DIAGNOSTIC SCREENING QUESTIONNAIRE; ILLNESS RATING-SCALE; REPORT QIDS-SR; MAJOR DEPRESSION; RELIEVE DEPRESSION; SOCIAL SUPPORT; DRUG RESPONSE; PSYCHOMETRIC EVALUATION AB Objective: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, but the rates, timing, and baseline predictors of remission in "real world" patients are not established. The authors' primary objectives in this study were to evaluate the effectiveness of citalopram, an SSRI, using measurement-based care in actual practice, and to identify predictors of symptom remission in outpatients with major depressive disorder. Method: This clinical study included outpatients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world" settings. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks. The clinicians were assisted by a clinical research coordinator in the application of measurement-based care, which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures. Remission was defined as an exit score of <= 7 on the 17-item Hamilton Depression Rating Scale (HAM-D) ( primary outcome) or a score of <= 5 on the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) ( secondary outcome). Response was defined as a reduction of >= 50% in baseline QIDS-SR score. Results: Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates. Conclusions: The response and remission rates in this highly generalizable sample with substantial axis I and axis III co-morbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results. C1 Univ Texas, SW Med Ctr, Mood Disorders Program & Clin, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, NIMH, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Mississippi, Dept Psychiat, Jackson, MS 39216 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, Sch Med, San Diego, CA 92103 USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Mood Disorders Program & Clin, Dept Psychiat, Exchange Pk Express,Amer Gen Tower,6363 Forest Pk, Dallas, TX 75390 USA. RI Biggs, Dr. Melanie/C-1468-2010; McGrath, Patrick/I-6410-2013; Howland, Robert/K-6937-2015; OI McGrath, Patrick/0000-0001-7217-7321; Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 71 TC 1479 Z9 1517 U1 27 U2 167 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2006 VL 163 IS 1 BP 28 EP 40 DI 10.1176/appi.ajp.163.1.28 PG 13 WC Psychiatry SC Psychiatry GA 999CU UT WOS:000234367100010 PM 16390886 ER PT J AU Harisinghani, MG Saksena, MA Hahn, PF King, B Kim, J Torabi, MT Weissleder, R AF Harisinghani, MG Saksena, MA Hahn, PF King, B Kim, J Torabi, MT Weissleder, R TI Ferumoxtran-10-enhanced MR lymphangiography: Does contrast-enhanced imaging alone suffice for accurate lymph node characterization? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast media; ferumoxtran-10; lymph nodes; MR lymphangiography; oncologic imaging ID SUPERPARAMAGNETIC IRON-OXIDE; LYMPHOGRAPHY; METASTASES; CANCER; AGREEMENT; AGENT; NECK AB OBJECTIVE. Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS. Seventy-seven patients (58 men. 19 women) with proven primary cancer(bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at 1.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was, performed separately for both reviewers. RESULTS. Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z)= areaunder ROC curve] reviewer 1, A(z)= 0.92; reviewer 2, A(z)= 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z)= 0.94; reviewer 2, A(z)= 0.93) showed a statistically significant difference (p = 0.01) for reviewer I but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION. On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization, However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM mharisinghani@partners.org NR 15 TC 68 Z9 70 U1 1 U2 4 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 JAN PY 2006 VL 186 IS 1 BP 144 EP 148 DI 10.1022/AJR.04.1287 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 998NY UT WOS:000234327000028 PM 16357394 ER PT J AU Blake, MA McKernan, M Setty, B Fischman, AJ Mueller, PR AF Blake, MA McKernan, M Setty, B Fischman, AJ Mueller, PR TI Renal oncocytoma displaying intense activity on F-18-FDG PET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; CELL CARCINOMA; CANCER C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Setty, Bindu/0000-0002-2749-6822 NR 4 TC 17 Z9 18 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2006 VL 186 IS 1 BP 269 EP 270 DI 10.2214/AJR.05.0110 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 998NY UT WOS:000234327000056 PM 16357422 ER PT J AU Ollila, DW Caudle, AS Cance, WG Kim, HJ Cusack, JC Swasey, JE Calvo, BF AF Ollila, DW Caudle, AS Cance, WG Kim, HJ Cusack, JC Swasey, JE Calvo, BF TI Successful minimally invasive parathyroidectomy for primary hyperparathyroidism without using intraoperative parathyroid hormone assays SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE hyperparathyroidism; minimally invasive parathyroidectomy; intraoperative PTH ID SURGICAL-TREATMENT; BREAST-CANCER; GAMMA-PROBE; SURGERY; LOCALIZATION; EXPLORATION; MANAGEMENT; OPERATION; IMPROVE; ERA AB Background: The need for intraoperative parathyroid hormone (iPTH) assays in minimally invasive parathyroidectomy (MIP) remains controversial. We report the results of MIP performed without the use of iPTH assays. Methods: This was a sin-le-institution retrospective review of patients with primary hyperparathyroidism treated with MIP between October 1, 1998, and December 31, 2002. Results: Seventy-seven patients were studied. The mean preoperative calcium level was 11.4 mg/dL. All patients had a normal calcium level postoperatively (range, 7.4-10.2 mg/dL, mean, 9.1 mg/dL). Three patients (4%) required re-exploration for various reasons including the development of a second adenoma, secondary hyperparathyroidism, and discordant pathology. All 3 patients initially were eucalcemic. Conclusions: Our success rate of 96% using a combination of preoperative sestamibi scans, intraoperative gamma probe localization, and selective frozen pathology is consistent with the published success rates using iPTH assays of 95% to 100%. We conclude that MIP can be performed successfully without using iPTH assays. (c) 2006 Excerpta Medica Inc. All rights reserved. C1 Univ N Carolina, Div Surg Oncol, Chapel Hill, NC 27599 USA. Univ Florida, Dept Surg, Gainesville, FL 32611 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ollila, DW (reprint author), Univ N Carolina, Div Surg Oncol, 3010 Old Clin Bldg,CB 7213, Chapel Hill, NC 27599 USA. EM abigailcaudle@att.net RI Caudle, Abigail/G-5355-2015 NR 32 TC 27 Z9 28 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 2006 VL 191 IS 1 BP 52 EP 56 DI 10.1016/j.amjsurg.2005.10.003 PG 5 WC Surgery SC Surgery GA 005UU UT WOS:000234850300010 PM 16399106 ER PT J AU Hull, MJ Mino-Kenudson, M Nishioka, NS Ban, S Sepehr, A Puricelli, W Nakatsuka, L Ota, S Shimizu, M Brugge, WR Lauwers, GY AF Hull, MJ Mino-Kenudson, M Nishioka, NS Ban, S Sepehr, A Puricelli, W Nakatsuka, L Ota, S Shimizu, M Brugge, WR Lauwers, GY TI Endoscopic mucosal resection - An improved diagnostic procedure for early gastroesophageal epithelial neoplasms SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endoscopic mucosal resection; Barrett esophagus stomach; dysplasia; intermucosal carcinoma; biopsy; diagnosis; staging ID HIGH-GRADE DYSPLASIA; EARLY GASTRIC-CANCER; LYMPH-NODE METASTASIS; BARRETTS-ESOPHAGUS; CLINICOPATHOLOGICAL ANALYSIS; ADENOCARCINOMA; CARCINOMA; ULTRASONOGRAPHY; INVASION; DEPTH AB Endoscopic mucosal resection (EMR), which is advocated for the treatment of early (superficial) gastroesophageal neoplasms, has also been alluded to represent a superior diagnostic and staging modality. We compared the diagnostic concordance of preceding biopsies with EMR specimens in 31 gastric and 10 esophageal EMRs consisting of 6 low-grade and 12 high-grade dysplasias, 21 intramucosal adenocarcinomas, and 2 submucosal invasive adenocarcinomas. Discrepancies were considered as either major or minor if the histologic grades differed by 2 or more, or by only 1, respectively. Discrepant and concordant cases were compared with regard to the size of lesion (maximum dimension and surface area), number of biopsy fragments, and extent of biopsy sampling (ratio between lesion size and number of biopsy fragments). These same variables were used to evaluate the differences seen between gastric and esophageal cases. Of the 41 cases, 16 (39%) had discrepant diagnoses, including 14 gastric and 2 esophageal neoplasms. A major discrepancy was seen in 2% of the cases (n = 1, gastric) and a minor discrepancy, in 15 cases. All but 2 of the discrepant cases were found to have a higher grade on EMR. The average number of biopsy fragments was 4.4 in both concordant and discrepant groups. The maximal dimension, surface area, and biopsy sampling ratios of the lesion were significantly greater in the discrepant cases than in the concordant cases. The esophageal cases trended toward having smaller size and a significantly extensive biopsy sampling. We conclude that EMR is superior to biopsy for diagnosing superficial gastroesophageal tumors. Discrepancies between the specimens occur in larger lesions (> 10 mm) with less extensive biopsy sampling. EMR can substantially modify the diagnostic grade of a lesion and therefore facilitate optimal therapeutic decisions by avoiding undertreatment and overtreatment based on inaccurate grading and staging. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Saitama Med Sch, Dept Pathol, Moroyama, Saitama, Japan. Saitama Med Sch, Dept Gastroenterol & Hepatol, Moroyama, Saitama, Japan. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, 55 Fruit St,WRN 2, Boston, MA 02114 USA. EM glauwers@partners.org NR 36 TC 78 Z9 81 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2006 VL 30 IS 1 BP 114 EP 118 DI 10.1097/01.pas.0000180438.56528.a0 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 998IV UT WOS:000234312900016 PM 16330950 ER PT J AU Wang, SA Olson, N Zukerberg, L Harris, NL AF Wang, SA Olson, N Zukerberg, L Harris, NL TI Splenic marginal zone lymphoma with micronodular T-Cell rich B-cell lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE splenic marginal zone lymphoma; micronodular T-cell rich B-cell lymphoma; transformation ID VILLOUS LYMPHOCYTES; HISTIOCYTE-RICH; FEATURES; SERIES; P53 AB The types of B-cell lymphoma commonly involving the spleen include splenic marginal zone lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. We describe a unique case of splenic marginal zone lymphoma associated with micronodular T cell/histiocyte-rich large B-cell lymphoma in the red pulp, a combination that has not previously reported in the literature. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Kaiser Permanente Hlth Syst, Dept Pathol, Portland, OR USA. RP Wang, SA (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 2-219, Boston, MA 02114 USA. EM swang13@partners.org NR 14 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2006 VL 30 IS 1 BP 128 EP 132 DI 10.1097/01.pas.0000174268.22331.8d PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 998IV UT WOS:000234312900019 PM 16330953 ER PT J AU Reoux, JP Oreskovich, MR AF Reoux, JP Oreskovich, MR TI A comparison of two versions of the clinical institute withdrawal assessment for alcohol: The CIWA-Ar and CIWA-AD SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID BENZODIAZEPINES; MANAGEMENT; DETOXIFICATION; CARE AB Scores from two versions of the Clinical Institute Withdrawal Assessment for Alcohol, the CIWA-Ar and CIWA-AD, were compared in 135 alcohol detoxification episodes. The paired mean score for withdrawal severity was statistically higher with the CIWA-AD (p < 0.001), but the mean difference of 0.45 (95% CI: 0.38-0.53, t=11.74) is not likely to be clinically significant. The difference in the total score between the two scales was 1 point or less 82.6% of the time, and nearly all (97.7%) of the CIWA-AD scores were within 3 points of the paired CIWA-Ar score ( range -6 to +6). C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Reoux, JP (reprint author), VAPSHCS-116ATC,1660 S Columbian Way, Seattle, WA 98108 USA. EM joe.reoux@med.va.gov NR 16 TC 8 Z9 8 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2006 VL 15 IS 1 BP 85 EP 93 DI 10.1080/10550490500419136 PG 9 WC Substance Abuse SC Substance Abuse GA 007TE UT WOS:000234991900012 PM 16449097 ER PT J AU Velmahos, GC Brown, CV Demetriades, D AF Velmahos, GC Brown, CV Demetriades, D TI The (absence of a) role of venous duplex scan in the diagnosis of pulmonary embolism after severe trauma SO AMERICAN SURGEON LA English DT Article ID DEEP-VEIN THROMBOSIS; INTENSIVE-CARE-UNIT; VENA-CAVAL FILTERS; COMPUTED-TOMOGRAPHY; THROMBOEMBOLISM; RISK; ANGIOGRAPHY; PREVENTION; INJURY; COST AB Venous duplex scan (VDS) has been used for interim bedside diagnosis of pulmonary embolism (PE) in severely injured patients deemed to be at risk if transported out of the intensive care unit. In combination with the level of clinical suspicion for PE, VDS helps select patients for temporary treatment until definitive diagnosis is made. We evaluate the sensitivity and specificity of VDS in critically injured patients with a high level of clinical suspicion for PE. We performed a prospective observational cohort study at the surgical intensive care unit of an academic level 1 trauma center. Patients were 59 critically injured patients suspected to have PE over a 30-month period. The level of clinical suspicion for PE was classified as low or high according to preset criteria. Interventions were VDS and a PE outcome test (conventional or computed tomographic pulmonary angiography). The sensitivity and specificity of VDS to detect PE in all patients and in patients with high level of clinical suspicion was calculated against the results of the outcome test. PE was diagnosed in 21 patients (35.5%). The sensitivity and specificity of VDS was 33 per cent and 89 per cent, respectively. Among the 28 patients who had a high level of clinical suspicion for PE, the sensitivity of VDS was 23 per cent and the specificity 93 per cent. In this latter population, 1 of the 4 (25%) positive VDS was of a patient without PE and 10 of the 24 (42%) negative VDS were of patients who had PE. VDS does not accurately predict PE in severely injured patients, even in the presence of a high level of clinical suspicion. C1 Univ So Calif, Dept Surg, Div Trauma & Surg Crit Care, Los Angeles, CA 90089 USA. USC, Ctr Med, Los Angeles, CA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 24 TC 1 Z9 1 U1 0 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JAN PY 2006 VL 72 IS 1 BP 7 EP 10 PG 4 WC Surgery SC Surgery GA 007JO UT WOS:000234965200002 PM 16494173 ER PT J AU Martyn, JAJ Richtsfeld, M AF Martyn, JAJ Richtsfeld, M TI Succinylcholine-induced hyperkalemia in acquired pathologic states - Etiologic factors and molecular mechanisms SO ANESTHESIOLOGY LA English DT Review ID NICOTINIC ACETYLCHOLINE-RECEPTORS; NEUROMUSCULAR BLOCKING-AGENTS; SERUM-CHOLINESTERASE ACTIVITY; CARDIAC-ARREST; D-TUBOCURARINE; UP-REGULATION; CRITICAL ILLNESS; SKELETAL-MUSCLE; PROFOUND HYPERKALEMIA; TRACHEAL INTUBATIONS AB Lethal hyperkalemic response to succinyleholine continues to be reported, but the molecular mechanisms for the hyperkalemia have not been completely elucidated. In the normal innervated mature muscle, the acetylcholine receptors (AChRs) are located only in the junctional area. in certain pathologic states, including upper or lower motor denervation, chemical denervation by muscle relaxants, drugs, or toxins, immobilization, infection, direct muscle trauma, muscle tumor, or muscle inflammation, and/or burn injury, there is up-regulation (increase) of AChRs spreading throughout the muscle membrane, with the additional expression of two new isoforms of AChRs. The depolarization of these AChRs that are spread throughout the muscle membrane by succinylcholine and its metabolites leads to potassium efflux from the muscle, leading to hyperkalemia. The nicotinic (neuronal) alpha 7 acetylcholine receptors, recently described to be expressed in muscle also, can be depolarized not only by acetylcholine and succinylcholine but also by choline, persistently, and possibly play a critical role in the hyperkalemic response to succinylcholine in patients with upregulated AChRs. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med,Clin 3, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Martyn, JAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med,Clin 3, 55 Fruit St, Boston, MA 02114 USA. EM jmartyn@etherdome.mgh.harvard.edu FU NIGMS NIH HHS [R001 GM51411-05, R01 GM055082, R01 GM31569-23, R01 GM55082-08] NR 82 TC 121 Z9 127 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2006 VL 104 IS 1 BP 158 EP 169 DI 10.1097/00000542-200601000-00022 PG 12 WC Anesthesiology SC Anesthesiology GA 000OR UT WOS:000234472200021 PM 16394702 ER PT J AU Bennett, GG Wolin, KY Avrunin, JS Stoddard, AM Sorensen, G Barbeau, E Emmons, KM AF Bennett, Gary G. Wolin, Kathleen Y. Avrunin, Jill S. Stoddard, Anne M. Sorensen, Glorian Barbeau, Elizabeth Emmons, Karen M. TI Does race/ethnicity moderate the association between job strain and leisure time physical activity? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID AFRICAN-AMERICAN WOMEN; ACTIVITY QUESTIONNAIRE; SEDENTARY BEHAVIOR; HEALTH BEHAVIORS; MINORITY WOMEN; HEART-DISEASE; UNITED-STATES; OLDER; WORK; EXERCISE AB Background: Racial/ethnic minorities report myriad barriers to regular leisure time physical activity (LTPA), including the stress and fatigue resulting from their occupational activities. Purpose: We sought to investigate whether an association exists between job strain and LTPA, and whether it is modified by race or ethnicity. Methods: Data were collected from 1, 740 adults employed in 26 small manufacturing businesses in eastern Massachusetts. LTPA and job strain data were self-reported. Adjusted mean hours of LTPA per week are reported. Results: In age and gender adjusted analyses, reports of job strain were associated with LTPA. There was a significant interaction between job strain and race or ethnicity (p = .04). Whites experiencing job strain reported 1 less hr of LTPA per week compared to Whites not reporting job strain. Collectively, racial/ethnic minorities reporting job strain exhibited comparatively higher levels of LTPA compared to their counterparts with no job strain, although patterns for individual groups did not significantly differ Conclusions: Job strain was associated with LTPA in a lower income, multiethnic population of healthy adult men and women. The association between job strain and LTPA was modified by race or ethnicity, highlighting the importance of investigating the differential effects of psychosocial occupational factors on LTPA levels by race or ethnicity. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Human Sci, Amherst, MA 01003 USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St,SM256, Boston, MA 02115 USA. EM gbennett@hsph.harvard.edu RI Wolin, Kathleen/I-2154-2014 OI Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [P01 CA075308-01A20002, 5 P01 CA75308, 5 T32 CA09001-28, P01 CA075308, P01 CA075308-030002, T32 CA009001, P01 CA075308-040002, P01 CA075308-020002] NR 66 TC 14 Z9 14 U1 2 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2006 VL 32 IS 1 BP 60 EP 67 DI 10.1207/s15324796abm3201_7 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 063XA UT WOS:000239052000007 PM 16827630 ER PT J AU Sepucha, K Ozanne, E Mulley, AG AF Sepucha, Karen Ozanne, Elissa Mulley, Albert G., Jr. TI Doing the right thing: Systems support for decision quality in cancer care SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Behavioral-Medicine CY APR 13-16, 2005 CL Boston, MA SP Soc Behav Med ID BREAST-CONSERVING SURGERY; 20-YEAR FOLLOW-UP; PATIENTS PREFERENCES; RADICAL-MASTECTOMY; PATIENT-PREFERENCE; OLDER WOMEN; HEALTH; THERAPY; PHYSICIANS; PATTERNS AB Background. There is considerable evidence of problems with the quality of cancer care. Wide variation in rates of interventions suggests that cancer care decisions may not reflect the preferences of informed patients. Purpose: To present a framework for systems support for improving the quality of decisions in cancer Methods: We outlined the types of decisions faced by cancer patients and categorized them based on the level of evidence available about effectiveness of choices and the amount of variation in patients' preferences for the key outcomes. Then we describe appropriate strategies to systematically improve the quality of decision making for each category. Results: The types of decisions faced by cancer patients and providers are varied. The appropriate strategy to drive improvements differs for different decisions. For complex, preference-sensitive decisions, improvements in decision quality require increasing patients' knowledge and the match between patients' preferences and treatments. Conclusions: Decision making in cancer care is complex. Neither patients nor providers can make treatment decisions alone. System support is needed to improve the quality of decisions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hlth Decis Res Unit,Gen Med Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Cambridge, MA 02138 USA. RP Sepucha, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hlth Decis Res Unit,Gen Med Div, 50 Staniford St,Suite 936, Boston, MA 02114 USA. EM ksepucha@partners.org NR 53 TC 19 Z9 19 U1 0 U2 8 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2006 VL 32 IS 3 BP 172 EP 178 DI 10.1207/s15324796abm3203_2 PG 7 WC Psychology, Multidisciplinary SC Psychology GA 114NN UT WOS:000242673000002 PM 17107289 ER PT J AU Blank, T Graves, K Sepucha, K Llewellyn-Thomas, H AF Blank, Thomas Graves, Kristi Sepucha, Karen Llewellyn-Thomas, Hilary TI Understanding treatment decision making: Contexts, commonalities, complexities, and challenges SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Behavioral-Medicine CY APR 13-16, 2005 CL Boston, MA SP Soc Behav Med ID BREAST-CANCER PATIENTS; PROMOTING PATIENT PARTICIPATION; 20-YEAR FOLLOW-UP; PROSTATE-CANCER; PATIENTS PREFERENCES; PHYSICIAN PERCEPTIONS; RADIATION-THERAPY; LARYNGEAL-CANCER; AFRICAN-AMERICAN; COMMUNICATION AB Background: The diagnosis of cancer sets off a cascade of complex decisions at a time when patients feel vulnerable and distressed. Although clinical decisions used to follow one standard, many guidelines now outline several options and include explicit recognition of the need to incorporate patients' p references to determine the most appropriate treatment. Purpose: The purpose of this article is to provide a brief overview of empirical studies about cancer patients' treatment-related decision making, to highlight the areas of congruence and divergence in that empirical literature, and then to generate a framework that points to future interventions and research. Methods: Through a group discussion. with a range of experts in the field, we generated a framework for the critical treatment decisions and key issues within those decisions. Then, we reviewed the literature describing the experiences of cancer patients and evaluating interventions designed to improve the quality of treatment decisions. Results: We identified four major differences that influence decision making across cancers and across individuals with the same diagnosis. We also identified four common themes across situations and people. There is considerable evidence that decision aids can improve the quality of decisions across a range of diseases, although the data for cancer treatment decision making are limited. Other interventions such as navigation-skill training are promising but have little evidence of benefit for cancer decisions. Conclusions: There are many opportunities for behavioral research to extend and contribute to the understanding and improvement of cancer treatment decision making. Some key areas in need of research include developing taxonomies of disease and patient characteristics and increasing understanding of the lived experiences of cancer survivors, of the influence of time and timing, of the relationship of information and preferences, and of participation in randomized clinical trials. C1 Univ Connecticut, Storrs, CT 06269 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20057 USA. Harvard Univ, Massachusetts Gen Hosp, Med Sch, Gen Med Div,Hlth Decis Res Unit, Cambridge, MA 02138 USA. RP Blank, T (reprint author), Univ Connecticut, 348 Mansfield Rd,U2058, Storrs, CT 06269 USA. EM Thomas.blank@uconn.edu NR 84 TC 18 Z9 18 U1 5 U2 11 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2006 VL 32 IS 3 BP 211 EP 217 DI 10.1207/s15324796abm3203_6 PG 7 WC Psychology, Multidisciplinary SC Psychology GA 114NN UT WOS:000242673000006 PM 17107293 ER PT J AU Parchman, ML Romero, RL Pugh, JA AF Parchman, ML Romero, RL Pugh, JA TI Encounters by patients with type 2 diabetes - Complex and demanding: An observational study SO ANNALS OF FAMILY MEDICINE LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Diabetes-Association CY JUN 04-08, 2004 CL Orlando, FL SP Amer Diabet Assoc DE diabetes mellitus; type 2; primary health care; quality of health care ID PRIMARY-CARE PRACTICE; COMPETING DEMANDS; QUALITY; VISITS; MANAGEMENT; SERVICES; DISEASES; CENTERS; MODEL; TIME AB PURPOSE We wanted to examine the relationships between quality of diabetes care delivered, the type and length of encounter, and time to the next follow-up encounter. METHODS The content of the physician-patient encounter was directly observed in 20 primary care clinics for 211 patients with type 2 diabetes mellitus. The quality of diabetes care was measured as the percentage of the 5 following services delivered during the encounter if they had not been offered in the previous year: foot examination, referral for an eye examination, a glycosylated hemoglobin (HbA(1c)) measurement, a lipid panel, and a urine microalbumin test. RESULTS All indicated services were performed in 33% of encounters. Compared with encounters for an acute illness, patients visiting for chronic disease follow-up were 4.8 (95% CI, 1.95%-12.01%) times more likely to receive 100% of all indicated services. Length of encounter was associated with percentage of services delivered, but only during chronic disease follow-up encounters (P =.02). Encounters during which 100% of all indicated services were delivered had a mean length of 19.4 minutes. The time to the next scheduled encounter was shorter if fewer services were delivered during the observed encounter (P =.009). CONCLUSIONS Competing demands during primary care encounters require patient and physician to prioritize services delivered and defer indicated services to subsequent visits. Current models of patient care in primary care settings are inadequate to address the multitude of tasks facing clinicians, especially among patients with complex chronic illnesses. Innovative approaches and new models are needed to improve the quality of diabetes care. C1 S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr, 11C6,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU AHRQ HHS [K08 HS013008-02] NR 28 TC 46 Z9 46 U1 1 U2 3 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD JAN-FEB PY 2006 VL 4 IS 1 BP 40 EP 45 DI 10.1370/afm.422 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 013UU UT WOS:000235436200007 PM 16449395 ER PT J AU Priplata, AA Patritti, BL Niemi, JB Hughes, R Gravelle, DC Lipsitz, LA Veves, A Stein, J Bonato, P Collins, JJ AF Priplata, AA Patritti, BL Niemi, JB Hughes, R Gravelle, DC Lipsitz, LA Veves, A Stein, J Bonato, P Collins, JJ TI Noise-enhanced balance control in patients with diabetes and patients with stroke SO ANNALS OF NEUROLOGY LA English DT Article ID STOCHASTIC RESONANCE; POSTURAL INSTABILITY; SENSORY NEUROPATHY; TACTILE SENSATION; OLDER ADULTS; DYNAMIC POSTUROGRAPHY; PERIPHERAL NEUROPATHY; MOVEMENT PERCEPTION; ELECTRICAL NOISE; MUSCLE-SPINDLES AB Objective: Somatosensory function declines with diabetic neuropathy and often with stroke, resulting in diminished motor performance. Recently, it has been shown that input noise can enhance human sensorimotor function. The goal of this study was to investigate whether subsensory mechanical noise applied to the soles of the feet via vibrating insoles can be used to improve quiet-standing balance control in 15 patients with diabetic neuropathy and 15 patients with stroke. Sway data of 12 healthy elderly subjects from a previous study on vibrating insoles were added for comparison. Methods. Five traditional sway parameters and three sway parameters from random-walk analysis were computed for each trial (no noise or noise). Results: Application of noise resulted in a statistically significant reduction in each of the eight sway parameters in the subjects with diabetic neuropathy, the subjects with stroke, and the elderly subjects. We also found that higher levels of baseline postural sway in sensory-impaired individuals was correlated with greater improvements in balance control with input noise. Interpretation This work indicates that noise-based devices could ameliorate diabetic and stroke impairments in balance control. C1 Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. Boston Univ, Ctr BioDynam, Boston, MA USA. Afferent Corp, Providence, RI USA. Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Cambridge, MA USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Cambridge, MA USA. Beth Israel Deaconess Med Ctr, Gerontol Div, Cambridge, MA USA. Harvard Univ, Sch Med, Div Aging, Cambridge, MA USA. Joslin Beth Israel Deaconess Foot Ctr, Dept Surg, Boston, MA USA. Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA USA. Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. RP Collins, JJ (reprint author), Boston Univ, Dept Biomed Engn, 44 Cummington St, Boston, MA 02215 USA. EM jcollins@bu.edu FU NIA NIH HHS [AG 08812]; NICHD NIH HHS [HD 37880]; NIDDK NIH HHS [DK 60295]; PHS HHS [H133P990003] NR 68 TC 126 Z9 129 U1 4 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2006 VL 59 IS 1 BP 4 EP 12 DI 10.1002/ana.20670 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 000FU UT WOS:000234447100001 PM 16287079 ER PT J AU Ho, ICK Passeri, JJ Guy, ML Ruskin, JN Ellinor, PT AF Ho, ICK Passeri, JJ Guy, ML Ruskin, JN Ellinor, PT TI Impact of the multicenter automatic defibrilator implantation trial on clinical practice SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE implantable cardioverter defibrillator; Multicenter Automatic Defibrillator Implantation Trial; ventricular arrhythmia; nonsustained ventricular tachycardia ID MALIGNANT VENTRICULAR ARRHYTHMIAS; ANTIARRHYTHMIC-DRUG THERAPY; ACUTE MYOCARDIAL-INFARCTION; CARDIOVERTER-DEFIBRILLATOR; CARDIAC DEFIBRILLATORS; SECONDARY PREVENTION; PROPHYLACTIC USE; SUDDEN-DEATH; HIGH-RISK; SURVIVAL AB Background: The first multicenter automatic defibrillator implantation trial (MADIT-I) was a I and mark study that identified a significant reduction in mortality among high-risk patients with ischemic cardiomyopathy treated prophylactically with an implantable cardioverter defibrillator (ICD), yet the direct and indirect impact of this trial on clinical practice is unknown. Methods: We performed a retrospective analysis of the 679 patients who underwent primary ICD implantation between 1994 and 2000 at a single academic center. The baseline characteristics of each patient were determined at the time of ICD implantation, and the vital status of all patients was determined as of January 1, 2004. Results: The number of patients who received an ICD based on the MADIT-I criteria increased from 1.4% in 1994 to 6.1% in 2000. An additional 60 patients were identified that met many but not all of the trial criteria and consisted of patients with a history of a recent revascularization or myocardial infarction, syncope, or an ejection fraction >= 35%. The number of patients who received ICDs in this expanded MADIT-I subset also grew from 5.6% in 1994 to 14.6% in 2000. Mortality during a mean follow-up of 4.7 years was significantly higher in the MADIT-I group than in the expanded MADIT-I, or the remaining primary prevention and secondary prevention subsets. Conclusion: The MADIT-I has not only led to an increase in the number of patients undergoing prophylactic ICD implantation, but in clinical practice it has also been extrapolated to a broader population that has a different degree of risk than originally studied. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM pellinor@partners.org FU NHLBI NIH HHS [HL71632] NR 24 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JAN PY 2006 VL 11 IS 1 BP 20 EP 27 DI 10.1111/j.1542-474X.2006.00061.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014HP UT WOS:000235470700004 PM 16472278 ER PT J AU Jain, RK AF Jain, RK TI Normalization of tumor vasculature and microenvironment by targeted therapies: From the bench to bedside and back SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th International Symposium on Targeted Anticancer Therapies CY MAR 16-18, 2006 CL Amsterdam, NETHERLANDS SP Novartis, AstraZeneca, Bayer HealthCare, Centocor, Johnson & Johnson, Lilly, Merck, MSD, OSI, Schering ID CANCER C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 3 BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 046GZ UT WOS:000237800900006 ER PT J AU Casali, P Garrett, C Blackstein, M Shah, M Verweij, J McArthur, G Judson, I Li, J Baum, C Demetri, G AF Casali, P. Garrett, C. Blackstein, M. Shah, M. Verweij, J. McArthur, G. Judson, I Li, J. Baum, C. Demetri, G. TI A phase III trial of sunitinib in GIST patients following failure of imatinib mesylate: Updated trial results SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Ist Nazl Tumori, I-20133 Milan, Italy. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Toronto, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands. Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. Royal Marsden Hosp, London SW3 6JJ, England. Pfizer Global Res & Dev, Ann Arbor, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 6 BP 21 EP 22 PG 2 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000012 ER PT J AU Corless, C Demetri, G Maki, R Antonescu, C Fletcher, J Fletcher, C Huang, X Baum, C Heinrich, M AF Corless, C. Demetri, G. Maki, R. Antonescu, C. Fletcher, J. Fletcher, C. Huang, X. Baum, C. Heinrich, M. TI Sunitinib activity in imatinib-resistant GITS patients: Correlation with KIT and PDGFRA mutation status SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. OHSU, Inst Canc, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 6 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000014 ER PT J AU Dileo, P Morgan, J Garrett, C Schutte, H Hurwitz, H Rosen, L Ruka, W Picus, J Baum, C Demetri, G AF Dileo, P. Morgan, J. Garrett, C. Schutte, H. Hurwitz, H. Rosen, L. Ruka, W. Picus, J. Baum, C. Demetri, G. TI Early results from a treatment-use trial of sunitinib in patients with advanced GITS following failure of imatinib therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Marien Hosp, Dusseldorf, Germany. Duke Univ, Med Ctr, Durham, NC USA. Canc Ctr Inst, Warsaw, Poland. Premiere Oncol, Santa Monica, CA USA. Siteman Canc Ctr, St Louis, MO USA. Pfizer Global Res & Dev, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 6 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000013 ER PT J AU Johnson, BE AF Johnson, BE TI Epidermal growth factor receptor (EGFR): Patient selection for EGFR SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th International Symposium on Targeted Anticancer Therapies CY MAR 16-18, 2006 CL Amsterdam, NETHERLANDS SP Novartis, AstraZeneca, Bayer HealthCare, Centocor, Johnson & Johnson, Lilly, Merck, MSD, OSI, Schering ID CELL LUNG-CANCER; GEFITINIB; MUTATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 3 BP 26 EP 27 PG 2 WC Oncology SC Oncology GA 046GZ UT WOS:000237800900025 ER PT J AU George, S Casali, P Blay, J Le Cesne, A Tyler, A Quigley, M Tassell, V Baum, C Demetri, G AF George, S. Casali, P. Blay, J. Le Cesne, A. Tyler, A. Quigley, M. Tassell, V Baum, C. Demetri, G. TI Continuous daily dosing of sunitinib in patients with advanced GIST: Initial results of a phase II study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Ctr Leon Berard, Lyon, France. Inst Gustave Roussy, Villejuif, France. Ist Nazl Tumori, Milan, Italy. Dana Farber Canc Inst, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 6 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000032 ER PT J AU Elson, PJ Bacik, JM Manola, JB Royston, P Mazumdar, M AF Elson, Paul J. Bacik, Jennifer. M. Manola, Judith. B. Royston, Patrick Mazumdar, Mahdu TI Prognostic factors in metastatic renal cell carcinoma, an international consensus SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Cleveland Clin, Cleveland, OH 44106 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MRC Clin Trials Unit, Canc Grp, London, England. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 32 EP 32 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900035 ER PT J AU Garber, J AF Garber, Judy TI Cancer prevention in the US: Progress and priorities SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 43 EP 44 PG 2 WC Oncology SC Oncology GA 190SH UT WOS:000248078900064 ER PT J AU Motzer, RJ Hutson, TE Tomczak, P Michaelson, MD Bukowski, RM Rixe, O Oudard, S Kim, ST Baum, CM Figlin, RA AF Motzer, R. J. Hutson, T. E. Tomczak, P. Michaelson, M. D. Bukowski, R. M. Rixe, O. Oudard, S. Kim, S. T. Baum, C. M. Figlin, R. A. TI Phase III randomized trial of sunitinib malate (SU11248) versus interferon- alfa (IFN-A) as first-line systemic therapy for patients with metastatic renal cell carcinoma (MRCC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Baylor Sammons Texas Oncol, Dallas, TX USA. Klin Oncol Oddzial Chemioterapii, Poznan, Poland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Hosp Pitie Salpetriere, Paris, France. Georges Pompidou European Hosp, Paris, France. Pfizer Inc, La Jolla, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 53 EP 54 PG 2 WC Oncology SC Oncology GA 190SH UT WOS:000248078900092 ER PT J AU Vahdat, L Bunnell, C Schwartzberg, L Gralow, J Poulart, V Klimovsky, J Peck, R Thomas, E AF Vahdat, Linda Bunnell, Craig Schwartzberg, Lee Gralow, Julie Poulart, Valerie Klimovsky, Judith Peck, Ronald Thomas, Eva TI Ixabepilone is effective in combination with capecitabine in ER, PR, HER-2 negative (triple negative) patients (PTS) resistant to taxanes and anthracyclines: Final results from a breast cancer exploratory program SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. West Clin, Memphis, TN USA. Univ Washington, Seattle, WA 98195 USA. Bristol Myers Squibb Co, Global Biometr Sci, Pharmaceut Res Inst, Braine LAlleud, Belgium. Bristol Myers Squibb Co, Oncol Global Clin Res, Wallingford, CT 06492 USA. Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 74 EP 74 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900170 ER PT J AU Janeway, K Matthews, D Butrynski, J D'Amato, G Agresta, S Garrett, C Corless, C Albritton, K Demetri, G AF Janeway, K. Matthews, D. Butrynski, J. D'Amato, G. Agresta, S. Garrett, C. Corless, C. Albritton, K. Demetri, G. TI Sunitinib treatment in pediatric patients with metastatic GIST following failure of imatinib SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp & Reg Canc Ctr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Seattle Canc Care Alliance, Seattle, WA USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 6 BP 102 EP 102 PG 1 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000329 ER PT J AU Raut, C Van den Abbeele, A Ramaiya, N Morgan, J George, S Quigley, M Dollard, A Bertagnolli, M Baum, C Demetri, G AF Raut, C. Van den Abbeele, A. Ramaiya, N. Morgan, J. George, S. Quigley, M. Dollard, A. Bertagnolli, M. Baum, C. Demetri, G. TI Pet imaging demonstrates two patterns of response in GIST patients benefiting from long-term sunitinib therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 6 BP 103 EP 103 PG 1 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000333 ER PT J AU Giantonio, BJ Catalano, PJ Meropol, NJ O'Dwyer, PJ Benson, AB AF Giantonio, Bruce J. Catalano, Paul J. Meropol, Neal J. O'Dwyer, Peter J. Benson, Al B., III TI The effect of bevacizumab dose reduction on hypertension and proteinuria for patients treated on the Eastern Cooperative Oncology Group study E3200 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 126 EP 127 PG 2 WC Oncology SC Oncology GA 190SH UT WOS:000248078900381 ER PT J AU Parodi, LA Pickering, EH Lee, DS Cisar, LA Sersch, MA Soufi-Mahjoubi, R Fuchs, CS AF Parodi, Luis A. Pickering, Eve H. Lee, Douglas S. Cisar, Laura A. Sersch, Martina A. Soufi-Mahjoubi, Raoudha Fuchs, Charles S. TI Multivariate models of irinotecan-induced neutropenia SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Pfizer Inc, Polyomics, New York, NY USA. Pfizer Inc, Clin Stat, Groton, CT 06340 USA. Pfizer Inc, WWMedical, New York, NY USA. Pfizer Inc, US Med, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 126 EP 126 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900378 ER PT J AU Reichardt, P Casali, PG Blay, JY von Mehren, M Schoffski, P Tanaka, C Jalaluddin, M Veronese, ML Demetri, GD AF Reichardt, Peter Casali, Paolo G. Blay, Jean-Yves von Mehren, Margaret Schoffski, Patrick Tanaka, Chiaki Jalaluddin, Muhammad Veronese, Maria Luisa Demetri, George D. TI A phase I study of nilotinib alone and in combination with imatinib in patients (PTS) with imatinib-resistant gastrointestinal stromal tumors (GIST) - Study update SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Ist Nazl Tumori, Ist Nazl Tumori, Adult Sarcoma Mdcl Oncol Unit, I-20133 Milan, Italy. Ctr Leon Berard, F-69373 Lyon, France. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Leuven Canc Inst, Louvain, Belgium. Novartis Pharma AG, Oncol Clin Pharmacol, E Hanover, NJ USA. Novartis Pharma AG, Oncol Biostat, E Hanover, NJ USA. Novartis Pharma AG, Oncol Clin Dev, Basel, Switzerland. Dana Farber Canc Inst, Sarcoma Ctr, Boston, MA 02115 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 138 EP 138 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900427 ER PT J AU Rini, BI George, DJ Michaelson, MD Rosenberg, JE Bukowski, RM Sosman, JA Stadler, WM Margolin, K Hutson, TE Baum, CM AF Rini, Brian I. George, Daniel J. Michaelson, M. Dror Rosenberg, Jonathan E. Bukowski, Ronald M. Sosman, Jeffrey A. Stadler, Walter M. Margolin, Kim Hutson, Thomas E. Baum, Charles M. TI Phase II study of sunitinib malate (SU11248) in bevacizumab-refractory metastatic renal cell carcinoma (MRCC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Cleveland Clin Fdn, Taussig Canc Ctr, Glickman Urol Inst, Cleveland, OH 44195 USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Univ Chicago, Chicago, IL 60637 USA. Baylor Sammons Texas Oncol, Cleveland, OH USA. Pfizer Inc, Global Res & Dev, La Jolla, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 144 EP 144 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900450 ER PT J AU Negrier, S Jager, E Porta, C McDermott, D Moore, M Bellmunt, J Schwartz, B Anderson, S Escudier, B Bukowski, R AF Negrier, Sylvie Jaeger, E. Porta, C. McDermott, D. Moore, M. Bellmunt, J. Schwartz, B. Anderson, S. Escudier, B. Bukowski, R. TI Sorafenib in patients with advanced renal cell carcinoma and prior cytokine therapy: Subgroup analysis of targets SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Ctr Leon Berard, Dept Med Oncol, F-69373 Lyon, France. Krankenhaus Nordw, Med Klin 2, Frankfurt, Germany. IRCCS San Matteo Univ Hosp, Pavia, Italy. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Hosp Gen Valle Hebron, Dept Oncol, Barcelona, Spain. Bayer Pharmaceut, Oncol, New Haven, CT USA. Bayer Pharmaceut, Dept Oncol, West Haven, CT USA. Inst Gustave Roussy, Villejuif, France. Cleveland Clin Fdn, Cleveland Clin Canc Ctr, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 145 EP 145 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900451 ER PT J AU Demetri, GD Mehren, MV Joensuu, H Huse, D Lenhart, G Feng, WW Blanke, C AF Demetri, George D. Mehren, Margaret V. Joensuu, Heikki Huse, Daniel Lenhart, Greg Feng, Weiwei Blanke, Charles TI Relation between gastrointestinal stromal tumor (GIST) response to imatinib therapy and long-term survival SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Helsinki, FIN-00014 Helsinki, Finland. Thomas Medstat Pharmaceut Outcome Res & Econometr, Cambridge, MA USA. Hlth Econ, Florhem Pk, NJ USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland Vet Med Ctr, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 161 EP 162 PG 2 WC Oncology SC Oncology GA 190SH UT WOS:000248078900515 ER PT J AU Dileo, P Morgan, JA Garrett, CR Schutte, HJ Hurwitz, H Rosen, LS Ruka, W Picus, J Baum, CM Demetri, GD AF Dileo, Palma Morgan, Jeffrey A. Garrett, Christopher R. Schutte, Hans J. Hurwitz, Herbert Rosen, Lee S. Ruka, Wlodzimierz Picus, Joel Baum, Charles M. Demetri, George D. TI Updated results from a "treatment-use" trial of sunitinib in advanced gastrointestinal stromal tumor (GIST) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Marien Hosp, Dept Oncol Hematol, Dusseldorf, Germany. Duke Univ, Med Ctr, Duke S Clin, Durham, NC 27706 USA. Premiere Oncol, Santa Monica, CA USA. Canc Ctr Inst, Warsaw, Poland. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63130 USA. Pfizer Inc, Global Res & Dev, La Jolla, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 162 EP 163 PG 2 WC Oncology SC Oncology GA 190SH UT WOS:000248078900519 ER PT J AU Huse, D Lenhart, G Feng, WW Blanke, C Joensuu, H Mehren, MV Demetri, GD AF Huse, Daniel Lenhart, Greg Feng, Weiwei Blanke, Charles Joensuu, Heikki Mehren, Margaret V. Demetri, George D. TI Cost-effectiveness (CE) of imatinib (IM) in the treatment of advanced gastrointestinal stromal tumors (GIST) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Thomas Medstat Pharmaceut Outcome Res & Econometr, Cambridge, MA USA. Novartis, Hlth Econ, Florhem Pk, NJ USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland Vet Med Ctr, Portland, OR 97201 USA. Univ Helsinki, FIN-00014 Helsinki, Finland. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 162 EP 162 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900517 ER PT J AU Judson, IR Casali, PG Garrett, CR Blackstein, ME Shah, M Verweij, J McArthur, G Li, J Baum, CM Demetri, GD AF Judson, Ian R. Casali, Paolo G. Garrett, Christopher R. Blackstein, Martin E. Shah, Manisha Verweij, Jaap McArthur, Grant Li, Jim Baum, Charles M. Demetri, George D. TI Updated results from a phase III trial of sunitinib in advanced gastrointestinal stromal tumor (GIST) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Royal Marsden Hosp, Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England. Ist Nazl Tumori, Milan, Italy. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Res Inst, Tampa, FL 33682 USA. Univ Toronto, Div Internal Med, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Erasmus Univ, Ctr Med, NL-3000 DR Rotterdam, Netherlands. Peter MacCallum Canc Ctr, Div Haematol Med Oncol, Melbourne, Vic 3000, Australia. Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 3000, Australia. Pfizer Inc, Global Res & Dev, La Jolla, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 162 EP 162 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900518 ER PT J AU Blay, JY George, S Casali, PG Le Cesne, A Morgan, JA Tyler, A Quigley, MT Tassell, V Baum, CM Demetri, GD AF Blay, Jean-Yves George, Suzanne Casali, Paolo G. Le Cesne, Axel Morgan, Jeffrey A. Tyler, Angela Quigley, Michael T. Tassell, Vanessa Baum, Charles M. Demetri, George D. TI Clinical benefit of continuous daily dosing of sunitinib in patients (pts) with advanced gastrointestinal stromal tumor (GIST) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Ctr Leon Berard, Lyon, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Ist Nazl Tumori, I-20133 Milan, Italy. Inst Gustave Roussy, Dept Med, F-94800 Villejuif, France. Pfizer Inc, Global Res & Dev, La Jolla, CA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 163 EP 163 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900520 ER PT J AU Forero-Torres, A Cohen, P Cheson, BD Robinson, KS La Casce, AS Fayad, L Camacho, ES Williams, ME van der Jagt, RH Friedberg, JW AF Forero-Torres, Andres Cohen, Philip Cheson, Bruce D. Robinson, K. Sue La Casce, Ann S. Fayad, Luis Camacho, Elber S. Williams, Michael E. van der Jagt, Richard H. Friedberg, Jonathan W. TI A phase II study of single-agent bendamustine in rituximab-refractory B-cell non-Hodgkin's lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Univ Alabama, Birmingham, AL USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Desert Reg Med Ctr, Palm Springs, CA USA. Univ Virginia, Charlottesville, VA USA. Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada. Univ Rochester, Rochester, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 203 EP 203 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900681 ER PT J AU Cappuzzo, F Janne, PA Bartolini, S Holmes, AJ Trisolini, R Magrini, E Rossi, E Crino, L Ciardiello, F Garcia, MV AF Cappuzzo, Federico Janne, Pasi A. Bartolini, Stefania Holmes, A. J. Trisolini, Rocco Magrini, Elisabetta Rossi, Elisa Crino, Lucio Ciardiello, Fortunato Garcia, Marileila Varella TI Gefitinib in EGFR fish positive/p-Akt positive or never smoker non-small cell lung cancer (NSCLC): Results of the oncobell trial SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 31st Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Bellaria Hosp, Bologna, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Maggiore Hosp, Bologna, Italy. Bellaria Hosp, Bologna, Italy. CINECA, Bologna, Italy. Silvestrini Hosp, Perugia, Italy. Univ Naples 2, Naples, Italy. Univ Colorado, Ctr Canc, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 215 EP 215 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900730 ER PT J AU Janne, PA Wang, XFF Krug, LM Hodgson, L Vokes, EE Kindler, HL AF Janne, Pasi A. Wang, Xiaofei F. Krug, Lee M. Hodgson, Lydia Vokes, Everett E. Kindler, Hedy L. TI Phase II trial of sorafenib (bay 43-9006) in malignant mesothelioma: CALGB 30307 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, New York, NY 10021 USA. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 216 EP 217 PG 2 WC Oncology SC Oncology GA 190SH UT WOS:000248078900735 ER PT J AU Mok, TS Lui, P To, KF Holmes, AJ Lai, P Wu, YL Anthony, Y Ho, S Janne, PA AF Mok, Tony S. Lui, Philip To, Ka Fai Holmes, Alison J. Lai, Paul Wu, Yi Long Anthony, Yim Ho, Simon Janne, Pasi A. TI Epidermal growth factor receptor (EGFR) exon 20 mutations in Asian lung and liver cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Dana Farber Canc Inst, Boston, MA 02115 USA. Guangdong Prov Peoples Hosp, Guangzhou, Peoples R China. RI Lai, Paul/K-8556-2015; Wu, Yi-Long/C-3396-2008 OI Lai, Paul/0000-0002-9469-6728; Wu, Yi-Long/0000-0002-3611-0258 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 251 EP 251 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900868 ER PT J AU Vera-Llonch, M Sonis, ST Keefe, D Elting, L Edelsberg, J Isitt, J Mayne, T Oster, G AF Vera-Llonch, Montserrat Sonis, Stephen T. Keefe, Dorothy Elting, Linda Edelsberg, John Isitt, John Mayne, Tracy Oster, Gerry TI Identifying potential mucositis-related infection resource use in solid tumor cancer patients SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Policy Anal Inc, Biostat, Brookline, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Adelaide, Royal Adelaide Hosp, Adelaide, SA 5000, Australia. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Policy Anal Inc, Brookline, MA USA. Amgen Inc, Global Hlth Econ, Thousand Oaks, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 286 EP 286 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900981 ER PT J AU Elting, LS Keefe, D Sonis, ST Morales, M Molassiotis, A Isitt, J Mayne, T Ostre, G Vera-Llonch, M AF Elting, Linda S. Keefe, Dorothy Sonis, Stephen T. Morales, Manual Molassiotis, Alexander Isitt, John Mayne, Tracy Ostre, Gerry Vera-Llonch, Monserrat TI Burden of illness and economic impact of mucosal injury (MUI) in solid tumor-a multinational prospective observational study design SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Univ Adelaide, Royal Adelaide Hosp, Dept Med, Adelaide, SA, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Santa Cruz de Tenerife, Santa Cruz de La Palma, Spain. Univ Manchester, Manchester, Lancs, England. Amgen Inc, Global Hlth Econ, Thousand Oaks, CA 91320 USA. Policy Anal Inc, Biostat, Brookline, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 297 EP 297 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078901023 ER PT J AU Enzinger, PC Fidias, P Stuart, K Fuchs, C Bhargava, P Meyerhardt, J Earle, C Attawia, M Regan, E Zhu, AX AF Enzinger, Peter C. Fidias, P. Stuart, K. Fuchs, C. Bhargava, P. Meyerhardt, J. Earle, C. Attawia, M. Regan, E. Zhu, A. X. TI Phase II study of bevacizumab and docetaxel (avatax) in metastatic esophageal and gastric cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 9 BP 310 EP 310 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078901070 ER PT J AU Kaufman, DS AF Kaufman, D. S. TI Challenges in the treatment of bladder cancer SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT Workshop on Gemcitabine - Ten Years of Clinical Experience CY SEP 19-21, 2005 CL Monastier di Treviso, ITALY ID GROWTH-FACTOR RECEPTOR; TRANSITIONAL-CELL-CARCINOMA; THERAPY ONCOLOGY GROUP; QUALITY-OF-LIFE; TRANSURETHRAL RESECTION; RADICAL RADIOTHERAPY; PROGNOSTIC FACTORS; RADIATION-THERAPY; PHASE-III; P53 AB Seventy to eighty percent of patients with newly-diagnosed bladder cancer will present with superficial tumors (Ta, Tis or T-1). There is, however, a continuum between superficial and muscle-invasive cancer, with the advanced cases usually associated with less-differentiated histology and aneuploidy. Common sites of metastasis include regional lymph nodes, bone, lung, skin and liver. From the low cure rates achieved with radical cystectomy, there is strong evidence that bladder cancer, from the outset, is a systemic disease. The limitations of local treatment are well-documented: a local control rate of 30% with radiation treatment, and 50-70% with radical cystectomy; and no improvement in surgical cure was seen with the use of preoperative radiation. Over the past 30 years, since the initial reports of the effectiveness of cisplatin in the treatment of advanced bladder cancer, there has been a steady flow of chemotherapeutic agents, singly and in combination, shown to be effective in the treatment of this tumor. While response rates and CR rates have increased with the use of combination chemotherapy, this has not translated into survival in advanced disease of greater than 16 months. While the search for more effective agents and combinations continues, attention has also been given to the roles of neoadjuvant and adjuvant chemotherapy in an effort to improve the cure rate achieved with surgery alone. Although radical cystectomy, with continent diversion or neobladder construction in selected cases remains the standard of care in the United States for patients with muscle-invasive bladder cancer, several groups have explored therapeutic strategies that aim at bladder preservation. Early approaches with the goal of bladder preservation consisted of radiation treatment as monotherapy (largely abandoned) or aggressive TURBT for smaller tumors. Over the past 20 years, the Massachusetts General Hospital (MGH) and the Radiation Therapy Oncology Group (RTOG) have studied patients with muscle-invading bladder cancer utilizing tri-modality treatment: a visibly complete transurethral resection followed by radiation with concurrent radiosensitizing chemotherapy and, subsequently, adjuvant chemotherapy. Thus, chemotherapy has been used in two phases of treatment (1) as radiosensitizers, given concurrently with radiation treatment and ( 2) as adjuvant treatment, recognizing that survival will only be improved by the successful treatment of micrometastases. Based on preliminary information from reports of the effectiveness of gemcitabine/cisplatin in advanced disease, that combination was chosen as the adjuvant regimen in one of our earlier protocols, recently completed and reported. Our current protocol utilizes the Bellmunt regimen as our adjuvant program with the highest RR in advanced disease. This study is ongoing, with early reports of tolerance of the three-drug regimen encouraging. The treatment options for muscularis propria-invasive bladder tumors can broadly be divided into those that spare the bladder and those that involve removing it. In the United States, radical cystectomy with pelvic lymph node dissection is the standard method used to treat patients with this tumor. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, Claire & John Bertucci Ctr Genitourinary Canc, Yawkey Bldg,Suite 7E, Boston, MA 02114 USA. NR 46 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2006 VL 17 SU 5 BP V106 EP V112 DI 10.1093/annonc/mdj963 PG 7 WC Oncology SC Oncology GA 190SF UT WOS:000248078700024 PM 16807436 ER PT J AU Resto, VA Krane, JF Faquin, WC Lin, DT AF Resto, VA Krane, JF Faquin, WC Lin, DT TI Immunohistochemical distinction of intestinal-type sinonasal adenocarcinoma from metastatic adenocarcinoma of intestinal origin SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cytokeratin 7; cytokeratin 20; intestinal-type sinonasal adenocarcinoma; mucin 2; sinonasal metastatic adenocarcinoma ID CLASSIFICATION; EXPRESSION; CDX-2; MUC2 AB Objectives: Distinction of intestinal-type sinonasal adenocarcinoma (ITAC) from adenocarcinoma of intestinal origin metastatic to the sinonasal cavity may be extremely difficult on histologic grounds alone. We studied the role of cytokeratin (CK) and mucin (MUC) expression in differentiating ITAC, metastatic adenocarcinoma of intestinal origin, and nonintestinal-type sinonasal adenocarcinoma (non-ITAC). Methods: We stained specimens from 5 cases of ITAC and 4 cases of non-ITAC, along with 4 colonic and 3 duodenal adenocarcinoma controls, with CK7 and CK20, MUC2 and MUC5, neuron-specific enolase (NSE), chromogranin (CHR), Z and carcinoembryonic antigen (CEA) in order to examine the possible combinations of markers that best aid in the diagnosis of these lesions. We also performed a retrospective review of our clinical experience with these rare lesions. Results: CK7 staining was positive in all ITAC and non-ITAC cases, whereas all cases displaying gastrointestinal-type differentiation (ITAC and metastatic intestinal cases) stained positive for both CK20 and MUC2. Staining for MUC5, NSE, CHR, and CEA was variable. Conclusions: Tumors with the CK7(+), CK20(+), MUC2(+) immunophenotype are likely primary sinonasal lesions, whereas tumors with the CK7(-), CK20(+), MUC2(+) profile warrant further clinical evaluation to exclude metastatic disease from the gastrointestinal tract. Complete surgical resection of ITAC remains the mainstay of therapy. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lin, DT (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RI Resto, Vicente/D-9891-2014 NR 9 TC 5 Z9 6 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2006 VL 115 IS 1 BP 59 EP 64 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 003BS UT WOS:000234657200009 PM 16466101 ER PT J AU Friedman, DM Sokal, SM Chang, YH Berger, DL AF Friedman, DM Sokal, SM Chang, YH Berger, DL TI Increasing operating room efficiency through parallel processing SO ANNALS OF SURGERY LA English DT Article AB Objective: Because of rising costs and shrinking reimbursements, hospitals must continually find ways to improve efficiency and productivity. This study attempts to increase caseloads in ambulatory surgery operating rooms while maintaining patient satisfaction and safety. Summary Background Data: In most hospitals, patients move through their operative day in a linear fashion, starting at registration and finishing in the recovery room. Given this pattern, only 1 patient may occupy the efforts of the operating room team at a time. By processing patients in a parallel fashion, operating room efficiency and patient throughput are increased while costs remain stable. Methods: Patients undergoing hernia repairs under local anesthesia with intravenous sedation were divided into a control group and an experimental group. Patients in the control group received their local anesthesia in the operating room at the start of the surgery. The experimental group patients received their local anesthesia in the induction room by the surgeon while the operating room was being cleaned and set up. Results: While operative time for the control group and the experimental group were nearly identical, the turnover time and the induction time were significantly shorter for the experimental group. The cumulative reduction in time during the operative day was sufficient to allow the addition of new operative cases. Conclusions: This study demonstrates a system of increasing operating room efficiency by changing patient flow rather than simply working to streamline existing steps. This increase in efficiency is not associated with the expansion of hospital budgets or a decrease in patient safety or satisfaction. C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Surg, Suite 465,15 Parkman St, Boston, MA 02114 USA. EM dberger@partners.org NR 3 TC 68 Z9 69 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2006 VL 243 IS 1 BP 10 EP 14 DI 10.1097/01.sla.0000193600.97748.b1 PG 5 WC Surgery SC Surgery GA 998IK UT WOS:000234311800003 PM 16371730 ER PT S AU Eggert, US Mitchison, TJ Field, CM AF Eggert, Ulrike S. Mitchison, Timothy J. Field, Christine M. TI Animal cytokinesis: From parts list to mechanisms SO ANNUAL REVIEW OF BIOCHEMISTRY SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE cleavage furrow; contractile ring; midzone microtubules; RNAi ID KINESIN-LIKE PROTEIN; ANAPHASE-PROMOTING COMPLEX/CYCLOSOME; CLEAVAGE PLANE SPECIFICATION; CENTRAL-SPINDLE FORMATION; ASYMMETRIC CELL-DIVISION; HEAVY-CHAIN GENE; MYOSIN-II; CONTRACTILE RING; CAENORHABDITIS-ELEGANS; ACTIN-FILAMENTS AB The mechanism underlying cytokinesis, the final step in cell division, remains one of the major unsolved questions in basic cell biology. Thanks to advances in functional genomics and proteomics, we are now able to assemble a "parts list" of proteins involved in cytokinesis. In this review, we discuss how to relate this parts list to biological mechanism. For easier analysis, we split cytokinesis into discrete steps: cleavage plane specification, rearrangement of microtubule structures, contractile ring assembly, ring ingression, and completion. We report on the advances that have been made to understand these steps and how they can be integrated into a global understanding of cytokinesis. We also discuss the extent to which classic questions have been answered and identify major outstanding questions. 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. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Eggert, US (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ulrike_eggert@hms.harvard.edu; timothy_mitchison@hms.harvard.edu; christine_field@hms.harvard.edu FU NIGMS NIH HHS [R01 GM023928-25] NR 174 TC 268 Z9 270 U1 0 U2 29 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 BN 978-0-8243-0875-9 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2006 VL 75 BP 543 EP 566 DI 10.1146/annurev.biochem.74.082803.133425 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074JD UT WOS:000239807600021 PM 16756502 ER PT S AU Nuiachristos, V AF Nuiachristos, Vasifis TI Fluorescence molecular imaging SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING SE ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review; Book Chapter DE optical imaging; optical tomography; fluorescence; drug discovery; small-animal imaging ID DIFFUSE OPTICAL TOMOGRAPHY; HETEROGENEOUS TURBID MEDIA; IN-VIVO; GENE-EXPRESSION; SCATTERING MEDIA; INDOCYANINE GREEN; BREAST-CANCER; STRUCTURAL INFORMATION; TRANSGENE EXPRESSION; RADIATIVE-TRANSFER AB There is a wealth of new fluorescent reporter technologies for tagging of many cellular and subcellular processes in vivo. This imposed contrast is now captured with an increasing number of imaging methods that offer new ways to visualize and quantify fluorescent markers distributed in tissues. This is an evolving field of imaging sciences that has already achieved major advances but is also facing important challenges. It is nevertheless well poised to significantly impact the ways of biological research, drug discovery, and clinical practice in the years to come. Herein, the most pertinent technologies associated with in vivo noninvasive or minimally invasive fluorescence imaging of tissues are summarized. Focus is given to small-animal imaging. However, a spectrum of fluorescence reporters and imaging methods is outlined with broader potential applications to biomedical research and the clinical practice as well. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nuiachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Boston, MA 02114 USA. EM vasilis@helix.mgh.harvard.edu NR 143 TC 55 Z9 56 U1 4 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 BN 978-0-8243-3508-3 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2006 VL 8 BP 1 EP 33 DI 10.1146/annurev.bioeng.8.061505.095831 PG 33 WC Engineering, Biomedical SC Engineering GA 081CI UT WOS:000240294400001 ER PT S AU Dykxhoorn, DM Lieberman, J AF Dykxhoorn, Derek M. Lieberman, Judy TI Running interference: Prospects and obstacles to using small interfering RNAs as small molecule drugs SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING SE ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review; Book Chapter DE RNA interference; drug development; in vivo delivery; therapy ID DOUBLE-STRANDED-RNA; SHORT HAIRPIN RNAS; HEPATITIS-B-VIRUS; INFLUENCES SIRNA EFFICACY; INDUCED SILENCING COMPLEX; IN-VIVO DELIVERY; MAMMALIAN-CELLS; MESSENGER-RNA; GENE-EXPRESSION; MOUSE MODEL AB RNA interference (RNAi) is a well-conserved, ubiquitous, endogenous mechanism that uses small noncoding RNAs to silence gene expression. The endogenous small RNAs, called microRNAs, are processed from hairpin precursors and regulate important genes involved in cell death, differentiation, and development. RNAi also protects the genome from invading genetic elements, encoded by transposons and viruses. When small double-stranded RNAs, called small interfering (si)RNAs, are introduced into cells, they bind to the endogenous RNAi machinery to disrupt the expression of mRNAs containing complementary sequences with high specificity. Any disease-causing gene and any cell type or tissue can potentially be targeted. This technique has been rapidly utilized for gene-function analysis and drug-target discovery and validation. Harnessing RNAi also holds great promise for therapy, although introducing siRNAs into cells in vivo remains an important obstacle. Pilot siRNA clinical studies began just three years after the discovery that RNAi works in mammalian cells. This review discusses recent progress and obstacles to using siRNAs as small molecule drugs. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Dykxhoorn, DM (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM dykxhoor@cbr.med.harvard.edu; lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NIAID NIH HHS [AI056695, AI56900] NR 130 TC 81 Z9 86 U1 1 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 BN 978-0-8243-3508-3 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2006 VL 8 BP 377 EP 402 DI 10.1146/annurev.bioeng.8.061505.095848 PG 26 WC Engineering, Biomedical SC Engineering GA 081CI UT WOS:000240294400012 PM 16834561 ER PT S AU Albert, MS Blacker, D AF Albert, Marilyn S. Blacker, Deborah TI Mild cognitive impairment and dementia SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY SE Annual Review of Clinical Psychology LA English DT Article; Book Chapter DE Alzheimer's disease; MCI; biomarkers; APOE; clinical trials ID EARLY ALZHEIMERS-DISEASE; CSF BIOMARKERS; RATES; RELIABILITY; PREVALENCE; ATROPHY; ENTITY AB Mild cognitive impairment (MCI) is a clinical syndrome thought to represent the transition between normal function and dementia. This review describes data that support the existence of such a transitional phase, outlines the heterogeneity of MCI and how that has influenced the evolving concept of MCI, and discusses the impact of heterogeneity on recent MCI clinical trials. C1 [Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21212 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Albert, MS (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21212 USA. EM malbert9@jhmi.edu; blacker@psych.mgh.harvard.edu NR 37 TC 20 Z9 21 U1 1 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1548-5943 BN 978-0-8243-3902-9 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2006 VL 2 BP 379 EP 388 DI 10.1146/annurev.clinpsy.1.102803.144039 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 295QD UT WOS:000255488100014 PM 17716075 ER PT S AU Jung, D Giallourakis, C Mostoslavsky, R Alt, FW AF Jung, David Giallourakis, Cosmas Mostoslavsky, Raul Alt, Frederick W. TI Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE IgH; lymphocyte development; transcriptional control elements; allelic exclusion; gene expression ID B-CELL DEVELOPMENT; VARIABLE REGION GENE; CLASS-SWITCH RECOMBINATION; V-H GENE; RAG2 C-TERMINUS; PRE-B; ALLELIC EXCLUSION; LIGHT-CHAIN; TRANSGENIC MICE; LYMPHOCYTE DEVELOPMENT AB V(D)J recombination assembles antigen receptor variable region genes from component germline variable M, diversity (D), and joining (J) gene segments. For B cells, such rearrangements lead to the production of immunoglobulin (Ig) proteins composed of heavy and light chains. V(D)J is tightly controlled at the Ig heavy chain locus (IgH) at several different levels, including cell-type specificity, intra- and interlocus ordering, and allelic exclusion. Such controls are mediated at the level of gene segment accessibility to V(D)J recombinase activity. Although much has been learned, many long-standing questions regarding the regulation of IgH locus rearrangements remain to be elucidated. In this review, we summarize advances that have been made in understanding how V(D)J recombination at the IgH locus is controlled and discuss important areas for future investigation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, CBR Inst Biomed Res, Gastrointestinal Unit, Boston, MA 02115 USA. RP Jung, D (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. EM david_jung@student.hms.harvard.edu; giallour@cbrinstitute.org; rmostosl@genetics.med.harvard.edu; alt@enders.tch.harvard.edu FU NIAID NIH HHS [AI-20047, R01 AI020047, R01 AI020047-25] NR 175 TC 280 Z9 287 U1 1 U2 27 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3024-8 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2006 VL 24 BP 541 EP 570 DI 10.1146/annurev.immunol.23.021704.115830 PG 30 WC Immunology SC Immunology GA 043ES UT WOS:000237583300018 PM 16551259 ER PT S AU Ansel, KM Djuretic, I Tanasa, B Rao, A AF Ansel, K. Mark Djuretic, Ivana Tanasa, Bogdan Rao, Anjana TI Regulation of Th2 differentiation and Il4 locus accessibility SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE cytokine; transcription factors; epigenetic regulation; chromatin; RNA interference/RNAi ID CYTOKINE GENE-EXPRESSION; T-CELL DIFFERENTIATION; BETA-GLOBIN LOCUS; RANGE INTRACHROMOSOMAL INTERACTIONS; CHROMATIN-REMODELING COMPLEXES; ALLERGIC AIRWAY INFLAMMATION; DROSOPHILA BITHORAX COMPLEX; TRANSCRIPTION FACTOR GATA-3; HISTONE H2B UBIQUITYLATION; ANTIGEN-PRESENTING CELLS AB Helper T cells coordinate immune responses through the production of cytokines. Th2 cells express the closely linked 114, 1113, and 115 cytokine genes, whereas these same genes are silenced in the Th1 lineage. The Th1/Th2 lineage choice has become a textbook example for the regulation of cell differentiation, and recent discoveries have further refined and expanded our understanding of how Th2 differentiation is initiated and reinforced by signals from antigen-presenting cells and cytokine-driven feedback loops. Epigenetic changes that stabilize the active or silent state of the 114 locus in differentiating helper T cells have been a major focus of recent research. Overall, the field is progressing toward an integrated model of the signaling and transcription factor networks, cis-regulatory elements, epigenetic modifications, and RNA interference mechanisms that converge to determine the lineage fate and gene expression patterns of differentiating helper T cells. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Ansel, KM (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM ansel@cbr.med.harvard.edu; arao@cbr.med.harvard.edu NR 258 TC 404 Z9 417 U1 1 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3024-8 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2006 VL 24 BP 607 EP 656 DI 10.1146/annurev.immunol.23.021704.115821 PG 50 WC Immunology SC Immunology GA 043ES UT WOS:000237583300020 PM 16551261 ER PT S AU Richardson, PG Mitsiades, C Hideshima, T Anderson, KC AF Richardson, PG Mitsiades, C Hideshima, T Anderson, KC TI Bortezomib: Proteasome inhibition as an effective anticancer therapy SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE multiple myeloma; lymphoma; nuclear factor-kappa B ID MULTIPLE-MYELOMA CELLS; PHASE-I TRIAL; NF-KAPPA-B; PREVIOUSLY UNTREATED PATIENTS; INDEPENDENT PROSTATE-CANCER; NON-HODGKINS-LYMPHOMA; HEMATOLOGIC MALIGNANCIES; CHEMOTHERAPEUTIC-AGENTS; CLINICAL-EXPERIENCE; REFRACTORY MYELOMA AB VELCADE((R)) (bortezomib, Millennium Pharmaceuticals, Inc., Cambridge, MA, and Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ) is a first-in-class proteasome inhibitor developed specifically for use as an antineoplastic agent. Inhibition of the proteasome results in disruption of homeostatic mechanisms within the cell that can lead to cell death. Bortezomib's first indication, for the treatment of relapsed myeloma in patients who have received at least two prior treatments and progressed on their previous treatment, was based in part on the magnitude of activity demonstrated in phase II trials. Bortezomib is currently indicated for patients who have received at least one prior therapy in the United States and European Union, although patients in the European Union must have already undergone bone marrow transplantation or be unsuitable for the procedure. A phase III trial demonstrated the superiority of bortezomib over high-dose dexamethasone in response rate, time to progression, and survival in patients with myeloma who had relapsed after 1-3 prior therapies. Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and earlier presentations of myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. EM Paul_Richardson@dfci.harvard.edu NR 55 TC 241 Z9 247 U1 4 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0557-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2006 VL 57 BP 33 EP 47 DI 10.1146/annurev.med.57.042905.122625 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 021KK UT WOS:000235981900003 PM 16409135 ER PT J AU Lleo, A Greenberg, SM Growdon, JH AF Lleo, A Greenberg, SM Growdon, JH TI Current pharmacotherapy for Alzheimer's disease SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE Alzheimer's disease treatment; acetylcholinesterase inhibitors; memantine; amyloid ID PLACEBO-CONTROLLED-TRIAL; RANDOMIZED CONTROLLED-TRIAL; BETA-SECRETASE ACTIVITY; DOUBLE-BLIND TRIAL; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; SENILE-DEMENTIA; VITAMIN-E; CHOLINE-ACETYLTRANSFERASE AB Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects approximately 4.5 million people in the United States. The mainstays of current pharmacotherapy for AD are compounds aimed at increasing the levels of acetylcholine in the brain, thereby facilitating cholinergic neurotransmission through inhibition of the cholinesterases. These drugs, known as acetylcholinesterase inhibitors (AChEIs), were first approved by the U.S. Food and Drug Administration (FDA) in 1995 based on clinical trials showing modest symptomatic benefit on cognitive, behavioral, and global measures. In 2004 the FDA approved memantine, an NMDA antagonist, for treating dementia symptoms in moderate to severe AD cases. In clinical practice, memantine may co-administered with an AChEI, altough neither drug individually or in combination affects the underlying pathophysiology of dementia. Dementia in AD results from progressive synaptic loss and neuronal death. As knowledge of the mechanisms responsible for neurodegeneration in AD increases, it is anticipated that neuroprotective drugs to slow or prevent neuronal dysfunction and death will be developed to complement current symptomatic treatments. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Hosp Santa Creu & Sant Pau, Dept Neurol, E-08025 Barcelona, Spain. RP Lleo, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM growdon@helix.mgh.harvard.edu NR 139 TC 167 Z9 177 U1 3 U2 28 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2006 VL 57 BP 513 EP 533 DI 10.1146/annurev.med.57.121304.131442 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 021KK UT WOS:000235981900032 PM 16409164 ER PT S AU Louis, DN AF Louis, David N. TI Molecular pathology of malignant gliomas SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE astrocytoma; glioblastoma; oligodendroglioma; genetics; pathology ID GROWTH-FACTOR-RECEPTOR; CHROMOSOME 1P; OLIGODENDROGLIAL TUMORS; ANAPLASTIC OLIGODENDROGLIOMAS; GLIOBLASTOMA-MULTIFORME; GENETIC ALTERATIONS; NEURAL PROGENITORS; TRANSCRIPT MAP; BRAIN-TUMORS; STEM-CELL AB Malignant gliomas, the most common type of primary brain tumor, are a spectrum of tumors of varying differentiation and malignancy grades. These tumors may arise from neural stem cells and appear to contain tumor stem cells. Early genetic events differ between astrocytic and oligodendroglial tumors, but all tumors have an initially invasive phenotype, which complicates therapy. Progression-associated genetic alterations are common to different tumor types, targeting growth-promoting and cell cycle control pathways and resulting in focal hypoxia, necrosis, and angiogenesis. Knowledge of malignant glioma genetics has already impacted clinical management of these tumors, and researchers hope that further knowledge of the molecular pathology of malignant gliomas will result in novel therapies. C1 Massachusetts Gen Hosp, Dept Pathol & Canc Ctr, Mol Pathol Unt, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Dept Pathol & Canc Ctr, Mol Pathol Unt, Boston, MA 02114 USA. EM dlouis@partners.org NR 75 TC 331 Z9 341 U1 4 U2 35 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4301-9 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2006 VL 1 IS 1 BP 97 EP 117 DI 10.1146/annurev.pathol.1.110304.100043 PG 21 WC Pathology SC Pathology GA 155GI UT WOS:000245565500004 PM 18039109 ER PT S AU Biddinger, SB Kahn, CR AF Biddinger, SB Kahn, CR TI From mice to men: Insights into the insulin resistance syndromes SO ANNUAL REVIEW OF PHYSIOLOGY SE Annual Review of Physiology LA English DT Review; Book Chapter ID PROTEIN-KINASE-C; ELEMENT-BINDING PROTEIN-1C; HEPATIC GLUCOSE-PRODUCTION; RECEPTOR SUBSTRATE FAMILY; STEAROYL-COA DESATURASE-1; FATTY-ACID SYNTHESIS; KNOCK-OUT MICE; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; ADIPOSE-TISSUE AB The insulin resistance syndrome refers to a constellation of findings, including glucose intolerance, obesity, dyslipidemia, and hypertension, that promote the development of type 2 diabetes, cardiovasculardisease, cancer, and other disorders. Defining the pathophysiological links between insulin resistance, the insulin resistance syndrome. and its sequelae is critical to understanding and treating these disorders. Over the past decade, two approaches have provided important insights into how changes in insulin signaling produce the spectrum of phenotypes associated with insulin resistance. First, studies using tissue-specific knockouts or tissue-specific reconstitution of the insulin receptor in vivo in mice have enabled us to deconstruct the insulin resistance syndromes by dissecting the contributions of different tissues to the insulin-resistant state. Second, in vivo and in vitro studies of the complex network of insulin signaling have provided insight into how insulin resistance can develop in some pathways whereas insulin sensitivity is maintained in others. These data, taken together, give us a framework for understanding the relationship between insulin resistance and the insulin resistance syndromes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Biddinger, SB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM sudha.biddinger@joslin.harvard.edu; c.ronald.kahn@joslin.harvard.edu NR 159 TC 365 Z9 382 U1 4 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 BN 978-0-8243-0368-6 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2006 VL 68 BP 123 EP 158 DI 10.1146/annurev.physiol.68.040104.124723 PG 36 WC Physiology SC Physiology GA 039AO UT WOS:000237272000007 PM 16460269 ER PT S AU Rolland, F Baena-Gonzalez, E Sheen, J AF Rolland, Filip Baena-Gonzalez, Elena Sheen, Jen TI Sugar sensing and signaling in plants: Conserved and novel mechanisms SO ANNUAL REVIEW OF PLANT BIOLOGY SE Annual Review of Plant Biology LA English DT Review; Book Chapter DE glucose; sucrose; trehalose; Arabidopsis; hexokinase; Snfl-related protein kinase ID ADP-GLUCOSE PYROPHOSPHORYLASE; SNF1-RELATED PROTEIN-KINASE; POSTTRANSLATIONAL REDOX ACTIVATION; HETEROTRIMERIC G-PROTEIN; 3' UNTRANSLATED REGION; ARABIDOPSIS-THALIANA; GENE-EXPRESSION; ABSCISIC-ACID; LEAF SENESCENCE; ALPHA-AMYLASE AB Sugars not only fuel cellular carbon and energy metabolism but also play pivotal roles as signaling molecules. The experimental amenability of yeast as a unicellular model system has enabled the discovery of multiple sugar sensors and signaling pathways. In plants, different sugar signals are generated by photosynthesis and carbon metabolism in source and sink tissues to modulate growth, development, and stress responses. Genetic analyses have revealed extensive interactions between sugar and plant hormone signaling, and a central role for hexokinase (HXK) as a conserved glucose sensor. Diverse sugar signals activate multiple HXK-dependent and HXK-independent pathways and use different molecular mechanisms to control transcription, translation, protein stability and enzymatic activity. Important and complex roles for Snf1-related kinases (SnRKs), extracellular sugar sensors, and trehalose metabolism in plant sugar signaling are now also emerging. C1 Katholieke Univ Leuven VIB, Dept Mol Microbiol, B-3001 Heverlee, Belgium. Katholieke Univ Leuven, Mol Cell Biol Lab, B-3001 Heverlee, Belgium. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Rolland, F (reprint author), Katholieke Univ Leuven VIB, Dept Mol Microbiol, B-3001 Heverlee, Belgium. EM filip.rolland@bio.kuleuven.be; baena@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu RI Baena-Gonzalez, Elena/G-5811-2013 OI Baena-Gonzalez, Elena/0000-0001-6598-3579 FU NIGMS NIH HHS [R01 GM060493] NR 158 TC 903 Z9 965 U1 39 U2 353 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1543-5008 BN 978-0-8243-0657-1 J9 ANNU REV PLANT BIOL JI Annu. Rev. Plant Biol. PY 2006 VL 57 BP 675 EP 709 DI 10.1146/annurev.arplant.57.032905.105441 PG 35 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 074JE UT WOS:000239807700026 PM 16669778 ER PT J AU Greenberg, RN Mullane, K van Burik, JAH Raad, I Abzug, MJ Anstead, G Herbrecht, R Langston, A Marr, KA Schiller, G Schuster, M Wingard, JR Gonzalez, CE Revankar, SG Corcoran, G Kryscio, RJ Hare, R AF Greenberg, RN Mullane, K van Burik, JAH Raad, I Abzug, MJ Anstead, G Herbrecht, R Langston, A Marr, KA Schiller, G Schuster, M Wingard, JR Gonzalez, CE Revankar, SG Corcoran, G Kryscio, RJ Hare, R TI Posaconazole as salvage therapy for zygomycosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CELL TRANSPLANT RECIPIENTS; INVASIVE FUNGAL-INFECTIONS; CARE CANCER CENTER; B LIPID COMPLEX; AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; RECEIVING VORICONAZOLE; MUCORMYCOSIS; ITRACONAZOLE; EPIDEMIOLOGY AB Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness. C1 Univ Kentucky, Sch Med, Dept Med, Lexington, KY 40536 USA. Dept Vet Affairs Med Ctr, Med Serv, Lexington, KY USA. Univ Chicago, Sch Med, Chicago, IL 60637 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Colorado, Denver, CO 80202 USA. Childrens Hosp, Denver, CO 80218 USA. S Texas Vet Healthcare Syst, Dept Med, San Antonio, TX USA. Hop Hautepierre, Strasbourg, France. Emory Univ Hosp, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Univ Florida, Gainesville, FL 32611 USA. Georgetown Univ Hosp, Lombardi Canc Ctr, Washington, DC USA. Dallas VA Med Ctr, Dallas, TX USA. Amgen Inc, Regulatory Affairs, Thousand Oaks, CA USA. Univ Kentucky, Dept Stat & Publ Hlth, Lexington, KY 40506 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Greenberg, RN (reprint author), Univ Kentucky, Sch Med, Dept Med, Room MN 672,800 Rose St, Lexington, KY 40536 USA. EM RNgree01@uky.edu RI Herbrecht, Raoul/D-3471-2013; Young, Jo-Anne/G-2617-2013; OI Young, Jo-Anne/0000-0003-4182-341X; Herbrecht, Raoul/0000-0002-9381-4876 NR 50 TC 265 Z9 284 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2006 VL 50 IS 1 BP 126 EP 133 DI 10.1128/AAC.50.1.126-133.2006 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 007RT UT WOS:000234988000016 PM 16377677 ER PT J AU Tegos, GP Hamblin, MR AF Tegos, GP Hamblin, MR TI Phenothiazinium antimicrobial photosensitizers are substrates of bacterial multidrug resistance pumps SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; PHOTODYNAMIC THERAPY; EFFLUX-PUMP; PHOTOBACTERICIDAL ACTIVITY; PSEUDOMONAS-AERUGINOSA; CELLS; BLUE; MECHANISM AB Antimicrobial photodynamic therapy (PDT) combines a nontoxic photoactivatable dye, or photosensitizer (PS), with harmless visible light to generate singlet oxygen and free radicals that kill microbial cells. Although the light can be focused on the diseased area, the best selectivity is achieved by choosing a PS that binds and penetrates microbial cells. Cationic phenothiazinium dyes, such as methylene blue and toluidine blue O, have been studied for many years and are the only PSs used clinically for antimicrobial PDT. Multidrug resistance pumps (MDRs) are membrane-localized proteins that pump drugs out of cells and have been identified for a wide range of organisms. We asked whether phenothiazinium salts with structures that are amphipathic cations could potentially be substrates of MDRs. We used MDR-deficient mutants of Staphylococcus aureus (NorA), Escherichia coli (TolC), and Pseudomonas aeruginosa (MexAB) and found 2 to 4 logs more killing than seen with wild-type strains by use of three different phenothiazinium PSs and red light. Mutants that overexpress MDRs were protected from killing compared to the wild type. Effective antimicrobial PSs of different chemical structures showed no difference in light-mediated killing depending on MDR phenotype. Differences in uptake of phenothiazinium PS by the cells depending on level of MDR expression were found. We propose that specific MDR inhibitors could be used in combination with phenothiazinium salts to enhance their photodestructive efficiency. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875-03, AI050875, R01 AI050875, R01 AI050875-04] NR 42 TC 97 Z9 100 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2006 VL 50 IS 1 BP 196 EP 203 DI 10.1128/AAC.50.1.196-203.2006 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 007RT UT WOS:000234988000025 PM 16377686 ER PT J AU Fitch, K Anderson, E Hubbard, J Carpenter, S Waddell, W Caliendo, A Grinspoon, S AF Fitch, K. Anderson, E. Hubbard, J. Carpenter, S. Waddell, W. Caliendo, A. Grinspoon, S. TI Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 24-26, 2006 CL San Francisco, CA C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA USA. Massachusetts Gen Hosp, Phys Therapy Dept, Boston, MA USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 7 BP L16 EP L16 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 104RG UT WOS:000241975800046 ER PT J AU Hadigan, C Liebau, J Torriani, M Andersen, R Grinspoon, S AF Hadigan, C. Liebau, J. Torriani, M. Andersen, R. Grinspoon, S. TI Improved triglycerides and insulin sensitivity with 3 months of acipimox in HIV-infected patients with hypertriglyceridemia SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 24-26, 2006 CL San Francisco, CA C1 Massachusetts Gen Hosp, Harvard Med Sch, Div Muscuskeletal Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 7 BP L14 EP L15 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 104RG UT WOS:000241975800043 ER PT J AU Hulgan, T McCauley, JL Motsinger, AA Haas, DW Levy, S Sutcliffe, CB Murdock, DG Robbins, GK Clifford, DB Canter, JA AF Hulgan, T. McCauley, J. L. Motsinger, A. A. Haas, D. W. Levy, S. Sutcliffe, C. B. Murdock, D. G. Robbins, G. K. Clifford, D. B. Canter, J. A. CA NWCS 256 Team TI A pilot study of chip-based whole mitochondrial genome sequencing in a subgroup of participants from AIDS Clinical Trials Group (ACTG) Study 384 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 24-26, 2006 CL San Francisco, CA C1 Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 7 BP L33 EP L33 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 104RG UT WOS:000241975800073 ER PT J AU Johnson, VA Hazelwood, JD Andersen, J Miller, AB Liu, T Alston-Smith, B Brosgart, CL Rooney, JF Polsky, B Peters, MG AF Johnson, V. A. Hazelwood, J. D. Andersen, J. Miller, A. B. Liu, T. Alston-Smith, B. Brosgart, C. L. Rooney, J. F. Polsky, B. Peters, M. G. TI Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are effective in chronic hepatitis B virus (HBV) infection in subjects who are co-infected with HIV: HBV and HIV drug resistance results of ACTG Protocol A5127 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Univ Alabama, Sch Med, Birmingham, AL 02115 USA. Birmingham VA Med Ctr, Birmingham, AL 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 94404 USA. NIAID, NIH, Bethesda, MD USA. Gilead Sci Inc, Foster City, CA USA. St Lukes Roosevelt Hosp, Div Infect Dis, New York, NY 94143 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Calif San Francisco, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S11 EP S11 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700029 ER PT J AU Tsibris, AMN Russ, C Lee, W Paredes, R Arnaout, R Honan, T Cahill, P Nusbaum, C Kuritzkes, DR AF Tsibris, A. M. N. Russ, C. Lee, W. Paredes, R. Arnaout, R. Honan, T. Cahill, P. Nusbaum, C. Kuritzkes, D. R. TI Detection and quantification of minority HIV-1 env V3 loop sequences by ultra-deep sequencing: Preliminary results SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02138 USA. Harvard Univ, Ctr Genome Res, Cambridge, MA USA. Fdn irsiCaixa, Lluita Contra SIDA, Badalona, Spain. Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S74 EP S74 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700086 ER PT J AU Kelly, PA AF Kelly, PA TI Automated essay scoring: A cross-disciplinary perspective SO APPLIED PSYCHOLOGICAL MEASUREMENT LA English DT Book Review C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RP Kelly, PA (reprint author), Baylor Coll Med, VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 4 TC 1 Z9 1 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-6216 J9 APPL PSYCH MEAS JI Appl. Psychol. Meas. PD JAN PY 2006 VL 30 IS 1 BP 66 EP 68 DI 10.1177/0146621605278217 PG 3 WC Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematical Methods In Social Sciences; Psychology GA 998TX UT WOS:000234343900008 ER PT J AU Prunier, F Hajjar, RJ AF Prunier, F Hajjar, RJ TI Hopes for gene therapy for cardiac failure SO ARCHIVES DES MALADIES DU COEUR ET DES VAISSEAUX LA French DT Review ID RECOMBINANT ADENOASSOCIATED VIRUS; RECEPTOR KINASE INHIBITOR; FAILING HUMAN HEARTS; MYOCYTES IN-VITRO; BETA(2)-ADRENERGIC RECEPTOR; RETICULUM CA2+-ATPASE; VENTRICULAR MYOCYTES; DELIVERY; VECTORS; VIVO AB Although the drug therapies developed over the last decades have improved the prognosis of congestive cardiac failure, the condition remains a principal cause of mortality and hospital admission in the industrialised world. The hopes for gene therapy in cardiac failure are based on the possibility of acting on the underlying physiopathological mechanisms by the transfer of genetic material to the failing myocardium. A number of experimental studies targeting the regulation of the calcium ATPase of the sarcoplasmic reticulum, the pathways of beta-adrenergic desensibilisation and the pathways of apoptosis reported encouraging results. Although improvements in the efficacy and safety of techniques of vector construction and methods of delivery to the myocardium incite a certain optimism, the clinical benefits of gene therapy in cardiac failure have yet to be demonstrated. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. UFR Sci Med, UPRES EA 3860, Preconditionnement & Remodelage Myocarde, Angers, France. RP Prunier, F (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Bldg 149,13th St,CNY-4, Charlestown, MA 02129 USA. EM fprunier@club-internet.fr NR 57 TC 0 Z9 0 U1 0 U2 2 PU J B BAILLIERE PI PARIS PA 2, CITE PARADIS, 75010 PARIS, FRANCE SN 0003-9683 J9 ARCH MAL COEUR VAISS JI Arch. Mal. Coeur Vaiss. PD JAN PY 2006 VL 99 IS 1 BP 41 EP 47 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016IZ UT WOS:000235615200009 PM 16479888 ER PT J AU Le, D Hofbauer, MA Towle, CA AF Le, D Hofbauer, MA Towle, CA TI Differential effects of hyperosmotic challenge on interleukin-1-activated pathways in bovine articular cartilage SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE articular cartilage; osmotic; interleukin-1; cyclooxygenase-2; nitric oxide; glycosaminoglycan; mechanical ID NITRIC-OXIDE SYNTHASE; MATRIX SYNTHESIS; IN-VIVO; CHONDROCYTE DIFFERENTIATION; CYCLOOXYGENASE-2 EXPRESSION; EXPERIMENTAL OSTEOARTHRITIS; PROINFLAMMATORY MEDIATORS; MECHANICAL COMPRESSION; PROTEOGLYCAN SYNTHESIS; OSMOTIC ENVIRONMENT AB Chondrocytes in situ experience fluctuations in extracellular osmolarity resulting from mechanical loading. The objective of this study was to determine whether hyperosmotic stress causes or exacerbates interleukin-1 (IL-1)-mediated effects in bovine articular cartilage. Disks of cartilage cut from the articular surface of calf radiocarpal joints were incubated for 24 It in the presence or absence of IL-1 in Dulbecco's modified Eagle's medium adjusted to various osmolalities with sucrose or NaCL Cyclooxygenase (COX)-2 levels in the cartilage were examined by Western blot. Culture media. were assayed for prostaglandin E-2 (PGE(2)), nitrite as an indicator of nitric oxide (NO) production, and sulfated glycosaminoglycan as an indicator of proteoglycan degradation. We report the osmolality-dependent potentiation of COX-2 and PGE(2) production, and the osmolality-dependent inhibition of NO production and proteoglycan degradation in IL-1-activated cartilage. The data demonstrate that osmotic and cytokine signaling interact to differentially modulate IL-1-stimulated effects in calf articular cartilage. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Tufts Univ, Sch Med, Boston, MA 02114 USA. RP Towle, CA (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. EM ctowle@partners.org FU NIA NIH HHS [AG20987] NR 53 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 1 PY 2006 VL 445 IS 1 BP 1 EP 8 DI 10.1016/j.abb.2005.11.012 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 002TX UT WOS:000234635500001 PM 16359637 ER PT J AU Peirce, TR Bray, NJ Williams, NM Norton, N Moskvina, V Preece, A Haroutunian, V Buxbaum, JD Owen, MJ O'Donovan, MC AF Peirce, TR Bray, NJ Williams, NM Norton, N Moskvina, V Preece, A Haroutunian, V Buxbaum, JD Owen, MJ O'Donovan, MC TI Convergent evidence for 2 ',3 '-cyclic nucleotide 3 '-phosphodiesterase as a possible susceptibility gene for schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; HUMAN BRAIN; DNA POOLS; MYELINATION; ASSOCIATION; EXPRESSION; POLYMORPHISMS; DYSFUNCTION; POSTMORTEM; LINKAGE AB Context: Convergent data make 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) a candidate gene for schizophrenia. Reduced expression has been reported in the schizophrenic brain. The CNP gene maps to a region to which we have reported linkage to schizophrenia. Mice in which the CNP gene has been knocked out display central nervous system pathological characteristics reminiscent of some features observed in schizophrenia. 2',3'Cyclic nucleotide 3'-phosphodiesterase is used as a marker of myelin-forming cells and is detectable in cells of oligodendrocyte lineage throughout life. Because CNP is thought to be important for oligodendrocyte function, altered expression has been interpreted as supportive of the hypothesis that altered oligodendrocyte function may be an etiological factor in schizophrenia. However, it is unclear whether the observed changes in the schizophrenic brain are primary or secondary. Objectives: To determine if CNP expression is influenced by DNA polymorphisms and to verify if these polymorphisms are associated with schizophrenia. Design: Allele-specific messenger RNA expression assay and genetic association studies. Setting: Unrelated subjects were ascertained from secondary psychiatric inpatient and outpatient services. Participants: We used brain tissue from 60 anonymous individuals with no known psychiatric disorder; a case-control sample of 708 white individuals from the United Kingdom meeting DSM-IV criteria for schizophrenia matched for age, sex, and ethnicity to 711 blood donor controls; and a pedigree with DNA from 6 affected siblings and 1 parent, showing evidence for linkage to CNP. Main Outcome Measures: Association between allele and gene expression. Association between allele and schizophrenia. Results: The exonic single nucleotide polymorphism rs2070106 was associated with CNP expression (P <.001). Compatible with underexpression of CNP messenger RNA in schizophrenia, the lower-expressing A allele was significantly associated with schizophrenia (P=.04) in the case-control sample. All affected individuals in the linked pedigree were homozygous for the lower-expression allele, providing independent support for the association (P=.03). Conclusions: Our data support the hypothesis that reduced CNP expression in the schizophrenic brain is relevant to disease etiology and therefore provide support for the general hypothesis that altered oligodendrocyte function is an etiological factor in schizophrenia. C1 Univ Cardiff Wales, Sch Med, Dept Med Psychol, Cardiff CF14 4XN, Wales. Univ Cardiff Wales, Sch Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, Wales. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Mental Illness Res Ctr, New York, NY USA. Bronx Vet Affairs Med Ctr, Mental Illness Educ Ctr, New York, NY USA. Bronx Vet Affairs Med Ctr, Mental Illness Clin Ctr, New York, NY USA. RP Owen, MJ (reprint author), Univ Cardiff Wales, Sch Med, Dept Med Psychol, Heath Pk, Cardiff CF14 4XN, Wales. EM owenmj@groupwise.cf.ac.uk RI turton, miranda/F-4682-2011; OI O'Donovan, Michael/0000-0001-7073-2379; Buxbaum, Joseph/0000-0001-8898-8313; Escott-Price, Valentina/0000-0003-1784-5483 FU Medical Research Council [G9810900] NR 25 TC 78 Z9 82 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2006 VL 63 IS 1 BP 18 EP 24 DI 10.1001/archpsyc.63.1.18 PG 7 WC Psychiatry SC Psychiatry GA 000DK UT WOS:000234440900002 PM 16389193 ER PT J AU Bartzokis, G Lu, PH Geschwind, DH Edwards, N Mintz, J Cummings, JL AF Bartzokis, G Lu, PH Geschwind, DH Edwards, N Mintz, J Cummings, JL TI Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals - Implications for cognitive decline, and dementia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID INDUCED INTRAMYELINIC EDEMA; E EPSILON-4 ALLELE; MATTER STRUCTURAL INTEGRITY; PRIMATE CEREBRAL-CORTEX; TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; E TYPE-4 ALLELE; ALZHEIMERS-DISEASE; WHITE-MATTER; RHESUS-MONKEY AB Context: Apolipoprotein E (APOE) genotype is the most influential Alzheimer disease (AD) risk factor after advanced age. The APOE4 alleles decrease and the APOE2 alleles increase age at onset of AD. Human and nonhuman primate data suggest that in midlife, the structural integrity of myelin sheaths begins breaking down, with an accelerating age-related trajectory most evident in the brain's later-myelinating association regions. This may result in a progressive "disconnection" of widely distributed neural networks that may underlie the age risk factor for AD. Objective: To assess, using magnetic resonance imaging, whether the shift in age at onset of AD observed with the APOE genotype is associated with the trajectory of age-related myelin breakdown. Design: Cross-sectional. Setting: Metropolitan university medical center. Participants: Healthy individuals (N=104) aged 55 to 75 years who underwent genotyping for APOE. Main Outcome Measures: Calculated transverse relaxation rates, an indirect measure of white matter structural integrity, for late-myelinating frontal lobe white matter (Fwm) and early- and later-myelinating regions of the corpus callosum, the splenium (Swm) and the genu (Gwm). Results: The presence of the protective APOE2 allele was associated with significantly higher relaxation rates in Fwm and Gwm but not in Swln. Furthermore, APOE status impacted the trajectory of age-related myelin breakdown in late-myelinating regions (Fwm and Gwm) but not in Swm. In Fwm and Gwm, APOE4+ individuals had a steeper slope of decline in relaxation rates with age than APOE2+ individuals; those with APOE3/3 alleles had an intermediate slope. Conclusions: In later-myelinating regions, the severity and rate of myelin breakdown in healthy older individuals are associated with APOE status and support the hypothesis that this process may contribute to age at onset of AD. Combining APOE status with noninvasive measures of myelin breakdown may be useful in assessing treatment strategies for the primary prevention of AD. C1 Univ Calif Los Angeles, David Geffen Sch Med, Alzheimers Dis Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Alzheimers Dis Ctr, Dept Neurol, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIA NIH HHS [P50 AG 16570]; NIMH NIH HHS [MH066029-01A2, MH51928, MH6357-01A1] NR 98 TC 65 Z9 67 U1 3 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2006 VL 63 IS 1 BP 63 EP 72 DI 10.1001/archpsyc.63.1.63 PG 10 WC Psychiatry SC Psychiatry GA 000DK UT WOS:000234440900007 PM 16389198 ER PT J AU Smith, EE Eichler, F AF Smith, EE Eichler, F TI Cerebral amyloid angiopathy and lobar intracerebral hemorrhage SO ARCHIVES OF NEUROLOGY LA English DT Article AB Cerebral amyloid angiopathy is caused by the deposition of P-amyloid in, the media and adventitia of small arteries and capillaries of the meninges and cerebral cortex. It is now recognized as a common cause of primary lobar intracerebral hemorrhage in elderly persons, and it is associated with frequent hemorrhage recurrence and the presence of asymptomatic petechial hemorrhages. interestingly, although it has been nearly a century since the first pathological descriptions of cerebral amyloid angiopathy, knowledge of its link with intracerebral hemorrhage developed only within the last 35 years. This review provides a historical perspective on the still-evolving concept of cerebral amyloid angiopathy-related disease. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [K23 NS046327] NR 13 TC 21 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2006 VL 63 IS 1 BP 148 EP 151 DI 10.1001/archneur.63.1.148 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 001OT UT WOS:000234546900024 PM 16401753 ER PT J AU Ganly, I Patel, SG Singh, B Kraus, DH Bridger, PG Cantu, G Cheesman, A De Sa, G Donald, P Fliss, DM Gullane, P Janecka, I Kamata, S Kowalski, LP Levine, PA dos Santos, LRM Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP AF Ganly, I Patel, SG Singh, B Kraus, DH Bridger, PG Cantu, G Cheesman, A De Sa, G Donald, P Fliss, DM Gullane, P Janecka, I Kamata, S Kowalski, LP Levine, PA dos Santos, LRM Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP TI Craniofacial resection for malignant melanoma of the skull base - Report of an international collaborative study SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the North-American-Skull-Base-Society CY APR 07-10, 2005 CL Toronto, CANADA SP N Amer Skull Base Soc ID PARANASAL SINUS CANCER; NASAL CAVITY; SURGERY; TUMORS; RADIOTHERAPY; SURVIVAL; NECK; HEAD AB Objective: To report postoperative mortality, complications, and outcomes in a subset of patients with the histologic diagnosis of malignant melanoma extracted from an existing database of a large cohort of patients accumulated from multiple institutions. Design: Retrospective outcome analysis. Setting: Seventeen international tertiary referral centers performing craniofacial surgery for malignant skull base tumors. Patients: A total of 53 patients were identified from a database of 1307 patients who had cramofacial resection for malignant tumors at 17 institutions. The median age was 63 years. Of the 53 patients, 25 (47%) had had prior single modality or combined treatment, which included surgery in 22 (42%), radiation in 11 (21%), and chemotherapy in 2 (4%). The margins of resection were close or microscopically positive in 7 (13%). Adjuvant radiotherapy was given in 22 (42%), chemotherapy in 3 (6%), and vaccine or interferon therapy in 2 (4%). Complications were classified into overall, local, central nervous system, systemic, and orbital. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined using the Kaplan-Meier method. Predictors of outcome were identified by multivariate analysis. Results: Postoperative mortality occurred in 3 patients (6%) and postoperative complications were reported in 14 patients (26%). Local wound complications occurred in 6 patients (11%), central nervous system in 7 (13%), systemic in 3 (6%), and orbital in 1 (2%). With a median follow-up of 10 months (range, 1-159 months), the 3-year OS, DSS, and RFS rates were 28.2%, 29.7%, and 25.5%, respectively. The extent of orbital involvement and adjuvant postoperative radiation therapy (PORT) were independent predictors of DSS and OS on multivariate analysis, whereas only PORT was an independent predictor of RFS. Patients treated with PORT had significantly better 3-year OS (39% vs 18%; relative risk, 2.9; P=.007), DSS (41% vs 19%; relative risk, 3.0; P=.007), and RFS (39% vs 15%; relative risk, 4.2; P=.001). Conclusions: Craniofacial resection in patients with malignant melanoma of the skull base has mortality (6%) and complication rates (26%) comparable to other malignant tumors of the skull base. However, malignant melanoma is associated with a much poorer OS, DSS, and RFS. Adjuvant PORT correlated with improved 3-year OS, DSS, and RFS on multivariate analysis. These factors must be taken into account when considering craniofacial resection in a patient with malignant melanoma invading the skull base. C1 Mem Sloan Kettering Canc Ctr, Head & Neck Serv, New York, NY 10021 USA. Prince Wales Hosp, Sydney, NSW, Australia. Ist Nazl Tumori, I-20133 Milan, Italy. Royal Natl Throat Nose & Ear Hosp, London WC1X 8DA, England. Ist Nacl Canc, Rio De Janeiro, Brazil. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. Toronto Gen Hosp, Toronto, ON, Canada. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Canc Inst Hosp, Tokyo, Japan. Hosp Canc AC Camargo, Sao Paulo, Brazil. Univ Virginia, Hlth Syst, Charlottesville, VA USA. Hosp Clin Sao Paulo, Sao Paulo, Brazil. Tata Mem Hosp, Bombay 400012, Maharashtra, India. Ctr Head & Neck Surg, Denver, CO USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. RP Shah, JP (reprint author), Mem Sloan Kettering Canc Ctr, Head & Neck Serv, 1275 York Ave, New York, NY 10021 USA. EM shahj@mskcc.org RI Francisco, Suely/D-9065-2014; Kowalski, Luiz/D-1701-2012; OI Kowalski, Luiz/0000-0001-5865-9308; Ganly, Ian/0000-0001-7636-5426; wei, william/0000-0002-6281-7126; Kowalski, Luiz Paulo/0000-0002-0481-156X; Shah, Jatin/0000-0002-6444-6592 NR 19 TC 19 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JAN PY 2006 VL 132 IS 1 BP 73 EP 78 DI 10.1001/archotol.132.1.73 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 001ZZ UT WOS:000234582500012 PM 16415433 ER PT J AU Renshaw, AA Haja, J Wilbur, DC Miller, TR AF Renshaw, AA Haja, J Wilbur, DC Miller, TR CA Cytology Comm Coll Am Pathologists TI Fine-needle aspirates of hepatocellular carcinoma that are misclassified as adenocarcinoma - Correlating Cytologic features and performance in the College of American Pathologists Nongynecologic Cytology Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID BIOPSY DIAGNOSIS; CYTODIAGNOSIS; LIVER AB 0 Context.-The cytologic features of hepatocellular carcinoma in fine-needle aspirates are well described. While some cases are easily distinguished from adenocarcinoma, poorly differentiated tumors can be difficult to differentiate. We reviewed the cytologic findings for 9 aspirates from cases of hepatocellular carcinoma that were frequently misclassified as adenocarcinoma and compared them with another 10 cases of hepatocellular carcinoma that were rarely misclassified. Objective.-To compare the cytologic features of cases of hepatocellular carcinoma in fine-needle aspirates that were both rarely and frequently misclassified as adenocarcinoma. Design.-We reviewed a total of 762 interpretations from 19 different cases of hepatocellular carcinoma in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. Results.-Overall, cases that were frequently misclassified as adenocarcinoma were misclassified 39% of the time (range, 18%-70%), while cases that were rarely misclassified were classified as adenocarcinoma 2% of the time (range, 0%-8%). The difference was statistically significant (P < .001). On review, 4 cytologic patterns were found. The most common pattern for cases that were rarely misclassified was prominent trabeculae of cells and endothelial cells wrapping the trabeculae (6/10 cases vs 2/9 cases that were frequently misclassified). The most common pattern among cases that were frequently misclassified was clusters of cells with granular cytoplasm and associated stripped nuclei (5/9 cases vs 2/10 cases that were rarely misclassified). However, the distribution of neither pattern was significantly different (P = .16 for both). One case with large atypical granular cells, as seen in the fibrolamellar variant, was rarely misclassified. The remaining 3 cases (2 frequently misclassified, 1 rarely misclassified) had a nonspecific a pattern of cells with granular cytoplasm without obvious trabeculae or stripped nuclei. Conclusion.-Correctly classifying hepatocellular carcinoma by cytology alone remains a significant challenge. While some patterns are more common in cases that performed well and other patterns are more common in cases that performed poorly, there was no significant difference in the distribution of these patterns. These results suggest that people should support their interpretations of aspirations with either immunologic evidence, biopsy evidence, or review by an experienced cytopathologist. Continued educational efforts in this area may be of value. C1 Baptist Hosp Miami, Dept Pathol, Miami, FL 33156 USA. Coll Amer Pathologists, Northfield, MN USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. RP Renshaw, AA (reprint author), Baptist Hosp Miami, Dept Pathol, 8900 N Kendall Dr, Miami, FL 33156 USA. EM andrewr@bhssf.org NR 14 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2006 VL 130 IS 1 BP 19 EP 22 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 001RE UT WOS:000234553200004 PM 16390232 ER PT J AU Kratz, A Stanganelli, N Van Cott, EM AF Kratz, A Stanganelli, N Van Cott, EM TI A comparison of glass and plastic blood collection tubes for routine and specialized coagulation assays - A comprehensive study SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID EVACUATED TUBES; SEPARATOR; TIME AB Context.-Blood collection tubes made from plastic are beginning to replace glass tubes. Coagulation test results can be influenced easily by preanalytic factors, including exposure to surfaces that activate the clotting cascade. Objective.-To compare the effects of the blood collection tube material on 22 coagulation assays performed in clinical laboratories. Design.-Paired blood samples from 28 healthy volunteers were drawn into BD Vacutainer Glass Citrate Tubes and BD Vacutainer Plus Plastic Citrate Tubes, and the results of coagulation assays were determined in parallel. Results.-No statistically significant differences were observed between glass and plastic for 14 assays: prothrombin time (and international normalized ratio); activated partial thromboplastin time; activated protein C resistance; antithrombin activity; factors II, V, VIII, and IX; alpha(2)-antiplasmin; plasminogen activity; von Willebrand factor antigen; ristocetin cofactor; thrombin time; and reptilase time. Statistically significant differences were found for fibrinogen; chromogenic protein C activity; protein S activity; PTT-LA lupus anticoagulant-sensitive activated partial thromboplastin time; and factors VII, X, XI, and XII. Mean differences ranged from 0.4% to 5.5% and were unlikely to be of clinical significance. Conclusions.-The results of this study suggest that plastic tubes can be used in place of glass tubes for a wide variety of coagulation assays. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,Gray Jackson 235, Boston, MA 02114 USA. NR 11 TC 27 Z9 28 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2006 VL 130 IS 1 BP 39 EP 44 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 001RE UT WOS:000234553200008 PM 16390236 ER PT J AU Wilens, TE McBurnett, K Bukstein, O McGough, J Greenhill, L Lerner, M Stein, MA Conners, K Duby, J Newcorn, J Bailey, CE Kratochvil, C Coury, D Casat, C Denisco, MJC Halstead, P Bloom, L Zimmerman, BA Gu, J Cooper, KM Lynch, JM AF Wilens, TE McBurnett, K Bukstein, O McGough, J Greenhill, L Lerner, M Stein, MA Conners, K Duby, J Newcorn, J Bailey, CE Kratochvil, C Coury, D Casat, C Denisco, MJC Halstead, P Bloom, L Zimmerman, BA Gu, J Cooper, KM Lynch, JM TI Multisite controlled study of OROS methylphenidate in the treatment of adolescents with attention-deficit/hyperactivity disorder SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ONCE-A-DAY; CLINICAL-PRACTICE GUIDELINE; TERM OPEN-LABEL; SELF-REPORT; GENERAL-POPULATION; CONTROLLED-TRIAL; ADHD TREATMENT; DOUBLE-BLIND; CHILDREN AB Background: Despite the persistence of attention-deficit/ hyperactivity disorder (ADHD) into adolescence, little is known about the efficacy and tolerability of stimulant medications in this age group. Objective: To report the results of a multisite controlled study among adolescents with ADHD evaluating the efficacy and tolerability of osmotic-release oral system (OROS) methylphenidate. Design: Adolescents (N = 220) having a confirmed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of ADHD underwent dose titration to identify dosages of OROS methylphenidate that improved symptoms to predefined criteria. Subjects successfully completing the dose titration phase (n = 177) (ie, tolerated and responded to treatment and adhered to the protocol) were randomized to receive 2 weeks' treatment with their individualized dosage of OROS methylpheniclate (18, 36, 54, or 72 mg once daily) or placebo. Treatment effectiveness was measured using investigator, parent, and adolescent assessments of ADHD. Results: A significant reduction from baseline in the investigator-rated ADHD Rating Scale, the primary efficacy measure, was found with OROS methylphemdate treatment compared with placebo. Similar findings were noted with parent- and adolescent-report measures. Based on a Clinical Global Impression improvement subscale score of much or very much improved, 52% of subjects in the OROS methylphenidate group improved compared with 31% receiving placebo. Thirty-seven percent of subjects required the maximum dosage of 72 mg/d. The incidence of drug-related adverse events was similar between the 2 study groups. Conclusion: In adolescents, once-daily OROS methylpherridate significantly reduced ADHD symptoms and was well tolerated using dosages up to 72 mg/d. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Childrens Ctr Langley Porter, San Francisco, CA USA. Univ Calif Los Angeles, Neuropsychiat Inst, Los Angeles, CA USA. Univ Calif Irvine, Dept Pediat, Irvine, CA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. McNeil Consumer & Specialty Pharmaceut, Fort, WA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, New York State Psychiat Inst, New York, NY USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Duke Univ, Ctr Med, Durham, NC USA. Behav Hlth Ctr, Charlotte, NC USA. Childrens Hosp, Med Ctr, Akron, OH USA. Columbus Childrens Hosp, Columbus, OH USA. CNS Healthcare Orlando Res Ctr, Orlando, FL USA. Nebraska Med Ctr, Omaha, NE USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, YAW-6-6A,32 Fruit St, Boston, MA 02114 USA. EM twitens@partners.org RI Coury, Daniel/E-2925-2011; OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 56 TC 91 Z9 92 U1 4 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 2006 VL 160 IS 1 BP 82 EP 90 DI 10.1001/archpedi.160.1.82 PG 9 WC Pediatrics SC Pediatrics GA 999JN UT WOS:000234385700012 PM 16389216 ER PT J AU Berger, DH AF Berger, DH TI Interdisciplinary work flow assessment and redesign decreases operating room turnover time and allows for additional caseload - Invited critique SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Michael E DeBakey Vet Affairs Med Ctr, Surg Serv, Houston, TX 77030 USA. RP Berger, DH (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Surg Serv, Mail Stop 1120CL,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dhb@bcm.tmc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JAN PY 2006 VL 141 IS 1 BP 70 EP 70 DI 10.1001/archsurg.141.1.70 PG 1 WC Surgery SC Surgery GA 000WR UT WOS:000234493600013 ER PT S AU Kazemi, H AF Kazemi, Homayoun BE Hayashida, Y Gonzalez, C Kondo, H TI Midbrain neurotransmitters in acute hypoxic ventilatory response SO ARTERIAL CHEMORECEPTORS SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th Meeting of the International-Society-for-Arterial-Chemoreception (ISAC) CY MAY 09-12, 2005 CL Sendai, JAPAN SP Int Soc Arterial Chemorecept ID ACID NEUROTRANSMITTERS; RAT C1 Harvard Univ, Sch Med, Pulm & Crit Care Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kazemi, H (reprint author), Harvard Univ, Sch Med, Pulm & Crit Care Unit, Massachusetts Gen Hosp, 55 Fruit St,BUL 148, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 0-387-31310-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 580 BP 223 EP 226 DI 10.1007/0-387-31311-7_34 PG 4 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BEI47 UT WOS:000237336900034 PM 16683723 ER PT J AU Huang, ZH Fitzgerald, ML Mazzone, T AF Huang, ZH Fitzgerald, ML Mazzone, T TI Distinct cellular loci for the ABCA1-dependent and ABCA1-independent lipid efflux mediated by endogenous apolipoprotein E expression SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apoE; ABCA1; macrophage; lipid efflux; atherosclerosis ID MONOCYTE-DERIVED MACROPHAGES; SCAVENGER RECEPTOR BI; CHOLESTEROL EFFLUX; PLASMA-MEMBRANE; A-I; INCREASED ATHEROSCLEROSIS; APOE EXPRESSION; STEROL EFFLUX; ABCA1; MICE AB Objective: Macrophage expression of both apolipoprotein E (apoE) and ABCA1 have been shown to modulate lipid efflux from these cells and to play an important atheroprotective role in vivo. We evaluated the relationship between apoE and ABCA1 for regulating cellular sterol efflux. Methods and Results: ApoE-mediated, but ABCA1-independent, lipid efflux was demonstrated in 3 model systems. First, adenoviral-mediated expression of apoE in dermal fibroblasts isolated from ABCA1(-/-) mice significantly increased both sterol and phospholipid efflux. Second, expression of human apoE in a macrophage cell line increased sterol efflux, and this increment in efflux was not reduced by suppressing ABCA1 expression. Third, reduction of apoE expression using an apoE small interfering RNA significantly reduced sterol efflux from ABCA1(-/-) mouse peritoneal macrophages. ApoE-mediated, but ABCA1-independent, lipid efflux could be differentiated from lipid efflux that was dependent on the extracellular accumulation of secreted apoE, because exogenous cell-derived apoE stimulated efflux only from cells expressing ABCA1. Sterol efflux was usually highest in cells expressing both ABCA1 and apoE, likely representing a summation of the ABCA1-dependent and -independent pathways for apoE-mediated sterol efflux. Conclusions: ABCA1 expression is required for apoE-mediated efflux when endogenously synthesized apoE accumulates extracellularly. Our results, however, establish the existence of an ABCA1-independent pathway for lipid efflux that requires the intracellular synthesis and/or transport of apoE. C1 Univ Illinois, Sect Diabet & Metab, Dept Med, Chicago, IL 60612 USA. Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mazzone, T (reprint author), Univ Illinois, Sect Diabet & Metab, Dept Med, MC 797,1819 W Polk St, Chicago, IL 60612 USA. EM tmazzone@uic.edu FU NHLBI NIH HHS [HL 39653] NR 39 TC 32 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2006 VL 26 IS 1 BP 157 EP 162 DI 10.1161/01.ATV.0000193627.12516.1d PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 996BI UT WOS:000234149000025 PM 16254198 ER PT J AU McClain, MT Poole, BD Bruner, BF Kaufman, KM Harley, JB James, JA AF McClain, MT Poole, BD Bruner, BF Kaufman, KM Harley, JB James, JA TI An altered immune response to Epstein-Barr nuclear antigen 1 in pediatric systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID VIRUS INFECTION; PEPTIDE IMMUNIZATION; HUMORAL AUTOIMMUNITY; B-LYMPHOCYTES; SM B/B'; EPITOPE; AUTOANTIBODIES; TRANSFORMATION; RECOGNITION; ANTIBODIES AB Objective. New examples support the concept that host immune responses to pathogenic organisms can act as the nidus for autoimmunity. Two such examples implicate the Epstein-Barr virus (EBV) in systemic lupus erythematosus (SLE), i.e., data consistent with SLE anti-Sm and anti-60-kd Ro autoantibodies emerging from distinct humoral immune responses to Epstein-Barr nuclear antigen I (EBNA-1). We undertook this study to further test whether the humoral immune response to EBNA-1 is a risk factor for pediatric SLE. Methods. Sera from pediatric lupus patients and healthy matched controls were tested for anti-EBNA-1 by Western blotting and enzyme-linked immunosorbent assay (ELISA). To define the fine specificity of their anti-EBNA-1 humoral immune response, fragments of EBNA-1 and the maximally overlapping unique octapeptides of EBNA-1 were tested by modified ELISAs Results. All 36 pediatric SLE patient sera tested recognized EBNA-1, while sera from only 25 of 36 matched EBV-positive controls targeted EBNA-1 (P < 0.005). Epitope mapping revealed that the humoral anti-EBNA-1 response in pediatric SLE was distinct from and less restricted than that in matched normal individuals. Meanwhile, no significant differences between SLE patient sera and control sera were observed in the responses to other herpesviruses or in binding to sequential epitopes from cytomegalovirus immediate-early antigen or EBNA-2. Conclusion. Anti-EBNA-1 antibodies are associated with pediatric-onset SLE. Furthermore, an altered humoral immune response to EBNA-1, characteristic of SLE, has been found and may be an important SLE susceptibility factor. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM jamesj@omrf.ouhsc.edu FU NCRR NIH HHS [RR 020143, RR 15577]; NIAID NIH HHS [AI 51347, AI 24717]; NIAMS NIH HHS [AR 45084, AR 048140, AR 42460, AR 31584, QAR 45451, AR 01981, AR 049084]; NIDCR NIH HHS [DE 015223] NR 40 TC 63 Z9 67 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2006 VL 54 IS 1 BP 360 EP 368 DI 10.1002/art.21682 PG 9 WC Rheumatology SC Rheumatology GA 002IO UT WOS:000234605200044 PM 16385527 ER PT J AU Chien, WD Ravicz, ME Merchant, SN Rosowski, JJ AF Chien, Wade Ravicz, Michael E. Merchant, Saumil N. Rosowski, John J. TI The effect of methodological differences in the measurement of stapes motion in live and cadaver ears SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE human middle ear; temporal bone studies; middle-ear function in live ears; stapes velocity ID HUMAN TEMPORAL BONES; MIDDLE-EAR; FOOTPLATE; VIBRATION; MOVEMENT AB Methodological differences in sound-induced stapes velocity ( Vs) measurements in live and cadaveric ears were examined using fresh cadaveric temporal bones. On average, differences in preparation ( sectioning the stapedius tendon, removing the facial nerve, and widely opening the facial recess) had statistically insignificant effects on measured Vs. Differences in the achievable measurement angle ( with respect to the axis of piston-like stapes motion) had a significant effect on measured Vs below 2 kHz. These results suggest that much if not all of the differences in Vs measurements between live and cadaveric ears can be explained by the differences in measurement angle between the two preparations. Measurement angle was found to have minimal effect on measured Vs above 2 kHz. This demonstrates that the commonly used method of estimating stapes translational velocity by dividing the measured velocity by the cosine of the measurement angle is not valid above 2 kHz. Copyright (C) 2006 S. Karger AG, Basel. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Chien, WD (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wadechien@hotmail.com FU NIDCD NIH HHS [R01 DC004798-07, R01 DC047998, R01 DC004798] NR 17 TC 35 Z9 35 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2006 VL 11 IS 3 BP 183 EP 197 DI 10.1159/000091815 PG 15 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 146DU UT WOS:000244915500006 PM 16514236 ER PT B AU Guinan, JJ Lin, T Cheng, H Cooper, NP AF Guinan, J. J. Lin, Tai Cheng, Holden Cooper, N. P. BE Nuttal, AL TI Medial-olivocochlear-efferent effects on basilar-membrane and auditory-nerve responses to clicks: Evidence for a new motion within the cochlea SO AUDITORY MECHANISMS: PROCESSES AND MODELS LA English DT Proceedings Paper CT 9th International Symposium on Auditory Mechanisms CY JUL 23-28, 2005 CL Portland, OR ID MAMMALIAN COCHLEA; FREQUENCY GLIDES; FIBER RESPONSES; CHINCHILLA; EXCITATION; PATTERNS; FEEDBACK; BASE AB We recorded guinea-pig, basilar-membrane (BM) motion, and cat, single auditory-nerve-fiber (AN) responses to clicks, with and without electrical stimulation of medial-olivocochlear (MOC) efferents. In both BM and AN responses, MOC stimulation inhibited almost completely at low click levels. However at moderate-to-high click levels, MOC inhibition was small on the first half cycle and built up over many cycles in BM click responses, but was large on the first half cycle and negligable in the second cycle in AN click responses. The data support the hypothesis that OHCs produce or influence a motion which bends inner-hair-cell stereocilia and can be inhibited by MOC efferents, a motion that is present through most, or all, of the cochlea, but that is not apparent in basal-turn BM motion. These data, from normally-working cochleas, highlight the need to shift the conceptual paradigm for cochlear mechanics to one in which the classic BM traveling wave is not the only motion that excites AN fibers. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu; n.p.cooper@cns.keele.ac.uk NR 36 TC 0 Z9 0 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-824-7 PY 2006 BP 3 EP 16 DI 10.1142/9789812773456_0001 PG 14 WC Otorhinolaryngology SC Otorhinolaryngology GA BFD85 UT WOS:000241277000001 ER PT B AU Songer, JE Rosowski, JJ AF Songer, J. E. Rosowski, J. J. BE Nuttal, AL TI Superior semicircular canal dehiscence: Mechanisms of air-conducted hearing SO Auditory Mechanisms: Processes and Models LA English DT Proceedings Paper CT 9th International Symposium on Auditory Mechanisms CY JUL 23-28, 2005 CL Portland, OR ID VERTIGO AB Both an animal and mechano-acoustic model of superior semicircular canal dehiscence (SCD) were developed. The animal model demonstrates that middle-ear input admittance and stapes velocity increase and that cochlear potential decreases in response to sound after introducing an SCD. These changes are consistent with the 'third-window' hypothesis as illustrated by a mechano-acoustic model of the effects of SCD on audition. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Songer, JE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-824-7 PY 2006 BP 113 EP 114 DI 10.1142/9789812773456_0019 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA BFD85 UT WOS:000241277000019 ER PT B AU Ravicz, ME Chien, W Songer, JE Merchant, SN Rosowski, JJ AF Ravicz, M. E. Chien, W. Songer, J. E. Merchant, S. N. Rosowski, J. J. BE Nuttal, AL TI Measurements and models of human inner-ear function with superior semicircular canal dehiscence SO Auditory Mechanisms: Processes and Models LA English DT Proceedings Paper CT 9th International Symposium on Auditory Mechanisms CY JUL 23-28, 2005 CL Portland, OR AB We, tested the hypothesis that hearing loss in superior semicircular canal dehiscence (SCD) syndrome is due to a "third cochlear window". SCD in human temporal bones produced a fluid motion in the dehiscence, a reduction in round window velocity comparable to the low-frequency hearing loss seen in SCD patients, and an increase in stapes velocity; all these results support the "third window" hypothesis. A functionally- and anatomically-based model predicts the temporal bone results. C1 Mass Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Ravicz, ME (reprint author), Mass Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-824-7 PY 2006 BP 506 EP 507 DI 10.1142/9789812773456_0082 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA BFD85 UT WOS:000241277000082 ER PT J AU Apostolou, I Kretschmer, K Von Boehmer, H AF Apostolou, Irina Kretschmer, Karsten Von Boehmer, Harald BE Rose, NR Mackay, IR TI Peptide-Based Instruction of Suppressor Commitment in Naive T Cells SO AUTOIMMUNE DISEASES, 4TH EDITION LA English DT Article; Book Chapter ID IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; GENERATED EX-VIVO; IN-VIVO; TGF-BETA; DENDRITIC CELLS; PERIPHERAL TOLERANCE; AUTOIMMUNE-DISEASES; REGULATORY CELLS; ORAL TOLERANCE C1 [Apostolou, Irina; Kretschmer, Karsten; Von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Apostolou, I (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045474-0 PY 2006 BP 133 EP 137 DI 10.1016/B978-012595961-2/50013-5 PG 5 WC Immunology SC Immunology GA BCW76 UT WOS:000311707200011 ER PT J AU Mackay, CR Von Andrian, UH AF Mackay, Charles R. Von Andrian, Ulrich H. BE Rose, NR Mackay, IR TI Adhesion Molecules and Chemoattractants in the Pathogenesis and Treatment of Autoimmune Diseases SO AUTOIMMUNE DISEASES, 4TH EDITION LA English DT Article; Book Chapter ID HIGH ENDOTHELIAL VENULES; CHEMOKINE RECEPTOR EXPRESSION; NONPEPTIDE CCR5 ANTAGONIST; SECONDARY LYMPHOID ORGANS; SELECTIN-DEFICIENT MICE; P-SELECTIN; T-CELLS; RHEUMATOID-ARTHRITIS; T-HELPER-2 CELLS; EOSINOPHIL CHEMOATTRACTANT C1 [Mackay, Charles R.] St Vincents Hosp, Garvan Inst Med Res, Dept Arthrit & Inflammat, Darlinghurst, NSW 2010, Australia. [Von Andrian, Ulrich H.] Harvard Univ, Sch Med, Ctr Blood Res, CBR Inst Biomed Res,Dept Pathol, Boston, MA 02115 USA. RP Mackay, CR (reprint author), St Vincents Hosp, Garvan Inst Med Res, Dept Arthrit & Inflammat, Darlinghurst, NSW 2010, Australia. RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 NR 84 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045474-0 PY 2006 BP 237 EP 248 DI 10.1016/B978-012595961-2/50021-4 PG 12 WC Immunology SC Immunology GA BCW76 UT WOS:000311707200019 ER PT J AU Cherayil, BJ AF Cherayil, Bobby J. BE McCormick, BA TI NF-kappa B-dependent responses activated by bacterial-epithelial interactions SO BACTERIAL-EPITHELIAL CELL CROSS-TALK: MOLECULAR MECHANISMS IN PATHOGENESIS SE Advances in Molecular and Cellular Microbiology LA English DT Article; Book Chapter ID TOLL-LIKE RECEPTOR-2; CLOSTRIDIUM-DIFFICILE TOXIN; INFLAMMATORY-BOWEL-DISEASE; NUCLEAR EXPORT SIGNAL; INNATE HOST-DEFENSE; HELICOBACTER-PYLORI; CROHNS-DISEASE; EXPERIMENTAL COLITIS; CYTOKINE PRODUCTION; TNF-ALPHA C1 [Cherayil, Bobby J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cherayil, Bobby J.] Harvard Univ, Sch Med, Boston, MA USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 130 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52185-244-9 J9 ADV M C M PY 2006 IS 13 BP 244 EP 268 DI 10.1017/CBO9780511541537.009 D2 10.1017/CBO9780511541537 PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BXM36 UT WOS:000296372800009 ER PT J AU McCormick, BA Mrsny, RJ AF McCormick, Beth A. Mrsny, Randall J. BE McCormick, BA TI NF-kappa B-independent responses activated by bacterial-epithelial interactions: the role of arachidonic acid metabolites SO BACTERIAL-EPITHELIAL CELL CROSS-TALK: MOLECULAR MECHANISMS IN PATHOGENESIS SE Advances in Molecular and Cellular Microbiology LA English DT Article; Book Chapter ID CYTOSOLIC PHOSPHOLIPASE A(2); CYSTIC-FIBROSIS AIRWAY; COMMUNITY-ACQUIRED PNEUMONIA; PROTEIN-KINASE-C; RIBOSYLATION FACTOR 6; HELICOBACTER-PYLORI; PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; LEUKOTRIENE C-4; NEUTROPHIL MIGRATION C1 [McCormick, Beth A.] Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Charlestown, MA 02129 USA. [McCormick, Beth A.] Harvard Univ, Sch Med, Charlestown, MA USA. [Mrsny, Randall J.] Cardiff Univ, Welsh Sch Pharm, Cardiff, S Glam, Wales. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Charlestown, MA 02129 USA. NR 128 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52185-244-9 J9 ADV M C M PY 2006 IS 13 BP 269 EP 298 DI 10.1017/CBO9780511541537.010 D2 10.1017/CBO9780511541537 PG 30 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BXM36 UT WOS:000296372800010 ER PT J AU Klein, R McNamara, P Albert, ML AF Klein, R McNamara, P Albert, ML TI Neuropharmacologic approaches to cognitive rehabilitation SO BEHAVIOURAL NEUROLOGY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Aphasia Res Ctr, Med Ctr Serv, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Harold Goodglass Aphasia Res Ctr, Boston, MA 02118 USA. RP Albert, ML (reprint author), VA Boston Healthcare Syst, Aphasia Res Ctr, Med Ctr Serv, 12A,150 So Huntington Ave, Boston, MA 02130 USA. EM malbert@bu.edu NR 0 TC 3 Z9 3 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2006 VL 17 IS 1 BP 1 EP 3 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 060AN UT WOS:000238773700001 ER PT J AU Romero, JR Babikian, VL Katz, DI Finklestein, SP AF Romero, JR Babikian, VL Katz, DI Finklestein, SP TI Neuroprotection and stroke rehabilitation: Modulation and enhancement of recovery SO BEHAVIOURAL NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TRANSCRANIAL MAGNETIC STIMULATION; RANDOMIZED CONTROLLED-TRIAL; PERMANENT FOCAL ISCHEMIA; DOUBLE-BLIND; MOTOR CORTEX; FUNCTIONAL RECOVERY; OXIDATIVE STRESS; PROGENITOR CELLS; DOSE-ESCALATION AB Recent advances in research are modifying our view of recovery after nervous system damage. New findings are changing previously held concepts and providing promising avenues for treatment of patients after stroke. This review discusses mechanisms of neuronal injury after brain ischemia and the attempts to study neuroprotection options based on such mechanisms. It also considers measures available at present to improve outcome after stroke and presents new areas of research, particularly stimulation techniques, neurogenesis and trophic factors to enhance recovery. In order to improve outcomes, medications that may be detrimental to recovery should be avoided, while symptomatic therapy of problems such as depression, pain syndromes and spasticity may contribute to better results. Continued surveillance and early treatment of complications associated with acute stroke, along with supportive care remain the mainstay of treatment for stroke patients in the recovery phase. Present research on limiting brain damage and improving recovery and plasticity enhance the prospects for better clinical treatments to improve recovery after stroke. C1 Boston Univ, Med Ctr, Dept Neurol, Boston, MA 02118 USA. Healthsouth Braintree Rehabil Hosp, Braintree, MA USA. Biotrofix Inc, Needham, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Romero, JR (reprint author), Boston Univ, Med Ctr, Dept Neurol, 715 Albany St,C329, Boston, MA 02118 USA. EM joromero@bmc.org NR 84 TC 8 Z9 9 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2006 VL 17 IS 1 BP 17 EP 24 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 060AN UT WOS:000238773700003 PM 16720957 ER PT J AU McNamara, P Durso, R AF McNamara, P Durso, R TI Neuropharmacological treatment of mental dysfunction in Parkinson's disease SO BEHAVIOURAL NEUROLOGY LA English DT Article ID FRONTAL-LOBE DYSFUNCTION; COGNITIVE FUNCTION; SENTENCE COMPREHENSION; MOTOR FUNCTION; L-DOPA; DEMENTIA; DEPRESSION; LEVODOPA; RIVASTIGMINE; PERFORMANCE AB Many patients with Parkinson's Disease (PD) experience significant cognitive and mood impairment-even early in the course of the disease. These mental impairments are only partially responsive to levodopa treatment and are often as disabling as the motor impairment, particularly in mid and late stages of the disease. Investigators have recently begun a search for new agents that can effectively treat mental dysfunction of PD. Although there have been only a handful of properly controlled clinical trials of interventions targeted at amelioration of mental dysfunction in PD, progress has been made. Based on the available evidence, targeting catecholaminergic and cholinergic function may be an effective strategy for amelioration of cognitve, mood and psychiatric disturbances in PD. C1 Boston Univ, Dept Neurol 127, Boston VA Healthcare Syst, Sch Med, Boston, MA 02130 USA. RP McNamara, P (reprint author), Boston Univ, Dept Neurol 127, Boston VA Healthcare Syst, Sch Med, 150 S Huntington Ave, Boston, MA 02130 USA. EM mcnamar@bu.edu NR 62 TC 6 Z9 6 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2006 VL 17 IS 1 BP 43 EP 51 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 060AN UT WOS:000238773700005 PM 16720959 ER PT J AU Stegmaier, K AF Stegmaier, K TI Genomic approaches in acute leukemia SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article; Proceedings Paper CT 9th Acute Leukemia Forum CY APR 08, 2005 CL San Francisco, CA DE genomic approaches; leukemia; expression profiling; DNA microarray; small molecule library screening ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION PROFILES; FLT3; CLASSIFICATION; INHIBITOR; PREDICTION; DISCOVERY; MLL AB The application of expression-based genomic approaches to medical research is traced here, particularly as they relate to hematologic malignancy. DNA microarray technology and its role in the refinement of the taxonomy of disease, the development of models of outcome prediction, and the identification of therapeutic targets are discussed. Particular attention is given to the exploration of a signature-based screening approach, which bypasses the need to have a priori knowledge of the target. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Stegmaier, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM kimberly_stegmaier@dfci.harvard.edu NR 14 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PY 2006 VL 19 IS 2 BP 263 EP 268 DI 10.1016/j.beha.2005.11.001 PG 6 WC Hematology SC Hematology GA 027KR UT WOS:000236415000002 PM 16516123 ER PT J AU Porter, DL Antin, JH AF Porter, David L. Antin, Joseph H. TI Donor leukocyte infusions in myeloid malignancies: new strategies SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE adoptive immunotherapy; graft-versus-leukemia; donor leukocyte infusions; allogeneic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; CYTOTOXIC T-LYMPHOCYTES; RESTRICTED TISSUE DISTRIBUTION; TERM-FOLLOW-UP; ADOPTIVE IMMUNOTHERAPY; RELAPSED LEUKEMIA AB Donor leukocyte infusion (DLI) provides direct and potent graft-versus-leukemia (GVL) activity to treat relapse after allogeneic stem-cell transplantation. DLI is dramatically effective for relapsed chronic myelogenous leukemia (CML), but has been less effective for relapse of other myeloid malignancies. Nevertheless, most recipients of DLI for relapsed CML, and many patients with relapsed acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), will experience prolonged remissions and probable cure. Graft-versus-host disease remains the major complication of DLI. New strategies for GVL induction explore novel dosing regimens and both methods of enhancing GVL activity of donor T cells and of minimizing toxicity from graft-versus-host disease. Ultimately, the identification of the effector cells and target antigens for GVL induction will lead to the use of tumor-specific adoptive immunotherapy to both prevent and treat relapse with minimal toxicity. Although many issues remain unsettled, the potential to harness the graft-versus-leukemia activity of allogeneic donor cells provides a powerful new paradigm for the immunotherapy of cancer. C1 Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Porter, DL (reprint author), Univ Penn, Med Ctr, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM david.porter@uphs.upenn.edu NR 99 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PY 2006 VL 19 IS 4 BP 737 EP 755 DI 10.1016/j.beha.2006.05.003 PG 19 WC Hematology SC Hematology GA 096UZ UT WOS:000241403600008 PM 16997180 ER PT B AU Yang, MQ Yang, JY AF Yang, Mary Qu Yang, Jack Y. GP IEEE COMPUTER SOC TI IUP: Intrinsically unstructured protein predictor - A software tool for analyzing polypeptide sequences SO BIBE 2006: SIXTH IEEE SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, PROCEEDINGS LA English DT Proceedings Paper CT 6th IEEE Syposium on BioInformatics and BioEngineering (BIBE 2006) CY OCT 16-18, 2006 CL Arlington, VA SP IEEE Comp Soc, Biol & Artificial Intelligence Soc, ITRI DE intrinsically unstructured proteins (IUP); feature selection; classification; ensemble methods ID DISORDER AB Many protein regions and some entire proteins have no definite tertiary structure, presenting instead as dynamic, disorder ensembles under different physiochemical circumstances. These proteins and regions are known as Intrinsically Unstructured Proteins (IUP). IUP have been associated with a wide range of protein functions and play essential roles in diseases characterized by protein misfolding and aggregation. Identifying IUP is an important but difficult task in today's structural and functional genomics. We exact useful features from polypeptide sequences and develop machine learning algorithms for the above task. We compare our IUP predictor with PONDR (R) (mainly neural-network-based predictors), disEMBL (also based on neural networks) and Globplot (based on IUP propensity). We find that augmenting features derived from physiochemical properties of amino acids (such as 9-gram encoding scheme and hydrophobicity) and using ensemble methods proved beneficial. The IUP predictor is a viable alternative software tool for identifying IUP regions and proteins. C1 [Yang, Mary Qu] US Dept HHS, NHGRI, Natl Inst Hlth, Bethesda, MD 20852 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. RP Yang, MQ (reprint author), US Dept HHS, NHGRI, Natl Inst Hlth, Bethesda, MD 20852 USA. EM yangma@mail.NIH.gov; jyang@hadron.mgh.Harvard.edu NR 16 TC 2 Z9 2 U1 0 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2727-2 PY 2006 BP 3 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BFK64 UT WOS:000242503800001 ER PT B AU Yang, JY Yang, MQ AF Yang, Jack Y. Yang, Mary Qu GP IEEE COMPUTER SOC TI Assessing protein function using a combination of supervised and unsupervised learning SO BIBE 2006: SIXTH IEEE SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, PROCEEDINGS LA English DT Proceedings Paper CT 6th IEEE Syposium on BioInformatics and BioEngineering (BIBE 2006) CY OCT 16-18, 2006 CL Arlington, VA SP IEEE Comp Soc, Biol & Artificial Intelligence Soc, ITRI AB The determination of protein function using experimental techniques is time-consuming and expensive; the use of machine learning techniques to rapidly assess protein function may be useful in streamlining this process. The problem of assigning functional classes to proteins is complicated by the fact that a single protein can participate in several different pathways and thus can have multiple functions. It follows that the instances in the resulting classification problem can carry multiple class labels. We have developed a tree-based classifier that capable of handling multiply-labeled data: we call the resulting tree a Recursive Maximum-Contrast Tree (RMCT). The name derives from the way in which nodes in the tree are split; this is done by selecting the two training instances with maximum contrast (that is, the two training instances with maximum separation according to some distance measure) and using them as seeds in a clustering algorithm to form a partition of the training instances and hence of the feature space. We test our algorithm on protein phylogenetic profiles generated from 60 completely sequenced genomes, and we compare our results to those achieved using existing algorithms such as support vector machines and decision trees. C1 [Yang, Jack Y.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, US Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Yang, JY (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jyang@hadron.mgh.harvard.edu; yangma@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2727-2 PY 2006 BP 35 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BFK64 UT WOS:000242503800005 ER PT J AU Sun, EY Josephson, L Kelly, KA Weissleder, R AF Sun, EY Josephson, L Kelly, KA Weissleder, R TI Development of nanoparticle libraries for biosensing SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MAGNETIC NANOPARTICLES; IN-VIVO; MOLECULAR-INTERACTIONS; TAT PEPTIDE; IRON-OXIDE; PROBES; AGENTS; CELLS AB Magnetic and magnetofluorescent nanoparticles have become important materials for biological applications especially for sensing, separation, and imaging. To achieve target specificity, these nanomaterials are often covalently modified with binding proteins such as antibodies or proteins. Here we report on the creation of nanoparticle libraries that achieve specificity through multivalent modification with small molecules. We explore different synthetic routes to attach small molecules with anhydride, amine, hydroxyl carboxyl, thiol, and epoxy handles. We show that the derived nanomaterials have unique biological functions, possess different behaviors in cell screens, and can be used as substrates for biological screens. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th Rd,Room 5403, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu FU NCI NIH HHS [P01 CA69246, P50 CA86355, R24 CA92782] NR 20 TC 80 Z9 82 U1 0 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 2006 VL 17 IS 1 BP 109 EP 113 DI 10.1021/bc050290e PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 006NZ UT WOS:000234905500015 PM 16417258 ER PT J AU Banerjee, P Weissleder, R Bogdanov, A AF Banerjee, P Weissleder, R Bogdanov, A TI Linear polyethyleneimine grafted to a hyperbranched poly(ethylene glycol)-like core: A copolymer for gene delivery SO BIOCONJUGATE CHEMISTRY LA English DT Article ID DNA; POLYETHYLENIMINES; TRANSFECTION; POLYESTERS; COMPLEXES; DENDRIMER; POLYMERS; DESIGN; SYSTEM; PEI AB A block copolymer of a hyperbranched poly(ethylene glycol)-like core and linear polyethylenimine (HBP) was synthesized by a facile synthetic route that included (1) a single-step cationic copolymerization of diepoxy and polyhydroxyl monomers, (2) derivatization of hydroxyl groups of the core HBPEG copolymer with either tosyl or chloromethylbenzoyl chlorides resulting in a corresponding macroinitiator, and (3) synthesis of HBPEG-block-poly(alkyl oxazolines). HBPEG-block-linear polyethyleneimine (HBP) was obtained by hydrolysis of HBPEG-block-poly(alkyl oxazolines). Linear PEI-bearing hyperbranched polycations (HBP) had lower inherent toxicity in cell culture than PEG-grafted linear polyethyleneimines (PEGLPEI). PEGLPEI formed a complex with DNA with an average diameter of 250 nm. The complexes were loosely condensed and formed aggregates and precipitates during storage. By contrast, hyperbranched polycations (HBP) formed similar to 50 nm nanocomplexes with DNA that were stable for several weeks and showed resistance to DNAse I-mediated degradation. The 'inverted' block copolymers showed several orders of magnitude higher transfection efficiency than PEGLPEI in vitro. Because of the biocompatibility and higher transfection efficiency, the 'inverted' block copolymer merits further investigation as a gene carrier. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu FU NCI NIH HHS [1P50CA86355-01] NR 26 TC 40 Z9 41 U1 4 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 2006 VL 17 IS 1 BP 125 EP 131 DI 10.1021/bc050083e PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 006NZ UT WOS:000234905500017 PM 16417260 ER PT J AU Wang, HB Ehnert, C Brenner, GJ Woolf, CJ AF Wang, HB Ehnert, C Brenner, GJ Woolf, CJ TI Bradykinin and peripheral sensitization SO BIOLOGICAL CHEMISTRY LA English DT Review DE bradykinin; ion channels; nociceptors; pain hypersensitivity; peripheral sensitization; TRPs ID 2ND-MESSENGER SIGNALING CASCADES; CAPSAICIN-RECEPTOR; PAIN HYPERSENSITIVITY; NOCICEPTIVE NEURONS; NONNEURONAL CELLS; GANGLION NEURONS; AFFERENT NEURONS; ION-CHANNEL; KAPPA-B; RAT AB Pain hypersensitivity after tissue injury and inflammation is contributed to by a reduction in the threshold and an increase in the responsiveness of the peripheral terminals of high-threshold nociceptor neurons, the phenomenon of peripheral sensitization. Bradykinin, acting via G-protein-coupled receptors expressed by the sensory neurons, links to multiple intracellular signaling pathways that in turn interact with voltage-gated and ligand-gated ion channels, changing their properties in such a way as to enhance the response to peripheral stimuli. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. EM cwoolf@partners.org FU NINDS NIH HHS [K08 NS044139] NR 33 TC 43 Z9 43 U1 1 U2 6 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JAN PY 2006 VL 387 IS 1 BP 11 EP 14 DI 10.1515/BC.2006.003 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 008ZU UT WOS:000235081700003 PM 16497159 ER PT J AU Harding, AL Byers, KB AF Harding, A. Lynn Byers, Karen Brandt BE Fleming, DO Hunt, DL TI Epidemiology of Laboratory-Associated Infections SO BIOLOGICAL SAFETY: PRINCIPLES AND PRACTICES, 4TH EDITION LA English DT Article; Book Chapter ID BRITISH CLINICAL LABORATORIES; ESCHERICHIA-COLI O157-H7; HEPATITIS-B-VIRUS; ACQUIRED GONOCOCCAL CONJUNCTIVITIS; HELICOBACTER-PYLORI INFECTION; SIMIAN IMMUNODEFICIENCY VIRUS; RECOMBINANT VACCINIA VIRUS; CREUTZFELDT-JAKOB DISEASE; TO-PERSON TRANSMISSION; HEALTH-CARE PERSONNEL C1 [Harding, A. Lynn] Biosafety Consultant, Chattanooga, TN 37415 USA. [Byers, Karen Brandt] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Harding, AL (reprint author), Biosafety Consultant, 2846 Crestwood Ave, Chattanooga, TN 37415 USA. NR 289 TC 10 Z9 10 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-339-0 PY 2006 BP 53 EP 77 PG 25 WC Medical Laboratory Technology; Microbiology SC Medical Laboratory Technology; Microbiology GA BOY56 UT WOS:000278066800005 ER PT J AU Sackstein, R AF Sackstein, R TI A revision of Billingham's tenets: The central role of lymphocyte migration in acute graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE acute graft-versus-host disease; allogeneic hematopoietic stem cell transplantation; cutaneous lymphocyte antigen; lymphocyte homing receptors; lymphocyte migration ID BONE-MARROW TRANSPLANTATION; T-CELLS; ADHESION MOLECULES; MYCOPHENOLATE-MOFETIL; MULTISTEP PARADIGM; HOMING RECEPTORS; REACTION GVHR; MURINE ACUTE; L-SELECTIN; EXPRESSION AB The migration of cells from vascular to extravascular compartments effects a sequential cascade of events, involving an interplay between adhesion molecules and chemokines. All T cell-mediated immune responses, of which acute graft-versus-host disease (GVHD) is an example, require that effector cells reach their target tissues. Lymphocytes do not enter specific tissues because they "see" a given antigen; they enter because they possess the requisite combination of homing receptors and chemokine receptors to engage the endothelium at the target tissue(s). Billingharn's tenets on the immunobiology of GVHD must be expanded to accommodate this obligatory homing component. Because GVHD is relatively organ specific-principally affecting the skin, gut, and liver-our increasing knowledge of the pertinent adhesion molecules and chemokines directing effector cell trafficking to these sites offers novel therapeutic approaches for prevention or treatment of GVHD. The potential efficiency of this form of therapy could eliminate the use of graft manipulations (eg, T-cell depletion) and broad immunosuppressives, thereby lessening infectious complications and preserving the potent graft-versus-malignancy effect of allogeneic hematopoietic stem cell transplantation. (C) 2 006 American Society for Blood and Marrow Transplantation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard Skin Dis Res Ctr,Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard Skin Dis Res Ctr,Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Suite 671, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA84156]; NHLBI NIH HHS [R01 HL60528, R01 HL073714, P01HL070149] NR 46 TC 45 Z9 49 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2006 VL 12 IS 1 SU 1 BP 2 EP 8 DI 10.1016/j.bbmt.2005.09.01 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 010FB UT WOS:000235171200002 PM 16399577 ER PT J AU Shulman, HM Kleiner, D Lee, SJ Morton, T Pavletic, SZ Farmer, E Moresi, JM Greenson, J Janin, A Martin, PJ McDonald, G Flowers, MED Turner, M Atkinson, J Lefkowitch, J Washington, MK Prieto, VG Kim, SK Argenyi, Z Diwan, AH Rashid, A Hiatt, K Couriel, D Schultz, K Hymes, S Vogelsang, GB AF Shulman, HM Kleiner, D Lee, SJ Morton, T Pavletic, SZ Farmer, E Moresi, JM Greenson, J Janin, A Martin, PJ McDonald, G Flowers, MED Turner, M Atkinson, J Lefkowitch, J Washington, MK Prieto, VG Kim, SK Argenyi, Z Diwan, AH Rashid, A Hiatt, K Couriel, D Schultz, K Hymes, S Vogelsang, GB TI Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: II. Pathology Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus diagnosis; pathology ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HEPATITIS-C; ALLOGRAFT-REJECTION; LIVER; EYE; RECIPIENTS; INFECTION; CIRRHOSIS; MUCOSAL AB This consensus document provides an update for pathologists and clinicians about the interpretation of biopsy results and use of this information in the management of hematopoietic cell transplantation patients. Optimal sampling and tissue preparation are discussed. Minimal criteria for the diagnosis of graft-versus-host disease (GVHD) are proposed, together with specific requirements for the diagnosis of chronic GVHD. Four final diagnostic categories (no GVHD, possible GVHD, consistent with GVHD, and definite GVHD) reflect the integration of histopathology with clinical, laboratory, and radiographic information. Finally, the Working Group developed a set of worksheets to facilitate communication of clinical information to the interpreting pathologist and to aid in clinicopathologic correlation studies. Forms are available at http://www.asbmt.org/cGvHD_Guidelines. The recommendations of the Working Group represent a consensus opinion supplemented by evaluation of available peer-reviewed literature. Consensus recommendations and suggusted data-capture forms should be validated in prospective clinicopathologic studies. (c) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Seattle, WA 98109 USA. Univ Washington, Seattle Canc Care Alliance, Dept Pathol, Seattle, WA 98109 USA. NCI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Sch Dent, Seattle, WA 98195 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Hosp St Louis, Paris, France. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Columbia Univ, New York, NY USA. Vanderbilt Univ, Nashville, TN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. RP Shulman, HM (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, 825 Eastlake Ave E, Seattle, WA 98109 USA. EM hshulman@seattlecca.org OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 49 TC 199 Z9 214 U1 0 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2006 VL 12 IS 1 BP 31 EP 47 DI 10.1016/j.bbmt.2005.10.023 PG 17 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 009DW UT WOS:000235092500002 PM 16399567 ER PT J AU Freedman, AS AF Freedman, AS TI Non-transplant-related treatment options in follicular lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE follicular lymphoma ID NON-HODGKINS-LYMPHOMA; ANTI-CD20 MONOCLONAL-ANTIBODY; PHASE-II TRIAL; RANDOMIZED CONTROLLED-TRIAL; IODINE I-131 TOSITUMOMAB; DETUDE DES LYMPHOMES; LOW-GRADE LYMPHOMA; TERM-FOLLOW-UP; SIGNIFICANTLY INCREASES; CONTAINING REGIMEN C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Arnold_Freedman@dfci.harvard.edu NR 37 TC 1 Z9 1 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2006 VL 12 IS 1 SU 1 BP 53 EP 58 DI 10.1016/j.bbmt.2005.10.003 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 010FB UT WOS:000235171200011 PM 16399586 ER PT J AU Pietrement, C Sun-Wada, GH Da Silva, N McKee, M Marshansky, V Brown, D Futai, M Breton, S AF Pietrement, C Sun-Wada, GH Da Silva, N McKee, M Marshansky, V Brown, D Futai, M Breton, S TI Distinct expression patterns of different subunit Isoforms of the V-ATPase in the rat epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article DE epididymis; vas deferens ID VACUOLAR H+-ATPASE; MALE REPRODUCTIVE-TRACT; RENAL TUBULAR-ACIDOSIS; PROTON-TRANSLOCATING ATPASE; SECRETING EPITHELIAL-CELLS; TISSUE-SPECIFIC ISOFORMS; KIDNEY COLLECTING DUCT; IN-VIVO DISSOCIATION; LUMINAL ACIDIFICATION; MOLECULAR-CLONING AB In the epididymis and vas deferens, the vacuolar H(+)ATPase (V-ATPase), located in the apical pole of narrow and clear cells, is required to establish an acidic luminal pH. Low pH is important for the maturation of sperm and their storage in a quiescent state. The V-ATPase also participates in the acidification of intracellular organelles. The V-ATPase contains many subunits, and several of these subunits have multiple isoforms. So far, only subunits ATP6V1B1, ATP6V1B2, and ATP6V1E2, previously identified as 131, 132, and E subunits, have been described in the rat epididymis. Here, we report the localization of V-ATPase subunit isoforms ATP6V1A, ATP6V1C1, ATP6V1C2, ATP6V1G1, ATP6V1G3, ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0D1, and ATP6V0D2, previously labeled A, C1, C2, G1, G3, a1, a2, a4, d1, and d2, in epithelial cells of the rat epididymis and vas deferens. Narrow and clear cells showed a strong apical staining for all subunits, except the ATP6V0A2 isoform. Subunits ATP6V0A2 and ATP6V1A were detected in intracellular structures closely associated but not identical to the TGN of principal cells and narrow/clear cells, and subunit ATP6V0D1 was strongly expressed in the apical membrane of principal cells in the apparent absence of other V-ATPase subunits. In conclusion, more than one isoform of subunits ATP6V1C, ATP6V1G, ATP6V0A, and ATP6V0D of the V-ATPase are present in the epididymal and vas deferens epithelium. Our results confirm that narrow and clear cells are well fit for active proton secretion. In addition, the diverse functions of the V-ATPase may be established through the utilization of specific subunit isoforms. In principal cells, the ATP6V0D1 isoform may have a physiological function that is distinct from its role in proton transport via the V-ATPase complex. C1 Massachusetts Gen Hosp, Simches Res Ctr, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Doshisha Womens Coll, Fac Pharmaceut Sci, Kyoto 6100332, Japan. Japan Sci & Technol Agcy, CREST, Tokyo 1410021, Japan. Japan Sci & Technol Agcy, Futai Special Lab, Microbial Chem Res Ctr, Microbial Chem Res Fdn, Tokyo 1410021, Japan. RP Breton, S (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,CPZN 8202, Boston, MA 02114 USA. EM sbreton@partners.org FU NICHD NIH HHS [HD40793]; NIDDK NIH HHS [DK42956, DK38452, DK57521, DK43351] NR 69 TC 92 Z9 97 U1 1 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2006 VL 74 IS 1 BP 185 EP 194 DI 10.1095/biolreprod.105.043752 PG 10 WC Reproductive Biology SC Reproductive Biology GA 996TG UT WOS:000234197100024 PM 16192400 ER PT J AU Henkes, LE Sullivan, BT Lynch, MP Davis, JS Rueda, BR AF Henkes, Luiz E. Sullivan, Brian T. Lynch, Maureen P. Davis, John S. Rueda, Bo R. TI Defining the importance of tumor necrosis factor alpha to prostaglandin F2 alpha - Induced luteal regression. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Colorado State Univ, Anim Reprod & Biotechnol Lab, Ft Collins, CO 80523 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Olson Ctr Womens Hlth, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 82 EP 82 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500104 ER PT J AU Friel, AM Guo, LK Kishi, S DiGirolamo, CM Lynch, MP Sergent, P Rueda, B AF Friel, Anne M. Guo, Lankai Kishi, Shuji DiGirolamo, Carla M. Lynch, Maureen P. Sergent, Petra Rueda, Bo TI Tissue specific reduction of telomerase activity in Cables-/- mice. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 86 EP 86 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500122 ER PT J AU Wood, AW Schlueter, PJ AF Wood, Antony W. Schlueter, Peter J. TI Functional divergence of duplicate Type-1 IGF receptors in zebrafish primordial germ cell development. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 94 EP 95 PG 2 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500158 ER PT J AU Taylor, JA Richter, CA Ruhlen, RL Johnson, GS Welshons, WV Suzuki, A Watanabe, H Iguchi, T Coser, KR Shioda, T vom Saal, FS AF Taylor, Julia A. Richter, Catherine A. Ruhlen, Rachel L. Johnson, Gary S. Welshons, Wade V. Suzuki, Atsuko Watanabe, Hajime Iguchi, Taisen Coser, Kathryn R. Shioda, Toshi vom Saal, Frederick S. TI Physiological concentrations of estradiol up-regulate androgen receptor mRNA through an estrogen receptor-mediated mechanism in fetal mouse urogenital sinus mesenchyme cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Univ Missouri, Columbia, MO USA. US Geol Survey, Columbia, MO USA. Natl Inst Nat Sci, Okazaki, Aichi, Japan. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 102 EP 102 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500191 ER PT J AU Townson, DH Putnam, AN Sullivan, BT Irving-Rodgers, HF AF Townson, David H. Putnam, Amanda N. Sullivan, Brian T. Irving-Rodgers, Helen F. TI Expression and potential role of cytokeratin 8/18 filaments in Fas ligand-induced apoptosis of bovine ovarian cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Univ New Hampshire, Durham, NH 03824 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Univ Adelaide, Adelaide, SA 5005, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 115 EP 115 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500245 ER PT J AU Castrillon, DH Gallardo, TD John, GB Bradshaw, K Welt, C Reijo-Pera, R Vogt, PH Touraine, P Bione, S Toniolo, D Nelson, L Zinn, AR AF Castrillon, Diego H. Gallardo, Teresa D. John, George B. Bradshaw, Karen Welt, Corrine Reijo-Pera, Renee Vogt, Peter H. Touraine, Philippe Bione, Silvia Toniolo, Daniela Nelson, Larry Zinn, Andrew R. TI Sequence variation at the human FOXO3 locus: A study of premature ovarian failure and primary amenorrhea. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 94143 USA. Univ Texas, SW Med Ctr, Simmond Comprehens Canc Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Reprod Endocrinol, Boston, MA USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, I-20132 San Francisco, CA USA. Heidelberg Univ, Dept Gynecol Endocrinol & Reprod Med, Heidelberg, Germany. Univ Paris 05, Necker Hosp, Dept Endocrinol & Reprod Med, Paris, France. Inst Mol Genet, Dept Human Genet & Genom, Pavia, Italy. Ist Sci San Raffaele, Dept Mol Biol & Genom, Milan, Italy. NICHHD, NIH, Rockville, MD USA. Univ Texas, SW Med Ctr, McDermott Ctr Human Growth & Dev, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 121 EP 121 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500274 ER PT J AU Pru, JK Zhang, HY Zhang, L Peluso, JJ AF Pru, James K. Zhang, Hongying Zhang, Ling Peluso, John J. TI Membrane-associated progestin receptors in the murine uterus. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 162 EP 163 PG 2 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500460 ER PT J AU Tamagnan, G Alagille, D Fu, X Kula, NS Baldessarini, RJ Innis, RB Baldwin, RM AF Tamagnan, G Alagille, D Fu, X Kula, NS Baldessarini, RJ Innis, RB Baldwin, RM TI Synthesis and monoamine transporter affinity of new 2 beta-carbomethoxy-3 beta-laryl or heteroaryllphenyltropanes SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE transporter; serotonin; dopamine; norepinephrine; tropane ID BETA-CIT; SEROTONIN; ANALOGS; SITES; DEPRESSION; DISEASE AB A series of 16 new 2 beta-carbomethoxy-3 beta-[aryl or heteroaryl]phenyltropane derivatives was synthesized and evaluated for binding to monoamine transporters. Most of the compounds exhibited nanomolar affinity for the serotonin transporter (SERT). Four compounds (29, 14, 11, and 10) presented a particularly attractive pharmacological profile, with very high SERT affinity (K-i 0.15-0.5 nM) and selectivity versus the dopamine transporter of 25- to 77-fold. (c) 2005 Elsevier Ltd. All rights reserved. C1 Yale Univ, Dept Psychiat, West Haven, CT 06516 USA. VA CT HCS 1162A2, West Haven, CT 06516 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Neurosci Program, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA 02478 USA. Inst Neurodegenerat Disorders, New Haven, CT 06510 USA. RP Tamagnan, G (reprint author), Yale Univ, Dept Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM gtamagnan@indd.org FU NIMH NIH HHS [MH-670066] NR 15 TC 4 Z9 4 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2006 VL 16 IS 1 BP 217 EP 220 DI 10.1016/j.bmcl.2005.09.016 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 987KG UT WOS:000233516200046 PM 16236497 ER PT S AU Hamblin, MR Castano, AP Mroz, P AF Hamblin, Michael R. Castano, Ana P. Mroz, Pawel BE Chen, WR TI Combination immunotherapy and photodynamic therapy for cancer - art. no. 608702 SO Biophotonics and Immune Repsonses SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses CY JAN 23-24, 2006 CL San Jose, CA SP SPIE DE photodynamic therapy; anti-tumor immunity; toll-like receptors; T regulatory cells; dendritic cells; cytotoxic T-cells; antigen presentation ID TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; REGULATORY T-CELLS; CONTACT HYPERSENSITIVITY; MOUSE-TUMORS; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID; ADOPTIVE IMMUNOTHERAPY; LOCALIZED TREATMENT; DENDRITIC CELLS; IMMUNE-SYSTEM AB Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 58 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6129-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6087 BP 8702 EP 8702 AR 608702 DI 10.1117/12.646275 PG 12 WC Biophysics; Immunology; Medicine, Research & Experimental SC Biophysics; Immunology; Research & Experimental Medicine GA BEF61 UT WOS:000237105800002 ER PT S AU Castano, AP Hamblin, MR AF Castano, Ana P. Hamblin, Michael R. BE Chen, WR TI Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation - art. no. 608703 SO Biophotonics and Immune Repsonses SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses CY JAN 23-24, 2006 CL San Jose, CA SP SPIE DE photodynamic therapy; breast cancer; cyclophosphamide; CpG oligonucleotides; T-regulatory cells ID REGULATORY T-CELLS; TUMOR-IMMUNITY; DENDRITIC CELLS; CPG-DNA; CYCLOPHOSPHAMIDE; IMMUNOTHERAPY; OLIGONUCLEOTIDES; ACTIVATION; MECHANISMS; REDUCTION AB One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines, chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Castano, AP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 29 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6129-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6087 BP 8703 EP 8703 AR 608703 DI 10.1117/12.646242 PG 8 WC Biophysics; Immunology; Medicine, Research & Experimental SC Biophysics; Immunology; Research & Experimental Medicine GA BEF61 UT WOS:000237105800003 ER PT S AU Chen, YC Redmond, RW AF Chen, Yin-Chu Redmond, Robert W. BE Chen, WR TI Time-lapse microscopy studies of bystander effects induced by photosensitization - art. no. 60870S SO Biophotonics and Immune Repsonses SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses CY JAN 23-24, 2006 CL San Jose, CA SP SPIE DE photosensitization; oxidative stress; bystander effects; reactive oxygen species; time-lapse microscopy ID PHOTODYNAMIC TREATMENT; ALPHA-PARTICLES; CELLS; RADIATION; PHOTOTOXICITY AB Reactive oxygen species (ROS) are involved in the pathogenesis of many critical diseases and are also utilized as cytotoxic agents in a variety of treatments for eradication of diseased tissue, including cancer. Oxidative stress ensues when the level of ROS in a system exceeds the antioxidant capacity. Oxidative stress can have local (direct) and long-range (bystander) effects in cells and tissue and this research was carried out to determine the spatial and temporal nature of the photosensitized bystander effect using time-lapse fluorescence microscopy. By initiating photosensitization in only a portion of the microscopic imaging field it was possible to differentiate direct from bystander effects in EMT-6 murine breast cancer cells in 6-well plates. Elevated ROS levels are seen immediately following photodynamic treatment in direct cells with a delayed increase in oxidative stress observed in bystander cells. Cytotoxicity is also seen at earlier times in direct cells and occurs in bystander cells in a delayed fashion. These studies confirm the existence of a bystander effect following photosensitization and implicate mediators capable of diffusing in an intercellular manner from directly photosensitized cells to bystander cells and also implicate increased oxidative stress as a mechanistic factor in generating damage in bystander cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chen, YC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6129-6 J9 P SOC PHOTO-OPT INS PY 2006 VL 6087 BP S870 EP S870 AR 60870S DI 10.1117/12.673641 PG 9 WC Biophysics; Immunology; Medicine, Research & Experimental SC Biophysics; Immunology; Research & Experimental Medicine GA BEF61 UT WOS:000237105800017 ER PT J AU Biederman, J AF Biederman, Joseph BE Akiskal, HS Tohen, M TI Pediatric Bipolar Disorder: The Promise of Psychopharmacotherapy SO BIPOLAR PSYCHOPHARMACOTHERAPY: CARING FOR THE PATIENT LA English DT Article; Book Chapter ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; PROSPECTIVE FOLLOW-UP; HOSPITALIZED AGGRESSIVE-CHILDREN; POSTTRAUMATIC-STRESS-DISORDER; MANIC-DEPRESSIVE ILLNESS; CATCHMENT-AREA SURVEY; CONDUCT DISORDER; DOUBLE-BLIND; JUVENILE MANIA C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Clin & Res Program Pediat Psychopharmacol, 15 Parkman St, Boston, MA 02114 USA. NR 90 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47001-795-1 PY 2006 BP 279 EP 299 DI 10.1002/0470017953.ch13 PG 21 WC Psychiatry SC Psychiatry GA BXY93 UT WOS:000297645900014 ER PT J AU Azadzoi, KM AF Azadzoi, KM TI Vasculogenic erectile dysfunction: Beyond the haemodynamic changes SO BJU INTERNATIONAL LA English DT Review DE erectile dysfunction; ischaemia; hypoxia; atherosclerosis; smooth muscle; fibrosis ID CAVERNOSUM SMOOTH-MUSCLE; TRANSFORMING GROWTH FACTOR-BETA(1); OXIDE SYNTHASE EXPRESSION; RABBIT CORPUS CAVERNOSUM; NITRIC-OXIDE; OXYGEN-TENSION; VENOOCCLUSIVE DYSFUNCTION; PENILE ARTERIES; ISCHEMIA; RELAXATION C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Azadzoi, KM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM kazadzoi@bu.edu NR 36 TC 19 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2006 VL 97 IS 1 BP 11 EP 16 DI 10.1111/j.1464-410X.2006.05778.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 999RE UT WOS:000234407400008 PM 16336320 ER PT J AU Chiaretti, S Guarini, A De Propris, MS Tavolaro, S Intoppa, S Vitale, A Iacobelli, S Elia, L Ariola, C Ritz, J Foa, R AF Chiaretti, S Guarini, A De Propris, MS Tavolaro, S Intoppa, S Vitale, A Iacobelli, S Elia, L Ariola, C Ritz, J Foa, R TI ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; IMATINIB MESYLATE THERAPY; POLYMERASE CHAIN-REACTION; GENE MUTATION STATUS; V-H GENES; PHILADELPHIA-CHROMOSOME; SIGNAL-TRANSDUCTION; TYROSINE KINASE; LUNG-CANCER AB We evaluated the expression of 2 members of the Syk family, ZAP-70 and Syk, in acute lymphoblastic leukemia (ALL) samples, using data derived from a series of 33 T-ALL and 95 B-lineage adult ALL patients analyzed by oligonucleotide arrays. Of the B-lineage ALL cases, 37 were BCR/ABL(+), 10 were ALL1/AF4(+), 5 were E2A/PBX1(+), and 43 carried no known molecular abnormality. ZAP-70 was highly expressed in T-ALL. A high ZAP-70 expression was also found in a proportion of B-lineage ALL, the highest levels being associated with the E2A/PBX1(+) group and the lowest with ALL1/AF4(+) cases (P < .001). A higher ZAP-70 expression was also observed in the pre-B group (P < .001). Remarkably, Syk expression was always preserved, suggesting that ZAP-70 expression is not substitutive of Syk. At the protein level, ZAP-70 was evaluated on 39 newly diagnosed ALL patients (25 adults, 14 children) and was detected in 23 cases (59%). ZAP-70 expression was consistently found in Ig mu(+) cases. Evaluation of long-term outcome in cases without molecular abnormalities showed that the higher levels of ZAP-70 were coupled to a higher relapse rate. in ALL, ZAP-70 expression is associated with the E2A/PBX1 rearrangement and pre-B stage and may have a prognostic role and be a candidate molecule for targeted therapies. C1 Univ Roma La Sapienza, Div Hematol, Dept Cellular Biotechnol, I-00161 Rome, Italy. Univ Roma La Sapienza, Div Hematol, Dept Hematol, I-00161 Rome, Italy. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Foa, R (reprint author), Univ Roma La Sapienza, Div Hematol, Dept Cellular Biotechnol, Via Benevento 6, I-00161 Rome, Italy. EM rfoa@bce.uniroma1.it RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 40 TC 17 Z9 19 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2006 VL 107 IS 1 BP 197 EP 204 DI 10.1182/blood-2005-04-1755 PG 8 WC Hematology SC Hematology GA 997HD UT WOS:000234235200038 PM 16160012 ER PT J AU Costa, LF Balcells, M Edelman, ER Nadler, LM Cardoso, AA AF Costa, LF Balcells, M Edelman, ER Nadler, LM Cardoso, AA TI Proangiogenic stimulation of bone marrow endothelium engages mTOR and is inhibited by simultaneous blockade of mTOR and NF-kappa B SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL-CYCLE PROGRESSION; GROWTH-FACTOR; IN-VITRO; TUMOR ANGIOGENESIS; MAMMALIAN TARGET; GENE-EXPRESSION; HEMATOLOGIC MALIGNANCIES; VASCULAR ENDOTHELIUM; COLORECTAL-CANCER AB Most bone marrow (SM) malignancies develop in association with an angiogenic phenotype and increased numbers of endothelial cells. The molecular mechanisms involved in the modulation and recruitment of SM endothelium are largely unknown and may provide novel therapeutic targets for neoplastic diseases. We observed that angiogenic stimulation of SM endothelial cells activates mTOR and engages its downstream pathways 4E-BP1 and S6K1, which are inhibited by the mTOR-specific blockers rapamycin and CCl-779. Both MTOR blockers significantly inhibit growth factor- and leukemia-induced proliferation of BM endothelium by inducing G(0)/G(1) cell-cycle arrest. This effect is associated with down-regulation of cyclin D1 and cdk2 phosphorylation, and up-regulation of the cdk inhibitors p27(kip1) and p21(cip1). Under conditions that reproduce the biomechanical fluidic environment of the BM, CCI-779 is equally effective in inhibiting BM endothelial-cell proliferation. Finally, simultaneous blockade of mTOR and NF-kappa B pathways synergize to significantly inhibit or abrogate the proliferative responses of BM endothelial cells to mitogenic stimuli. This study identifies mTOR as an important pathway for the proangiogenic stimulation of BM endothelium. Modulation of this pathway may serve as a valid therapeutic intervention in BM malignancies evolving in association with an angiogenic phenotype. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Lisbon, Inst Mol Med, Lisbon, Portugal. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA 02138 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Inst Quim Sarria, Barcelona, Spain. RP Cardoso, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Rm D-540B,44 Binney St, Boston, MA 02115 USA. EM cardoso@mbcrr.harvard.edu OI Balcells, Mercedes/0000-0002-2532-0516 FU NCI NIH HHS [P01-CA68484]; NHLBI NIH HHS [HL49309, HL62456] NR 61 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2006 VL 107 IS 1 BP 285 EP 292 DI 10.1182/blood-2005-06-2208 PG 8 WC Hematology SC Hematology GA 997HD UT WOS:000234235200048 PM 16141350 ER PT J AU Heidel, F Solem, FK Breitenbuecher, F Lipka, DB Kasper, S Thiede, MH Brandts, C Serve, H Roesel, J Giles, F Feldman, E Ehninger, G Schiller, GJ Nimer, S Stone, RM Wang, YF Kindler, T Cohen, PS Huber, C Fischer, T AF Heidel, F Solem, FK Breitenbuecher, F Lipka, DB Kasper, S Thiede, MH Brandts, C Serve, H Roesel, J Giles, F Feldman, E Ehninger, G Schiller, GJ Nimer, S Stone, RM Wang, YF Kindler, T Cohen, PS Huber, C Fischer, T TI Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; ACTIVATING MUTATION; CELL-LINES; AML; IDENTIFICATION; LOOP; MALIGNANCIES; PROGNOSIS; IMATINIB; THERAPY AB Activating mutations in the FLT3 tyrosine kinase (TK) occur in approximately 35% of patients with acute myeloid leukemia (AML). Therefore, targeting mutated FLT3 is an attractive therapeutic strategy, and early clinical trials testing FLT3 TK inhibitors (TKI) showed measurable clinical responses. Most of these responses were transient; however, in a subset of patients blast recurrence was preceded by an interval of prolonged remission. The etiology of clinical resistance to FLT3-TKI in AML is unclear but is of major significance for the development of future therapeutic strategies. We searched for mechanisms of resistance in 6 patients with AML who had relapses upon PKC412 treatment. In an index AML patient, an algorithm of analyses was applied using clinical material. In vivo and in vitro investigation of primary blasts at relapse revealed persistent TK phosphorylation of FLT3 despite sufficient PKC412 serum levels. Through additional molecular analyses, we identified a single amino acid substitution at position 676 (N676K) within the FLT3 kinase domain as the sole cause of resistance to PKC412 in this patient. Reconstitution experiments expressing the N676K mutant in 32D cells demonstrated that FLT3-ITD-N676K was sufficient to confer an intermediate level of resistance to PKC412 in vitro. These studies point out that a genetically complex malignancy such as AML may retain dependence on a single oncogenic signal. C1 Univ Mainz, Dept Med 3, D-55101 Mainz, Germany. Thanares Analyt & Res, Dresden, Germany. Univ Munster, Dept Med A, D-4400 Munster, Germany. Univ Carl Gustav Carus, Dept Med 1, Dresden, Germany. Novartis Pharma, Basel, Switzerland. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cornell Univ, Ctr Canc, New York, NY 10021 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Oncol, Florham Pk, NJ USA. RP Fischer, T (reprint author), Univ Mainz, Dept Med 3, Langenbeckstr 1, D-55101 Mainz, Germany. EM t.fischer@3-med.klinik.uni-mainz.de RI Kindler, Thomas/K-5995-2013; Kasper, Stefan/I-4521-2015 OI Kasper, Stefan/0000-0002-5947-8733 NR 31 TC 128 Z9 130 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2006 VL 107 IS 1 BP 293 EP 300 DI 10.1182/blood-2005-06-2469 PG 8 WC Hematology SC Hematology GA 997HD UT WOS:000234235200049 PM 16150941 ER PT J AU Prabhala, RH Neri, P Bae, JE Tassone, P Shammas, MA Allam, CK Daley, JF Chauhan, D Blanchard, E Thatte, HS Anderson, KC Munshi, NC AF Prabhala, RH Neri, P Bae, JE Tassone, P Shammas, MA Allam, CK Daley, JF Chauhan, D Blanchard, E Thatte, HS Anderson, KC Munshi, NC TI Dysfunctional T regulatory cells in multiple myeloma SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; PERIPHERAL-BLOOD; DENDRITIC CELLS; IN-VIVO; LYMPHOCYTES; MECHANISMS; LYMPHOMA; INHIBIT; GROWTH; BETA AB Multiple myeloma (MM) is characterized by the production of monoclonal immunoglobulin and is associated with suppressed uninvolved immunoglobulins and dysfunctional T-cell responses. The biologic basis of this dysfunction remains ill defined. Because T regulatory (T-reg) cells play an important role in suppressing normal immune responses, we evaluated the potential role of Treg cells in immune dysfunction in MM. We observed a significant increase in CD4(+)CD25(+) T cells in patients with monoclonal gammopathy of undetermined significance (MGUS) and in patients with MM compared with healthy donors (25% and 26%, respectively, vs 14%); however, T-reg cells as measured by FOXP3 expression are significantly decreased in patients with MGUS and MM compared with healthy donors. Moreover, even when they are added in higher proportions, T-reg cells in patients with MM and MGUS are unable to suppress anti-CD3-mediated T-cell proliferation. This decreased number and function of T-reg cells in MGUS and in MM may account, at least in part, for the nonspecific increase in CD4(+)CD25(+) T cells, thereby contributing to dysfunctional T-cell responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Vet Adm Boston Healthcare Syst, Boston, MA 02115 USA. Univ Magna Graecia, Catanzaro, Italy. Ctr Canc, Catanzaro, Italy. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU PHS HHS [P01-78378, P50-100707, R01-50947] NR 29 TC 131 Z9 144 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2006 VL 107 IS 1 BP 301 EP 304 DI 10.1182/blood-2005-08-3101 PG 4 WC Hematology SC Hematology GA 997HD UT WOS:000234235200050 PM 16150935 ER PT J AU Berman, JN Wang, M Berry, W Neuberg, DS Guinan, EC AF Berman, JN Wang, M Berry, W Neuberg, DS Guinan, EC TI Herpes zoster infection in the post-hematopoietic stem cell transplant pediatric population may be preceded by transaminitis: an institutional experience SO BONE MARROW TRANSPLANTATION LA English DT Article DE herpes virus infection; pediatric transplantation; transaminitis ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; RISK-FACTORS; VIRUS-INFECTION; IMMUNE RECONSTITUTION; HOST DISEASE; CHILDREN; RECIPIENTS; RECOVERY; LEUKEMIA AB Herpes zoster (HZ), a varicella-zoster virus reactivation, frequently complicates hematopoietic stem cell transplantation (HSCT). Its incidence, complications, and associated risk factors in 310 children undergoing HSCT were reviewed. In all, 61 of 201 (32%) patients who had undergone allogeneic and 10 of 109 (9%) patients who had undergone autologous HSCT developed HZ. Of 90 VZV seropositive allogeneic patients, 50 (53%) developed HZ. Seven (17%) of 41 VZV seropositive autologous patients developed HZ. Although a substantial number of patients develop HZ in the early post-HSCT period, risk for HZ persists and HZ can occur up to 5 years post-HSCT. Risk factors for HZ included age 410 years (P < 0.0001), allogeneic HSCT (P < 0.001), and total body irradiation (TBI) (P < 0.059) in allogeneic recipients. Of 37, 22 (59%) patients experienced an elevated alanine aminotransferase (ALT), unassociated with GVHD, in the month preceding HZ. Of the 48/64 patients (75%) hospitalized for treatment ( median stay, 6 days; range, 2-39), length of stay was unaffected by donor type but increased by cutaneous dissemination and visceral involvement (P = 0.023 and 0.034, respectively) in allogeneic patients. Consideration of HZ infection particularly in patients 410 years of age with elevated ALT after TBI-conditioned allogeneic HSCT may permit earlier diagnosis and therapeutic intervention. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Eva_Guinan@dfci.harvard.edu FU NCI NIH HHS [P01 CA100265]; NICHD NIH HHS [K12 HD00850] NR 29 TC 24 Z9 25 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2006 VL 37 IS 1 BP 73 EP 80 DI 10.1038/sj.bmt.1705191 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 996JC UT WOS:000234169200010 PM 16247423 ER PT J AU Zhang-Nunes, SX Maat-Schieman, MLC van Duinen, SG Roos, RAC Frosch, MP Greenberg, SM AF Zhang-Nunes, SX Maat-Schieman, MLC van Duinen, SG Roos, RAC Frosch, MP Greenberg, SM TI The cerebral beta-amyloid angiopathies: Hereditary and sporadic SO BRAIN PATHOLOGY LA English DT Article ID PRECURSOR PROTEIN GENE; APOLIPOPROTEIN-E EPSILON-2; CENTRAL-NERVOUS-SYSTEM; LOBAR INTRACEREBRAL HEMORRHAGE; ALZHEIMERS-DISEASE BRAIN; WHITE-MATTER LESIONS; DUTCH-TYPE; A-BETA; SENILE PLAQUES; E GENOTYPE AB We review the clinical, radiologic, and neuropathologic features of the hereditary and sporadic forms of cerebral amyloid angiopathy (CAA) associated with vascular deposition of the beta-amyloid peptide. Amino acid substitutions at 4 sites in the beta-amyloid precursor protein, all situated within the beta-amyloid peptide sequence itself, have been shown to cause heritable forms of CAA. The vascular diseases caused by these mutations are associated primarily with cerebral hemorrhages, white matter lesions, and cognitive impairment, and only variable extents of the plaque and neurofibrillary pathologies characteristic of Alzheimer disease. Sporadic CAA typically presents 20 or more years later than hereditary CAA, but is otherwise characterized by a comparable constellation of recurrent cerebral hemorrhages, white matter lesions, and cognitive impairment. The clinical, radiologic and pathologic similarities between hereditary and sporadic CAA suggest that important lessons for this common age-related process can be learned from the mechanisms by which mutation makes beta-amyloid tropic or toxic to vessels. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Boston, MA 02114 USA. Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RA Leiden, Netherlands. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Wang ACC 836, Boston, MA 02114 USA. EM sgreenberg@partners.org FU NIA NIH HHS [AG26484]; NINDS NIH HHS [NS041409, NS042147] NR 109 TC 118 Z9 121 U1 0 U2 4 PU INT SOC NEUROPATHOLOGY PI LOS ANGELES PA UCLA MEDICAL CENTER, SECTION NEUROPATHOLGY, C H S 18-126, LOS ANGELES, CA 90095-1732 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2006 VL 16 IS 1 BP 30 EP 39 DI 10.1111/j.1750-3639.2006.tb00559.x PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 021DH UT WOS:000235963200005 PM 16612980 ER PT S AU Dietrich, J Kempermann, G AF Dietrich, J Kempermann, G BE Bahr, M TI Role of endogenous neural stem cells in neurological disease and brain repair SO BRAIN REPAIR SE Advances in Experimental Medicine and Biology LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; TEMPORAL-LOBE EPILEPSY; FIBROBLAST-GROWTH-FACTOR; OLIGODENDROCYTE PRECURSOR CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; MULTIPLE-SCLEROSIS LESIONS; TRANSIENT GLOBAL-ISCHEMIA; GLIAL PROGENITOR-CELL; ADULT MAMMALIAN FOREBRAIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Dietrich, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RI Kempermann, Gerd/F-5416-2010 OI Kempermann, Gerd/0000-0002-5304-4061 NR 359 TC 28 Z9 34 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-306-47859-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 557 BP 191 EP 220 PG 30 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Clinical Neurology; Neurosciences SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BDL05 UT WOS:000234080800012 PM 16955712 ER PT J AU Colditz, GA Rosner, BA AF Colditz, Graham A. Rosner, Bernard A. TI What can be learnt from models of incidence rates? SO BREAST CANCER RESEARCH LA English DT Review ID BREAST-CANCER RISK; PROGESTERONE-RECEPTOR STATUS; HORMONE REPLACEMENT THERAPY; ESTROGEN-RECEPTOR; NURSES HEALTH; MULTISTAGE CARCINOGENESIS; SUSCEPTIBILITY GENES; CIGARETTE-SMOKING; OVARIAN-CANCER; FEMALE BREAST AB Models of breast cancer incidence have evolved from the observation by Armitage and Doll in the 1950s that the pattern of incidence by age differs for reproductive cancers from those of other major malignancies. Both two-stage and multistage models have been applied to breast cancer incidence. Consistent across modeling approaches, risk accumulation or the rate of increase in breast cancer incidence is most rapid from menarche to first birth. Models that account for the change in risk after menopause and the temporal sequence of reproductive events summarize risk efficiently and give added insights to potentially important mechanistic features. First pregnancy has an adverse impact on progesterone receptor negative tumors, while increasing parity reduces the risk of estrogen/progesterone receptor positive tumors but not estrogen/progesterone receptor negative tumors. Integrated prediction models that incorporate prediction of carrier status for highly penetrant genes and also account for lifestyle factors, mammographic density, and endogenous hormone levels remain to be efficiently implemented. Models that both inform and reflect the emerging understanding of the molecular and cell biology of carcinogenesis are still a long way off. C1 Brigham & Womens Hosp, Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Harvard Canc Ctr, Biostat Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Colditz, GA (reprint author), Brigham & Womens Hosp, Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, 75 Francis St, Boston, MA 02115 USA. EM graham.colditz@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA87969, P01 CA055075, P01 CA087969] NR 66 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 3 AR 206 DI 10.1186/bcr1414 PG 7 WC Oncology SC Oncology GA 065DW UT WOS:000239140600002 PM 16762045 ER PT J AU Cox, DG Blanche, H Pearce, CL Calle, EE Colditz, GA Pike, MC Albanes, D Allen, NE Amiano, P Berglund, G Boeing, H Buring, J Burtt, N Canzian, F Chanock, S Clavel-Chapelon, F Feigelson, HS Freedman, M Haiman, CA Hankinson, SE Henderson, BE Hoover, R Hunter, DJ Kaaks, R Kolonel, L Kraft, P LeMarchand, L Lund, E Palli, D Peeters, PHM Riboli, E Stram, DO Thun, M Tjonneland, A Trichopoulos, D Yeager, M AF Cox, David G. Blanche, Helene Pearce, Celeste L. Calle, Eugenia E. Colditz, Graham A. Pike, Malcolm C. Albanes, Demetrius Allen, Naomi E. Amiano, Pilar Berglund, Goran Boeing, Heiner Buring, Julie Burtt, Noel Canzian, Federico Chanock, Stephen Clavel-Chapelon, Francoise Feigelson, Heather Spencer Freedman, Matthew Haiman, Christopher A. Hankinson, Susan E. Henderson, Brian E. Hoover, Robert Hunter, David J. Kaaks, Rudolf Kolonel, Laurence Kraft, Peter LeMarchand, Loic Lund, Eiliv Palli, Domenico Peeters, Petra H. M. Riboli, Elio Stram, Daniel O. Thun, Michael Tjonneland, Anne Trichopoulos, Dimitrios Yeager, Meredith CA Breast Prostate Canc TI A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) SO BREAST CANCER RESEARCH LA English DT Article ID BASE-LINE CHARACTERISTICS; CAG REPEAT POLYMORPHISM; SEX-HORMONE LEVELS; VITAMIN-D-RECEPTOR; POSTMENOPAUSAL WOMEN; DEHYDROEPIANDROSTERONE-SULFATE; POLYGLUTAMINE TRACTS; MULTIETHNIC COHORT; NURSES HEALTH; CELL-LINES AB Introduction Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/ or androgen receptor ( AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium ( BPC3). Methods The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships ( blocks) across the gene were then identified, and haplotypetagging single nucleotide polymorphisms ( htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts ( 5,603 breast cancer cases and 7,480 controls). Results We found no association between any genetic variation ( SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed. Conclusion Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. Epidemiol & Surveillance Res Amer Canc Soc, Atlanta, GA 30329 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Oxford, Canc Res UK Epidemiol Unit, Oxford OX3 7LF, England. Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, I-50131 Florence, Italy. Lund Univ, Dept Med, S-22100 Lund, Sweden. German Inst Human Nutr, Dept Epidemiol, D-14558 Nuthetal, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. German Canc Res Ctr, Genom Epidemiol Grp, Div Mol Genet Epidemiol, D-69121 Heidelberg, Germany. NCI, Core Genotyping Facil, Gaithersburg, MD 20892 USA. Inst Gustave Roussy, INSERM, F-94805 Villejuif, France. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Int Agcy Res Canc, Nutr & Hormones Grp, F-69008 Lyon, France. Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. Univ Tromso, Inst Community Med, N-9037 Tromso, Norway. Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, NL-3508 Utrecht, Netherlands. Univ London Imperial Coll Sci & Technol, Fac Med, Div Epidemiol Publ Hlth & Primary Care, London W2 1PG, England. Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. RP Cox, DG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM dcox@hsph.harvard.edu RI Cox, David/A-2023-2009; Clavel-Chapelon, Francoise/G-6733-2014; Albanes, Demetrius/B-9749-2015; Colditz, Graham/A-3963-2009; OI Cox, David/0000-0002-2152-9259; Colditz, Graham/0000-0002-7307-0291; PALLI, Domenico/0000-0002-5558-2437 NR 49 TC 31 Z9 31 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 5 AR R54 DI 10.1186/bcr1602 PG 9 WC Oncology SC Oncology GA 121PI UT WOS:000243169100007 PM 16987421 ER PT J AU Frackelton, AR Lu, L Davol, PA Bagdasaryan, R Hafer, LJ Sgroi, DC AF Frackelton, A. Raymond, Jr. Lu, Li Davol, Pamela A. Bagdasaryan, Robert Hafer, Laurie J. Sgroi, Dennis C. TI p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy SO BREAST CANCER RESEARCH LA English DT Article ID FACTOR RECEPTOR EXPRESSION; ESTROGEN-RECEPTOR; CANCER PATIENTS; PLASMA-MEMBRANE; KINASE PATHWAY; PROTEIN SHC; RESISTANCE; MECHANISMS; EGF; ASSOCIATION AB Introduction Shc adapter proteins are secondary messenger proteins involved in various cellular pathways, including those mediating receptor tyrosine kinase signaling and apoptosis in response to stress. We have previously reported that high levels of tyrosine-phosphorylated Shc (PY-Shc) and low levels of its inhibitory p66 Shc isoform are strongly prognostic for identifying both early node-negative and more advanced, node-positive, primary breast cancers with high risk for recurrence. Because aberrant activation of tyrosine kinases upstream of Shc signaling proteins has been implicated in resistance to tamoxifen - the most widely prescribed drug for treatment of estrogen receptorpositive breast cancer - we hypothesized that Shc isoforms may identify patients at increased risk of relapsing despite tamoxifen treatment. Methods Immunohistochemical analyses of PY-Shc and p66 Shc were performed on archival primary breast cancer tumors from a population-based cohort (60 patients, 9 relapses) and, for validation, an independent external cohort (31 patients, 13 relapses) in which all patients received tamoxifen as a sole systemic adjuvant prior to relapse. Results By univariate and multivariate analyses, the Shc proteins were very strong and independent predictors of treatment failure in both the population-based cohort (interquartile hazard ratio = 8.3, 95% confidence interval [CI] 1.8 to 38, P = 0.007) and the validating cohort (interquartile relative risk = 12.1, 95% CI 1.7 to 86, P = 0.013). Conclusion These results suggest that the levels of PY-Shc and p66 Shc proteins in primary tumors identify patients at high risk for relapsing despite treatment with tamoxifen and therefore with further validation may be useful in guiding clinicians to select alternative adjuvant treatment strategies. C1 Roger Williams Med Ctr, Res Dept, Providence, RI 02908 USA. Brown Univ, Dept Med, Providence, RI 02912 USA. Brown Univ, Dept Pathol, Providence, RI 02912 USA. Brown Univ, Dept Lab Med, Providence, RI 02912 USA. Roger Williams Med Ctr, Dept Surg, Providence, RI 02908 USA. Roger Williams Med Ctr, Dept Pathol, Providence, RI 02908 USA. Catalyst Oncol Inc, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. RP Frackelton, AR (reprint author), Roger Williams Med Ctr, Res Dept, 825 Chalkstone Ave, Providence, RI 02908 USA. EM A_Frackelton_Jr@brown.edu FU NCI NIH HHS [R01-1CA112021-01, R01 CA112021] NR 29 TC 16 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 6 AR R73 DI 10.1186/bcr1631 PG 8 WC Oncology SC Oncology GA 133WW UT WOS:000244045600016 PM 17196107 ER PT J AU Friedman, E Kotsopoulos, J Lubinski, J T Lynch, H Ghadirian, P Neuhausen, SL Isaacs, C Weber, B D Foulkes, W Moller, P Rosen, B Kim-Sing, C Gershoni-Baruch, R Ainsworth, P Daly, M Tung, N Eisen, A Olopade, OI Karlan, B Saal, HM Garber, JE Rennert, G Gilchrist, D Eng, C Offit, K Osborne, M Sun, P Narod, SA AF Friedman, E Kotsopoulos, J Lubinski, J T Lynch, H Ghadirian, P Neuhausen, SL Isaacs, C Weber, B D Foulkes, W Moller, P Rosen, B Kim-Sing, C Gershoni-Baruch, R Ainsworth, P Daly, M Tung, N Eisen, A Olopade, OI Karlan, B Saal, HM Garber, JE Rennert, G Gilchrist, D Eng, C Offit, K Osborne, M Sun, P Narod, SA CA Hereditary Breast Canc Clin Study TI Spontaneous and therapeutic abortions and the risk of breast cancer among BRCA mutation carriers SO BREAST CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; GENETIC-HETEROGENEITY; WOMEN; FAMILIES AB Introduction BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk of breast cancer in mutation carriers, but the effects of spontaneous and therapeutic abortions on the risk of hereditary breast cancer risk have not been well studied to date. Methods In a matched case-control study, the frequencies of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950 BRCA2 mutation carriers and 657 related non-carrier controls. The rates of spontaneous and therapeutic abortions were compared for carriers with and without breast cancer. Results There was no difference in the rate of spontaneous abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The number of spontaneous abortions was not associated with breast cancer risk among BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds ratio=0.36; 95% confidence interval 0.16-0.83; p=0.02). Conclusion Carrying a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and spontaneous abortions do not appear to influence the risk of breast cancer in carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic abortions may be associated with a lowered risk of breast cancer among BRCA2 carriers. C1 Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON, Canada. Chaim Sheba Med Ctr, Suzanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. Pomeranian Med Univ, Hereditary Canc Ctr, Szczecin, Poland. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. Univ Montreal, Epidemiol Res Unit, CHUM Hotel Dieu, Res Ctr,Ctr Hosp,Dept Nutr,Fac Med, Quebec City, PQ, Canada. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Montreal, PQ, Canada. Norwegian Radium Hosp, Dept Canc Genet, Oslo, Norway. Princess Margaret Hosp, Familial Ovarian Canc Clin, Toronto, ON M4X 1K9, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Rambam Med Ctr, Inst Genet, Haifa, Israel. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Beth Israel Med Ctr, Boston, MA USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Childrens Hosp Med Ctr, Hereditary Canc Program, Div Human Genet, Cincinnati, OH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Carmel Hosp, Natl Canc Control Ctr, Haifa, Israel. WCM Univ Alberta, Edmonton, AB, Canada. Ohio State Univ, Clin Canc Genet Program, Ctr Comprehens Canc, Div Human Genet,Dept Internal Med, Columbus, OH 43210 USA. Mem Sloan Kettering Canc Ctr, Dept Human Genet & Med, New York, NY 10021 USA. Strang Canc Prevent Ctr, New York, NY USA. RP Narod, SA (reprint author), Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Bay St, Toronto, ON, Canada. EM steven.narod@sw.ca OI foulkes, william/0000-0001-7427-4651; Eng, Charis/0000-0002-3693-5145; Evans, Gareth/0000-0002-8482-5784 NR 16 TC 24 Z9 25 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 2 AR R15 DI 10.1186/bcr1387 PG 7 WC Oncology SC Oncology GA 039HX UT WOS:000237297700010 PM 16563180 ER PT J AU Harris, LN Broadwater, G Lin, NU Miron, A Schnitt, SJ Cowan, D Lara, J Bleiweiss, I Berry, D Ellis, M Hayes, DF Winer, EP Dressler, L AF Harris, Lyndsay N. Broadwater, Gloria Lin, Nancy U. Miron, Alexander Schnitt, Stuart J. Cowan, David Lara, Jonathan Bleiweiss, Ira Berry, Donald Ellis, Matthew Hayes, Daniel F. Winer, Eric P. Dressler, Lynn TI Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342 SO BREAST CANCER RESEARCH LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID GENE-EXPRESSION PATTERNS; ADJUVANT CHEMOTHERAPY; EXTRACELLULAR DOMAIN; VINCA ALKALOIDS; P53 GENE; DOXORUBICIN; SENSITIVITY; RESISTANCE; OVEREXPRESSION; MUTATIONS AB Introduction The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. Methods Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m(2), adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. Results Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). Conclusion None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. St Barnabas Hosp, Livingston, NJ 07039 USA. Mt Sinai Sch Med, New York, NY 10029 USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Washington Univ, Med Ctr, St Louis, MO 63110 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Harris, LN (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM lyndsay.harris@yale.edu FU NCI NIH HHS [5 R01 CA86774-02, T32 CA009172] NR 47 TC 79 Z9 85 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 6 AR R66 DI 10.1186/bcr1622 PG 12 WC Oncology SC Oncology GA 133WW UT WOS:000244045600009 PM 17129383 ER PT J AU Abusief, ME Missmer, SA Ginsburg, ES Weeks, JC Winer, EP Partridge, AH AF Abusief, M. E. Missmer, S. A. Ginsburg, E. S. Weeks, J. C. Winer, E. P. Partridge, A. H. TI The effect of paclitaxel, dose density and trastuzumab on chemotherapy-related amenorrhea (CRA) in premenopausal women with breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 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 SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S107 EP S107 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100309 ER PT J AU Anderson, KS Aronzon, D Keshaviah, A Keung, EZ Kamma, M Winer, EP Burstein, HJ Harris, LN AF Anderson, K. S. Aronzon, D. Keshaviah, A. Keung, E. Z. Kamma, M. Winer, E. P. Burstein, H. J. Harris, L. N. TI Role of host immune response genes in the clinical response to trastuzumab-based therapies. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S78 EP S79 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100227 ER PT J AU Black, D Golshan, M Christian, R Nakhlis, F Dominguez, F Smith, BL Lesnikoski, BA AF Black, D. Golshan, M. Christian, R. Nakhlis, F. Dominguez, F. Smith, B. L. Lesnikoski, B-A TI Post-operative outcomes of mastectomy with breast tumescence infiltration. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S123 EP S123 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100357 ER PT J AU Black, D Younger, J Martei, Y Michaelson, J Dominguez, F Bhan, A Burstein, H Winer, E Goss, P Smith, B AF Black, D. Younger, J. Martei, Y. Michaelson, J. Dominguez, F. Bhan, A. Burstein, H. Winer, E. Goss, P. Smith, B. TI Recurrence risk in T1a-b, node negative, HER2 positive breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S92 EP S93 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100267 ER PT J AU Braithwaite, D Moore, D Liebman, M Belkora, J West, D Satariano, W Ozanne, E Esserman, L AF Braithwaite, D. Moore, D. Liebman, M. Belkora, J. West, D. Satariano, W. Ozanne, E. Esserman, L. TI New comorbidity model to optimize decisions about interventions for breast cancer patients. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Calif San Francisco, San Francisco, CA USA. Winberd Res Inst, San Francisco, CA USA. No Calif Canc Ctr, Fremont, CA USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S273 EP S273 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101365 ER PT J AU Burris, HA Krop, IE Modi, S Rodon, J Lutzker, SG Holden, SN Bhattacharya, S Sliwkowski, M Beeram, M AF Burris, H. A. Krop, I. E. Modi, S. Rodon, J. Lutzker, S. G. Holden, S. N. Bhattacharya, S. Sliwkowski, M. X. Beeram, M. TI A phase I study of a first-in-class HER2 antibody-drug conjugate in patients with HER2-overexpressing metastatic breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Int Drug Dev, San Antonio, TX USA. Genentech Inc, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S104 EP S104 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100300 ER PT J AU Collins, LC Martyniak, A Kandel, M Miron, A Harris, L Richardson, A Stadler, Z Schnitt, SJ Garber, JE AF Collins, L. C. Martyniak, A. Kandel, M. Miron, A. Harris, L. Richardson, A. Stadler, Z. Schnitt, S. J. Garber, J. E. TI Correlation of BRCA1 mutation status with basal cytokeratin and epidermal growth factor receptor expression in women with "triple negative" breast cancers. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S178 EP S178 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101083 ER PT J AU Garber, JE Richardson, A Harris, LN Miron, A Silver, D Golshan, M Ryan, PD Ganesan, S Li, X Wang, ZC Clarke, K Tung, NM Iglehart, JD Winer, EP AF Garber, J. E. Richardson, A. Harris, L. N. Miron, A. Silver, D. Golshan, M. Ryan, P. D. Ganesan, S. Li, X. Wang, Z. C. Clarke, K. Tung, N. M. Iglehart, J. D. Winer, E. P. TI Neo-adjuvant cisplatin (CDDP) in "triple-negative" breast cancer (BC). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 16 Z9 17 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S149 EP S149 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100431 ER PT J AU Goetz, MP Suman, V Couch, F Ames, M Rae, J Erlander, M Knox, S Ma, XJ Reynolds, C Visscher, D Lingle, W Flockhart, D Desta, Z Sgroi, D Goss, P Perez, E Ingle, J AF Goetz, M. P. Suman, V Couch, F. Ames, M. Rae, J. Erlander, M. Knox, S. Ma, X. J. Reynolds, C. Visscher, D. Lingle, W. Flockhart, D. Desta, Z. Sgroi, D. Goss, P. Perez, E. Ingle, J. TI An index based on HOXB13/IL17BR and CYP2D6 for determination of relapse and survival in tamoxifen-treated node negative breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Indiana Univ, Indianapolis, IN 46204 USA. AviaraDX, Carlsbad, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S53 EP S53 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100151 ER PT J AU Goss, PE Qi, S Hu, H Blanchett, D Langecker, P Lang, W AF Goss, P. E. Qi, S. Hu, H. Blanchett, D. Langecker, P. Lang, W. TI The effects of atamestane, toremifene or tamoxifen alone or combined on bone, serum lipids and uterus in ovariectomized rats. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, Hlth Sci Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Intarcia Therapeut Inc, Emeryville, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S288 EP S288 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101409 ER PT J AU Gunnarsdottir, K Jensen, MB Zahrieh, D Gelber, R Knoop, A Bonetti, M Mouridsen, H Ejlertsen, B AF Gunnarsdottir, K. Jensen, M-B Zahrieh, D. Gelber, R. Knoop, A. Bonetti, M. Mouridsen, H. Ejlertsen, B. TI CEF is superior to CMF for tumors with topoisomerase II alpha gene alterations: a STEPP (subpopulation treatment effect pattern plot) analysis on Danish breast cancer cooperative group study 89D. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 DBCG, Copenhagen, Denmark. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Bocconi, Milan, Italy. NR 0 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S46 EP S46 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100131 ER PT J AU Hughes, KS Schnaper, LA Berry, D Hodgson, L Cirrincione, C McCormick, B Shank, B Champion, LA Smith, TJ Smith, BL Shapiro, C Muss, H Winer, E Hudis, C Wood, W Henderson, IC Sugarbaker, D Norton, L AF Hughes, K. S. Schnaper, L. A. Berry, D. Hodgson, L. Cirrincione, C. McCormick, B. Shank, B. Champion, L. A. Smith, T. J. Smith, B. L. Shapiro, C. Muss, H. Winer, E. Hudis, C. Wood, W. Henderson, I. C. Sugarbaker, D. Norton, L. TI Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer: a report of further follow-up. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Greater Baltimore Med Ctr, Baltimore, MD USA. Canc & Leukemia Grp B Sta Ctr, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mt Sinai Sch Med, New York, NY USA. Alta Bates Comprehensive Canc Ctr, Sutter Hlth, Berkeley, CA USA. Morristown Mem Hosp, Morristown, NJ USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Vermont, Vermont Canc Ctr, Burlington, VT USA. Dana Farber Partners Canc Ctr, Boston, MA USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S8 EP S8 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100025 ER PT J AU Krop, IE Kosh, M Fearen, I Savoie, J Dallob, A Stone, J Winer, E Freedman, SJ LoRusso, P AF Krop, I. E. Kosh, M. Fearen, I Savoie, J. Dallob, A. Stone, J. Winer, E. Freedman, S. J. LoRusso, P. TI Phase I pharmacokinetic, and pharmacodynamic trial of the novel oral notch inhibitor MK-0752 in patients with advanced breast cancer and other solid tumors. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Merck Res Labs, N Wales, PA USA. Barbara Ann Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S287 EP S287 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101407 ER PT J AU Moy, B Elliott, CR Chapman, JAW Pater, JL Ding, Z Goss, PE AF Moy, B. Elliott, C. R. Chapman, J-AW Pater, J. L. Ding, Z. Goss, P. E. TI NCICCTG MA.27: Menopausal symptoms of ethnic minority women. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S144 EP S144 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100417 ER PT J AU Muss, HB Tu, D Ingle, JN Martino, S Robert, NJ Pater, JL Whelan, T Palmer, MJ Piccart, MJ Shepherd, LE Pritchard, KI He, Z Goss, PE AF Muss, H. B. Tu, D. Ingle, J. N. Martino, S. Robert, N. J. Pater, J. L. Whelan, T. Palmer, M. J. Piccart, M. J. Shepherd, L. E. Pritchard, K., I He, Z. Goss, P. E. TI The benefits of letrozole in postmenopausal women with early stage breast cancer who have had five years of tamoxifen are independent of age. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Vermont, Ctr Canc, Burlington, VT USA. Queens Univ, Kingston, ON, Canada. Mayo Clin, Ctr Canc, Rochester, MN USA. Univ So Calif, Los Angeles, CA USA. Fairfax Hosp, Fairfax, VA USA. McMaster Univ, Hamilton, ON, Canada. Jules Bordet Canc Inst, Brussels, Belgium. Univ Toronto, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Whelan, Timothy/D-3185-2017 NR 0 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S23 EP S23 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100066 ER PT J AU Narayan, M You, F Vachon, J Desroches, D Iglehart, JD Winer, EP Harris, LN AF Narayan, M. You, F. Vachon, J. Desroches, D. Iglehart, J. D. Winer, E. P. Harris, L. N. TI The HER2 amplicon gene FLJ20940 (PP1R1B) is upregullated in trastuzumab sensitive human breast cancer cell lines and HER2 amplified tumors that achieve a complete response to preoperative therapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Yale Univ, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S50 EP S50 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100144 ER PT J AU Nguyen, PL Boon, WL Silver, BJ Harris, JR AF Nguyen, P. L. Boon, W. L. Silver, B. J. Harris, J. R. TI Pathologic differences identified using receptor status and grade to approximate biological subtype among women with invasive breast cancer undergoing breast-conserving therapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S262 EP S262 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101331 ER PT J AU Partridge, AH LaFountain, A Taylor, B Asnis-Alibozek, A AF Partridge, A. H. LaFountain, A. Taylor, B. Asnis-Alibozek, A. TI Adherence with adjuvant anastrozole therapy among women with early stage breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Astra Zeneca Pharmaceut, Wilmington, DE USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S186 EP S186 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101106 ER PT J AU Patel, SA Jogsi, R Cook, N Parkinson, C Chao, K Hansen, E Huang, E Petit, J Wilson, J Hughes-Davies, L AF Patel, S. A. Jogsi, R. Cook, N. Parkinson, C. Chao, K. Hansen, E. Huang, E. Petit, J. Wilson, J. Hughes-Davies, L. TI Survey of breast oncology teaching of medical and radiation oncology trainees in the United States and the United Kingdom. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Maryland, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Addenbrookes Hosp, Cambridge, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S95 EP S96 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100276 ER PT J AU Pater, JL Tu, D Ingle, JN Shepherd, LE Goss, PE AF Pater, J. L. Tu, D. Ingle, J. N. Shepherd, L. E. Goss, P. E. TI An evaluation of the early termination (ET) of MA.17 extended adjuvant therapy trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Queens Univ, Kingston, ON, Canada. Mayo Clin, Ctr Canc, Rochester, MN USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S107 EP S108 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100311 ER PT J AU Rocca, A Viale, G Gelber, RD Bottiglieri, L Ghisini, R Balduzzi, A Pietri, E D'Alessandro, C Goldhirsch, A Colleoni, M AF Rocca, A. Viale, G. Gelber, R. D. Bottiglieri, L. Ghisini, R. Balduzzi, A. Pietri, E. D'Alessandro, C. Goldhirsch, A. Colleoni, M. TI Patients with p63 overexpressing breast cancer might benefit from cisplatin-based primary chemotherapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 European Inst Oncol, Milan, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S140 EP S140 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100405 ER PT J AU Tolaney, SM Partridge, AH Scheib, RG Ligibel, JA Shulman, LN Winer, EP Burstein, HJ AF Tolaney, S. M. Partridge, A. H. Scheib, R. G. Ligibel, J. A. Shulman, L. N. Winer, E. P. Burstein, H. J. TI Lymphopenia in dose-dense chemotherapy for early stage breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S112 EP S112 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100323 ER PT J AU Torres, AM Kung, A Lane, H Brown, M AF Torres, Arzayus M. Kung, A. Lane, H. Brown, M. TI Targeting the AIB1 oncogene through mTOR inhibition in the mammary gland. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S287 EP S287 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101406 ER PT J AU Van den Abbeele, AD Lin, NU Yap, JT Urban, T de Vries, DJ Barnes, AS Carey, LA Liu, MC Winer, EP AF Van den Abbeele, A. D. Lin, N. U. Yap, J. T. Urban, T. de Vries, D. J. Barnes, A. S. Carey, L. A. Liu, M. C. Winer, E. P. TI Evaluation of response to lapatinib in patients with HER2-positive metastatic breast cancer using FDG-PET. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Georgetown Univ Hosp, Washington, DC 20007 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S67 EP S68 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100194 ER PT J AU Yen, TW Kuerer, HM Ottesen, RA Rouse, L Niland, JC Edge, SB Theriault, RL Weeks, JC AF Yen, T. W. Kuerer, H. M. Ottesen, R. A. Rouse, L. Niland, J. C. Edge, S. B. Theriault, R. L. Weeks, J. C. TI Impact of randomized clinical trial results on the use of tamoxifen (TAM) following breast surgery for ductal carcinoma in situ (DCIS) in the national comprehensive cancer network (NCCN). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. MD Anderson Canc Ctr, Houston, TX USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S75 EP S75 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100215 ER PT J AU Kakinohana, M Nakamura, S Fuchigami, T Davison, KJ Marsala, M Sugahara, K AF Kakinohana, M Nakamura, S Fuchigami, T Davison, KJ Marsala, M Sugahara, K TI Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE agonists; DAMGO; DPDPE; U50488H; complications; paraparesis; complications; spinal cord ischaemia; receptors; opioid ID NONINJURIOUS INTERVAL; INTRATHECAL MORPHINE; NEURAXIAL MORPHINE; AORTIC OCCLUSION; DOSE-RESPONSE; BLOOD-FLOW; AMINO-ACID; PARAPLEGIA; NEURONS AB Background. Intrathecal (IT) morphine given after a short interval of aortic occlusion in a rodent model induced transient spastic paraparesis via opioid receptor-predicted actions in spinal cord. To determine the role(s) of spinal opioid receptor subtypes we investigated whether IT administration of various selective opioid receptor agonists can induce paraparesis following a short period of spinal cord ischaemia in rats. Methods. In Sprague-Dawley rats implanted with an IT catheter, spinal cord ischaemia was induced for 6 min using an intraaortic balloon. Mu ([d-Ala(2), N-Me Phe(4), Gly-ol(5)] enkephalin), kappa (U50488H) or delta ([d-Pen(2,5)] enkephalin) selective agonists were injected intrathecally 30 min after reperfusion. A separate group of animals was used to investigate the dose-response effect on this motor dysfunction. For this purpose, three doses of mu, kappa, or delta agonists were injected intrathecally after ischaemia. After IT injection, recovery of motor function was assessed periodically using the motor deficit index (0=complete recovery; 6=complete paraplegia). Results. IT administration of mu and delta but not kappa agonists produced dose-dependent effects in the induction of spastic paraparesis. In addition, this spasticity induced by IT mu and delta agonists was reversed completely by IT naloxone and naltrindole, respectively. Conclusion. These results suggest that the effect of various opioids on motor function after a short period of spinal cord ischaemia depends upon individual opioid receptor subtypes. C1 Univ Ryukyus, Fac Med, Dept Anesthesiol, Okinawa 9030215, Japan. Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA. RP Kakinohana, M (reprint author), Univ Ryukyus, Fac Med, Dept Anesthesiol, 207 Uehara, Okinawa 9030215, Japan. EM mnb-shk@ryukyu.ne.jp NR 22 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JAN PY 2006 VL 96 IS 1 BP 88 EP 94 DI 10.1093/bja/aei285 PG 7 WC Anesthesiology SC Anesthesiology GA 000AM UT WOS:000234433300015 PM 16317029 ER PT B AU Krebs, DE Huddleston, JI Goldvasser, D Scarborough, DM Harris, WH Malchau, H AF Krebs, David E. Huddleston, James I. Goldvasser, Dov Scarborough, Donna M. Harris, William H. Malchau, Henrik GP IEEE COMPUTER SOC TI Biomotion community-wearable human activity monitor: Total knee replacement and healthy control subjects SO BSN 2006: International Workshop on Wearable and Implantable Body Sensor Networks, Proceedings LA English DT Proceedings Paper CT International Workshop on Wearable and Implantable Body Sensor Networks CY APR 03-05, 2006 CL MIT, Cambridge, MA SP EMB, IEEE CAS Soc HO MIT AB The arrival of copious and cheap flash memory, as well as micromanufacturing techniques, permitted us to generate a pager-sized whole-body activity and knee range of motion monitor-and record these kinematics continuously at 32 Hz for two days on a single AA battery. Thus, we report here data from a healthy convenience sample of 5 males and 5 females, and 3 women and 7 men who had total knee replacements (TKR) 25 +/- 4 mo previously. Prior to our project, TKRs, artificial (transfemoral) limbs, airline seats, and other ergonomic knee-motion based designs were based on simulated motion lab studies. These latter indicated that <= 105 degrees knee flexion was sufficient to accommodate most activities; recently, however, TKR manufacturers began supplying "high flexion" knees that permit > 150 degrees knee flexion. Our data show that healthy Caucasian health care workers rarely employ > 120 degrees knee flexion, nor do Caucasians even with high flexion TKRs-even outside the lab environment. C1 Harvard Univ, Sch Med, Orthopaed Biomech & Biomat Lab, Boston, MA 02129 USA. MIT, Boston, MA 02129 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. RP Krebs, DE (reprint author), Harvard Univ, Sch Med, Orthopaed Biomech & Biomat Lab, 36 1st Ave, Boston, MA 02129 USA. NR 2 TC 0 Z9 0 U1 1 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2547-4 PY 2006 BP 109 EP 112 PG 4 WC Computer Science, Cybernetics; Engineering, Biomedical; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BEE18 UT WOS:000236909800027 ER PT B AU Patel, S Sherrill, D Hughes, R Hester, T Huggins, N Lie-Nemeth, T Standaert, D Bonato, P AF Patel, Shyamal Sherrill, Delsey Hughes, Richard Hester, Todd Huggins, Nancy Lie-Nemeth, Theresa Standaert, David Bonato, Paolo GP IEEE COMPUTER SOC TI Analysis of the severity of dyskinesia in patients with Parkinson's disease via wearable sensors SO BSN 2006: International Workshop on Wearable and Implantable Body Sensor Networks, Proceedings LA English DT Proceedings Paper CT International Workshop on Wearable and Implantable Body Sensor Networks CY APR 03-05, 2006 CL MIT, Cambridge, MA SP EMB, IEEE CAS Soc HO MIT DE wearable sensors; clustering; Parkinson's disease; dyskinesia ID 2 PARTS AB The aim of this study is to identify, movement characteristics associated with motor fluctuations in patients with Parkinson's disease by relying on wearable sensors. Improved methods of assessing longitudinal changes in Parkinson's disease would enable optimization of treatment and maximization of patient function. We used eight accelerometers on the tipper and lower limbs to monitor patients while they performed a set of standardized motor tasks. A video of the subjects was used by an expert to assign clinical scores. We focused on a motor complication referred to as dyskinesia, which is observed in association with medication intake. The sensor data were processed to extract a feature set responsive to the motor fluctuations. To assess the ability of accelerometers to capture the motor fluctuation patterns, the feature space was visualized using PCA and Sammon's mapping. Clustering analysis revealed the existence of intermediate clusters that were observed when changes occurred in the severity of dyskinesia. We present quantitative evidence that these intermediate clusters are the result of the high sensitivity of the proposed technique to changes in the severity of dyskinesia observed during motorfluctuation cycles. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept PM&R, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Patel, S (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept PM&R, Boston, MA 02115 USA. OI Standaert, David/0000-0003-2921-8348 NR 12 TC 2 Z9 2 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2547-4 PY 2006 BP 123 EP 126 PG 4 WC Computer Science, Cybernetics; Engineering, Biomedical; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BEE18 UT WOS:000236909800030 ER PT J AU Rosenberg, JE Galsky, MD Rohs, NC Weinberg, VK Oh, WK Kelly, WK Small, EJ AF Rosenberg, JE Galsky, MD Rohs, NC Weinberg, VK Oh, WK Kelly, WK Small, EJ TI A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma - Second-line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy SO CANCER LA English DT Article DE epothilones; hormone-refractory prostate carcinoma; multidrug-resistance protein; prostate-specific antigen; taxanes ID PHASE-II; CANCER PATIENTS; DOCETAXEL; ESTRAMUSTINE; MITOXANTRONE; PREDNISONE; TRIALS AB BACKGROUND. Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown. METHODS. Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method. RESULTS. Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines >= 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines >= 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline >= 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01). CONCLUSIONS. Second-line taxane chemotherapy after ixabepilone resulted in a Substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones. C1 Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94115 USA. Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Rosenberg, JE (reprint author), Univ Calif San Francisco, Div Hematol Oncol, 1600 Divisadero St,3rd Floor,Box 1711, San Francisco, CA 94115 USA. EM jrosenbe@medicine.ucsf.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 19 TC 23 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2006 VL 106 IS 1 BP 58 EP 62 DI 10.1002/cncr.21559 PG 5 WC Oncology SC Oncology GA 998ZK UT WOS:000234358200008 PM 16329138 ER PT J AU Rozhansky, F Chen, MH Cox, MC Dahut, W Figg, WD D'Amico, AV AF Rozhansky, F Chen, MH Cox, MC Dahut, W Figg, WD D'Amico, AV TI Prostate-specific antigen velocity and survival for patients with hormone-refractory metastatic prostate carcinoma SO CANCER LA English DT Article DE cytostatic therapy; prostate carcinoma; survival; prostate-specific antigen ID PHASE-II TRIAL; RADICAL RETROPUBIC PROSTATECTOMY; LEUKEMIA GROUP-B; PROGNOSTIC FACTORS; CLINICAL-TRIALS; CANCER; THERAPY; ESTRAMUSTINE; DOCETAXEL; BONE AB BACKGROUND. The authors investigated whether prostate-specific antigen (PSA) velocity was associated significantly with the time to death after randomization among patients with hormone-refractory metastatic prostate carcinoma (HRMPC) who were treated with cytotoxic, cytotatic, or combination therapy. METHODS. The study cohort included 213 men with HRMPC who were treated on 3 prospective, randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether there was a significant association between PSA velocity and the time to death after randomization, controlling for treatment and known prognostic factors. RESULTS. increasing PSA velocity was associated significantly with shorter survival after randomization (P = 0.005) controlling for treatment and known prognostic factors. The adjusted hazard ratic, for death was 1.8 (95% confidence interval [95% CI], 1.3-2.5; P = 0.0004) for men who had a PSA velocity > 0.0 ng/mL per month compared with men who had a PSA velocity : 0.0 ng/mL per month. Estimates of Survival 2 years after randomization for these men were 16% (95% CI, 7-25%) and 44% (95% CI, 35-53%), respectively. CONCLUSIONS. PSA velocity was associated significantly with the length of survival among men with HRMPC who received cytotoxic, cytostatic, or combination therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu RI Figg Sr, William/M-2411-2016 NR 34 TC 20 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2006 VL 106 IS 1 BP 63 EP 67 DI 10.1002/cncr.21576 PG 5 WC Oncology SC Oncology GA 998ZK UT WOS:000234358200009 PM 16333854 ER PT J AU Landis, MW Pawlyk, BS Li, T Sicinski, P Hinds, PW AF Landis, MW Pawlyk, BS Li, T Sicinski, P Hinds, PW TI Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis SO CANCER CELL LA English DT Article ID DEPENDENT-KINASE; TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR; D1-DEFICIENT MICE; TRANSGENIC MICE; D1; P27(KIP1); GENE; ARREST; CDK4 AB Cyclin D1 is a multifunctional protein that activates CDK4 and CDK6, titrates Cip/Kip CDK inhibitors to increase CDK2 activity, and modulates the function of certain transcription factors. To specifically test the importance of cyclin D1-associated kinase activity, we generated "knockin" mice expressing mutant cyclin D1 deficient in activating CDK4/6. The development of several cyclin D1-dependent compartments, including mammary glands, proceeds relatively normally in these animals, demonstrating that cyclin D1-associated kinase activity is largely dispensable for development of these tissues. Strikingly, knockin mice were resistant to breast cancers initiated by ErbB-2. These results demonstrate a differential requirement for cyclin D1-CDK4/6 kinase activity in development versus tumorigenesis and strongly support cyclin D1-dependent kinase activity as a specific therapeutic target in breast cancer. C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Dept Radiat Oncol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Howe Lab,Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hinds, PW (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, 750 Washington St 5609, Boston, MA 02111 USA. EM phinds@tufts-nemc.org FU NCI NIH HHS [CA083688, CA096527] NR 35 TC 176 Z9 179 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2006 VL 9 IS 1 BP 13 EP 22 DI 10.1016/j.ccr.2005.12.019 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 004ZA UT WOS:000234790100006 PM 16413468 ER PT J AU Yu, QY Sicinska, E Geng, Y Ahnstrom, M Zagozdzon, A Kong, YX Gardner, H Kiyokawa, H Harris, LN Stal, O Sicinski, P AF Yu, QY Sicinska, E Geng, Y Ahnstrom, M Zagozdzon, A Kong, YX Gardner, H Kiyokawa, H Harris, LN Stal, O Sicinski, P TI Requirement for CDK4 kinase function in breast cancer SO CANCER CELL LA English DT Article ID CYCLIN-DEPENDENT KINASES; MAMMARY-GLAND DEVELOPMENT; TOPOISOMERASE-II-ALPHA; GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; GENE AMPLIFICATION; SQUAMOUS-CELL; D1 OVEREXPRESSION; POOR-PROGNOSIS; NEU ONCOGENE AB Cyclin D1 is overexpressed in the majority of human breast cancers. We previously found that mice lacking cyclin D1 are resistant to mammary carcinomas triggered by the ErbB-2 oncogene. In this study, we investigated which function of cyclin D1 is required for ErbB-2-driven mammary oncogenesis. We report that the ability of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role for cyclin D1 in breast cancer formation. We also found that the continued presence of CDK4-associated kinase activity is required to maintain breast tumorigenesis. We analyzed primary human breast cancers and found high cyclin D1 levels in a subset (similar to 25%) of Erb B-2-overexpressing tumors. We propose that this subset of breast cancer patients might benefit from inhibiting CDK4 kinase. C1 Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Linkoping Univ, Fac Hlth Sci, Div Oncol, Dept Biomed & Surg, SE-58185 Linkoping, Sweden. Biogen Inc, Dept Pathol Res, Cambridge, MA 02142 USA. Northwestern Univ, Dept Mol Pharmacol & Biochem Chem, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02215 USA. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA083688] NR 57 TC 171 Z9 179 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2006 VL 9 IS 1 BP 23 EP 32 DI 10.1016/j.ccr.2005.12.012 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 004ZA UT WOS:000234790100007 PM 16413469 ER PT J AU Rocco, JW Leong, CO Kuperwasser, N DeYoung, MP Ellisen, LW AF Rocco, JW Leong, CO Kuperwasser, N DeYoung, MP Ellisen, LW TI p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis SO CANCER CELL LA English DT Article ID KINASE C-ABL; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS; TUMOR SUPPRESSION; MAMMALIAN-CELLS; LUNG-CANCER; NECK-CANCER; P53 FAMILY; P73; HEAD AB We demonstrate that Delta Np63 alpha is an essential survival factor in head and neck squamous cell carcinoma (HNSCC) through its ability to suppress p73-dependent apoptosis. Inhibition of endogenous p63 expression by RNAi induces apoptosis selectively in HNSCC cells that overexpress Delta Np63 alpha. Knockdown of p63 induces the proapoptotic bcl-2 family members Puma and Noxa, and both their induction and subsequent cell death are p53 independent but require transactivating isoforms of p73. Inhibition of p73-dependent transcription by Delta Np63 alpha involves both direct promoter binding and physical interaction with p73. In HNSCC cells lacking endogenous Delta Np63 alpha expression, bc1-2 is instead upregulated and can suppress p73-mediated death. Together, these data define a pathway whereby Delta Np63 alpha promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program. C1 Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NIDCR NIH HHS [R01 DE015945, R01 DE15945] NR 59 TC 267 Z9 273 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2006 VL 9 IS 1 BP 45 EP 56 DI 10.1016/j.ccr.2005.12.013 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 004ZA UT WOS:000234790100009 PM 16413471 ER PT J AU Duan, ZF Foster, R Brakora, KA Yusuf, RZ Seiden, MV AF Duan, ZF Foster, R Brakora, KA Yusuf, RZ Seiden, MV TI GBP1 overexpression is associated with a paclitaxel resistance phenotype SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE gene array; GBP1; paclitaxel; chemotherapy; multi-drug resistance ID CANCER-CELL-LINES; BINDING PROTEIN-1 EXPRESSION; HUMAN OVARIAN-CARCINOMA; BETA-TUBULIN GENE; BREAST-CANCER; ENDOTHELIAL-CELLS; INFLAMMATORY CYTOKINES; MULTIDRUG-RESISTANCE; TAXOL-RESISTANT; GTP AB In the search for novel genes involved in the paclitaxel resistance phenotype, prior studies of gene expression in paclitaxel-resistant cell lines and their paired drug-sensitive parental lines using high-density Affymetrix GeneChip arrays identified guanylate-binding protein 1 (GBP1) gene as an overexpressed transcript. The GBP1 gene encodes a large GTPase that is induced by interferon gamma (IFN-gamma) in a variety of eukaryotic cells. In this report we characterize GBP1 and demonstrate that GBP1 expression is consistently upregulated in 7 of 8 paclitaxel or doxorubicin-resistant human cancer cell lines as compared to its expression in the relevant drug-sensitive parental lines. Analysis of GBP1 expression using the Cancer Profiling Array showed that GBP1 is ubiquitously expressed with no significant difference in expression levels between normal and tumor tissue. Parallel analysis of the Cancer Cell Line Profiling Array determined that GBP1 expression in a majority of cell lines derived from human tumors of different tissue origin was induced to variable levels following exposure to multiple stress agents including paclitaxel and doxorubicin. Importantly, stable expression of a GBP1 transgene in the paclitaxel-sensitive ovarian cancer cell line OVCAR8 was sufficient to confer moderate paclitaxel resistance. Our data suggest that increased expression of the GBP1 gene may play an important. role in the development of multi-drug resistance (MDR). C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, 55 Fruit St, Boston, MA 02114 USA. EM zduan@partners.org FU NCI NIH HHS [CA 89150] NR 41 TC 25 Z9 25 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2006 VL 57 IS 1 BP 25 EP 33 DI 10.1007/s00280-005-0026-3 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 990XG UT WOS:000233776100004 PM 16028104 ER PT J AU Volpp, KG Levy, AG Asch, DA Berlin, JA Murphy, JJ Gomez, A Sox, H Zhu, JS Lerman, C AF Volpp, KG Levy, AG Asch, DA Berlin, JA Murphy, JJ Gomez, A Sox, H Zhu, JS Lerman, C TI A randomized controlled trial of financial incentives for smoking cessation SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT 117th Annual Meeting of the American-Economic-Association CY JAN 07-09, 2005 CL Philadelphia, PA SP Amer Econ Assoc ID COST-EFFECTIVENESS; EXTRINSIC MOTIVATION; ABSTINENCE; RECOMMENDATIONS; MAINTENANCE; DISPARITIES; PROGRAMS; SERVICES; SUCCESS AB Background: Although 435,000 Americans die each year of tobacco-related illness, only similar to 3% of smokers quit each year. Financial incentives have been shown to be effective in modifying behavior within highly structured settings, such as drug treatment programs, but this has not been shown in treating chronic disease in less structured settings. The objective of this study was to determine whether modest financial incentives increase the rate of smoking cessation program enrollment, completion, and quit rates in a outpatient clinical setting. Methods: 179 smokers at the Philadelphia Veterans Affairs Medical Center who reported smoking at least 10 cigarettes per day were randomized into incentive and nonincentive groups. Both groups were offered a free five-class smoking cessation program at the Philadelphia Veterans Affairs Medical Center. The incentive group was also offered $20 for each class attended and $100 if they quit smoking 30 days post program completion. Self-reported smoking cessation was confirmed with urine cotinine tests. Results: The incentive group had higher rates of program enrollment (43.3% versus 20.2%; P < 0.001) and completion (25.8% versus 12.2%; P = 0.02). Quit rates at 75 days were 16.3% in the incentive group versus 4.6% in the control group (P = 0.01). At 6 months, quit rates in the incentive group were not significantly higher (6.5%) than in the control group (4.6%; P > 0.20). Conclusion: Modest financial incentives are associated with significantly higher rates of smoking cessation program enrollment and completion and short-term quit rates. Future studies should consider including an incentive for longer-term cessation. C1 Univ Penn, Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Volpp, KG (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, CHERP, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM volpp70@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [P50CA84718] NR 40 TC 92 Z9 93 U1 4 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2006 VL 15 IS 1 BP 12 EP 18 DI 10.1158/1055-9965.EPI-05-0314 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200005 PM 16434580 ER PT J AU DiGianni, LM Rue, M Emmons, K Garber, JE AF DiGianni, LM Rue, M Emmons, K Garber, JE TI Complementary medicine use before and 1 year following genetic testing for BRCA1/2 mutations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID BREAST-CANCER SURVIVORS; QUALITY-OF-LIFE; PROPHYLACTIC SURGERY; ALTERNATIVE MEDICINE; OVARIAN-CANCER; POSTMENOPAUSAL WOMEN; SOY PHYTOESTROGENS; FAMILY-HISTORY; UNITED-STATES; HOT FLASHES AB Purpose: We explored change in complementary and alternative medicine (CAM) use by unaffected women and cancer survivors from enrollment into a randomized BRCA1/2 testing program to CAM use 1 year following results disclosure. Methods: A cohort of 243 high-risk women completed questionnaires at enrollment into a BRCA1/2 randomized trial and 1 year post results disclosure. Uses of several CAMs for cancer prevention were explored, including ingestible, behavioral, and physical modalities. Assessment of the change in CAM use from baseline to 1 year follow-up was conducted using a repeated self-administered questionnaire. Correlates of the number of CAMs used at 1 year were explored using multivariable linear regression models. Results: Among the subset of women who changed their CAM behavior from enrollment to 1 year following BRCA1/2 results disclosure, there was a significantly higher proportion who changed from no CAM use to CAM use among the overall cohort (P = 0.01), among women without cancer at enrollment (P = 0.003), among women found to be BRCA1/2 carriers (P = 0.03), and among women randomized to the genetic counseling intervention arm of the study (P = 0.009). Number of CAMs used at 1 year was positively associated with number of CAMs used at baseline, sunscreen use, and BRCA1/2 mutation status. Conclusion: High-risk women who have received BRCA1/2 counseling and testing frequently adopt new CAM use in the first year after learning their genetic status. Mutation carriers frequently initiate CAM use after learning their genetic status as part of their cancer preventive regimen. Further studies are warranted to determine the efficacy of CAM-related strategies for cancer prevention. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Catalan Hlth Dept, Catalonia, Spain. RP DiGianni, LM (reprint author), Dana Farber Canc Inst, 44 Binney St,SM228, Boston, MA 02115 USA. EM lisa_digianni@dfci.harvard.edu RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NHGRI NIH HHS [R01 HG012044] NR 40 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2006 VL 15 IS 1 BP 70 EP 75 DI 10.1158/1055-9965.EPI-05-0646 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200014 PM 16434589 ER PT J AU Spurdle, AB Antoniou, AC Kelemen, L Holland, H Peock, S Cook, MR Smith, PL Greene, MH Simard, J Plourde, M Southey, MC Godwin, AK Beck, J Miron, A Daly, MB Santella, RM Hopper, JL John, EM Andrulis, IL Durocher, F Struewing, JP Easton, DF Chenevix-Trench, G AF Spurdle, AB Antoniou, AC Kelemen, L Holland, H Peock, S Cook, MR Smith, PL Greene, MH Simard, J Plourde, M Southey, MC Godwin, AK Beck, J Miron, A Daly, MB Santella, RM Hopper, JL John, EM Andrulis, IL Durocher, F Struewing, JP Easton, DF Chenevix-Trench, G TI The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RECEPTOR COACTIVATOR AIB1; OVARIAN-CANCER; GENE; POLYMORPHISM; ESTROGEN; FAMILY; SUSCEPTIBILITY; AMPLIFICATION; EXPRESSION; POSITIVITY AB This is by far the largest study of its kind to date, and further suggests that AIB1 does not play a substantial role in modifying the phenotype of BRCA1 and BRCA2 carriers. The AIB1 gene encodes the AIB1/SRC-3 steroid hormone receptor coactivator, and amplification of the gene and/or protein occurs in breast and ovarian tumors. A CAG/CAA repeat length polymorphism encodes a stretch of 17 to 29 glutamines in the HR-interacting carboxyl-terminal region of the protein which is somatically unstable in tumor tissues and cell lines. There is conflicting evidence regarding the role of this polymorphism as a modifier of breast cancer risk in BRCA1 and BRCA2 carriers. To further evaluate the evidence for an association between AM glutamine repeat length and breast cancer risk in BRCA1 and BRCA2 mutation carriers, we have genotyped this polymorphism in 1,090 BRCA1 and 661 BRCA2 mutation carriers from Australia, Europe, and North America. There was no evidence for an increased risk associated with AIB1 glutamine repeat length. Given the large sample size, with more than adequate power to detect previously reported effects, we conclude that the AM glutamine repeat does not substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers. C1 Queensland Inst Med Res, Canc & Cell Biol Div, Brisbane, Qld 4029, Australia. Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. NCI, Clin Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Univ Quebec, Canc Genom Lab, Oncol & Mol Endocrinol Res Ctr, Ctr Hosp, Quebec City, PQ, Canada. Univ Laval, Quebec City, PQ, Canada. Univ Melbourne, Ctr Genet Epidemiol, Parkville, Vic 3052, Australia. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Coriell Inst Med Res, Camden, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. No Calif Canc Ctr, Union City, CA USA. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. RP Spurdle, AB (reprint author), Queensland Inst Med Res, Canc & Cell Biol Div, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. EM Amanda.Spurdle@qimr.edu.au RI Struewing, Jeffery/C-3221-2008; Spurdle, Amanda/A-4978-2011; Andrulis, Irene/E-7267-2013; Struewing, Jeffery/I-7502-2013 OI Spurdle, Amanda/0000-0003-1337-7897; Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [CA 69638, CA-95-003, U01 CA069417, U01 CA069417-10]; NIEHS NIH HHS [P30 ES009089] NR 19 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2006 VL 15 IS 1 BP 76 EP 79 DI 10.1158/1055-9965.EPI-05-0709 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200015 PM 16434590 ER PT J AU Setiawan, VW Cheng, I Strarn, DO Penney, KL Le Marchand, L Altshuler, D Kolonel, LN Hirschhorn, J Henderson, BE Freedman, ML AF Setiawan, VW Cheng, I Strarn, DO Penney, KL Le Marchand, L Altshuler, D Kolonel, LN Hirschhorn, J Henderson, BE Freedman, ML TI IGF-I genetic variation and breast cancer: the multiethnic cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID GROWTH-FACTORS; RISK; POLYMORPHISM; GENOTYPE; REPEAT; WOMEN C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. Dept Pediat, Boston, MA USA. Univ Hawaii, Canc Res Ctr Hawaii, Canc Etiol Program, Honolulu, HI 96813 USA. RP Freedman, ML (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Mol Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM freedman@broad.mit.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA54281, CA63464] NR 11 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2006 VL 15 IS 1 BP 172 EP 174 DI 10.1158/1055-9965.EPI-05-0625 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200032 PM 16434607 ER PT J AU Mezhir, JJ Smith, KD Posner, MC Senzer, N Yamini, B Kufe, DW Weichselbaum, RR AF Mezhir, JJ Smith, KD Posner, MC Senzer, N Yamini, B Kufe, DW Weichselbaum, RR TI Ionizing radiation: a genetic switch for cancer therapy SO CANCER GENE THERAPY LA English DT Review DE ionizing radiation; TNFerade (TM); tumor necrosis factor; gene therapy; genetic radiotherapy; adenovirus ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; HYDROGEN-PEROXIDE; INTERFERON-GAMMA; PHASE-I; VASCULATURE; CISPLATIN; TNF; TRANSCRIPTION; RADIOTHERAPY AB Gene therapy of cancer represents a promising but challenging area of therapeutic research. The discovery of radiation-inducible genes led to the concept and development of radiation-targeted gene therapy. In this approach, promoters of radiation-inducible genes are used to drive transcription of transgenes in the response to radiation. Constructs in which the radiation-inducible promoter elements activate a transgene encoding a cytotoxic protein are delivered to tumors by adenoviral vectors. The tumoricidal effects are then localized temporally and spatially by X-rays. We review the conceptual development of TNFerade(TM), an adenoviral vector containing radiation-inducible elements of the early growth response-1 promoter upstream of a cDNA encoding human tumor necrosis factor-alpha. We also summarize the preclinical work and clinical trials utilizing this vector as a treatment for diverse solid tumors. C1 Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Sammons Canc Ctr, Mary Crowley Med Res Ctr, Dallas, TX USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Pharmacol, Boston, MA 02115 USA. Univ Chicago Hosp, Dept Radiat Oncol, Chicago, IL 60637 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Dept Radiat & Cellular Oncol, Ctr Adv Med, Room 1329,Mail Code 9006,5758 S Maryland Ave, Chicago, IL 60637 USA. EM rrw@rover.uchicago.edu NR 28 TC 26 Z9 35 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2006 VL 13 IS 1 BP 1 EP 6 DI 10.1038/sj.cgt.7700879 PG 6 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 995LY UT WOS:000234103000001 PM 16082378 ER PT J AU Zhang, L Sharma, S Hershman, JM Brent, GA Dubinett, SM Huang, M AF Zhang, L Sharma, S Hershman, JM Brent, GA Dubinett, SM Huang, M TI Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation SO CANCER GENE THERAPY LA English DT Article DE lung cancer; iodide; radiation; gene therapy ID JUNCTIONAL-INTERCELLULAR COMMUNICATION; SYMPORTER GENE; SODIUM/IODIDE SYMPORTER; RADIO-SENSITIZATION; THYROID-CELLS; THERAPY; EXPRESSION; TRANSPORT; SYSTEM; MECHANISMS AB While external ionizing radiation has been used for treating non-small cell lung cancer (NSCLC), improved efficacy of this modality would be an important advance. Ectopic expression of the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes in NSCLC cells facilitated concentration of iodide in NSCLC cells, which markedly induced apoptosis in vitro and in vivo. Preincubation of the NIS/TPO-modified NSCLC cells in iodide followed by ionizing radiation generates bystander tumoricidal effects and potently enhances tumor cell killing. This iodide-induced bystander effect is associated with enhanced gap junction intercellular communication (GJIC) activity and increased connexin-43 (Cx43) expression. Thus, iodide may serve as an enhancer to markedly improve the efficacy of radiation therapy in combined therapeutic modalities. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol & Metab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. RP Huang, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm Med, 37-131 CHS,Mail Code 169017, Los Angeles, CA 90095 USA. EM minhuang@mednet.ucla.edu FU NCI NIH HHS [R01 CA085686, P50 CA90388] NR 37 TC 5 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2006 VL 13 IS 1 BP 74 EP 81 DI 10.1038/sj.cgt.7700875 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 995LY UT WOS:000234103000009 PM 16052231 ER PT J AU Gostjeva, EV Zukerberg, L Chung, D Thilly, WG AF Gostjeva, EV Zukerberg, L Chung, D Thilly, WG TI Bell-shaped nuclei dividing by symmetrical and asymmetrical nuclear fission have qualities of stem cells in human colonic embryogenesis and carcinogenesis SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID UNITED-STATES; CANCER; MACRONUCLEUS; RISK AB Large cell nuclei with at least eight distinct morphologies have been discovered throughout the fetal gut (5-7 weeks), colonic adenomas, and adenocarcinomas, five of which are not present in the normal adult colon. The most remarkable nuclear forms are hollow bells, approximately 10-15 microns in height and about 7-10 microns in bell mouth diameter. When encased in tubular syncytia, these bell-shaped structures divide symmetrically by an amitotic nuclear fission process resembling the separation of two paper cups. Seven other nuclear morphotypes emerge from the bell-shaped nuclei within the syncytia by asymmetrical amitotic nuclear fission. Cells containing these differentiated nuclear forms subsequently divide extra-syncytially by mitoses that form clonal populations of cells with identical nuclear morphotypes in embryos, adenomas, adenocarcinomas, and metastases. Cells with bell-shaped nuclei thus appear to be responsible for both net growth and differentiation in the embryonic gut, adenomas, and adenocarcinomas, and fulfill the requirements for post-embryonic stem cells in colon organogenesis and carcinogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 MIT, Biol Engn Div, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ukrainian Acad Agr Sci, Inst Agroecol & Biotechnol, UA-12252143 Kiev, Ukraine. RP Thilly, WG (reprint author), MIT, Biol Engn Div, 21 Ames St, Cambridge, MA 02139 USA. EM thilly@mit.edu NR 19 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN 1 PY 2006 VL 164 IS 1 BP 16 EP 24 DI 10.1016/j.cancergencyto.2005.05.005 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 003IK UT WOS:000234675000003 PM 16364758 ER PT J AU Baehring, JM Hochberg, FH AF Baehring, JM Hochberg, FH TI Primary lymphoma of the nervous system SO CANCER JOURNAL LA English DT Review DE primary CNS lymphoma; neurolymphomatosis; ocular lymphoma; methotrexate; intravascular lymphoma; posttransplant lymphoproliferative disorder ID PRIMARY-CNS-LYMPHOMA; HIGH-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PRIMARY CEREBRAL LYMPHOMA; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; MAGNETIC-RESONANCE SPECTROSCOPY; POLYMERASE-CHAIN-REACTION; B-CELL LYMPHOMAS AB This review article provides guidelines for the diagnosis, staging, and management of primary nervous system lymphoma based on the results of clinical trials conducted during the last decade. Recent progress in our understanding of the pathogenesis of primary nervous system lymphoma is summarized, and implications of these findings for the development of diagnostic tools and new therapeutic strategies are outlined. We performed a search of the PubMed database (National Center for Biotechnology Information) for articles on primary nervous system lymphoma published between 1970 and May 2005. Primary nervous system lymphoma affects the brain, eye, and meninges as well as cranial, spinal, and peripheral nerves. Although important lessons have been learned from the pathogenesis of extraneural non-Hodgkin's lymphoma, the unique organotropism of primary nervous system lymphoma remains poorly understood. Diagnosis is facilitated by modern imaging techniques and molecular markers. Clinically recognizable "precursors" may exist but frequently elude specific diagnosis. Insight into the peculiar pharmacokinetics of chemotherapy aimed at tumors within the nervous system has led to the development of methotrexate-based regimens that can achieve prolonged progression-free survival without the use of radiation. Longterm survival and, in selected cases, even a cure are possible in primary nervous system lymphoma. Treatment should be provided in specialized multidisciplinary centers. In spite of remarkable progress through methotrexate-based chemotherapy, the majority of patients experience relapse within a few years. Better diagnostic tools are required for earlier diagnosis and monitoring of treatment response. A deeper understanding of the pathogenesis of primary nervous system lymphoma may reveal new therapeutic targets. C1 Massachusetts Gen Hosp, Pappas Ctr Neuooncol, Dept Neurol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neuooncol, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM fhochberg@partners.org NR 108 TC 3 Z9 6 U1 1 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2006 VL 12 IS 1 BP 1 EP 13 DI 10.1097/00130404-200601000-00001 PG 13 WC Oncology SC Oncology GA 014RB UT WOS:000235496500001 PM 16613654 ER PT J AU Reilly, KM Broman, KW Bronson, RT Tsang, S Loisel, DA Christy, ES Sun, ZH Diehl, J Munroe, DJ Tuskan, RG AF Reilly, KM Broman, KW Bronson, RT Tsang, S Loisel, DA Christy, ES Sun, ZH Diehl, J Munroe, DJ Tuskan, RG TI An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model SO CANCER RESEARCH LA English DT Article ID QUANTITATIVE TRAIT LOCI; HUMAN GRB10; GENOME; CANCER; GENES; NF1; SUSCEPTIBILITY; RHABDOMYOSARCOMA; RELAXATION; MUTATION AB Cancer is a complex disease in which cells acquire many genetic and epigenetic alterations. We have examined how three types of alterations, mutations in tumor suppressor genes, changes in an imprinted locus, and polymorphic loci, interact to affect tumor susceptibility in a mouse model of neurofibromatosis type 1 (NF1). Mutations in tumor suppressor genes such as TP53 and in oncogenes such as KRAS have major effects on tumorigenesis due to the central roles of these genes in cell proliferation and cell survival. Imprinted genes expressed from only one parental chromosome affect tumorigenesis if their monoallelic expression is lost or duplicated. Because imprinted loci are within regions deleted or amplified in cancer, the parental origin of genomic rearrangements could affect tumorigenesis. Gene polymorphisms can vary tumor incidence by affecting rate-limiting steps in tumorigenesis within tumor cells or surrounding stroma. In our mouse model of NF1, the incidence of tumors mutant for the tumor suppressor genes Nf1 and Trp53 is strongly modified by a linked imprinted locus acting epistatically on two unlinked polymorphic loci, Nstr1 and Nstr2. This interaction of an imprinted locus and polymorphic susceptibility loci has profound implications for human mapping studies where the parental contribution of alleles is often unknown. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick, Lab Mol Technol, Frederick, MD 21702 USA. Johns Hopkins Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Dana Farber Canc Ctr, Dept Pathol, Boston, MA USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, Room 32-31B,Bldg 560,W 7th St Ft Detrick,POB B, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov RI Loisel, Dagan/A-6671-2010 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400, Z01 BC010539-03] NR 44 TC 27 Z9 29 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 62 EP 68 DI 10.1158/0008-5472.CAN-05-1t8O PG 7 WC Oncology SC Oncology GA 001JN UT WOS:000234529500011 PM 16397217 ER PT J AU Hruban, RH Adsay, NV Albores-Saavedra, J Anver, MR Biankin, AV Boivin, GP Furth, EE Furukawa, T Klein, A Klimstra, DS Kloppel, G Lauwers, GY Longnecker, DS Luttges, J Maitra, A Offerhaus, GJA Perez-Gallego, L Redston, M Tuveson, DA AF Hruban, RH Adsay, NV Albores-Saavedra, J Anver, MR Biankin, AV Boivin, GP Furth, EE Furukawa, T Klein, A Klimstra, DS Kloppel, G Lauwers, GY Longnecker, DS Luttges, J Maitra, A Offerhaus, GJA Perez-Gallego, L Redston, M Tuveson, DA TI Pathology of genetically engineered mouse models of pancreatic exocrine cancer: Consensus report and recommendations SO CANCER RESEARCH LA English DT Article ID K-RAS ONCOGENE; TRANSGENIC MICE; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; CELL DIFFERENTIATION; HEDGEHOG; CLASSIFICATION; PROGRESSION; COOPERATE; CARCINOMA AB Several diverse genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These mouse models have a spectrum of pathologic changes; however, until now, there has been no uniform nomenclature to characterize these changes. An international workshop, sponsored by The National Cancer Institute and the University of Pennsylvania, was held from December 1 to 3, 2004 with the goal of establishing an internationally accepted uniform nomenclature for the pathology of genetically engineered mouse models of pancreatic exocrine neoplasia. The pancreatic pathology in 12 existing mouse models of pancreatic neoplasia was reviewed at this workshop, and at standardized nomenclature with definitions and associated images was developed. It is our intention that. this nomenclature will standardize the reporting of genetically engineered mouse models of pancreatic exocrine neoplasia, that it: will facilitate comparisons between genetically engineered mouse models and human pancreatic disease, and that it will he broad enough to accommodate newly emerging mouse models of pancreatic neoplasia. C1 Johns Hopkins Med Inst, Sol Goldman Ctr Pancreat Canc Res, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sol Goldman Ctr Pancreat Canc Res, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sol Goldman Ctr Pancreat Canc Res, Dept Surg, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sol Goldman Ctr Pancreat Canc Res, Inst Med Genet, Baltimore, MD 21205 USA. Wayne State Univ, Dept Pathol, Harper Hosp, Detroit, MI 48202 USA. Louisiana State Univ, Dept Pathol, Shreveport, LA 70803 USA. SAIC Frederick Inc, Pathol Histochem Lab, Frederick, MD USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH 45221 USA. Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. Tokyo Womens Med Univ, Int Res & Educ Inst Integrated Med Sci, Tokyo, Japan. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ Kiel, Dept Pathol, D-24098 Kiel, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. Univ Saarbrucken, Teaching Hosp, Dept Pathol, Saarbrucken, Germany. Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. Spanish Natl Canc Ctr, Madrid, Spain. RP Hruban, RH (reprint author), Johns Hopkins Univ Hosp, Sol Goldman Pancreat Canc Ctr, 401 N Broadway,Weinberg 2242, Baltimore, MD 21231 USA. EM rhruban@jhmi.edu OI Biankin, Andrew/0000-0002-0362-5597 FU NCI NIH HHS [CA62924, N01-CO-12400] NR 44 TC 204 Z9 209 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 95 EP 106 DI 10.1158/0008-5472.CAN-05-2168 PG 12 WC Oncology SC Oncology GA 001JN UT WOS:000234529500015 PM 16397221 ER PT J AU Roccaro, AM Hideshima, T Raje, N Kumar, S Ishitsuka, K Yasui, H Shiraishi, N Ribatti, D Nico, B Vacca, A Dammacco, F Richardson, PG Anderson, KC AF Roccaro, AM Hideshima, T Raje, N Kumar, S Ishitsuka, K Yasui, H Shiraishi, N Ribatti, D Nico, B Vacca, A Dammacco, F Richardson, PG Anderson, KC TI Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells SO CANCER RESEARCH LA English DT Article ID PROTEASOME INHIBITOR PS-341; EMBRYO CHORIOALLANTOIC MEMBRANE; GROWTH-FACTOR; BONE-MARROW; TUMOR ANGIOGENESIS; SIGNALING CASCADES; MURINE MODEL; METASTASIS; MIGRATION; CANCER AB Bone marrow angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma. Recent studies have shown that proteasome inhibitor bortezomib (Velcade, formerly PS-341) can overcome conventional drug resistance in vitro and in vivo; however, its antiangiogenic activity in the bone marrow milieu has not yet been defined. In the present study, we examined the effects of bortezomib on the angiogenic phenotype of multiple myeloma patient-derived endothelial cells (MMEC). At clinically achievable concentrations, bortezomib inhibited the proliferation of MMECs and human umbilical vein endothelial cells in a dose-dependent and time-dependent manner. In functional assays of angiogenesis, including chemotaxis, adhesion to fibronectin, capillary formation on Matrigel, and chick embryo chorioallantoic membrane assay, bortezomib induced a dose-dependcnt inhibition of angiogenesis. Importantly, binding of MM.1S cells to MMECs triggered multiple myeloma cell proliferation, which was also abrogated by bortezomib in a dose-dependent fashion. Bortezomib triggered a dose-dependent inhibition of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) secretion by the MMECs, and reverse transcriptase-PCR confirmed drug-related down-regulation of VEGF, IL-6, insulin-like growth factor-I, Angio-poietin 1 (Ang1),and Ang2 transcription. These data, therefore, delineate the mechanisms of the antiangiogenic effects of bortezomib on multiple myeloma cells in the bone marrow milieu. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Univ Bari, Dept Human Anat & Histol, Sch Med, I-70121 Bari, Italy. Univ Bari, Dept Internal Med & Oncol, Sch Med, I-70121 Bari, Italy. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer Bldg 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [IP30 CA10070]; PHS HHS [P0-1 78378, R0-1 50947] NR 49 TC 173 Z9 183 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 184 EP 191 DI 10.1158/0008-5472.CAN-05-1195 PG 8 WC Oncology SC Oncology GA 001JN UT WOS:000234529500025 PM 16397231 ER PT J AU Jagadeeswaran, R Ma, PC Seiwert, TY Jagadeeswaran, S Zumba, O Nallasura, V Ahmed, S Filiberti, R Paganuzzi, M Puntoni, R Kratzke, RA Gordon, GJ Sugarbaker, DJ Bueno, R Janamanchi, V Bindokas, VP Kindler, HL Salgia, R AF Jagadeeswaran, R Ma, PC Seiwert, TY Jagadeeswaran, S Zumba, O Nallasura, V Ahmed, S Filiberti, R Paganuzzi, M Puntoni, R Kratzke, RA Gordon, GJ Sugarbaker, DJ Bueno, R Janamanchi, V Bindokas, VP Kindler, HL Salgia, R TI Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; RECEPTOR TYROSINE KINASE; DOMAIN BINDING-SITE; JUXTAMEMBRANE DOMAIN; GASTRIC-CANCER; MET INHIBITOR; HGF; ACTIVATION; EXPRESSION; MUTATIONS AB c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma (MPM). In this study, c-Met was overexpressed and activated in most of the mesothelioma cell lines tested. Expression in MPM tissues by immunohistochemistry was increased (82%) in MPM in general compared with normal. c-Met was internalized with its ligand hepatocyte growth factor (HGF) in H28 MPM cells, with robust expression of c-Met. Serum circulating HGF was twice as high in mesothelioma patients as in healthy controls. There was a differential growth response and activation of AKT and extracellular signal-regulated kinase 1/2 in response to HGF for the various cell lines. Dose-dependent inhibition (IC50 < 2.5 mu mol/L) of cell growth in mesothelioma cell lines, but not in H2052, H2452, and nonmalignant MeT-5A (IC50 > 10 mu mol/L), was observed with the small-molecule c-Met inhibitor SU11274. Furthermore, migration of H28 cells was blocked with both SU11274 and c-Met small interfering RNA. Abrogation of HGF-induced c-Met and downstream signaling was seen in mesothelioma cells. Of the 43 MPM tissues and 7 cell lines, we have identified mutations within the semaphorin domain (N375S, M431V, and N454I), the juxtarnembrane domain (T1010I and G1085X), and an alternative spliced product with deletion of the exon 10 of c-Met in some of the samples. Interestingly, we observed that the cell lines H513 and H2596 harboring the T1010I mutation exhibited the most dramatic reduction of cell growth with SU11274 when compared with wild-type 1128 and nonmalignant MeT-5A cells. Ultimately, c-Met would be an important target for therapy against MPNI. C1 Univ Chicago, Med Ctr, Dept Med,Canc Res Ctr, Hematol Oncol Sect,Pritzker Sch Med, Chicago, IL 60637 USA. Natl Inst Canc Res, Genoa, Italy. Univ Minnesota, Sch Med, Dept Surg, Div Cardiovasc & Thorac Surg, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Dept Surg,Dana Farber Canc Inst, Div Thorac Surg,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Salgia, R (reprint author), Univ Chicago, Med Ctr, Dept Med,Canc Res Ctr, Hematol Oncol Sect,Pritzker Sch Med, 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu RI Nallasura, Vidya/D-8947-2011; Jagadeeswaran, Ramasamy/C-9987-2013 FU NCI NIH HHS [R01 CA100750-02] NR 41 TC 125 Z9 128 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 352 EP 361 DI 10.1158/0008-5472.CAN-04-4567 PG 10 WC Oncology SC Oncology GA 001JN UT WOS:000234529500043 PM 16397249 ER PT J AU Cai, DP Byth, KF Shapiro, GI AF Cai, DP Byth, KF Shapiro, GI TI AZ703, an imidazo[1,2-a]pyridine inhibitor of cyclin-dependent kinases 1 and 2, induces E2F-1-dependent apoptosis enhanced by depletion of cyclin-dependent kinase 9 SO CANCER RESEARCH LA English DT Article ID CYCLIN-DEPENDENT KINASES; FLAVOPIRIDOL-INDUCED APOPTOSIS; CELL-CYCLE; S-PHASE; RETINOBLASTOMA PROTEIN; CTD PHOSPHORYLATION; TRANSFORMED-CELLS; SELECTIVE CLASS; IN-VITRO; E2F-1 AB Preclinical studies were performed of a novel selective imidazopyridine cyclin-dependent kinase (cdk) inhibitor, AZ703. In vitro kinase assays showed that IC50 values for AZ703 against purified cyclin E/cdk2 and cyclin B/cdk1 were 34 and 29 nmol/L, respectively. In contrast, the IC50 against cdk4 was > 10 mu mol/L. AZ703 also inhibited cdk7 and cdk9 with IC50 values of 2.1 mu mol/L and 521 nmol/L, respectively. Treatment of U20S, NCl-H1299, and A549 cells for 24 hours resulted in growth arrest involving multiple cell cycle phases. At low drug concentrations (< 2 mu mol/L), G(2) arrest predominated, whereas at higher concentrations (>= 2 mu mol/L), S-G(2) arrest was observed. When cells were synchronized in G, by starvation and released into AZ703, a block in G, occurred that was not evident in exponentially growing cells. Cell cycle arrest was associated with reduced phosphorylation of the retinoblastoma protein and p27(Kip1) at cdk2 phospho-sites. Following longer exposures, apoptosis was evident. Cells were further sensitized to AZ703 following recruitment to S phase by synchronization. Consistent, with the inhibition of cdks during S and G2 that modulate the activity and stability of E2F-1, AZ703 treatment induced E2F-1 expression. In U20S and NCl-H1299 cells engineered to inducibly express the dominant-negative mutant E2F-1 (1-374), expression of the mutant decreased AZ703-mediated apoptosis, indicating dependence on E2F-1 transcriptional targets. AZ703-induced apoptosis in NCl-HI299 cells was enhanced by small interfering RNA-mediated depletion of cdk9, which caused reduced levels of Mcl-1 and XIAP, suggesting that cdk2, cdk1, and cdk9 represent a rational subset of family members for drug targeting. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. AstraZeneca, Alderley Pk, Cheshire, England. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [P20 CA90578, R01 CA090687, R01 CA90687] NR 58 TC 53 Z9 56 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 435 EP 444 DI 10.1158/0008-5472.CAN-05-1769 PG 10 WC Oncology SC Oncology GA 001JN UT WOS:000234529500053 PM 16397259 ER PT J AU Schittenhelm, MM Shiraga, S Schroeder, A Corbin, AS Griffith, D Lee, FY Bokemeyer, C Deininger, MWN Druker, BJ Heinrich, MC AF Schittenhelm, MM Shiraga, S Schroeder, A Corbin, AS Griffith, D Lee, FY Bokemeyer, C Deininger, MWN Druker, BJ Heinrich, MC TI Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT Isoforms associated with human malignancies SO CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; RECEPTOR TYROSINE KINASE; LIGAND-INDEPENDENT ACTIVATION; CHRONIC MYELOID-LEUKEMIA; PROTOONCOGENE C-KIT; MAST-CELL LEUKEMIA; BETA-CATENIN GENE; IN-VITRO; STI-571 INHIBITION; IMATINIB STI571 AB Activating mutations of the activation loop of KIT are associated with certain human neoplasms, including the majority of patients with systemic mast cell disorders, as well as cases of seminoma, acute myelogenous leukemia (AML), and gastrointestinal stromal tumors (GISTs). The small-molecule tyrosine kinase inhibitor imatinib mesylate is a potent inhibitor of wild-type (WT) KIT and certain mutant KIT isoforms and has become the standard of care for treating patients with metastatic GIST. However, KIT activation loop mutations involving codon D816 that are typically found in AML, systemic mastocytosis, and semitioma are insensitive to imatinib mesylate (IC50 > 5-10 mu mol/L), and acquired KIT activation loop mutations can be associated with imatinib mesylate resistance in GIST. Dasatinib (formerly BMS-354825) is a small-molecule, ATP-competitive inhibitor of SRC and ABL tyrosine kinases with potency in the low nanomolar range. Some small-molecule SRC/ABL inhibitors also have potency against WT KIT kinase. Therefore, we hypothesized that dasatinib might inhibit the kinase activity of both WT and mutant KIT isoforms. We report. herein that dasatinib potently inhibits WT KIT and juxtamembrane domain mutant KIT autophosphorylation and KIT-dependent activation of downstream pathways important for cell viability and cell survival, such as Ras/mitogen-activated protein kinase, phosphoinositide 3-kinase/Akt, and Janus-activated kinase/signal transducers and activators of transcription. Furthermore, dasatinib is a potent inhibitor of imatinib-resistant KIT activation loop mutants and induces apoptosis in mast cell anti leukemic cell lines expressing these mutations (potency against KIT D816Y >> D81613 > D816V). Our studies suggest. that dasatinib may have clinical efficacy against human neoplasms that. tire associated with gain-of-function KIT mutations. C1 Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Div Hematol Oncol, Portland, OR 97201 USA. Bristol Myers Squibb Co, Oncol Drug Discovery, Princeton, NJ USA. Univ Hamburg, Med Ctr Eppendorf, Dept Med, Hamburg, Germany. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Heinrich, MC (reprint author), Portland Vet Affairs Med Ctr, R&D-19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu FU NCI NIH HHS [P30 CA69533] NR 47 TC 313 Z9 321 U1 4 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 473 EP 481 DI 10.1158/0008-5472.CAN-05-2050 PG 9 WC Oncology SC Oncology GA 001JN UT WOS:000234529500057 PM 16397263 ER PT J AU Smith, MR AF Smith, MR TI Markers of bone metabolism in prostate cancer SO CANCER TREATMENT REVIEWS LA English DT Review DE metastatic prostate cancer; bone markers; skeletal complications; alkaline phosphatase; NTX; BAP ID SKELETAL COMPLICATIONS; ANDROGEN-DEPRIVATION; PROGNOSTIC FACTORS; TURNOVER MARKERS; ZOLEDRONIC ACID; MINERAL DENSITY; LUNG-CANCER; METASTASES; CARCINOMA; THERAPY AB Although bone metastases from prostate cancer are described as osteoblastic, markers of both osteoblastic and osteoclastic activity are strikingly elevated in men with metastatic prostate cancer. Elevated markers of osteoblastic and osteoclastic activity are, associated with adverse clinical outcomes. in men with prostate cancer - outcomes including shorter time to skeletal complications, disease progression, and death. Bone marker measurement appears to be a promising method for monitoring the efficacy of bone-targeted therapy. Additional studies are needed to assess the potential role of bone markers in identifying men at highest risk for development of bone metastases. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 36 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PY 2006 VL 32 SU 1 BP 23 EP 26 DI 10.1016/S0305-7372(06)80006-X PG 4 WC Oncology SC Oncology GA 030KJ UT WOS:000236633100006 PM 16680835 ER PT J AU Moses, HL AF Moses, H. L. TI TGF-beta and its role in cancer progression SO CANCER TREATMENT REVIEWS LA English DT Meeting Abstract CT 6th International Conference on Cancer Induced Bone Disease CY DEC 10-14, 2006 CL San Antonio, TX SP Canc & Bone Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PY 2006 VL 32 SU 3 MA 01 BP S11 EP S11 PG 1 WC Oncology SC Oncology GA 121JO UT WOS:000243154100002 ER PT J AU Scadden, DT AF Scadden, D. T. TI The hematopoietic stem cell niche SO CANCER TREATMENT REVIEWS LA English DT Meeting Abstract CT 6th International Conference on Cancer Induced Bone Disease CY DEC 10-14, 2006 CL San Antonio, TX SP Canc & Bone Soc C1 Massachusetts Gen Hosp, Ctr Reg Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PY 2006 VL 32 SU 3 MA 37 BP S22 EP S22 PG 1 WC Oncology SC Oncology GA 121JO UT WOS:000243154100036 ER PT J AU Sharma, SD Katiyar, SK AF Sharma, SD Katiyar, SK TI Dietary grape-seed proanthocyanidin inhibition of ultraviolet B-induced immune suppression is associated with induction of IL-12 SO CARCINOGENESIS LA English DT Article ID TEA POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE; DELAYED-TYPE HYPERSENSITIVITY; ANTIGEN-PRESENTING CELLS; CONTACT HYPERSENSITIVITY; SKIN-CANCER; SYSTEMIC SUPPRESSION; IN-VIVO; INDUCED IMMUNOSUPPRESSION; TRANSPLANT RECIPIENTS; OXIDATIVE STRESS AB We have shown previously that dietary grape seed proanthocyanidins (GSPs) inhibit UVB-induced photocarcinogenesis in mice. As UVB-induced immune suppression has been implicated in the development of skin cancer risk, we investigated whether dietary GSPs can modulate the effects of UVB on the immune system. We found that the UVB-induced (180 mJ/cm(2)) ear swelling response (inflammatory reaction) was significantly lower in mice fed with a GSP-supplemented (0.5 and 1.0%, w/w) diet than mice fed with the standard AIN76A diet. Dietary GSPs markedly inhibited UVB-induced (180 mJ/cm(2)) suppression of contact hypersensitivity responses in a local model of immunosuppression but had only moderate inhibitory effect in a systemic model of immunosuppression. Dietary GSPs reduced the UVB-induced increase in immunosuppressive cytokine interleukin (IL)-10 in skin and draining lymph nodes compared with mice that did not receive GSPs. In contrast, GSPs enhanced the production of immunostimulatory cytokine IL-12 in the draining lymph nodes. Intraperitoneal injection of GSPs-fed mice with a neutralizing anti-IL-12 antibody abrogated the protective effects of the GSPs against UVB-induced suppression of the contact hypersensitivity response. These data indicate for the first time that GSPs modulate UVB-induced immunosuppression and suggest that this may be one of the possible mechanisms by which they prevent photocarcinogenesis in mice. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCI NIH HHS [CA104428]; NIAMS NIH HHS [AR050948-01] NR 43 TC 32 Z9 44 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2006 VL 27 IS 1 BP 95 EP 102 DI 10.1093/carcin/bgi169 PG 8 WC Oncology SC Oncology GA 997BF UT WOS:000234219300009 PM 15987716 ER PT J AU Ma, TS Hayes, TG Levine, GN Carabello, BA AF Ma, TS Hayes, TG Levine, GN Carabello, BA TI Malignant pleural/pericardial effusion with tamponade and life-threatening reversible myocardial depression in a case of an initial presentation of lung adenocarcinoma SO CARDIOLOGY LA English DT Article DE myopericarditis; pericardial effusion; lung neoplasm; cardiac metastasis; cardiac tamponade ID NONBACTERIAL THROMBOTIC ENDOCARDITIS; WOMAN; PERICARDIUM; METASTASES; CARCINOMA; CANCER; TUMORS; HEART AB We present a case of a middle-aged woman in cardiac tamponade. Following pericardiocentesis that removed 1,500 ml of hemorrhagic fluid, the patient exhibited cardiogenic shock; LVEF, at its nadir, on inotrope, was less than 20%. Ventricular function slowly improved, with inotropic support, to the normal range by the 25th day of hospitalization. Cardiac failure in malignancy has often been attributed to multi-system failure; this case showed a hereto unrecognized clinical phenomenon 'malignancy-associated myopericarditis'. While the direct link of cause and effect cannot be made with certainty, the case should be instructive to other clinicians who encounter similar life-threatening presentations of cardiac decompensation in malignancy. Copyright (c) 2006 S. Karger AG, Basel. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Hematol & Oncol, Houston, TX USA. RP Ma, TS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, 2002 Holocombe Blvd, Houston, TX 77030 USA. EM tma@bcm.tmc.edu NR 14 TC 2 Z9 2 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2006 VL 105 IS 1 BP 30 EP 33 DI 10.1159/000088344 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 982ZR UT WOS:000233201400007 PM 16179783 ER PT J AU Esteghamati, A Abbasi, M Nakhjavani, M Yousefizadeh, A Basa, AP Afshar, H AF Esteghamati, Alireza Abbasi, Mehrshad Nakhjavani, Manouchehr Yousefizadeh, Abbas Basa, Amelita P. Afshar, Hamid TI Prevalence of diabetes and other cardiovascular risk factors in an Iranian population with acute coronary syndrome SO CARDIOVASCULAR DIABETOLOGY LA English DT Article AB Background: Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population. Methods: The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows. Results: Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 +/- 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 +/- 11.6 vs. 59.7 +/- 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p < 0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 +/- 11.6 vs. 59.2 +/- 13 years, p < 0.005) and had higher total serum cholesterol (200 +/- 41.8 vs. 192 +/- 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 +/- 22 vs. 40 +/- 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels). Conclusion: In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease. C1 [Abbasi, Mehrshad] Univ Tehran Med Sci, Endocrine Dept, Vali Asr Hosp, Tehran 1419733147, Iran. [Esteghamati, Alireza] Univ Tehran Med Sci, Fac Med, Tehran 1419733147, Iran. [Nakhjavani, Manouchehr] Univ Tehran Med Sci, Div Endocrine, Vali Asr Hosp, Tehran 1419733147, Iran. [Yousefizadeh, Abbas] Bank Melli Hosp, Dept Internal Med, Tehran, Iran. [Basa, Amelita P.] Baylor Coll Med, Endocrine Dept, VA Med Ctr, Houston, TX 77030 USA. [Afshar, Hamid] Alton Ochsner Med Fdn & Ochsner Clin, Dept Cardiol, New Orleans, LA 70121 USA. RP Abbasi, M (reprint author), Univ Tehran Med Sci, Endocrine Dept, Vali Asr Hosp, Keshavarz Blvd, Tehran 1419733147, Iran. EM Esteghamati@sina.tums.ac.ir; mehrshad_abbasi@Yahoo.com; nakhjavanim@sina.tums.ac.ir; Abbasyousefizadeh@yahoo.com; amyloubasa@yahoo.com; hamidafshar@yahoo.com RI Abbasi, Mehrsahd/J-4064-2012 OI Abbasi, Mehrsahd/0000-0001-5011-897X NR 31 TC 28 Z9 30 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2840 J9 CARDIOVASC DIABETOL JI Cardiovasc. Diabetol. PY 2006 VL 5 AR 15 DI 10.1186/1475-2840-5-15 PG 6 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA V23DE UT WOS:000208322700015 PM 16842631 ER PT J AU Tan, HM Jiang, XH Yang, F Li, ZH Liao, D Trial, J Magera, MJ Durante, W Yang, XF Wang, H AF Tan, HM Jiang, XH Yang, F Li, ZH Liao, D Trial, J Magera, MJ Durante, W Yang, XF Wang, H TI Hyperhomocysteinemia inhibits post-injury reendothelialization in mice SO CARDIOVASCULAR RESEARCH LA English DT Article DE homocysteine; carotid injury; reendothelialization ID CYSTATHIONINE BETA-SYNTHASE; RAT CAROTID-ARTERY; ENDOTHELIAL-CELLS; NEOINTIMA FORMATION; GROWTH-FACTOR; MOUSE MODEL; ACCELERATES REENDOTHELIALIZATION; S-ADENOSYLHOMOCYSTEINE; VASCULAR DYSFUNCTION; OXIDATIVE STRESS AB Objective: Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease and has been reported to inhibit endothelial cell (EC) growth. Notwithstanding, precisely how HHcy regulates EC growth in vivo remains unknown. In this study, we established a mouse model of endothelial injury and reendothelialization and examined the role and mechanism of HHcy in endothelial repair. Methods and results: A mouse model of carotid artery air-dry endothelium denudation and reendothelialization was established and used to evaluate post-injury endothelial repair in mice with the gene deletion of cystathionine-beta-synthase (CBS). Moderate and severe HHcy were induced in CBS+/+ and CBS-/+ mice through a high-methionine diet. Post-injury reendothelialization, which correlated with increased post-injury neointima formation, was impaired in severe HHcy mice. To elucidate the underlying mechanism, we examined circulating endothelial progenitor cells (EPC) in HHcy mice and studied the effect of homocysteine (Hcy) on proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVEC). The peripheral EPC population was not significantly altered in HHcy mice. Hey had a profound inhibitory effect on EC proliferation and migration at physiologically relevant concentrations and inhibited EC adhesion at concentrations of 200 mu M and higher. Conclusion: We have established a convenient and accurate mouse model of carotid injury in which the reendothelialization process can be precisely quantified. In addition, we have observed impaired reendothelialization and increased neointimal formation in severe HHcy mice. The capacity of Hey to inhibit proliferation and migration of EC may be responsible for impaired reendothelialization and contribute to arteriosclerosis in HHcy. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Sun Yat Sen Univ, Sch Med, Guangzhou, Peoples R China. Mayo Clin, Rochester, MN 55905 USA. RP Wang, H (reprint author), Baylor Coll Med, VA Med Ctr, 2002 Holocombe Blvd, Houston, TX 77030 USA. EM hongw@bcm.tmc.edu FU NHLBI NIH HHS [R01 HL067033, HL36045, HL59976, HL67033, HL74925, HL77288, K02 HL074925, R01 HL036045, R01 HL059976, R01 HL077288] NR 43 TC 37 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JAN PY 2006 VL 69 IS 1 BP 253 EP 262 DI 10.1016/j.cardiores.2005.08.016 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 004HT UT WOS:000234743300029 PM 16226235 ER PT J AU McNulty, E Cohen, J Chou, T Shunk, K AF McNulty, E Cohen, J Chou, T Shunk, K TI A "grapple hook" technique using a deflectable tip catheter to facilitate complex proximal circumflex interventions SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous coronary intervention; chronic total occlusion; angulation ID CHRONIC TOTAL OCCLUSIONS; SIROLIMUS-ELUTING STENT; CORONARY ANGIOPLASTY; DETERMINANTS; IMMEDIATE; OUTCOMES; SUCCESS AB We present two patients with angulated, proximal left circumflex lesions, one a chronic total occlusion and one an acute subtotal occlusion. In both cases, use of the deflectable tip Venture Catheter (Velocimed, Minneapolis, MN) facilitated guide wire passage and successful percutaneous coronary intervention (PCI) after prior attempts at guide wire passage with standard wires were unsuccessful. (c) 2005 Wiley-Liss, Inc. C1 Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, Dept Cardiol, San Francisco, CA 94121 USA. RP McNulty, E (reprint author), Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, Dept Cardiol, 111C,4150 Clement St, San Francisco, CA 94121 USA. EM Edward.mcnulty2@med.va.gov NR 12 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN PY 2006 VL 67 IS 1 BP 46 EP 48 DI 10.1002/ccd.20547 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 003TW UT WOS:000234705500011 PM 16331693 ER PT J AU Yoneyama, R Kawase, Y Hoshino, K McGregor, J Mac Neill, BD Lowe, HC Burkhoff, D Boekstegers, P Hajjar, RJ Hayase, M AF Yoneyama, R Kawase, Y Hoshino, K McGregor, J Mac Neill, BD Lowe, HC Burkhoff, D Boekstegers, P Hajjar, RJ Hayase, M TI Magnetic resonance assessment of myocardial perfusion via catheter-based ventricle-coronary vein bypass in porcine myocardial infarction model SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE coronary vein; left ventricle; coronary bypass; catheterization ID ARTERIALIZATION; SINUS AB Objective: The goal of this study was to investigate the efficacy of VPASS with physiological measurements, magnetic resonance imaging (MRI), and histology in a porcine model of myocardial infarction. Background: A catheter-based ventricle-to-coronary vein bypass (VPASS (TM)) has been proposed as a potential treatment strategy for refractory coronary artery disease patients. Methods: In an acute setting, the VPASS implant was deployed percutaneously in three swine. The partial pressure of oxygen (1302) in the anterior interventricular vein (AIV) and left ventricle (LV) were measured before and after VPASS implant with various combinations of balloon occlusion in the AIV and left anterior descending artery (LAD). In a separate chronic study, the VPASS procedure was completed on three swine with a mid-LAD occlusion. Thirty days post-VPASS procedure, angiography, contrast-enhanced MRI, and histology were performed to assess myocardial viability. Perfusion was analyzed using the average percent signal intensity change (APSIC) in the anterior walls (AW) and inferior walls (IW). Results: The VPASS implant was performed without complication. Post-VPASS implantation, the distal AIV PO2 increased up to the LV PO2 level during simultaneous AIV and LAD blockage (432 +/- 24 mmHg). At day 30, quantitative perfusion analysis demonstrated no difference in APSIC between AW and IW (125 +/- 26% vs. 137 +/- 38%, P = 0.46). Delayed enhancement and histology showed focal subendomyocardial infarction. Conclusions: VPASS implant with simultaneous AIV and LAD occlusion allows perfusion of oxygenated blood to the distal AIV, which in the setting of an acute myocardial infarction model was capable of rescuing most of the myocardium at risk. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Cardiol Lab Integrat Physiol & Imaging, Div Cardiol,Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, Dept Surg & Med, New York, NY USA. Grosshadern Univ Hosp, Dept Internal Med 1, Munich, Germany. RP Hayase, M (reprint author), Harvard Univ, Cardiol Lab Integrat Physiol & Imaging, Div Cardiol,Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 161, Boston, MA 02114 USA. EM mhayase@crf.org RI Burkhoff, Daniel/D-7674-2011 NR 14 TC 1 Z9 1 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN PY 2006 VL 67 IS 1 BP 58 EP 67 DI 10.1002/ccd.20548 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 003TW UT WOS:000234705500014 PM 16345049 ER PT J AU Luo, J Sobkiw, CL Hirshman, MF Logsdon, MN Li, TQ Goodyear, LJ Cantley, LC AF Luo, Ji Sobkiw, Cassandra L. Hirshman, Michael F. Logsdon, M. Nicole Li, Timothy Q. Goodyear, Laurie J. Cantley, Lewis C. TI Loss of class I(A)PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia SO CELL LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE PATHWAY; FOXO TRANSCRIPTION FACTORS; LHERMITTE-DUCLOS-DISEASE; P85 REGULATORY SUBUNIT; MICE LACKING; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3'-KINASE; TARGETED DISRUPTION; GLUCOSE-HOMEOSTASIS; CARDIAC-HYPERTROPHY AB The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). We have generated mice deficient in both the p85 alpha/p55 alpha/p50 alpha and the p85 beta regulatory subunits of class I-A PI3K in skeletal muscles. PI3K signaling in the muscle of these animals is severely impaired, leading to a significant reduction in muscle weight and fiber size. These mice also exhibit muscle insulin resistance and whole-body glucose intolerance. Despite their ability to maintain normal fasting and fed blood glucose levels, these mice show increased body fat content and elevated serum free fatty acid and triglyceride levels. These results demonstrate that in vivo p85 is a critical mediator of class I-A PI3K signaling in the regulation of muscle growth and metabolism. Our finding also indicates that compromised muscle PI3K signaling could contribute to symptoms of hyperlipidemia associated with human type 2 diabetes. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu NR 51 TC 1 Z9 1 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PY 2006 VL 127 IS 3 SU S BP 42 EP 54 DI 10.1016/j.cmet.2006.04.003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 105HV UT WOS:000242021900005 ER PT J AU Zhang, BX Ma, XY Shu, ZJ Yeh, CK Swerdlow, RH Katz, MS AF Zhang, BX Ma, XY Shu, ZJ Yeh, CK Swerdlow, RH Katz, MS TI Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE intracellular Ca2+; mitochondria; gap junction; calcium oscillation; p0 NT2 cells ID CA2+ INFLUX; INOSITOL 1,4,5-TRISPHOSPHATE; SYMPATHETIC NEURONS; INSULIN-SECRETION; CYTOSOLIC CA2+; ACINAR-CELLS; STORE; ENTRY; HEMICHANNELS; ASTROCYTES AB Fluctuations of intracellular Ca2+ ([Ca2+](i)) regulate a variety of cellular functions. The classical Ca2+ transport pathways in the endoplasmic reticulum (ER) and plasma membrane are essential to [Ca2+], oscillations. Although mitochondria have recently been shown to absorb and release Ca2+ during G protein-coupled receptor (GPCR) activation, the role of mitochondria in [Ca2+](i) oscillations remains to be elucidated. Using fluo-3-loaded human teratocarcinoma NT2 cells, we investigated the regulation of [Ca2+](i) oscillations by mitochondria. Both the muscarinic GPCR agonist carbachol and the ER Ca2+-adenosine triphosphate inhibitor thapsigargin (Tg) induced [Ca2+](i) oscillations in NT2 cells. The [Ca2+](i) oscillations induced by carbachol were unsynchronized among individual NT2 cells; in contrast, Tg-induced oscillations were synchronized. Inhibition of mitochondrial functions with either mitochondrial blockers or depletion of mitochondrial DNA eliminated carbachol-but not Tg-induced [Ca2+](i) oscillations. Furthermore, carbachol-induced [Ca2+](i) oscillations were partially restored to mitochondrial DNA-depleted NT2 cells by introduction of exogenous mitochondria. Treatment of NT2 cells with gap junction blockers prevented Tg-induced but not carbachol-induced [Ca2+](i) oscillations. These data suggest that the distinct patterns of [Ca2+](i) oscillations induced by GPCR and Tg are differentially modulated by mitochondria and gap junctions. C1 S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol, Charlottesville, VA 22908 USA. RP Zhang, BX (reprint author), S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM binxz@yahoo.com FU NHLBI NIH HHS [023565N/HL75011] NR 50 TC 2 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2006 VL 44 IS 2 BP 187 EP 203 DI 10.1385/CBB:44:2:187 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 043FS UT WOS:000237586000002 PM 16456221 ER PT J AU Stanger, BZ Dor, Y AF Stanger, BZ Dor, Y TI Dissecting the cellular origins of pancreatic cancer SO CELL CYCLE LA English DT Article DE pancreatic cancer; development; centroacinar cells; PTEN; PI3-kinase; cell-of-origin; metaplasia ID STEM-CELLS; TGF-ALPHA; ENDOCRINE DEVELOPMENT; TRANSGENIC MICE; DIFFERENTIATION; OVEREXPRESSION; METAPLASIA; CARCINOMA; TUMORS AB Although putative premalignant lesions like metaplasia-the replacement of one mature cell type with another-have been identified in a variety of cancers, the normal cellular targets of malignant transformation are largely unknown. Pancreatic ductal adenocarcinoma (PDAC) is a particularly aggressive and lethal cancer. Despite its ductal histology, however, it is unknown whether PDAC originates from pancreatic ducts or another cell type within the pancreas. Recent analysis of mice with pancreas-specific deletion of the PTEN tumor suppressor gene has provided new insight into the mechanism of metaplasia and focuses attention on pancreatic centroacinar cells as candidates for the cellular origin of PDAC. Characterization of the "cell-of-origin" could lead to a better understanding of the molecular substrate for tumor initiation and eventually to early diagnosis and treatment. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Cellular Biochem & Human Genet, IL-91010 Jerusalem, Israel. RP Stanger, BZ (reprint author), 7 Divin Ave, Cambridge, MA 02138 USA. EM bstanger@partners.org; dor@md.huji.ac.il RI Dor, Yuval/C-2405-2011 FU NIDDK NIH HHS [K08 DK064136] NR 27 TC 25 Z9 29 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2006 VL 5 IS 1 BP 43 EP 46 DI 10.4161/cc.5.1.2291 PG 4 WC Cell Biology SC Cell Biology GA 016HG UT WOS:000235610700010 PM 16322695 ER PT J AU Boxem, M AF Boxem, Mike TI Cyclin-dependent kinases in C. elegans SO CELL DIVISION LA English DT Review AB Cell division is an inherent part of organismal development, and defects in this process can lead to developmental abnormalities as well as cancerous growth. In past decades, much of the basic cell-cycle machinery has been identified, and a major challenge in coming years will be to understand the complex interplay between cell division and multicellular development. Inevitably, this requires the use of more complex multicellular model systems. The small nematode Caenorhabditis elegans is an excellent model system to study the regulation of cell division in a multicellular organism, and is poised to make important contributions to this field. The past decade has already seen a surge in cell-cycle research in C. elegans, yielding information on the function of many basic cell-cycle regulators, and making inroads into the developmental control of cell division. This review focuses on the in vivo roles of cyclin-dependent kinases in C. elegans, and highlights novel findings implicating CDKs in coupling development to cell-cycle progression. C1 [Boxem, Mike] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Boxem, Mike] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Boxem, Mike] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. RP Boxem, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM mboxem@partners.org RI Boxem, Mike/B-8857-2011 OI Boxem, Mike/0000-0003-3966-4173 NR 100 TC 11 Z9 11 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2006 VL 1 AR 6 DI 10.1186/1747-1028-1-6 PG 12 WC Cell Biology SC Cell Biology GA V14GT UT WOS:000207723600006 PM 16759361 ER PT J AU Chua, KF Mostoslavsky, R Lombard, DB Pang, WW Saito, S Franco, S Kaushal, D Cheng, HL Fischer, M Stokes, N Murphy, MM Appella, E Alt, FW AF Chua, KF Mostoslavsky, R Lombard, DB Pang, WW Saito, S Franco, S Kaushal, D Cheng, HL Fischer, M Stokes, N Murphy, MM Appella, E Alt, FW TI Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress (vol 2, pg 67, 2005) SO CELL METABOLISM LA English DT Correction C1 Childrens Hosp, Howard Hughes Med Inst, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JAN PY 2006 VL 3 IS 1 BP 75 EP 75 DI 10.1016/j.cmet.2005.12.006 PG 1 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 002CP UT WOS:000234589300011 ER PT J AU Noguchi, H Xu, G Matsumoto, S Kaneto, H Kobayashi, N Bonner-Weir, S Hayashi, S AF Noguchi, Hirofumi Xu, Gang Matsumoto, Shinichi Kaneto, Hideaki Kobayashi, Naoya Bonner-Weir, Susan Hayashi, Shuji TI Induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Japan-Society-of-Organ-Preservation-and-Medical-Biology CY MAR 23, 2004-MAR 25, 2005 CL Tsukuba, JAPAN SP Japan Soc Organ Preservat & Med Biol DE PDX-1; BETA2/NeuroD; Ngn3; Pax4; pancreatic duct cells ID EMBRYONIC STEM-CELLS; PROTEIN TRANSDUCTION; PDX-1 PROTEIN; TRANSCRIPTION FACTOR; ISLET CELLS; BETA-CELLS; DIFFERENTIATION; EXPRESSION; NEUROD; DUCT AB beta-Cell replacement therapy via islet transplantation is a promising possibility for the optimal treatment of type I diabetes; however, such an approach is severely limited by the shortage of donor organs. This problem could be overcome if it were possible to generate transplantable islets from stem cells. We showed previously that adult beta-cells might originate from duct or duct-associated cells. Ductal progenitor cells in the pancreas would become particularly useful for therapies that target beta-cell replacement in diabetic patients, because duct cell types are abundantly available in the pancreas of these patients and in donor organs. In this study, we examined which embryonic transcription factors in adult mouse and human duct cells could efficiently induce their differentiation into insulin-expressing cells. Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression. NeuroD was the most effective inducer of insulin expression in primary duct cells. Surprisingly, adenovirus Pax4 strongly induced Ngn3 expression, while Pax4 is considered the downstream target of Ngn3. These data suggest that the overexpression of transcription factors, especially NeuroD, facilitates pancreatic stem/progenitor cell differentiation into insulin-producing cells. C1 Nagoya Univ, Grad Sch Med, Dept Adv Med Biotechnol & Robot, Showa Ku, Nagoya, Aichi 4668550, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Kyoto Univ, Grad Sch Med, Dept Transplantat & Immunol, Kyoto 6068507, Japan. Fujita Hlth Univ, Dept Surg 2, Toyoake, Aichi 4701192, Japan. Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Osaka 5650871, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Surg, Okayama 7008558, Japan. Diabet Res Inst Japan, Toyoake, Aichi 4701192, Japan. RP Noguchi, H (reprint author), Nagoya Univ, Grad Sch Med, Dept Adv Med Biotechnol & Robot, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM noguchih@med.nagoya-u.ac.jp NR 42 TC 60 Z9 65 U1 0 U2 4 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2006 VL 15 IS 10 BP 929 EP 938 DI 10.3727/000000006783981431 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 130DQ UT WOS:000243780000012 PM 17299998 ER PT J AU Chen, DC Avansino, JR Agopian, VG Hoagland, VD Woolman, JD Pan, S Ratner, BD Stelzner, M AF Chen, David C. Avansino, Jeffrey R. Agopian, Vatche G. Hoagland, Vicki D. Woolman, Jacob D. Pan, Sheng Ratner, Buddy D. Stelzner, Matthias TI Comparison of polyester scaffolds for bioengineered intestinal mucosa SO CELLS TISSUES ORGANS LA English DT Article DE intestinal stem cell; polyglycolic acid; polylactic acid; tissue-engineered small intestine; polyester scaffolds ID SHORT-BOWEL SYNDROME; EPITHELIAL ORGANOID UNITS; STEM-CELLS; PORE-SIZE; TRANSPLANTATION; MANAGEMENT; RAT; REGENERATION; CHILDREN; ADHESION AB Introduction: Biodegradable polyester scaffolds have proven useful for growing neointestinal tissue equivalents both in vitro and in vivo. These scaffolds allow cells to attach and grow in a 3-dimensional space while nutrient flow is maintained throughout the matrix. The purpose of this study was to evaluate different biopolymer constructs and to determine mucosal engraftment rates and mucosal morphology. Hypothesis: We hypothesized that different biopolymer constructs may vary in their ability to provide a good scaffolding onto which intestinal stem cell organoids may be engrafted. Study Design: Eight different microporous biodegradable polymer tubes composed of polyglycolic acid (PGA), polylactic acid, or a combination of both, using different fabrication techniques were seeded with intestinal stem cell clusters obtained from neonatal rats. Three different seeded polymer constructs were subsequently placed into the omentum of syngeneic adult recipient rats (n = 8). Neointestinal grafts were harvested 4 weeks after implantation. Polymers were microscopically evaluated for the presence of mucosal growth, morphology, scar formation and residual polymer. Results: Mucosal engraftment was observed in 7 out of 8 of the polymer constructs. A maximal surface area engraftment of 36% (range 5-36%) was seen on nonwoven, randomly entangled, small fiber PGA mesh coated with aerosolized 5% poly-L-lactic acid. Villous and crypt development, morphology and created surface area were best on PGA nonwoven mesh constructs treated with poly-L-lactic acid. Electrospun microfiber PGA had poor overall engraftment with little or no crypt or villous formation. Conclusion: Intestinal organoids can be engrafted onto biodegradable polyester scaffoldings with restitution of an intestinal mucosal layer. Variability in polymer composition, processing techniques and material properties (fiber size, luminal dimensions and pore size) affect engraftment success. Future material refinements should lead to improvements in the development of a tissue-engineered intestine. Copyright (c) 2007 S. Karger AG, Basel. C1 Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90024 USA. Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. RP Agopian, VG (reprint author), Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, 10833 Conte Ave, Los Angeles, CA 90024 USA. EM vagopian@mednet.ucla.edu NR 32 TC 15 Z9 15 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2006 VL 184 IS 3-4 BP 154 EP 165 DI 10.1159/000099622 PG 12 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 156LL UT WOS:000245649400006 PM 17409741 ER PT J AU Fraga, S Luo, YJ Jose, PA Zandi-Nejad, K Mount, DB Soares-da-Silva, P AF Fraga, Sonia Luo, Yingjin Jose, Pedro A. Zandi-Nejad, Kambiz Mount, David B. Soares-da-Silva, Patricio TI Dopamine D-1-like receptor-mediated inhibition of Cl-/HCO3- exchanger activity in rat intestinal epithelial IEC-6 cells is regulated by G protein-coupled receptor kinase 6 (GRK 6) SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE dopamine D-1-like receptors; GRK; Cl-/HCO3- exchanger; desensitization ID K+-ATPASE ACTIVITY; NA+/H+ EXCHANGER; ESSENTIAL-HYPERTENSION; GENETIC-HYPERTENSION; ANION-EXCHANGERS; PH REGULATION; D-1 RECEPTOR; DESENSITIZATION; KIDNEY; TRANSPORT AB The present study investigated the effect of dopamine D-1-like receptor stimulation on the Cl-/HCO3- exchange activity in rat intestinal epithelial IEC-6 cells. The Cl-/ HCO3-exchange activity was found to be a chloride-dependent, DIDS-sensitive and niflumate-insensitive process. The presence of the SLC26A6 anion exchanger was detected by both RT-PCR and immunoblotting analysis in IEC-6 cells, in which three different small interfering RNAs (siRNAs) targeting SLC26A6 markedly inhibited Cl-/HCO3(-) exchange. Activation of dopamine D-1-like receptors with SKF 38393 inhibited Cl-/HCO3- exchanger activity, this being antagonized by the D 1 selective antagonist SKF 83566. However, effects of SKF 38393 were maximal at 5 min of exposure to the agonist and rapidly diminished with no effect at 15 min, suggestive of agonist-induced desensitization of D-1-like receptors. Pretreatment of cells with heparin, a non-selective inhibitor of G protein-coupled receptor kinases (GRKs), prevented the observed attenuation of SKF 38393-induced inhibition of Cl-/HCO3- exchange. Overnight pretreatment with anti-GRK6A and antiGRK6B, but not with anti-GRK4 antibodies, prevented the loss of SKF 38393-mediated effects. Both PKA and PKC signaling pathways participate in SKF 38393-mediated inhibition of Cl-/HCO3- exchange. These findings suggest that SLC26A6 is at least one of the anion exchanger's family members responsible for Cl-/HCO3- exchange in IEC-6 cells. Dopamine D-1 receptors in IEC-6 rapidly desensitize to D-1-like agonist stimulation and GRK 6, but not GRK 4, appear to be involved in agonist-mediated responsiveness and desensitization. C1 Fac Med, Inst Pharmacol & Therapeut, P-4200319 Oporto, Portugal. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Gen Internal Med, Boston, MA 02115 USA. RP Soares-da-Silva, P (reprint author), Fac Med, Inst Pharmacol & Therapeut, P-4200319 Oporto, Portugal. EM pss@med.up.pt RI Fraga, Sonia/D-8155-2013; REQUIMTE, TOXI/M-6171-2013; REQUIMTE, UCIBIO/N-9846-2013; Soares-da-Silva, Patricio/A-6704-2015 OI Fraga, Sonia/0000-0001-9386-2336; Soares-da-Silva, Patricio/0000-0002-2446-5078 FU NHLBI NIH HHS [P01 HL074949, R01 HL23081]; NIDDK NIH HHS [R01 DK57708] NR 59 TC 7 Z9 7 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 EI 1421-9778 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2006 VL 18 IS 6 BP 347 EP 360 DI 10.1159/000097612 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 130IP UT WOS:000243793600006 PM 17170521 ER PT J AU Chaves, C Hreib, K Allam, G Liberman, RF Lee, G Caplan, LR AF Chaves, Claudia Hreib, Kinan Allam, Gregory Liberman, Rebecca F. Lee, Grace Caplan, Louis R. TI Patterns of cerebral perfusion in patients with asymptomatic internal carotid artery disease SO CEREBROVASCULAR DISEASES LA English DT Article DE perfusion; computed tomography; internal carotid artery ID POSITRON-EMISSION-TOMOGRAPHY; IMAGING BOLUS TRACKING; BLOOD-FLOW; CEREBROVASCULAR REACTIVITY; VASOMOTOR REACTIVITY; ACUTE STROKE; STENOSIS; OCCLUSION; CT; ENDARTERECTOMY AB Background: The perfusion profile of patients with asymptomatic internal carotid artery (ICA) disease has not been well studied. The purpose of this study is to describe the perfusion patterns of patients with asymptomatic ICA disease using computed tomography perfusion (CTP) and its potential value in identifying patients at higher risk for transient ischemic attacks (TIAs) or strokes. Methods: We analyzed 32 patients with asymptomatic high grade ICA disease who had CTP and computed tomography angiography (CTA) of the head and neck. Twenty-four patients had severe ICA stenosis and eight had ICA occlusion. The degree of ipsilateral external carotid artery (ECA) and contralateral ICA stenosis, patency of the anterior communicating artery (ACOM), A1 segment and posterior communicating artery (PCOM) were evaluated in all patients. Results: Sixteen patients had normal CTP and the other 16 patients had cerebral hypoperfusion, characterized by abnormalities in one or more of the three perfusion maps. Ipsilateral hypoplastic A1 segment was more frequent in the group with cerebral hypoperfusion (p = 0.025). Ipsilateral TIAs occurred in two patients, both with cerebral hypoperfusion. Conclusion: Cerebral hypoperfusion is present in half of the patients with asymptomatic ICA disease, predominantly in patients with a hypoplastic ipsilateral A1 segment. These patients likely represent a higher-risk group for symptomatic brain ischemia. Copyright (c) 2006 S. Karger AG, Basel. C1 Lahey Clin Fdn, Dept Neurol, Lexington, MA 02421 USA. Lahey Clin Fdn, Dept Clin Res, Lexington, MA 02421 USA. Lahey Clin Fdn, Dept Neuroradiol, Lexington, MA 02421 USA. BIDMC, Dept Neurol, Boston, MA USA. RP Chaves, C (reprint author), Lahey Clin Fdn, Dept Neurol, 16 Hayden Ave, Lexington, MA 02421 USA. EM claudia.j.chaves@lahey.org NR 31 TC 10 Z9 11 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2006 VL 22 IS 5-6 BP 396 EP 401 DI 10.1159/000094858 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 127NG UT WOS:000243592400012 PM 16888382 ER PT J AU Gobron, C Viswanathan, A Bousser, MG Chabriat, H AF Gobron, Claire Viswanathan, Anand Bousser, Marie-Germaine Chabriat, Hugues TI Multiple simultaneous cerebral infarctions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy SO CEREBROVASCULAR DISEASES LA English DT Editorial Material ID BRAIN INFARCTION; CADASIL; LESIONS; MRI C1 CHU Lariboisiere, AP HP, Dept Neurol, Paris, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chabriat, H (reprint author), Hop Lariboisiere, Serv Neurol, 2 Rue Ambroise Pare, FR-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 NR 9 TC 14 Z9 14 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2006 VL 22 IS 5-6 BP 445 EP 446 DI 10.1159/000095287 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 127NG UT WOS:000243592400020 PM 16931882 ER PT J AU Cheng, E Chen, A Vassar, S Lee, M Cohen, SN Vickrey, B AF Cheng, E Chen, A Vassar, S Lee, M Cohen, SN Vickrey, B TI Comparison of secondary prevention care after myocardial infarction and stroke SO CEREBROVASCULAR DISEASES LA English DT Article DE secondary prevention; stroke; transient ischemic attack; cardiovascular disease; quality of health care ID AMERICAN-HEART-ASSOCIATION; ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE; ISCHEMIC-STROKE; RISK-FACTORS; HEALTH; PROFESSIONALS; STATEMENT; QUALITY; ATTACK; GUIDELINES AB Background: Whether secondary prevention of atherosclerosis is performed as frequently after cerebrovascular events ( stroke or transient ischemic attack) as after cardiac events ( myocardial infarction or angina) is unknown. Methods: We compared the receipt of six secondary preventive care processes among 943 persons with a prior cardiac event to that among 523 persons with a prior cerebrovascular event using a representative sample of the US population. Results: The cardiac event group had higher rates for three care processes: antithrombotic medication use in the past year (83-77%, p = 0.01), ever advised to exercise more (66-52%, p < 0.001), and ever advised to eat fewer high-fat or high-cholesterol foods ( 70-54%, p < 0.001). Conclusions: Compared to the cardiac event group, the quality of care of the cerebrovascular event group is lower and should be improved. C1 VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. Univ So Calif, Dept Pediat, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Dept Neurol, Hlth Serv Res Program, David Geffen Sch Med, Los Angeles, CA USA. Sunrise Hosp & Med Ctr, Stroke Prevent Program, Las Vegas, NV USA. RP Cheng, E (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, 11301 Wilshire Blvd,Bldg 500,ML 127, Los Angeles, CA 90073 USA. EM eric.cheng@med.va.gov NR 26 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2006 VL 21 IS 4 BP 235 EP 241 DI 10.1159/000091220 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 015WA UT WOS:000235580800004 PM 16446536 ER PT J AU Dalgarno, D Stehle, T Narula, S Schelling, P van Schravendijk, MR Adams, S Andrade, L Keats, J Ram, M Jin, L Grossman, T MacNeil, I Metcalf, C Shakespeare, W Wang, Y Keenan, T Sundaramoorthi, R Bohacek, R Weigele, M Sawyer, T AF Dalgarno, D Stehle, T Narula, S Schelling, P van Schravendijk, MR Adams, S Andrade, L Keats, J Ram, M Jin, L Grossman, T MacNeil, I Metcalf, C Shakespeare, W Wang, Y Keenan, T Sundaramoorthi, R Bohacek, R Weigele, M Sawyer, T TI Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article ID CYCLIN-DEPENDENT KINASES; C-SRC; CRYSTAL-STRUCTURE; FAMILY KINASES; DRUG DISCOVERY; ACTIVATION; COMPLEX; TARGETS; PHOSPHORYLATION; IDENTIFICATION AB The tyrosine kinase pp60src (Src) is the prototypical member of a family of proteins that participate in a broad array of cellullar signal transduction processes, including cell growth, differentiation, survival, adhesion, and migration. Abnormal Src family kinase (SFK) signaling has been linked to several disease states, including osteoporosis and cancer metastases. Src has thus emerged as a molecular target for the discovery of small-molecule inhibitors that regulate Src kinase activity by binding to the ATP pocket within the catalytic domain. Here, we present crystal structures of the kinase domain of Src in complex with two purine-based inhibitors: AP23451, a small-molecule inhibitor designed to inhibit Src-dependent bone resorption, and AP23464, a small-molecule inhibitor designed to inhibit the Src-dependent metastatic spread of cancer. On each case, a trisubstituted purine template core was elaborated using structure-based drug design to yield a potent Src kinase inhibitor. These structures represent early examples of high affinity purine-based Src family kinase-inhibitor complexes, and they provide a detailed view of the specific protein-ligand interactions that lead to potent inhibition of Src. On particular, the 3-hydroxyphenethyl N9 substituent of AP23464 forms unique interactions with the protein that are critical to the picomolar affinity of this compound fair Src. The comparison of these new structures with two relevant kinase-inhibitor complexes provides a structural basis for the observed kinase inhibitory selectivity. Further comparisons reveal a concerted induced-fit movement between the N- and C-terminal lobes of the kinase that correlates with the affinity of the ligand. Binding of the most potent inhibitor, AP23464, results in the largest induced-fit movement, which can be directly linked to interactions of the hydrophenethyl N9 substituent with a region at the interface between the two lobes. A less pronounced induced-fit movement is also observed in the Src-AP23451 complex. These new structures illustrate how the combination of structural, computationall, and medicinal chemistry can be used to rationalize the process of developing high affinity, selective tyrosine kinase inhibitors as potential therapeutic agents. C1 ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Suntory Pharmaceut Res, Cambridge, MA 02139 USA. RP Dalgarno, D (reprint author), ARIAD Pharmaceut Inc, 26 Landsdowne St, Cambridge, MA 02139 USA. EM dalgarno@ariad.com NR 45 TC 56 Z9 58 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD JAN PY 2006 VL 67 IS 1 BP 46 EP 57 DI 10.1111/j.1747-0285.2005.00316.x PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 019XM UT WOS:000235871500007 PM 16492148 ER PT J AU Kumar, S Choi, WT Dong, CZ Madan, N Tian, SM Liu, SX Wang, YL Pesavento, J Wang, J Fan, XJ Yuan, J Fritzsche, WR An, J Sodroski, JG Richman, DD Huang, ZW AF Kumar, S Choi, WT Dong, CZ Madan, N Tian, SM Liu, SX Wang, YL Pesavento, J Wang, J Fan, XJ Yuan, J Fritzsche, WR An, J Sodroski, JG Richman, DD Huang, ZW TI SMM-chemokines: A class of unnatural synthetic molecules as chemical probes of chemokine receptor biology and leads for therapeutic development SO CHEMISTRY & BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 ENTRY; VMIP-II; N-TERMINUS; CXCR4; CORECEPTOR; RANTES; ANTAGONIST; ACTIVATION; PROTEIN AB Chemokines and their receptors play important roles in numerous physiological and pathological processes. To develop natural chemokines into receptor probes and inhibitors of pathological processes, the lack of chemokine-receptor selectivity must be overcome. Here, we apply chemical synthesis and the concept of modular modifications to generate unnatural synthetically and modularly modified (SMM)-chemokines that have high receptor selectivity and affinity, and reduced toxicity. A proof of the concept was shown by transforming the nonselective viral macrophage inflammatory protein-II into new analogs with enhanced selectivity and potency for CXCR4 or CCR5, two principal coreceptors for human immunodeficiency virus (HIV)-1 entry. These new analogs provided insights into receptor binding and signaling mechanisms and acted as potent HIV-1 inhibitors. These results support the concept of SMM-chemokines for studying and controlling the function of other chemokine receptors. C1 Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Univ Illinois, Dept Chem, Urbana, IL 61801 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Calif San Diego, Dept Mol Pathol, Ctr AIDS Res, La Jolla, CA 92093 USA. Raylight Corp, Chemokine Pharmaceut Inc, La Jolla, CA 92037 USA. RP Huang, ZW (reprint author), Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. EM ziweihuang@burnham.org FU NIAID NIH HHS [U01AI38858, AI29164, AI27670, AI043638, AI 36214, AI047745]; NIGMS NIH HHS [GM57761] NR 47 TC 20 Z9 22 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN PY 2006 VL 13 IS 1 BP 69 EP 79 DI 10.1016/j.chembiol.2005.10.012 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 009DH UT WOS:000235090900011 PM 16426973 ER PT J AU Montet, X Rajopadhye, M Weissleder, R AF Montet, Xavier Rajopadhye, Milind Weissleder, Ralph TI An albumin-activated far-red fluorochrome for in vivo imaging SO CHEMMEDCHEM LA English DT Article AB The far-red indocyanine fluorochrome VM315 significantly increases its fluorescence upon binding albumin, but not other proteins. Experimental tumor detection in multiple xenograft cancer models is greatly improved. This small-molecule probe is expected to find wide-spread application in the in vivo fluorescence imaging of various disease processes. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.horvard.edu OI Montet, Xavier/0000-0003-2442-5866 NR 29 TC 3 Z9 3 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD JAN PY 2006 VL 1 IS 1 BP 66 EP + DI 10.1002/cmdc.200500028 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V43OX UT WOS:000202945500010 PM 16892337 ER PT J AU Schatz, M Clark, S Camargo, CA AF Schatz, M Clark, S Camargo, CA TI Sex differences in the presentation and course of asthma hospitalizations SO CHEST LA English DT Article DE acute asthma; gender; hospitalizations; management; prevalence; severity; sex differences ID HEALTH-CARE UTILIZATION; EMERGENCY-DEPARTMENT; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; SPECIALTY CARE; AGE; GENDER; PREVALENCE; ADMISSIONS; POPULATION AB Objective: To distinguish between differences in prevalence, asthma severity, and treatment to explain sex-related differences in hospitalized asthma patients. Design: Medical record review. Setting: Thirty US hospitals as part of the University HealthSystem Consortium Asthma Clinical Benchmarking Project. Patients: A random sample of patients aged 2 to 54 years and admitted to the hospital for acute asthma from 1999 to 2000. Measurements: Demographics, medical history, initial oxygen saturation, initial peak expiratory flow (adults), initial pulmonary index (children), emergency department course, length of hospital stay, and discharge plans. Results: The cohort included 606 pediatric (aged 2 to 17 years) and 680 adult ((aged IS to 54 years) inpatients. The sex ratio varied significantly by age: 40% were girls 2 to 17 years of age, and 68% were women 18 to 54 years of age p < 0.001). Among children, girls did not differ from boys according to asthma history, pulmonary index scores, or hospital length of stay. Among adults, women were more likely to have a primary care provider (90% vs 73%, p < 0.001) but did not differ according to asthma history or recent medication use. Women had a higher mean initial PEF compared to men (43% of predicted vs 36% of predicted, p < 0.001) and higher median initial oxygen saturation (95% vs 93%, p = 0.002) but did not differ by hospital length of stay. No sex differences in discharge regimens were identified in children or adults. Conclusions: Among US inpatients with acute asthma, male children are more common than female children, while women are more common in adults. The results in children are probably explained by prevalence differences, since no sex differences were seen in markers of asthma severity or treatment. in adults, increased symptoms in response to a given level of airway obstruction in women may contribute to the female predominance in asthma hospitalizations. C1 Kaiser Permanente Med Care Program, Dept Allergy, San Diego, CA 92111 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Schatz, M (reprint author), Kaiser Permanente Med Care Program, Dept Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111 USA. EM Michael.x.schatz@kp.org FU NIAID NIH HHS [AI52338]; NIEHS NIH HHS [T32 ES07069] NR 34 TC 51 Z9 51 U1 2 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2006 VL 129 IS 1 BP 50 EP 55 DI 10.1378/chest.129.1.50 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 007CI UT WOS:000234944900011 PM 16424412 ER PT J AU Prince, JB AF Prince, JB TI Pharmacotherapy of attention-deficit hyperactivity disorder in children and adolescents: Update on new stimulant preparations, atomoxetine, and novel treatments SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID PLACEBO-CONTROLLED TRIAL; ONCE-A-DAY; CLINICAL-PRACTICE GUIDELINE; HEALTH MULTIMODAL TREATMENT; AMPHETAMINE SALTS ADDERALL; PROOF-OF-CONCEPT; DEFICIT/HYPERACTIVITY-DISORDER; DOUBLE-BLIND; TOURETTES-SYNDROME; SLEEP DISTURBANCES AB Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric condition shown to occur in 3% to 10% of school-aged children worldwide [1-3]. The classic triad of impaired attention, impulsivity, and excessive motor activity characterizes ADHD, although up to one third of children may manifest only the inattentive aspects of ADHD [4]. In most patients ADHD persists to some degree from childhood through adolescence and into adulthood [5,6]. Pharmacotherapy remains the cornerstone of ADHD treatment [7-10]. As the number of children and adolescents diagnosed with and treated for ADHD tripled during the 1990s [11], research on the pharmacotherapy of ADHD has grown, enhancing the understanding of youth who have ADHD. Recent developments have improved the care of youth who have ADHD. First, the development and availability of novel delivery systems for methylphenidate (MPH) and mixed amphetamine salts (MAS) make it possible to extend coverage by a single dose. Second, the noradrenergic medication atomo-stop-signal reaction time. Nicotine, but not MPH, decreased the Stroop effect (interference by irrelevant stimuli) compared with placebo. These results support the neurobiologic hypothesis of impaired fronto-strial attentional networks. Although cigarette smoking remains an ongoing challenge in the treatment of adolescents who have ADHD, nicotine is, at this point, not a viable or recommended treatment. The nicotinic system remains a potential target for development of novel treatments, however. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. N Shore Med Ctr, Salem, MA 01970 USA. RP Prince, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat, 6900 Yawkey Bldg,15 Parkman St, Boston, MA 02114 USA. EM jprince@partners.org NR 126 TC 38 Z9 40 U1 10 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2006 VL 15 IS 1 BP 13 EP + DI 10.1016/j.chc.2005.08.002 PG 40 WC Psychiatry SC Psychiatry GA 001GU UT WOS:000234522400004 PM 16321724 ER PT J AU Martin, A Bostic, JQ AF Martin, A Bostic, JQ TI Generation Rx SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material ID CHILDREN C1 Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Martin, A (reprint author), Yale Univ, Sch Med, Yale Child Study Ctr, 230 S Frontage Rd, New Haven, CT 06520 USA. EM andres.martin@yale.edu; roboz@adelphia.net NR 19 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2006 VL 15 IS 1 BP XIX EP XXII DI 10.1016/j.chc.2005.09.001 PG 4 WC Psychiatry SC Psychiatry GA 001GU UT WOS:000234522400002 PM 16321721 ER PT J AU King, BH Bostic, JQ AF King, BH Bostic, JQ TI An update on pharmacologic treatments for autism spectrum disorders SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; OPEN-LABEL; DOUBLE-BLIND; RETROSPECTIVE ASSESSMENT; ADOLESCENT AUTISM; BRAIN OVERGROWTH; CASE SERIES; OPEN-PILOT; CHILDREN; RISPERIDONE AB Autism spectrum disorders (ASDs) are a heterogeneous group of conditions that include autism, Asperger disorder, Rett disorder, childhood disintegrative disorder, and sometimes less severe or otherwise atypical presentations currently diagnosed as pervasive developmental disorder (PDD) not otherwise specified. By definition, the diagnosis of an ASD indicates that the affected individual will experience significant difficulty in reciprocal social interactions and communication and will exhibit repetitive or nonfunctional stereotyped behaviors or preoccupations. Affected individuals commonly avoid eye contact, do not develop normal social relationships appropriate for their age, do not seem to show interest in others' thoughts or feelings, and have difficulty understanding or seeing the world through the perspective of others. Affected individuals may have restricted speech or even be nonverbal, may use language unusually (invert pronouns, repeat phrases over and over), and frequently have difficulty sustaining conversations with others. Persons who have autism are often quite concrete and may be preoccupied with parts of objects or use objects in unusual ways. They may have routines that cannot be disrupted without conflict (eg, lining up toys in a certain way) and may exhibit unusual motor behaviors such as hand flapping, body twisting, or even head banging. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Seattle, WA USA. Univ Washington, Reg Med Ctr, Seattle, WA USA. RP Bostic, JQ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey 6926,55 Fruit St, Boston, MA 02114 USA. EM roboz@adelphia.net NR 78 TC 38 Z9 39 U1 5 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2006 VL 15 IS 1 BP 161 EP + DI 10.1016/j.chc.2005.08.005 PG 16 WC Psychiatry SC Psychiatry GA 001GU UT WOS:000234522400009 PM 16321729 ER PT J AU Bostic, JQ Rho, Y AF Bostic, JQ Rho, Y TI Target-symptom psychopharmacology: Between the forest and the trees SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; GENERAL-POPULATION; AUTISTIC DISORDER; CLINICAL-TRIALS; ADOLESCENTS; PSYCHOSIS; PHARMACOTHERAPY; DIMENSIONS; ADULTHOOD; SPECTRUM AB Psychopharmacology practice seeks to fit specific treatments to specific disease processes. Although categorical diagnoses have improved focus on observable symptom constellations, these approximately 300 categories have limited benefits for illuminating underlying disease pathophysiology. Existing medications do not couple well to the symptom constellations of given disorders. Rather, current medications ameliorate symptoms overlapping among various disorders. Harnessing technology to identify a patient's wider symptom constellation, prioritizing and targeting symptoms across disorders, considering symptoms more dimensionally instead of "present or not," and eliciting factors necessary to improve adherence may allow medication selections to be tailored better to individual patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge Hosp, Cambridge, MA USA. RP Bostic, JQ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey 6926,55 Fruit St, Boston, MA 02114 USA. EM roboz@adelphia.net NR 30 TC 4 Z9 4 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2006 VL 15 IS 1 BP 289 EP + DI 10.1016/j.chc.2005.08.003 PG 16 WC Psychiatry SC Psychiatry GA 001GU UT WOS:000234522400015 PM 16321735 ER PT J AU Ferrando, AA Rubnitz, JE Look, AT AF Ferrando, Adolfo A. Rubnitz, Jeffrey E. Look, A. Thomas BE Pui, CH TI Molecular genetics of acute lymphoblastic leukemia SO CHILDHOOD LEUKEMIAS, 2ND EDITION LA English DT Article; Book Chapter ID T-CELL LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; ABL TYROSINE KINASE; ACUTE LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; LOOP-HELIX PROTEINS; ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION C1 [Ferrando, Adolfo A.] Columbia Univ, Irving Canc Res Ctr, Inst Canc Genet, New York, NY 10027 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Rubnitz, Jeffrey E.] St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. [Rubnitz, Jeffrey E.] St Jude Childrens Hosp, Fellowship Program, Memphis, TN 38105 USA. RP Ferrando, AA (reprint author), Columbia Univ, Irving Canc Res Ctr, Inst Canc Genet, New York, NY 10027 USA. RI Ferrando, Adolfo /Q-7026-2016 NR 383 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52182-519-1 PY 2006 BP 272 EP 297 D2 10.1017/CBO9780511471001 PG 26 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA BXZ02 UT WOS:000297649900011 ER PT J AU Jin, M Wener, MH Bankson, DD AF Jin, M Wener, MH Bankson, DD TI Evaluation of automated sex hormone binding globulin immunoassays SO CLINICAL BIOCHEMISTRY LA English DT Article DE SHBG; sex hormone binding globulin; sex steroid binding globulin; SSBG; testosterone; free testosterone; bioavailable testosterone; method comparison ID BIOAVAILABLE TESTOSTERONE; SERUM AB Background: Sex hormone binding globulin (SHBG) is an important regulator of testosterone and estradiol. Study design: We validated the Diagnostic Products Corporation (DPC) and Roche Diagnostic SHBG immunoassays on the DPC Immulite 2000 and Roche Modular E170 analyzers. Results: The coefficient of variation for SHBG kits from both manufacturers was in the range of 3.9-7.7% (between-run) and 0.95-5.0% (within-run), free of interference from hemoglobin, bilirubin, lipid, and rheumatoid factor, and linear up to at least 170 nM SHBG. The results of the two methods, however, were biased by up to 29% depending on the SHBG concentration. Conclusion: The SHBG assays perform well but standardization is needed. Published by The Canadian Society of Clinical Chemists. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Clin Chem & STAT Labs, Seattle, WA 98108 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Bankson, DD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Clin Chem & STAT Labs, 1660 S Columbian Way S-113, Seattle, WA 98108 USA. EM daniel.bankson@med.va.gov RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 9 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD JAN PY 2006 VL 39 IS 1 BP 91 EP 94 DI 10.1016/j.clinbiochem.2005.10.012 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 005AH UT WOS:000234793600014 PM 16325792 ER PT J AU Catley, L Anderson, KC AF Catley, L Anderson, KC TI Velcade and vitamin C: Too much of a good thing? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ARSENIC TRIOXIDE; MULTIPLE-MYELOMA; ASCORBIC-ACID; PHARMACOKINETICS; GLUTATHIONE; VOLUNTEERS; DEPLETION; CELLS C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Catley, L (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. EM Laurence_Catley@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 NR 10 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2006 VL 12 IS 1 BP 3 EP 4 DI 10.1158/1078-0432.CCR-05-2272 PG 2 WC Oncology SC Oncology GA 001AG UT WOS:000234503700002 PM 16397016 ER PT J AU Febbo, PG Thorner, A Rubin, MA Loda, M Kantoff, PW Oh, WK Golub, T George, D AF Febbo, PG Thorner, A Rubin, MA Loda, M Kantoff, PW Oh, WK Golub, T George, D TI Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; GROWTH-FACTOR-RECEPTOR; BREAST-CANCER; CHEMOTHERAPY; INHIBITION; PREDICTION; APOPTOSIS; SURVIVAL AB Purpose: Neoadjuvant administration of antineoplastic therapies is used to rapidly assess the clinical and biological activity of novel systemic treatments. To assess the feasibility of using microarrays to assess molecular end points following targeted treatment in a heterogeneous tumor, we measured global gene expression in localized prostate cancer before and following neoadjuvant treatment with imatinib mesylate. Patients and Methods: Patients with intermediate-risk to high-risk prostate cancer were treated for 6 weeks with 200 to 300 mg of oral imatinib mesylate. Frozen tissue was obtained from pretreatment ultrasound-guided biopsies and posttreatment radical prostatectomy specimens. Oligonucleotide microarray analysis following laser capture microdissection (LCM) and RNA amplification was used to assess gene expression changes associated with imatinib mesylate therapy. Immunohistochemistry was used to measure protein expression of MKP1 and CD31 and to assess cellular apoptosis. Results: Of the 11 patients enrolled, high-quality microarray data was obtained from both biopsies (n = 7) and radical prostatectomy specimens (n = 9). Technically introduced intrasample gene expression variability was found to be significantly less than intertumor biological variability. Large gene expression differences were observed, and the gene with the most consistent differential expression (MKP1) was validated by immunohistochemistry. Gene set enrichment analysis suggests that imatinib mesylate therapy results in apoptosis of microvascular endothelial cells, an observation anecdotally supported by immunohistochemistry. Conclusions: This study shows that high-quality microarray data can be generated using LCM and RNA amplification to discover potential mechanisms of targeted therapy in cancer. C1 Duke Univ, Med Ctr, Inst Genom Sci & Policy, Div Med Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Microbiol & Mol Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. RP Febbo, PG (reprint author), Duke Univ, Med Ctr, Inst Genom Sci & Policy, Div Med Oncol, DUMC Box 3382,101 Sci Dr,Room 2349,CIEMAS Bldg, Durham, NC 27710 USA. EM phil.febbo@duke.edu RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [K23 CA089031-04, K23 CA089031, K23 CA89031] NR 44 TC 21 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2006 VL 12 IS 1 BP 152 EP 158 DI 10.1158/1078-0432.CCR-05-1652 PG 7 WC Oncology SC Oncology GA 001AG UT WOS:000234503700023 PM 16397037 ER PT J AU Evans, JA Poneros, JM Bouma, BE Bressner, J Halpern, EF Shishkov, M Lauwers, GY Mino-Kenudson, M Nishioka, NS Tearney, GJ AF Evans, JA Poneros, JM Bouma, BE Bressner, J Halpern, EF Shishkov, M Lauwers, GY Mino-Kenudson, M Nishioka, NS Tearney, GJ TI Optical coherence tomography to identify intramucosal carcinoma and high-grade dysplasia in Barrett's esophagus SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INTESTINAL METAPLASIA; ENDOSCOPIC SURVEILLANCE; EARLY ADENOCARCINOMA; BIOPSY SURVEILLANCE; OBSERVER VARIATION; LIGHT-SCATTERING; DIAGNOSIS; RISK; CANCER; TRACT AB Background & Aims: Optical coherence tomography (OCT) is an optical technique that produces high-resolution images of the esophagus during endoscopy. OCT can distinguish specialized intestinal metaplasia (SIM) from squamous mucosa, but image criteria for differentiating intramucosal carcinoma (IMC) and high-grade dysplasia (HGD) from low-grade dysplasia (LGD), indeterminate-grade dysplasia (IGD), and SIM without dysplasia have not been validated. The purpose of this study was to establish OCT image characteristics of IMC and HGD in Barrett's esophagus. Methods: Biopsy-correlated OCT images were acquired from patients with Barrett's esophagus undergoing endoscopic surveillance. Two pathologists rendered consensus diagnoses of the biopsy specimens. A blinded investigator reviewed the biopsycorrelated OCT images and scored each for surface maturation and gland architecture. For each image the scores were summed to determine an OCT dysplasia index." Results: A total of 177 biopsy-correlated images were analyzed. The corresponding histopathology diagnosis was IMC/HGD in 49 cases, LGD in :15, IGD in 8, SIM in 100, and gastric mucosa in 5. A significant relationship was found between a histopathologic diagnosis of IMC/HGD and scores for each image feature (dysplasia index [Spearman correlation coefficient, r = 0.50, P < .0001], surface maturation [r = 0.48, P < .0001], and gland architecture [r = 0.41, P < .0001]). When a dysplasia index threshold of >= 2 was used, the sensitivity and specificity for diagnosing IMC/HGD were 83% and 75%, respectively. Conclusions: An OCT image scoring system based on histopathologic characteristics has the potential to identify IMC and HGD in Barrett's esophagus. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. RP Tearney, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 40 Blossom St,BAR 703, Boston, MA 02114 USA. EM gtearney@partners.org FU NCI NIH HHS [R01 CA103769, R01 CA103769-03] NR 29 TC 110 Z9 114 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2006 VL 4 IS 1 BP 38 EP 43 DI 10.1053/S1542-3565(05)00746-9 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 007TI UT WOS:000234992300010 PM 16431303 ER PT J AU Davila, JA El-Serag, HB AF Davila, JA El-Serag, HB TI Racial differences in survival of hepatocellular carcinoma in the United States: A population-based study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID TRENDS AB Background & Aims: Survival after hepatocellular carcinoma (HCC) diagnosis is generally dismal, but there are patients with more favorable outcomes. Racial variation in survival of patients with HCC could be associated with observed differences in survival; however this has not been previously examined. Methods: During 1987-2001, HCC patients were identified from 9 Surveillance, Epidemiology, and End-Results registries. One- and 3-year survival rates were calculated and compared by race. Models were constructed to examine the effects of race on the mortality risk. Results: Asians had the highest 1- and 3-year observed and relative survival, followed by whites, Hispanics, and blacks. Compared with whites, Asians (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.11-1.69) were more likely to receive local or surgical therapy, whereas blacks (OR, 0.62; 95% CI, 0.49-0.78) and Hispanics (OR, 0.81; 95% CI, 0.60-1.09) were less likely to receive therapy. Adjusting for differences in receipt of therapy, stage of HCC, year of diagnosis, and other demographics, Asians (hazard rate [HR], 0.84; 95% CI, 0.78-0.91) maintained a lower mortality risk compared with whites. In adjusted models, Hispanics (HR, 1.13; 95% CI, 1.03-1.24) maintained a higher mortality risk, whereas the mortality risk for blacks became nonsignificant different from whites (HR, 1.06; 95% CI, 0.99-1.14). Last, a 22% improvement in survival was observed between 1987-1991 and 1997-2001, which was mostly explained by increased receipt of local or surgical therapy. Conclusions: We observed significant racial variation in survival. These variations in survival are partly explained by a lower likelihood of receipt of therapy and more advanced HCC at diagnosis among blacks and Hispanics. C1 Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 14 TC 55 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2006 VL 4 IS 1 BP 104 EP 110 DI 10.1053/S1542-3565(05)00745-7 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 007TI UT WOS:000234992300019 PM 16431312 ER PT J AU Astier, A Beriou, G Eisenhoure, T Hafler, D Hacohen, N AF Astier, Anne Beriou, Gaelle Eisenhoure, Thomas Hafler, David Hacohen, Nir TI Identifying regulators of cytokine production in primary human T-Cells using a lentiviral RNAi library. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammat Dis, Charlestown, MA USA. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S35 EP S35 DI 10.1016/j.clim.2006.04.385 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300081 ER PT J AU Haining, WN Ebert, B Subramanian, A Kaech, S Ahmed, R Nadler, L Wherry, EJ Golub, T AF Haining, W. Nicholas Ebert, Benjamin Subramanian, Aravind Kaech, Susan Ahmed, Rafi Nadler, Lee Wherry, E. John Golub, Todd TI Memory T-cells in mice and humans share a common molecular program of differentiation regardless of phenotype, lineage or species. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Canc Program, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Yale Univ, New Haven, CT USA. Emory Univ, Atlanta, GA 30322 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S182 EP S183 DI 10.1016/j.clim.2006.04.493 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300487 ER PT J AU Loftis, J Pagel, R Bussell, C Menasco, D Hauser, P AF Loftis, Jennifer Pagel, Rebecca Bussell, Cara Menasco, Daniel Hauser, Peter TI Pegylated interferon-alpha does not induce sickness behavior in prairie votes. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S130 EP S130 DI 10.1016/j.clim.2006.04.305 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300347 ER PT J AU Orban, T Kis, J Engelmann, P Szereday, L Richman, G Shawn, E Treszl, A AF Orban, Tihamer Kis, Janos Engelmann, Peter Szereday, Laszlo Richman, Geoffrey Shawn, Eck Treszl, Andras TI Impaired function of the CD4+T-cells in human type 1 diabetes mellitus. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S166 EP S166 DI 10.1016/j.clim.2006.04.446 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300440 ER PT J AU Porcheray, F Miklos, D Floyd, B Sarantopoulos, S Bellucci, R Alyea, E Ritz, J Zorn, E AF Porcheray, Fabrice Miklos, David Floyd, Blair Sarantopoulos, Stefanie Bellucci, Roberto Alyea, Edwin Ritz, Jerome Zorn, Emmanuel TI High frequency CD4+ T-cell and antibody responses to h-y minor histocompatibility antigen DBY following allogeneic hematopoietic stem cell transplantation. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S37 EP S37 DI 10.1016/j.clim.2006.04.391 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300087 ER PT J AU Roland, L Cabarrocas, J Casson, C Magnusson, F Piaggio, E Mars, L Derbinski, J Kyewski, B Gross, DA Salomon, B Khazaie, K Saoudi, A AF Roland, Liblau Cabarrocas, Julie Casson, Cecile Magnusson, Fay Piaggio, Eliane Mars, Lennart Derbinski, Jens Kyewski, Bruno Gross, D. A. Salomon, Benoit Khazaie, Khash Saoudi, Abdel TI FOXP3+CD25+ regulatory T-cells specific for a glial self-antigen develop at the double positive thymic stage. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 INSERM, U563, Toulouse, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. German Res Ctr, Tumor Immunol Programme, Div Dev Immunol, Heidelberg, Germany. Genethon, CNRS, UMR 8115, Immunol Lab, Evry, France. Hop La Pitie Salpetriere, CNRS, UMR 7087, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S19 EP S19 DI 10.1016/j.clim.2006.04.197 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300042 ER PT J AU Muder, RR Brennen, C Rihs, JD Wagener, MM Obman, A Stout, JE Yu, VL AF Muder, RR Brennen, C Rihs, JD Wagener, MM Obman, A Stout, JE Yu, VL TI Isolation of Staphylococcus aureus from the urinary tract: Association of isolation with symptomatic urinary tract infection and subsequent staphylococcal bacteremia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID TERM-CARE FACILITY; CONTROLLED TRIAL; BACTERIURIA; RESIDENTS; SUSCEPTIBILITY; COLONIZATION; CATHETERS; FEVER; WOMEN AB Background. Staphylococcus aureus is frequently isolated from urine samples obtained from long-term care patients. The significance of staphylococcal bacteriuria is uncertain. We hypothesized that S. aureus is a urinary pathogen and that colonized urine could be a source of future staphylococcal infection. Methods. We performed a cohort study of 102 patients at a long-term care Veterans Affairs facility for whom S. aureus had been isolated from clinical urine culture. Patients were observed via urine and nasal cultures that were performed every 2 months. We determined the occurrence of (1) symptomatic urinary tract infection concurrent with isolation of S. aureus (by predetermined criteria), (2) staphylococcal bacteremia concomitant with isolation of S. aureus from urine, and (3) subsequent episodes of staphylococcal infection. Results. Of 102 patients, 82% had undergone recent urinary catheterization. Thirty-three percent of patients had symptomatic urinary tract infection at the time of initial isolation of S. aureus, and 13% were bacteremic. Eight-six percent of the initial urine isolates were methicillin-resistant S. aureus. Seventy-one patients had follow-up culture data; 58% of cultures were positive for S. aureus at >= 2 months (median duration of staphylococcal bacteriuria, 4.3 months). Sixteen patients had subsequent staphylococcal infections, occurring up to 12 months after initial isolation of S. aureus; 8 late-onset infections were bacteremic. In 5 of 8 patients, the late blood isolate was found to have matched the initial urine isolate by pulsed-field gel electrophoresis typing. Conclusions. S. aureus is a cause of urinary tract infection among patients with urinary tract catheterization. The majority of isolates are methicillin-resistant S. aureus. S. aureus bacteriuria can lead to subsequent invasive infection. The efficacy of antistaphylococcal therapy in preventing late-onset staphylococcal infection in patients with persistent staphylococcal bacteriuria should be tested in controlled trials. C1 VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM Robert.Muder@med.va.gov NR 25 TC 45 Z9 46 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2006 VL 42 IS 1 BP 46 EP 50 DI 10.1086/498518 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 989UH UT WOS:000233698900013 PM 16323090 ER PT J AU Anzueto, A Niederman, MS Pearle, J Restrepo, MI Heyder, A Choudhri, SH AF Anzueto, A Niederman, MS Pearle, J Restrepo, MI Heyder, A Choudhri, SH CA Community Acquired Pneumonia Recov TI Community-acquired pneumonia recovery in the elderly (CAPRIE): Efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 101st International Conference of the American-Thoracic-Society CY MAY 20-25, 2005 CL San Diego, CA SP Amer Thorac Soc, Fogarty AIDS Int Training & Res Program ID CLOSTRIDIUM-DIFFICILE; CLARITHROMYCIN; POPULATION; GUIDELINES; MANAGEMENT; PROGNOSIS; ADULTS; TRIAL AB Background. Limited prospective data are available for elderly patients with community-acquired pneumonia (CAP). This study aimed to determine the efficacy and safety of moxifloxacin versus that of levofloxacin for the treatment of CAP in hospitalized elderly patients (age, >= 65 years). Methods. We conducted a prospective, double-blind, randomized, controlled trial. Eligible patients were stratified by CAP severity before randomization to receive treatment with either intravenous/oral moxifloxacin (400 mg daily) or intravenous/oral levofloxacin (500 mg daily) for 7-14 days. Clinical response at test-of-cure (the primary efficacy end point was between days 5 and 21 after completion of therapy), and clinical response during therapy (between days 3 and 5 after the start of therapy) and bacteriologic response were secondary end points. Results. The safety population included 394 patients ( 195 in the moxifloxacin group and 199 in the levofloxacin group). The population eligible for clinical efficacy analysis (i.e., the clinically valid population) included 281 patients (141 in the moxifloxacin group and 140 in the levofloxacin group); 51.3% were male, and the mean age (+/- SD) was years. Cure rates at test-of-cure for the clinically valid population were 92.9% in the 77.4 +/- 7.7 moxifloxacin arm and 87.9% in the levofloxacin arm (95% confidence interval [CI], -1.9 to 11.9; P=.2). Clinical recovery by days 3-5 after the start of treatment was 97.9% in the moxifloxacin arm vs. 90.0% in the levofloxacin arm (95% CI, 1.7-14.1; P=.01). In the moxifloxacin group, cure rates were 92.6% for patients with mild or moderate CAP and 94.7% for patients with severe CAP, compared with cure rates of 88.6% and 84.6%, respectively, in the levofloxacin group (significant). Cure rates in the moxifloxacin arm were 90.0% for patients aged 65-74 years and 94.5% for patients aged >= 75 years, compared with 85.0% and 90.0%, respectively, in the levofloxacin arm (significant). There were no statistically significant differences between the treatment groups Ppnot with regard to drug-related adverse events. Conclusions. Intravenous/ oral moxifloxacin therapy was efficacious and safe for hospitalized elderly patients with CAP, achieving > 90% cure in all severity and age subgroups, and was associated with faster clinical recovery than intravenous/oral levofloxacin therapy, with a comparable safety profile. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Healthcare Syst, Dept Med, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. Calif Res Med Grp, Fullerton, CA USA. Carolina Res Specialists, Elizabeth City, NC USA. Bayer Pharmaceut, West Haven, CT USA. RP Anzueto, A (reprint author), 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Anzueto@uthscsa.edu NR 22 TC 57 Z9 65 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2006 VL 42 IS 1 BP 73 EP 81 DI 10.1086/498520 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 989UH UT WOS:000233698900018 PM 16323095 ER PT J AU Abramson, JS Neuzil, KM Tamblyn, SE AF Abramson, JS Neuzil, KM Tamblyn, SE TI Annual universal influenza vaccination: Ready or not? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHILDREN; SCHOOLCHILDREN AB Influenza causes annual worldwide epidemics of respiratory disease. Currently, the United States and many other countries recommend influenza vaccination for persons who are at high risk for influenza-related complications. This commentary explores the potential benefits of a policy advocating universal annual influenza vaccination and outlines obstacles that need to be overcome to make such a recommendation feasible. The 5-year experience of a free influenza vaccination program for everyone >= 6 months of age in the Canadian province of Ontario is reviewed. C1 Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. Univ Western Ontario, Dept Epidemiol & Biostat, Fac Med & Dent, London, ON, Canada. RP Abramson, JS (reprint author), Wake Forest Univ, Sch Med, Dept Pediat, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jabrams@wfubmc.edu NR 15 TC 11 Z9 14 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2006 VL 42 IS 1 BP 132 EP 135 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 989UH UT WOS:000233698900027 PM 16323103 ER PT J AU Gallagher, RM AF Gallagher, RM TI Management of neuropathic pain - Translating mechanistic advances and evidence-based research into clinical practice SO CLINICAL JOURNAL OF PAIN LA English DT Article DE neuropathic pain; management; evidence-based ID LIDOCAINE PATCH 5-PERCENT; CHRONIC POSTHERPETIC NEURALGIA; DOUBLE-BLIND; DIABETIC-NEUROPATHY; RANDOMIZED-TRIAL; EFFICACY; GABAPENTIN; CAPSAICIN; ANTIDEPRESSANTS; HYPOTHESES AB The concept of rational polypharmacy is now well established in the field of pain management. This concept has evolved in concert with progress in understanding the pathophysiologic mechanisms of pain diseases and disorders and how medications affect these processes. Other clinical factors must be considered in formulating the pain management strategy most likely to succeed in both controlling pain and improving function in a given patient. This article will review how pain diagnosis, pain mechanisms, pain phenomenology, medication efficacy, and risk profile influence medication selection in pain medicine practice, with a selective focus on the treatment of neuropathic pain. In addition, the role of psychosocial factors as they affect pain managernent will be discussed. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Anesthesiol, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Vet Affairs Med Ctr, Woodland Ave, Philadelphia, PA 19014 USA. EM rgallagh@mail.med.upenn.edu NR 31 TC 18 Z9 22 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD JAN PY 2006 VL 22 IS 1 SU S BP S2 EP S8 DI 10.1097/01.ajp.0000193827.07453.d6 PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 001TB UT WOS:000234558200002 PM 16344609 ER PT J AU Gallagher, RM AF Gallagher, RM TI Analgesic selection in the management of chronic pain - Linking mechanisms & evidence-based research to clinical practice SO CLINICAL JOURNAL OF PAIN LA English DT Editorial Material C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19014 USA. Univ Penn, Dept Anesthesiol, Philadelphia, PA 19014 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19014 USA. RP Gallagher, RM (reprint author), Univ Penn, Vet Affairs Med Ctr, Woodland Ave, Philadelphia, PA 19014 USA. EM rgallagh@mail.med.upenn.edu NR 1 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD JAN PY 2006 VL 22 IS 1 SU S BP S1 EP S1 DI 10.1097/01.ajp.0000193828.45571.06 PG 1 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 001TB UT WOS:000234558200001 PM 16344608 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI Epidemiology of acute renal failure: The tip of the iceberg SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID MORTALITY; INSUFFICIENCY C1 VA Pittsburgh Healthcare Syst, Univ Dr Div, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr Div, Renal Sect, Room 7E123 111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 12 TC 29 Z9 31 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2006 VL 1 IS 1 BP 6 EP 7 DI 10.2215/CJN.01521005 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 106DA UT WOS:000242080000003 PM 17699185 ER PT J AU Temel, JS Pirl, WF Lynch, TJ AF Temel, Jennifer S. Pirl, William F. Lynch, Thomas J. TI Comprehensive symptom management in patients with advanced-stage non-small-cell lung cancer SO CLINICAL LUNG CANCER LA English DT Review DE anorexia; dyspnea; fatigue; pain; palliative care ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE PULMONARY-DISEASE; BODY-COMPOSITION CHANGES; MEGESTROL-ACETATE; WEIGHT-LOSS; AMBULATORY PATIENTS; DOUBLE-BLIND; SUBCUTANEOUS MORPHINE; EICOSAPENTAENOIC ACID AB Although we have made steady improvements in the survival rates of patients with advanced-stage lung cancer, the majority of patients still experience distress and suffering. Although the symptom burden is greatest in patients in the end stages of life, many patients living with lung cancer suffer from troubling symptoms and side effects of therapy. Even long-term survivors with early-stage non-small-cell lung cancer (NSCLC) often experience respiratory symptoms, such as dyspnea and cough. Because of the high prevalence of NSCLC and the frequency with which it presents in an incurable stage, symptom management is a large component of the care of these patients. Dyspnea, cough, fatigue, anorexia/cachexia, and pain are the most common symptoms in patients with advanced-stage NSCLC. Cancer-directed therapy can improve some of these symptoms but often incompletely and temporarily. Therefore, comprehensive care of patients with advanced-stage NSCLC must include therapies targeted at these difficult and distressing symptoms. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,Yawkey Bldg,7th Floor, Boston, MA 02114 USA. EM jtemel@partners.org NR 116 TC 40 Z9 40 U1 4 U2 7 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JAN PY 2006 VL 7 IS 4 BP 241 EP 249 DI 10.3816/CLC.2006.n.001 PG 9 WC Oncology SC Oncology GA 106CK UT WOS:000242078400002 PM 16512977 ER PT J AU Dransfield, MT Lock, BJ Graver, RI AF Dransfield, Mark Thomas Lock, Brion Jacob Graver, Robert I., Jr. TI Improving the lung cancer resection rate in the US Department of Veterans Affairs Health System SO CLINICAL LUNG CANCER LA English DT Article DE diagnosis; non-small-cell lung cancer; practice organization; thoracic surgery ID POSITRON-EMISSION-TOMOGRAPHY; STAGE-I; SURGICAL RESECTION; CELL; CARCINOMA; SURVIVAL; MANAGEMENT; DIAGNOSIS; PROGNOSIS; SURGERY AB BACKGROUND: The optimal treatment for non-small-cell lung cancer (NSCLC) is surgical resection; however, most patients are ineligible because of advanced disease. Although resection rates of 25%, have been reported nationally, rates in the Veterans Affairs (VA) system appear lower, perhaps because of limited access to specialized care. We hypothesized that, since the introduction of a specialized Lung Mass Clinic in 1999, the resection rate at the Birmingham VA Medical Center would be comparable with US benchmarks. We also sought to identify the medical and nonmedical factors that influenced the use of surgery. PATIENTS AND METHODS: We reviewed the electronic medical records of all veterans seen in the Lung Mass Clinic from 1999 to 2003 and identified patients with NSCLC. Demographics, comorbidities, diagnostic methods, times to diagnosis/resection, and postoperative survival were recorded. Reasons for nonresection were documented and tabulated, and differences between the resected and nonresected subgroups were examined. RESULTS: One hundred fifty-six patients with NSCLC were identified, and 31 (20%) underwent resection. There were no differences in age, ethnicity, or sex between those undergoing resection and those denied surgery. Patients who underwent resection were less likely to have chronic obstructive pulmonary disease and had better pulmonary function. Eighty-four percent of those who did not undergo resection had advanced disease, poor pulmonary function, or had refused therapy. Although the median time to resection was longer than expected (104 days), overall survival was comparable with other reports (65% at 3 years). CONCLUSION: Since the inception of the Lung Mass Clinic, the resection rate at Birmingham VA Medical Center has improved. The primary limitation to resection was late presentation and not preoperative delays. C1 Birmingham Vet Affairs Med Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Dransfield, MT (reprint author), Birmingham Vet Affairs Med Ctr, Div Pulm Allergy & Crit Care Med, 215 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. EM mdransfield99@msn.com NR 27 TC 20 Z9 20 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JAN PY 2006 VL 7 IS 4 BP 268 EP 272 PG 5 WC Oncology SC Oncology GA 106CK UT WOS:000242078400006 PM 16512981 ER PT J AU Palsson, R Laliberte, KA Niles, JL AF Palsson, R Laliberte, KA Niles, JL TI Choice of replacement solution and anticoagulant in continuous venovenous hemofiltration SO CLINICAL NEPHROLOGY LA English DT Article; Proceedings Paper CT World Congress of Nephrology CY SEP, 2001 CL San Francisco, CA SP ASN, ISN DE anticoagulation; citrate; continuous renal replacement therapy (CRRT); continuous venovenous hemofiltration (CVVH); replacement fluid ID REGIONAL CITRATE ANTICOAGULATION; ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; HEMODIALYSIS; HEMODIAFILTRATION; DIALYSATE; THERAPY; HEPARIN; THROMBOCYTOPENIA; FLUIDS AB Background: Several types of replacement fluid and methods of anticoagulation have been employed for continuous renal replacement therapy, but there is no consensus on a preferred approach. We evaluated the indications for the selection of replacement fluid and anticoagulant among critically ill patients receiving continuous venovenous hemofiltration (CVVH) and assessed the effect of the selection on the efficacy of anticoagulation and complications. Methods: We retrospectively studied 29 consecutive patients who received CVVH in the Medical Intensive Care Unit at Massachusetts General Hospital. There were 3 types of replacement solution available, an isotonic citrate solution which was also used for regional anticoagulation of the extracorporeal circuit, and bicarbonate and lactate solutions which were used with low-dose heparin or no anticoagulant. Blood flow rate was set at 120 ml/min when citrate replacement fluid was used and at 200 ml/min with bicarbonate or lactate. The replacement fluid was administered proximal to the hemofilter at a constant rate of 1,600 ml/h. Results: There were 22 patients who received citrate replacement fluid which was mainly chosen for the purpose of anticoagulation in the setting of contraindications to heparin. 12 patients received bicarbonate, predominantly when citrate was considered contraindicated due to liver failure or high-anion gap metabolic acidosis, and 2 received lactate; 8 of these 14 patients were anticoagulated with heparin and 6 were managed without anticoagulation. There were 44 filters used in the patients receiving citrate with a median filter life of 42.0 (interquartile range 22.2-70.7) hours. Only 8 of the 44 filters were lost due to clotting. Heparin was used for anticoagulation of 17 filters and no anticoagulation was used in the case of 15 filters, resulting in a median filter life of 43.0 (13.5-75.0) and 12.0 (4.0-33.0) hours, respectively. Clinically significant bleeding occurred in 2 patients, 1 receiving citrate and another receiving heparin. No patient had evidence for citrate toxicity, metabolic alkalosis or hypernatremia. 14 (48.3%) patients survived. Conclusions: The use of regional citrate anticoagulation of the CVVH circuit appears advantageous in patients with increased risk of bleeding and bicarbonate-based replacement fluid seems desirable in patients with lactic acidosis due to shock and/or severe liver failure. Tailoring the type of replacement fluid and method of anticoagulation to the individual patient leads to long filter lives, excellent metabolic control and minimal complications. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Landspitali Univ Hosp, Div Nephrol, Reykjavik, Iceland. Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland. Massachusetts Gen Hosp, Med Intens Care 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, Renal Unit, Bartlett 901,55 Fruit St, Boston, MA 02114 USA. EM JLNiles@Partners.org NR 24 TC 10 Z9 15 U1 1 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JAN PY 2006 VL 65 IS 1 BP 34 EP 42 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 000RH UT WOS:000234479600006 PM 16429840 ER PT J AU Siefert, CJ Hilsenroth, MJ Weinberger, J Blagys, MD Ackerman, SJ AF Siefert, CJ Hilsenroth, MJ Weinberger, J Blagys, MD Ackerman, SJ TI The relationship of patient defensive functioning and alliance with therapist technique during short-term psychodynamic psychotherapy SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article ID BRIEF DYNAMIC PSYCHOTHERAPY; CHILDHOOD SEXUAL-ABUSE; IV AXIS-V; DSM-IV; THERAPEUTIC ALLIANCE; TRANSFERENCE INTERPRETATIONS; PSYCHOLOGICAL-ASSESSMENT; PERSONALITY-DISORDERS; DISCRIMINANT VALIDITY; WORKING ALLIANCE AB This study investigates the relationship of patient defensive functioning, therapeutic alliance and therapists' use of technical interventions in Short-Term Psychodynamic Psychotherapy (STPP; Book, 1998; Luborsky, 1984; Strupp & Binder, 1984; Wachtel, 1993). Participants in this study were 44 patients admitted for individual psychotherapy at a university based outpatient community clinic. Patient defensive functioning was assessed with the Defensive Functioning Scale (DFS) of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). Therapeutic alliance was assessed using patient ratings from the Combined Alliance Short Form (CASF; Hatcher & Barends, 1996). External raters coded videotaped sessions using the Comparative Psychotherapy Process Scale (CPPS; Hilsenroth, Blagys, Ackerman Bonge & Blais, in press) to assess the use of Psychodynamic-Interpersonal (PI) and Cognitive-Behavioral (CB) techniques early (third or fourth session) in psychotherapy. Patient Overall Defensive Functioning (ODF) was found to predict therapists' overall use of PI interventions, as well as specific PI and CB interventions. Additionally, patients who utilized fewer adaptive defenses were found to receive more PI interventions in general. The implications of these findings for treatment planning and intervention are discussed. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. Austen Riggs Ctr Inc, Erik Erikson Inst, Stockbridge, MA USA. RP Siefert, CJ (reprint author), 10 Wellington Apt B, Boston, MA 02118 USA. EM csiefert17@yahoo.com NR 77 TC 16 Z9 16 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD JAN-FEB PY 2006 VL 13 IS 1 BP 20 EP 33 DI 10.1002/cpp.469 PG 14 WC Psychology, Clinical SC Psychology GA 013LX UT WOS:000235411900003 ER PT J AU McNamara, P Durso, R Harris, E AF McNamara, Patrick Durso, Raymon Harris, Erica TI Life goals of patients with Parkinson's disease: a pilot study on correlations with mood and cognitive functions SO CLINICAL REHABILITATION LA English DT Article ID ANXIETY STRESS SCALES; DEPRESSION; REHABILITATION; SAMPLE AB Objective: To identify the life goals of people with Parkinson's disease, to assess whether patients felt that these goals were 'on track', and to assess the relation of these life goals to neuropsychologic and mood function. Design: Cross-sectional descriptive study with an age-matched control group. Setting: Outpatient Movement Disorders Clinics Veterans Hospital. Subjects: Twenty-two patients with mid-stage Parkinson's disease and 22 age-matched controls. Measures: Rivermead Life Goals Inventory, neuropsychological and mood scales. Results: People with Parkinson's disease were less likely than age-matched controls to cite religion, social contacts, leisure activities and personal care as 'extremely important life goals'. People with Parkinson's disease assigned significantly lower 'importance' ratings to leisure activities and religion than did controls. In addition, people with Parkinson's disease assigned significantly lower 'on track' ratings for leisure activities, work, social contacts, religion and financial affairs compared with controls' rating on the same items. Although people with Parkinson's disease showed significantly greater levels of cognitive and mood dysfunction than did controls, their mean importance ratings on life goals correlated only with mood function scores. Conclusions: The leisure activities, work, social contacts, religion and financial affairs of people with Parkinson's disease are less 'on track' than are their personal and family relationships. Subjective importance ratings of particular life goals of people with Parkinson's disease were found to be significantly related to mood function and not to cognitive function. Goal derailment ratings on the other hand were significantly related to both mood and cognitive impairment. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. RP McNamara, P (reprint author), VA Boston Healthcare Syst, Dept Neurol 127, 150 S Huntington Ave, Boston, MA 02130 USA. EM mcnamar@bu.edu NR 16 TC 16 Z9 16 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-2155 J9 CLIN REHABIL JI Clin. Rehabil. PY 2006 VL 20 IS 9 BP 818 EP 826 DI 10.1177/0269215506070811 PG 9 WC Rehabilitation SC Rehabilitation GA 101IL UT WOS:000241734400007 PM 17005505 ER PT J AU Mularski, RA Grazer, RE Santoni, L Strother, JS Bizovi, KE AF Mularski, RA Grazer, RE Santoni, L Strother, JS Bizovi, KE TI Treatment advice on the Internet leads to a life-threatening adverse reaction: Hypotension associated with niacin overdose SO CLINICAL TOXICOLOGY LA English DT Article DE niacin; nicotinic acid; overdose; poisoning; critical care; Internet; dietary supplement; over-the-counter; hypotension; schizophrenia ID ALTERNATIVE MEDICAL THERAPIES; FULMINANT HEPATIC-FAILURE; NICOTINIC-ACID THERAPY; ADVISING PATIENTS; UNITED-STATES; COMPLEMENTARY; SCHIZOPHRENIA; PHYSICIAN; TRENDS AB We describe a case of massive oral niacin overdose that resulted in severe persistent hypotension without the manifestation of cutaneous flushing. This case is the highest overdose of niacin reported in the literature to date and the first time severe persistent hypotension has been attributed to niacin. A 56-year-old male with a history of schizophrenia presented to the emergency department after orally ingesting 11,000 mg of niacin. The patient cited an Internet resource that recommended high-dose niacin for therapy of schizophrenia as the reason for his ingestion. He stopped his psychiatric medications several weeks prior to his niacin overdose. At presentation, the patient was alert and normothermic. His pulse was 68 beats per minute and his blood pressure was initially 92/41 mmHg. Hypotension with a blood pressure of 58/40 developed over the next few hours and persisted despite intravenous infusion of over 4 liters of normal saline. The physical exam was otherwise unremarkable, specifically without signs of an allergic reaction or cutaneous flushing. He required intravenous dopamine infusion for 12 hours to support a mean arterial blood pressure greater than 60 mmHg. Evaluation for other etiologies of hypotension was unrevealing. Serum niacin levels were 8.2 ug/mL and 5.6 ug/mL at 48 and 96 hours post ingestion, respectively, giving an apparent T1/2 of 87 hours. Massive overdose of niacin appears to be capable of causing severe, persistent hypotension in the absence of cutaneous flushing. In this case, the ingestion of a dietary supplement based on Internet advice led to a severe adverse reaction. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RAND Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90073 USA. Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. RP Mularski, RA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd Mailcode 111G, Los Angeles, CA 90073 USA. EM rmularsk@ucla.edu NR 36 TC 6 Z9 6 U1 6 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0731-3810 J9 CLIN TOXICOL JI Clin. Toxicol. PY 2006 VL 44 IS 1 BP 81 EP 84 DI 10.1080/15563650500394928 PG 4 WC Toxicology SC Toxicology GA 011OY UT WOS:000235279100012 PM 16496499 ER PT J AU Shimizu, A Yamada, K AF Shimizu, A Yamada, K TI Pathology of renal xenograft rejection in pig to non-human primate transplantation SO CLINICAL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 9th Japanese Clinico-Pathological Conference on Renal Allorgragft Pathology CY JUL 09, 2005 CL Tokyo, JAPAN DE acute cellular xenograft rejection; acute humoral xenograft rejection; baboon; chronic xenograft rejection; endothelial cells; hyperacute rejection; pig; xenotransplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; EPITOPE-MEDIATED ACTIVATION; AORTIC ENDOTHELIAL-CELLS; HEART-TRANSPLANTATION; MINIATURE SWINE; PORCINE KIDNEY; CARDIAC XENOGRAFTS; THYMIC TISSUE; XENOTRANSPLANTATION; BABOONS AB Xenotransplantation has the potential to alleviate the critical shortage of organs for transplantation in humans. Miniature swine are a promising donor species for xenotransplantation. However, when swine organs are transplanted into primates, hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR), and chronic xenograft rejection prevent successful engraftment. Developing a suitable regimen for preventing xenograft rejection requires the ability to accurately diagnosis the severity and type of rejection in the graft. For this purpose, histopathology remains the most definitive and reliable tool. We discuss here the characteristic features of xenograft rejection in a preclinical pig-to-non-human primate transplantation model. In miniature swine to baboon xenotransplantation, marked interstitial hemorrhage develops in HAR, and renal microvascular injury develops with multiple platelet-fibrin microthrombi in both HAR and AHXR. T-cell-mediated cellular immunity plays an important role in ACXR. Chronic humoral and cellular rejection may induce chronic xenograft rejection, and will be a major cause of graft loss in discordant xenotransplantation. C1 Nippon Med Coll, Dept Pathol, Bunkyo Ku, Tokyo 1138602, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Shimizu, A (reprint author), Nippon Med Coll, Dept Pathol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan. FU NIAID NIH HHS [5P01AI45897, 5R01AI31046, 5P01AI39755] NR 52 TC 16 Z9 17 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PY 2006 VL 20 SU 15 BP 46 EP 52 DI 10.1111/j.1399-0012.2006.00550.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 058HP UT WOS:000238656400010 PM 16848876 ER PT J AU Baker, SG Kramer, BS McIntosh, M Patterson, BH Shyr, Y Skates, S AF Baker, SG Kramer, BS McIntosh, M Patterson, BH Shyr, Y Skates, S TI Evaluating markers for the early detection of cancer: overview of study designs and methods SO CLINICAL TRIALS LA English DT Review ID PROSTATE-SPECIFIC ANTIGEN; BREAST-CANCER; SCREENING STRATEGIES; EARLY INTERVENTION; DIAGNOSTIC-TESTS; CUMULATIVE RISK; OVARIAN-CANCER; FECAL DNA; BIOMARKERS; EFFICACY AB Background: The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. Purpose: To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. Methods: We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. Results: For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Conclusion: Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention. C1 Natl Inst Hlth, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Baker, SG (reprint author), NCI, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 76 TC 45 Z9 46 U1 2 U2 10 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 1 BP 43 EP 56 DI 10.1191/1740774506cn130oa PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 017XJ UT WOS:000235726300005 PM 16539089 ER PT J AU Espeland, MA Dotson, K Jaramillo, SA Kahn, SE Harrison, B Montez, M Foreyt, JP Montgomery, B Knowler, WC AF Espeland, M. A. Dotson, K. Jaramillo, S. A. Kahn, S. E. Harrison, B. Montez, M. Foreyt, J. P. Montgomery, B. Knowler, W. C. CA Look Ahead Res Grp TI Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD) SO CLINICAL TRIALS LA English DT Article ID INFORMED CONSENT; RECRUITMENT; POPULATION; SAMPLES; COHORT AB Background: Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. Purpose and methods: We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. Results: IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. Limitations: The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. Conclusions: Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships. C1 Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NIDDK, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Baylor Coll Med, Behav Med Res Ctr, Houston, TX 77030 USA. NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Espeland, MA (reprint author), Wake Forest Univ, Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mespelan@wfubmc.edu OI Kriska, Andrea/0000-0002-3522-0869; Kahn, Steven/0000-0001-7307-9002; Redmon, J. Bruce/0000-0002-1883-9467 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR000051, M01 RR000056, M01 RR000056 44, M01 RR000211, M01 RR00051, M01 RR001066, M01 RR002719, M01-RR-01066, M01-RR-02719, M01RR00211-40]; NIDDK NIH HHS [DK57154, DK 046204, DK56990, DK56992, DK57002, DK57008, DK57078, DK57131, DK57135, DK57136, DK57149, DK57151, DK57171, DK57177, DK57178, DK57182, DK57219, P30 DK046204, P30 DK048520, P30DK48520, U01 DK056990, U01 DK056992, U01 DK057002, U01 DK057008, U01 DK057078, U01 DK057131, U01 DK057135, U01 DK057136, U01 DK057136-09, U01 DK057149, U01 DK057151, U01 DK057154, U01 DK057171, U01 DK057177, U01 DK057178, U01 DK057182, U01 DK057219] NR 25 TC 21 Z9 21 U1 2 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 5 BP 443 EP 456 DI 10.1177/1740774506070727 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 109TK UT WOS:000242331500004 PM 17060218 ER PT J AU Brandt, DK Hind, JA Robbins, J Lindblad, AS Gensler, G Gill, G Baum, H Lilienfeld, D Logemann, JA AF Brandt, Diane K. Hind, Jacqueline A. Robbins, JoAnne Lindblad, Anne S. Gensler, Gary Gill, Gary Baum, Herb Lilienfeld, David Logemann, Jeri A. CA Commun Sciences Disorders Clinical TI Challenges in the design and conduct of a randomized study of two interventions for liquid aspiration SO CLINICAL TRIALS LA English DT Article ID PRACTICAL CLINICAL-TRIALS; INFORMED-CONSENT; OLDER-PEOPLE; RISK-FACTORS; ELDERLY PATIENTS; PNEUMONIA; CARE; MORTALITY; DISEASE; RECOMMENDATIONS AB Background. Liquid aspiration during swallowing has been linked to pneumonia, the most common cause of infectious death in the elderly. This paper examines the key issues in the design and implementation of the first multisite, randomized behavioral trial in dysphagia in an aging population. The study evaluated two commonly used treatments with respect to short-term and long-term management of liquid aspiration and subsequent pneumonia in dysphagic geriatric participants with dementia and/or Parkinson's disease. Methods. Discussed are lessons learned during the conduct of this trial and include (1) ethical and methodological design issues, (2) pragmatic implementation of procedures and forms, (3) importance of multiple communication and monitoring strategies, (4) response to funding issues, and (5) changes in staff and facilities. Results. In order to complete this trial the researchers were required to provide more support than anticipated in tasks such as completion of regulatory requirements by sites, supplementing site staff to identify potential study participants using a 'circuit rider' approach, continued recruitment of new sites and staff throughout the course of the trial, adapting forms and procedures and managing within economic constraints in a changing trial environment. Limitations. Many of the challenges faced by the researchers were not anticipated when the study began. Successful strategies are described for these unanticipated difficulties, based on retrospective evaluation. Conclusions. Successful conduct of clinical trials in long-term care environments that are heavily impacted by changes extraneous to the trial design and with staff typically new to clinical trials is possible but success depends on logistical flexibility. C1 EMMES Corp, Rockville, MD USA. Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. ORC Macro, Calverton, MD USA. Prot Design Labs Inc, Fremont, CA USA. Northwestern Univ, Chicago, IL 60611 USA. RP Brandt, DK (reprint author), CSDRG Stat & Data Ctr, Commun Sci & Disorders Clin Trials Res Grp, 401 N Washington St,Suite 700, Rockville, MD 20850 USA. EM dbrandt@emmes.com OI Tuite, Paul/0000-0003-1413-7924 FU NIDCD NIH HHS [DC03206] NR 54 TC 12 Z9 12 U1 1 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 5 BP 457 EP 468 DI 10.1177/1740774506070731 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 109TK UT WOS:000242331500005 PM 17060219 ER PT J AU Masand, PS Keuthen, NJ Gupta, S Virk, S Yu-Siao, B Kaplan, D AF Masand, PS Keuthen, NJ Gupta, S Virk, S Yu-Siao, B Kaplan, D TI Prevalence of irritable bowel syndrome in obsessive-compulsive disorder SO CNS SPECTRUMS LA English DT Article ID GASTROINTESTINAL SYMPTOMS; RECEPTOR; GUT; DERIVATIVES; SEROTONIN; ANXIETY AB Introduction: Irritable bowel syndrome (IBS) occurs more frequently in psychiatric patients, especially those with anxiety and mood disorders. Methods: We sought to determine the prevalence and phenomenology of IBS in patients diagnosed with obsessive-compulsive disorder (OCD). A semi-structured diagnostic interview was administered to patients seeking treatment for OCD in outpatient settings. Structured questions regarding gastrointestinal functioning and IBS symptoms were administered. IBS was diagnosed by a gastroenterologist using Rome I criteria. Results: Thirty-seven patients (35.1%) with OCD met criteria for IBS. Of these, 53.8% had IBS with both diarrhea and constipation, 30.8% had diarrhea-predominant IBS, and 15.4% had constipation-predominant IBS. The prevalence rate of IBS in an age- and sex-matched control group (n=40) of medical patients in a family practice was 2.5%. IBS prevalence rates were significantly higher for OCD patients than control subjects (P=.0002). Conclusion: IBS and psychiatric illness have high rates of bi-directional comorbidity. This study shows that 35.1% of patients with OCID satisfied criteria for IBS in contrast to 2.5% of the controlled subjects. In most patients the IBS was characterized by both diarrhea and constipation. While taking the initial history clinicians should inquire about bowel symptoms in patients presenting with psychiatric illnesses, including OCD. SSRIs could potentially worsen such symptoms and lead to non-adherence. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Olean Gen Hosp, Dept Psychiat, New York, NY USA. SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. Syracuse Gastroenterol Associates, New York, NY USA. RP Masand, PS (reprint author), 110 Swift Ave,Suite 1, Durham, NC 27705 USA. EM pmasand@psycbcme.net NR 32 TC 14 Z9 16 U1 0 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JAN PY 2006 VL 11 IS 1 BP 21 EP 25 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 007LG UT WOS:000234969900009 PM 16400252 ER PT S AU Pierce, MC Shishkov, M Park, BH Nassif, N Bouma, BE Tearney, GJ De Boer, JF AF Pierce, Mark C. Shishkov, Milen Park, B. Hyle Nassif, Nader Bouma, Brett E. Tearney, Guillermo J. de Boer, Johannes F. BE Tuchin, VV Izatt, JA Fujimoto, JG TI Endoscopic polarization-sensitive optical coherence tomography - art. no. 607928 SO Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine X SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine X CY JAN 23-25, 2006 CL San Jose, CA SP SPIE DE birefringence; Poincare sphere; Stokes vector; optical imaging; osteoarthritis; vulnerable plaque ID HUMAN SKIN; BIREFRINGENCE; INTERFEROMETER; CATHETER; TISSUE AB Development of endoscope-compatible fiber-optic probes and polarization-sensitive detection schemes have each independently expanded the utility of optical coherence tomography. Several application areas have emerged which require polarization-sensitive measurements to be combined with endoscopic imaging techniques, in order to proceed to in vivo studies. Endoscopic-OCT typically requires a section of the sample arm fiber to be scanned during image acquisition, which produces a dynamically changing polarization state of light incident on the sample. Here, we demonstrate the effects of linear-scanning, and rotary-scanning probes in the sample arm of a PS-OCT system, and demonstrate the necessary modifications to be made for successful endoscopic PS-OCT imaging. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6121-0 J9 P SOC PHOTO-OPT INS PY 2006 VL 6079 BP 7928 EP 7928 AR 607928 DI 10.1117/12.649107 PG 6 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BEF80 UT WOS:000237132000056 ER PT J AU Hayes, GD Ruvkun, G AF Hayes, G. D. Ruvkun, G. TI Misexpression of the Caenorhabditis elegans miRNA let-7 is sufficient to drive developmental programs SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Proceedings Paper CT 71th Cold Spring Harbor Symposium on Quantitative Biology CY MAY 31-JUN 05, 2006 CL Cold Spring, NY ID SMALL TEMPORAL RNAS; C-ELEGANS; REGULATORY RNA; POSTTRANSCRIPTIONAL REGULATION; DROSOPHILA-MELANOGASTER; HETEROCHRONIC MUTANTS; REDUCED EXPRESSION; MICRORNA FAMILY; CELL LINEAGES; GENE AB The Caenorhabditis elegans microRNAs (miRNAs) lin-4 and let-7 promote transitions between stage-specific events in development by down-regulating the translation of their target genes. Expression of let-7 is required at the fourth larval stage for the proper transition from larval to differentiated, adult fates in the hypodermis; however, it was not known whether expression of let-7 is sufficient to specify these adult fates. To test this, we created fusion genes between lin-4 and let-7 that direct the expression of let-7 two stages early, at the L2 stage. We find that animals bearing the fusion genes show precocious adult development at the L4 stage, indicating that temporal misexpression of let-7 is sufficient to direct the larval-to-adult transition. Additionally, an RNA interference (RNAi)-based screen for enhancers of the precocious phenotype identified the period ortholog lin-42, among other genes, which are candidate modulators of the effects of let-7 expression. let-7 is conserved throughout bilaterian phylogeny, and orthologs of its targets have roles in vertebrate development, suggesting the importance of understanding how let-7 promotes terminal differentiation in C. elegans and other organisms. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Hayes, GD (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM44619] NR 41 TC 17 Z9 39 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2006 VL 71 BP 21 EP 27 DI 10.1101/sqb.2006.71.018 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 160SO UT WOS:000245962800004 PM 17381276 ER PT J AU Anguera, MC Sun, BK Xu, N Lee, JT AF Anguera, M. C. Sun, B. K. Xu, N. Lee, J. T. TI X-chromosome kiss and tell: How the Xs go their separate ways SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Proceedings Paper CT 71th Cold Spring Harbor Symposium on Quantitative Biology CY MAY 31-JUN 05, 2006 CL Cold Spring, NY ID IMPRINTED XIST EXPRESSION; INACTIVATION CENTER; TSIX TRANSCRIPTION; DROSOPHILA-MELANOGASTER; HETEROCHROMATIC GENES; DOSAGE COMPENSATION; RNA STABILIZATION; COUNTING PROCESS; METHYLATION; MOUSE AB Loci associated with noncoding RNAs have important roles in X-chromosome inactivation (XCI), the dosage compensation mechanism by which one of two X chromosomes in Female cells becomes transcriptionally silenced. The Xs start out as epigenetically equivalent chromosomes, but XCI requires a cell to treat two identical X chromosomes in completely different ways: We X chromosome must remain transcriptionally active while the other becomes repressed. In the embryo of eutherian mamma s. the choice to inactivate the maternal or paternal X chromosome is random. The fact that the Xs always adopt opposite fates hints at the existence of a trans-sensing mechanism to ensure the mutually exclusive silencing of one of the two Xs. This paper highlights recent evidence supporting a model for mutually exclusive choice that involves homologous chromosome pairing and the placement of asymmetric chromatin marks on the two Xs. C1 Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol,Howard Hughe, Boston, MA 02114 USA. RP Anguera, MC (reprint author), Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol,Howard Hughe, Boston, MA 02114 USA. OI Sun, Bryan/0000-0002-0740-0125 FU NIGMS NIH HHS [GM076955-01] NR 76 TC 20 Z9 22 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2006 VL 71 BP 429 EP 437 DI 10.1101/sqb.2006.71.012 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 160SO UT WOS:000245962800054 PM 17381325 ER PT J AU Matthews, AG Betensky, RA Anton-Culver, H Bowen, D Griffin, C Isaacs, C Kasten, C Mineau, G Nayfield, S Schildkraut, J Strong, L Weber, B Finkelstein, DM AF Matthews, AG Betensky, RA Anton-Culver, H Bowen, D Griffin, C Isaacs, C Kasten, C Mineau, G Nayfield, S Schildkraut, J Strong, L Weber, B Finkelstein, DM TI Analysis of co-aggregation of cancer based on registry data SO COMMUNITY GENETICS LA English DT Article DE familial aggregation; association; family study; Cancer Genetics Network ID COLORECTAL-CANCER; OVARIAN-CANCER; FAMILY-HISTORY; LUNG-CANCER; BREAST; SUSCEPTIBILITY; RISKS; AGGREGATION; LEUKEMIA; MODELS AB Objective: An exploratory analysis of co-aggregation of cancers using registry-based data. Methods:We utilized sibships from over 18,000 families who had been recruited to the NCI-sponsored multi-institutional Cancer Genetics Network. The analysis assesses co-aggregation at the individual and family level and adjusts for ascertainment. Results: We found statistically significant familial co-aggregation of lung cancer with pancreatic (adjusted p < 0.001), prostate (adjusted p < 0.003), and colorectal cancers (adjusted p = 0.004). In addition, we found significant familial co-aggregation of pancreatic and colorectal cancers (adjusted p = 0.018), and co-aggregation of hematopoietic and (non-ovarian) gynecologic cancers (adjusted p = 0.01). Conclusion: This analysis identified familial aggregation of cancers for which a genetic component has yet to be established. Copyright (C) 2006 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Calif Irvine, Irvine, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Johns Hopkins Univ, Baltimore, MD USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. EM dfinkelstein@partners.org FU NCI NIH HHS [CA 74302, CA 75971] NR 32 TC 3 Z9 3 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2006 VL 9 IS 2 BP 87 EP 92 DI 10.1159/000091485 PG 6 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 031EY UT WOS:000236688200003 PM 16612058 ER PT S AU Goransson, K Ehrenberg, A Ehnfors, M Fonteyn, M AF Goransson, Katarina Ehrenberg, Anna Ehnfors, Margareta Fonteyn, Marsha BE Park, HA Murray, P Delaney, C TI The use of qualitative data analysis software (QDAS) to manage and support the analysis of think aloud (TA) data SO CONSUMER-CENTERED COMPUTER-SUPPPORTED CARE FOR HEALTHY PEOPLE SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 9th International Congress on Nursing Informatics CY 2006 CL Seoul, SOUTH KOREA SP Korean Soc Med Informat DE qualitative data analysis software; think aloud; method; protocol analysis; emergency care; triage ID DECISIONS AB This methodological paper describes how qualitative data analysis software (QDAS) is being used to manage and support a three-step protocol analysis (PA) of think aloud (TA) data in a study examining emergency nurses' reasoning during triage. The authors believe that QDAS program QRS NVivo (c) will greatly facilitate the PA and will allow them to identify and describe the information that triage nurses concentrate on during triage, and how they structure this information to make a triage decision. These findings could assist in designing and creating decision support systems to guide nurses' triaging. Additionally, details about how to use QRS NVivoo for PA of TA data may assist and guide future informatics research using similar methodology are presented here. This innovative use Of QDAS holds great promise for future nursing informatics research. C1 [Goransson, Katarina; Ehrenberg, Anna; Ehnfors, Margareta] Univ Orebro, Dept Hlth Sci, Orebro, Sweden. [Ehrenberg, Anna] Dalarno Univ, Dept Hlth & Social Sci, Falun, Sweden. [Fonteyn, Marsha] Dana Farber Canc Ctr, Boston, MA USA. RP Goransson, K (reprint author), Univ Orebro, Dept Hlth Sci, Orebro, Sweden. NR 8 TC 1 Z9 1 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-622-5 J9 STUD HEALTH TECHNOL PY 2006 VL 122 BP 143 EP + PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medical Informatics SC Computer Science; Medical Informatics GA BGD77 UT WOS:000246181100029 PM 17102236 ER PT S AU Mahoney, DF Tarlow, B AF Mahoney, Diane F. Tarlow, Barbara BE Park, HA Murray, P Delaney, C TI Workplace response to virtual caregiver support and remote home monitoring of elders: the WIN project SO Consumer-Centered Computer-Suppported Care for Healthy People SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 9th International Congress on Nursing Informatics CY 2006 CL Seoul, SOUTH KOREA SP Korean Soc Med Informat DE on-line support group; internet-based intervention; nursing informatics AB Research has demonstrated the health and financial cost to working caregivers of older adults and the cost to business in lost productivity. This paper describes the implementation of the Worker Interactive Networking (WIN) project, a Web-based program designed to support employed caregivers at work. WIN innovatively linked working caregivers via the Internet to home to monitor elders' status using wireless sensor technology and included an online information and support group for a six-month period. Twenty-seven employees from thirteen business sites participated Despite problems with wireless carrier service, feasibility outcomes were achieved We were able to collect six months of continuous real time data wirelessly from multiple types of homes across 4 states. This model demonstrates that businesses can offer a similar program and not be overwhelmed by employee demand or abuse of technology access. Reluctance to consider home monitoring was apparent and was influenced by familial relationships and values of privacy and independence. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Mahoney, DF (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. OI Mahoney, Diane/0000-0002-6415-475X NR 8 TC 8 Z9 8 U1 0 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-622-5 J9 ST HEAL T PY 2006 VL 122 BP 676 EP 680 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medical Informatics SC Computer Science; Medical Informatics GA BGD77 UT WOS:000246181100142 PM 17102349 ER PT J AU Gettings, EM Brush, KA Van Cott, EM Hurford, WE AF Gettings, Elise M. Brush, Kathryn A. Van Cott, Elizabeth M. Hurford, William E. TI Outcome of postoperative critically ill patients with heparin-induced thrombocytopenia: an observational retrospective case-control study SO CRITICAL CARE LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED HEPARIN; CARDIOPULMONARY BYPASS; DIAGNOSIS; FLUSHES; ANTIBODIES; MANAGEMENT; THROMBOSIS; SURGERY AB Introduction Heparin-induced thrombocytopenia ( HIT) is described as a decrease in platelet count associated with heparin administration and is an immune-mediated adverse drug reaction that can cause both arterial and venous thromboses. It can be a life-threatening complication of heparin exposure. Little data concerning incidence, predisposing factors, or outcome in critically ill surgical patients are available. Methods All critically ill, postoperative patients admitted between January 1, 2000, and December 31, 2001, to a surgical intensive care unit (SICU) who tested positive by an enzyme-linked immunosorbent assay for the HIT antibody ( HPIA; Diagnostica Stago, Inc., Parsippany, NJ, USA) were identified. Patient risk factors and outcomes were abstracted retrospectively from the medical record and compared with those from control patients matched for age, gender, diagnosis, severity of illness, and date of SICU admission. Results Two hundred and ten patients out of 2,046 patients (10%) admitted to the SICU had HIT assays performed. Nineteen patients (0.9% of admissions; 9% of tested individuals) had positive tests. HIT-antibody-positive patients, compared with 19 matched controls, had an increased risk of death or major thrombotic complications (37% versus 10%; P < 0.05) and prolonged length of intensive care unit (ICU) stay (20 days versus 10 days; P < 0.05). Exposure to heparin via intravascular flushes alone was sufficient to generate HIT antibodies in 12 of 19 (63%) patients. Five patients received platelet transfusions after the diagnosis of HIT was known; four of these patients died. Conclusion Heparin flushes were the most common cause of HIT in this study. HIT-antibody-positive patients had an increased risk of death or major complications and a prolonged length of ICU stay. Platelet transfusions often were administered despite a positive HIT test result and were associated with a high mortality rate. Treatment algorithms that minimize exposure to heparin and contraindicate platelet transfusions merit further study. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Clin Pathol, Boston, MA 02114 USA. RP Hurford, WE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM William.hurford@uc.edu RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 28 TC 21 Z9 22 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2006 VL 10 IS 6 AR R161 DI 10.1186/cc5100 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 185NU UT WOS:000247718500009 PM 17109753 ER PT J AU Januzzi, JL Morss, A Tung, R Pino, R Fifer, MA Thompson, BT Lee-Lewandrowski, E AF Januzzi, James L. Morss, Alexander Tung, Roderick Pino, Richard Fifer, Michael A. Thompson, B. Taylor Lee-Lewandrowski, Elizabeth TI Natriuretic peptide testing for the evaluation of critically ill patients with shock in the intensive care unit: a prospective cohort study SO CRITICAL CARE LA English DT Article ID PULMONARY-ARTERY CATHETERIZATION; HEART-FAILURE; HOSPITAL MORTALITY; BASE DEFICIT; APACHE-II; RISK; SEVERITY; SEPSIS; MARKER; DEATH AB Introduction Amino-terminal pro-brain natriuretic peptide (NTproBNP) is useful in evaluating heart failure, but its role in evaluating patients with shock in the intensive care unit (ICU) is not clear. Method Forty-nine consecutive patients in four different ICUs with shock of various types and with an indication for pulmonary artery catheter placement were evaluated. Analyses for NTproBNP were performed on blood obtained at the time of catheter placement and results were correlated with pulmonary artery catheter findings. Logistic regression identified independent predictors of mortality. Results A wide range of NT-proBNP levels were observed ( 106 to > 35,000 pg/ml). There was no difference in median NTproBNP levels between patients with a cardiac and those with a noncardiac origin to their shock ( 3,046 pg/ml versus 2,959 pg/ ml; P = 0.80), but an NT-proBNP value below 1,200 pg/ ml had a negative predictive value of 92% for cardiogenic shock. NTproBNP levels did not correlate with filling pressures or hemodynamics ( findings not significant). NT-proBNP concentrations were higher in patients who died in the ICU ( 11,859 versus 2,534 pg/ml; P = 0.03), and the mortality rate of patients in the highest log-quartile of NT-proBNP (66.7%) was significantly higher than those in other log-quartiles ( P < 0.001); NT-proBNP independently predicted ICU mortality ( odds ratio 14.8, 95% confidence interval 1.8 - 125.2; P = 0.013), and was superior to Acute Physiology and Chronic Health Evaluation II score and brain natriuretic peptide in this regard. Conclusion Elevated levels of NT-proBNP do not necessarily correlate with high filling pressures among patients with ICU shock, but marked elevation in NT-proBNP is strongly associated with ICU death. Low NT-proBNP values in patients with ICU shock identifed those at lower risk for death, and may be useful in excluding the need for pulmonary artery catheter placement in such patients. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pulm Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 27 TC 43 Z9 46 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2006 VL 10 IS 1 AR R37 DI 10.1186/cc4839 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 082JN UT WOS:000240382800037 PM 16507171 ER PT J AU Kacmarek, RM AF Kacmarek, Robert M. TI Ventilatory management of ARDS: high frequency oscillation and lung recruitment! SO CRITICAL CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; CONVENTIONAL MECHANICAL VENTILATION; GAS-EXCHANGE; INJURY AB Many aspects of ventilatory management in patients with ARDS are still controversial and one of the major controversies is should HFO or CMV ideally be used to manage this patients. As shown by David et al. when the two approaches to ventilatory support are applied using similar principles the physiologic outcomes appear to be similar. With both approaches the use of lung recruitment maneuvers early in ARDS ( 1 to 3 day) after hemodynamic stabilization in patients without baratrauma is promising. The key to managing ARDS regardless of mode is to use an open lung protective ventilatory strategy. It is not the mode that makes the difference, it is the approach used to apply the mode! C1 Massachusetts Gen Hosp, Harvard Med Sch & Resp Care, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Harvard Med Sch & Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 9 TC 1 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2006 VL 10 IS 4 AR 158 DI 10.1186/cc5018 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 185LK UT WOS:000247712300039 PM 16934131 ER PT J AU O'Mahony, DS Liles, WC Altemeier, WA Dhanireddy, S Frevert, CW Liggitt, D Martin, TR Matute-Bello, G AF O'Mahony, D. Shane Liles, W. Conrad Altemeier, William A. Dhanireddy, Shireesha Frevert, Charles W. Liggitt, Denny Martin, Thomas R. Matute-Bello, Gustavo TI Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction SO CRITICAL CARE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; LIPOPOLYSACCHARIDE-BINDING PROTEIN; EPITHELIAL-CELL APOPTOSIS; MITOCHONDRIAL DYSFUNCTION; INFLAMMATORY RESPONSE; EXPERIMENTAL-MODEL; CRITICAL ILLNESS; FAS CD95; IN-VIVO; LUNG AB Introduction Multiple organ dysfunction syndrome ( MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. Methods We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 mu g/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg ( LPS + MV). Comparison groups received ventilation but no LPS ( MV), LPS but no ventilation ( LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). Results Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-alpha. Conclusion Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury. C1 Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. RP Matute-Bello, G (reprint author), Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. EM matuteb@u.washington.edu FU NHLBI NIH HHS [K08 HL070840, K08-HL70840, P50 HL073996, P50 HL73996] NR 28 TC 42 Z9 45 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2006 VL 10 IS 5 AR R136 DI 10.1186/cc5050 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 185NS UT WOS:000247718300012 PM 16995930 ER PT J AU Schoenfeld, D AF Schoenfeld, David TI Survival methods, including those using competing risk analysis, are not appropriate for intensive care unit outcome studies SO CRITICAL CARE LA English DT Editorial Material ID MODEL AB The preferred analysis for studies of mortality among patients treated in an intensive care unit should compare the proportions of patients who died during hospitalization. Studies that look for prognostic covariates should use logistic regression. Survival methods, such as the proportional hazards model, or methods based on competing risk analysis are not appropriate because prolonged survival among patients that die during their hospitalization does not benefit the patient and, therefore, should not be measured in the statistical analysis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02114 USA. RP Schoenfeld, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Staniford St, Boston, MA 02114 USA. EM dschoenfeld@partners.org FU NHLBI NIH HHS [N01HR46064, HR-46064] NR 7 TC 21 Z9 21 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2006 VL 10 IS 1 AR 103 DI 10.1186/cc3949 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 082JN UT WOS:000240382800042 PM 16420653 ER PT J AU Hess, DR Thompson, BT AF Hess, DR Thompson, BT TI Patient-ventilator dyssynchrony during lung protective ventilation: What's a clinician to do? SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACUTE RESPIRATORY-DISTRESS; PRESSURE SUPPORT VENTILATION; MECHANICAL VENTILATION; ASSISTED VENTILATION; INJURY; MORTALITY; SEDATION; PATTERN; MODES; WORK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 26 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2006 VL 34 IS 1 BP 231 EP 233 DI 10.1097/01.CCM.0000196083.45897.E9 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 999IB UT WOS:000234381900033 PM 16374181 ER PT J AU Chen, B Pogue, BW Hoopes, PJ Hasan, T AF Chen, Bin Pogue, Brian W. Hoopes, P. Jack Hasan, Tayyaba TI Vascular and cellular targeting for photodynamic therapy SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE photodynamic therapy (PDT); photosensitizer; vascular targeting; cellular targeting; targeted therapy; drug delivery ID MOUSE-TUMOR MODEL; GROWTH-FACTOR RECEPTOR; ASPARTYL CHLORIN E6; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; INTERNALIZING MONOCLONAL-ANTIBODIES; WATER-SOLUBLE PHOTOSENSITIZER; ETHYL ETIOPURPURIN SNET2; OVARIAN-CANCER MODEL; OF-THE-ART; IN-VIVO AB Photodynamic therapy (PDT) involves the combination of photosensitizers (PS) with light as a treatment, and has been an established medical practice for about 10 years. Current primary applications of PDT are age-related macular degeneration (AMD) and several types of cancer and precancer. Tumor vasculature and parenchyma cells are both potential targets of PDT damage. The preference of vascular versus cellular targeting is highly dependent upon the relative distribution of photosensitizers in each compartment, which is governed by the photosensitizer pharmacokinetic properties and can be effectively manipulated by the photosensitizer drug administration and light illumination interval (drug-light interval) during PDT treatment, or by the modification of photosensitizer molecular structure. PDT using shorter PS-light intervals mainly targets tumor vasculature by confining photosensitizer localization within blood vessels, whereas if the sensitizer has a reasonably long pharmacokinetic lifetime, then PDT at longer PS-light intervals can induce more tumor cellular damage, because the photosensitizer has then distributed into the tumor cellular compartment. This passive targeting mechanism is regulated by the innate photosensitizer physicochemical properties. In addition to the passive targeting approach, active targeting of various tumor endothelial and cellular markers has been studied extensively. The tumor cellular markers that have been explored for active photodynamic targeting are mainly tumor surface markers, including growth factor receptors, low-density lipoprotein (LDL) receptors, transferrin receptors, folic acid receptors, glucose transporters, integrin receptors, and insulin receptors. In addition to tumor surface proteins, nuclear receptors are targeted, as well. A limited number of studies have been performed to actively target tumor endothelial markers (ED-B domain of fibronectin, VEGF receptor-2, and neuropilin-1). Intracellular targeting is a challenge due to the difficulty in achieving sufficient penetration into the target cell, but significant progress has been made in this area. In this review, we summarize current studies of vascular and cellular targeting of PDT after more than 30 years of intensive efforts. C1 Harvard Univ, Wellman Ctr Photomed, Dept Dermatol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. Univ Sci Philadelphia, Coll Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19104 USA. Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Surg, Lebanon, NH 03756 USA. RP Hasan, T (reprint author), Harvard Univ, Wellman Ctr Photomed, Dept Dermatol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. EM thasan@partners.org FU NCI NIH HHS [P01CA84203] NR 158 TC 121 Z9 129 U1 8 U2 49 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 2006 VL 16 IS 4 BP 279 EP 305 PG 27 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 113PD UT WOS:000242608900001 PM 17206921 ER PT J AU Fagerlie, SR Bagby, GC AF Fagerlie, SR Bagby, GC TI Immune defects in Fanconi anemia SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Review DE aplastic anemia; immunodeficiency; T cell; tumor surveillance; chromosomal instability ID TUMOR-NECROSIS-FACTOR; DEPENDENT PROTEIN-KINASE; GROUP-C GENE; DOUBLE-STRANDED-RNA; HEMATOPOIETIC PROGENITOR CELLS; INDUCED APOPTOTIC RESPONSES; HUMAN-PAPILLOMAVIRUS HPV; NF-KAPPA-B; NATURAL-KILLER; INTERFERON-GAMMA AB Fanconi anemia (FA) is a genetic disorder characterized by sensitivity to DNA cross-linking agents, multiple congenital anomalies, progressive bone marrow failure, and an increased prevalence of malignancy. The nature of chromosomal instability in FA is better understood today than in the past, but the molecular pathogenesis of bone marrow failure in this disease has not been clarified. Although there is documented evidence that FA hematopoietic stem cells (HSC) have inherent defects that reduce their survival, the potential influence of auxiliary cells on the ability of the FA bone marrow microenvironment to maintain and support HSC in unknown. Historically, FA has not been represented as a disease that affects the lymphoid compartment. In this article we review the results of studies that suggest that the FA immune system is dysfunctional and may contribute to the pathogenesis of both FA bone marrow failure and neoplastic disease. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Transplantat Biol Program, Seattle, WA 98109 USA. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Fagerlie, SR (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, Transplantat Biol Program, D1-100,1100 Fairview Ave N, Seattle, WA 98109 USA. EM sfagerli@fhcre.org OI Bagby, Grover/0000-0001-6830-2046 FU NCI NIH HHS [T32 CA080416] NR 137 TC 20 Z9 20 U1 0 U2 3 PU BEGELL HOUSE INC PI NEW YORK PA 145 MADISON AVE, STE 601, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2006 VL 26 IS 1 BP 81 EP 96 PG 16 WC Immunology SC Immunology GA 011DP UT WOS:000235248400004 PM 16472069 ER PT J AU Hock, H Orkin, SH AF Hock, H Orkin, SH TI Zinc-finger transcription factor Gfi-1: versatile regulator of lymphocytes, neutrophils and hematopoietic stem cells SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE Gfi-1; hematopoietic stem cells; lymphoid; myeloid; neutrophils; progenitor ID GROWTH-FACTOR INDEPENDENCE-1; BINDING-PROTEIN-EPSILON; ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL; REPRESSOR GFI1; C/EBP-ALPHA; LINEAGE COMMITMENT; TRANSGENIC MICE; DEFICIENT MICE; FACTOR PU.1 AB Purpose of review. Gfi-1, originally identified as a transcriptional repressor in lymphoid cells, is now recognized to have essential, independent functions in neutrophil maturation and hematopoietic stem cell biology. Here we review recent studies pertaining to Gfi-1 and its cell context specific functions in hematopoietic development. Recent findings. Progress in mapping the precise timing of requirements for myeloid transcription factors during hematopoietic development reveals a more refined picture of their sequence of action, We contrast Gfi-1's role in neutrophil development with PU.1, C/EBP alpha, and C/EBP epsilon. Gfi-1 has been found to be a major regulator of adult hematopoietic stem cells. It is required for restricting the proliferation of hematopoietic stem cells and maintaining their functional integrity. We discuss its role and compare its function with that of other regulators recently implicated in the biology of hematopoietic stem cells. Summary. Considerable progress has been made in understanding Gfi-1's context-sensitive roles at defined stages of hematopoietic differentiation. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Ctr Regenerat Med, Boston, MA 02114 USA. Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Hock, H (reprint author), Massachusetts Gen Hosp, Ctr Canc, Simches Bldg,CPZN 4200 4th Floor,185 Cambridge St, Boston, MA 02114 USA. EM hock.hanno@mgh.harvard.edu; stuart_orkin@dfci.harvard.edu NR 57 TC 56 Z9 58 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2006 VL 13 IS 1 BP 1 EP 6 DI 10.1097/01.moh.0000190111.85284.8f PG 6 WC Hematology SC Hematology GA 995CZ UT WOS:000234078800001 PM 16319680 ER PT J AU Afshar-Kharghan, V Thiagarajan, P AF Afshar-Kharghan, V Thiagarajan, P TI Leukocyte adhesion and thrombosis SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE leukocyte adhesion; microvesicles; selectins; thrombosis; tissue factor ID TISSUE-FACTOR; P-SELECTIN; PLATELET ACTIVATION; CATHEPSIN-G; ESSENTIAL THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; BLOOD-COAGULATION; FIBRIN DEPOSITION; FACTOR-VIIA; IN-VITRO AB Purpose of the review. The consequences of arterial thrombosis such as myocardial infarction, stroke and peripheral vascular occlusion are the leading causes of morbidity and mortality. A high leukocyte count and an elevation in inflammatory markers are identified as significant risk factors for thrombosis. Leukocytes form the front line in defense against infection and are the first cells arriving at the site of inflammation. This review summarizes the cellular and molecular mechanisms by which adherent leukocytes can induce a prothrombotic state. Recent findings. Circulating tissue factor has been recognized as a potential prothrombotic factor initiating thrombosis after vascular injury, The tissue factor is present on microvesicles originated from activated leukocytes. Leukocytes generate tissue factor containing microvesicles following stimulation with cytokines and following platelet adhesion via P-selectin. Additionally, activated leukocytes release several mediators, such as cathepsin G and elastase, which can activate both the coagulation cascade and platelets. Furthermore, new roles for leukocytes have been identified in vascular injury in sickle cell anemia, in vascular occlusion following the rupture of atherosclerotic plaque, and in thrombotic complications of myeloproliferative diseases. Summary. Leukocyte adhesion to endothelium and platelets plays an important role in the activation of the coagulation cascade. An excessive activation of leukocytes during the inflammatory process may induce a systemic procoagulant state. Elucidation of critical steps in activation of coagulation by leukocytes may offer a new therapeutic target for antithrombotic therapy based on blocking leukocyte adhesion. C1 Baylor Coll Med, Dept Pathol & Med Thrombosis Res, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Thiagarajan, P (reprint author), VA Med Ctr, Mail Stop 113,2002 Holcombe Blvd, Houston, TX 77030 USA. EM perumalt@bcm.tmc.edu OI Thiagarajan, Perumal/0000-0003-2186-7036 FU NHLBI NIH HHS [HL 65096] NR 49 TC 59 Z9 64 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2006 VL 13 IS 1 BP 34 EP 39 DI 10.1097/01.moh.0000190107.54790.de PG 6 WC Hematology SC Hematology GA 995CZ UT WOS:000234078800006 PM 16319685 ER PT J AU Martinez, V Tache, Y AF Martinez, V. Tache, Y. TI CRF1 receptors as a therapeutic target for irritable bowel syndrome SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE CRF; CRF receptors; CRF antagonists; IBS; stress; gastrointestinal; colon ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; UROCORTIN-LIKE IMMUNOREACTIVITY; STRESS-RELATED ALTERATIONS; LOCUS-COERULEUS NEURONS; PITUITARY-ADRENAL AXIS; COLONIC MOTOR FUNCTION; FACTOR MESSENGER-RNA; LONG-EVANS RATS; CRH-1-RECEPTOR ANTAGONIST R121919 AB The characterization of the corticotropin-releasing factor (CRF) family of neuroendocrine regulatory peptides, the cloning and pharmacological characterization of two CRF receptor subtypes (CRF1 and CRF2), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress and the potential involvement of the CRF system in different pathophysiological conditions, including functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and psychopathologies such as anxiety/depression. Compelling pre-clinical data showed that brain CRF administration mimics acute stress-induced colonic responses and enhances colorectal distension-induced visceral pain in rats through CRF1 receptors. Similarly, peripheral CRF reduced the pain threshold to colonic distension and increased colonic motility in humans and rodents. These observations mimic the manifestations of IBS, characterized by abdominal bloating/discomfort and altered bowel habits, Moreover, CRF-CRF1 pathways have been implicated in the development of anxiety/depression. These psychopathologies, together with stressful life events, have high comorbidity with IBS, and are considered significant components of the disease. From these observations, CRF1 receptors have been suggested as a target to treat IBS. Peripherally acting CRF1 antagonists might directly improve IBS symptoms, as related to motility, secretion and immune response. On the other hand, central actions will be beneficial as to prevent the psychopathologies that co-exist with IBS and as a way to modulate the central processing of stress- and visceral pain-related signals. Here, we review the pre-clinical and clinical data supporting these assumptions, and address the efforts done at a pharmaceutical level to develop effective therapies targeting CRF1 receptors for functional gastrointestinal disorders. C1 Univ Calif Los Angeles, Dept Med, W Los Angeles VA Med Ctr, Div Diges Dis,CURE,DDRCVA Greater Los Angeles Hea, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Ctr Neurovisceral Sci & Womens Hlth, W Los Angeles VA Med Ctr,Div Digest Dis, Los Angeles, CA 90073 USA. AstraZeneca R&D, Integrat Pharmacol Gastrointestinal Biol, Molndal, Sweden. RP Tache, Y (reprint author), Univ Calif Los Angeles, Dept Med, W Los Angeles VA Med Ctr, Div Diges Dis,CURE,DDRCVA Greater Los Angeles Hea, Bldg 115,Rm 117,11301 Wilshire blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIAMS NIH HHS [P50 AR-049550]; NIDDK NIH HHS [R01 DK-33061, R01 DK-57236, DK-41301] NR 246 TC 60 Z9 66 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 31 BP 4071 EP 4088 DI 10.2174/138161206778743637 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097ZG UT WOS:000241488300007 PM 17100612 ER PT S AU Bartlett, JD Ganss, B Goldberg, M Moradian-Oldak, J Paine, ML Snead, ML Wen, X White, SN Zhou, YL AF Bartlett, John D. Ganss, Bernhard Goldberg, Michel Moradian-Oldak, Janet Paine, Michael L. Snead, Malcolm L. Wen, Xin White, Shane N. Zhou, Yan L. BE Schatten, GP TI Protein-protein interactions of the developing enamel matrix SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 74 SE Current Topics in Developmental Biology LA English DT Review ID LINKED AMELOGENESIS IMPERFECTA; BIGLYCAN GENE-EXPRESSION; GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL INTERACTIONS; ATOMIC-FORCE MICROSCOPY; EMBRYONIC BOVINE ENAMEL; CELL-SURFACE EXPRESSION; MURINE MOLAR TOOTH; INCREASES OSTEOCLAST FORMATION; BONE MORPHOGENETIC PROTEINS AB Extracellular matrix proteins control the formation of the inorganic component of hard tissues including bone, dentin, and enamel. The structural proteins expressed primarily in the enamel matrix are amelogenin, ameloblastin, enamelin, and amelotin. Other proteins, like biglycan, are also present in the enamel matrix as well as in other mineralizing and nonmineralizing tissues of mammals. In addition, the presence of sulfated enamel proteins, and "tuft" proteins has been examined and discussed in relation to enamel formation. The structural proteins of the enamel matrix must have specific protein-protein interactions to produce a matrix capable of directing the highly ordered structure of the enamel crystallites. Protein-protein interactions are also likely to occur between the secreted enamel proteins and the plasma membrane of the enamel producing cells, the ameloblasts. Such protein-protein interactions are hypothesized to influence the secretion of enamel proteins, establish short-term order of the forming matrix, and to mediate feedback signals to the transcriptional machinery of these cells. Membrane-bound proteins identified in ameloblasts, and which interact with the structural enamel proteins, include Cd63 (cluster of differentiation 63 antigen), annexin A2 (Anxa2), and lysosomal-associated glycoprotein 1 (Lamp1). These and related data help explain the molecular and cellular mechanisms responsible for the removal of the organic enamel matrix during the events of enamel mineralization, and how the enamel matrix influences its own fate through signaling initiated at the cell surface. The knowledge gained from enamel developmental studies may lead to better dental and nondental materials, or materials inspired by Nature. These data will be critical to scientists, engineers, and dentists in their pursuits to regenerate an entire tooth. For tooth regeneration to become a reality, the protein-protein interactions involving the key dental proteins must be identified and understood. The scope of this review is to discuss the current understanding of protein-protein interactions of the developing enamel matrix, and relate this knowledge to enamel biomineralization. (c) 2006, Elsevier Inc. C1 Forsyth Inst, Boston, MA 02115 USA. Univ Toronto, Fac Dent, Canadian Inst Hlth Res Grp, Toronto, ON M5S 3E2, Canada. Univ Paris 05, EA 2496, Fac Chirurgie Dent, F-92120 Montrouge, France. Univ So Calif, Sch Dent, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. RP Bartlett, JD (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 014084, DE 006988, DE 013045, DE 013404, DE 013414, DE 014189, DE 014867, DE 015332, DE 015644, R01 DE014084] NR 325 TC 82 Z9 84 U1 4 U2 30 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 0-12-153174-0 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2006 VL 74 BP 57 EP + DI 10.1016/S0070-2153(06)74003-0 PG 62 WC Developmental Biology SC Developmental Biology GA BEY63 UT WOS:000240136100003 PM 16860665 ER PT J AU Joshi, VA Kucherlapati, R AF Joshi, V. A. Kucherlapati, R. TI Lung cancer genetics and pharmacogenomics SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; PHASE-III TRIAL; KINASE DOMAIN; COPY NUMBER; GEFITINIB SENSITIVITY; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; TYROSINE KINASE; HIGH-FREQUENCY; ERLOTINIB AB Epidermal growth factor receptor (EGFR)-targeted therapies have demonstrated remarkable success in a small subset of non-small cell lung cancer patients. The mechanism of response has been an area of active research, with somatic mutation in a number of genes in the EGFR signal transduction pathway and copy number alterations of genes of the EGFR family as candidates contributing towards response. Continuing studies should help determine an appropriate biomarker or combination of biomarkers that can be used to predict response to this class of therapy. C1 Harvard Univ, Med Sch Partners, Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Joshi, VA (reprint author), 65 Landsdowne St, Cambridge, MA 02139 USA. EM vjoshi@partners.org NR 44 TC 1 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2006 VL 115 IS 3-4 BP 298 EP 302 DI 10.1159/000095927 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 110PS UT WOS:000242391500014 PM 17124413 ER PT J AU Lieb, JD Beck, S Bulyk, ML Farnham, P Hattori, N Henikoff, S Liu, XS Okumura, K Shiota, K Ushijima, T Greally, JM AF Lieb, J. D. Beck, S. Bulyk, M. L. Farnham, P. Hattori, N. Henikoff, S. Liu, X. S. Okumura, K. Shiota, K. Ushijima, T. Greally, J. M. TI Applying whole-genome studies of epigenetic regulation to study human disease SO CYTOGENETIC AND GENOME RESEARCH LA English DT Review ID TRANSCRIPTION FACTOR-BINDING; ISLAND METHYLATOR PHENOTYPE; SITE-SPECIFIC METHYLATION; HUMAN EPIGENOME PROJECT; DNA METHYLATION; CPG-ISLANDS; CHROMATIN-IMMUNOPRECIPITATION; GENE-EXPRESSION; CANCER-CELLS; IN-VIVO C1 Univ N Carolina, Dept Biol, Chapel Hill, NC 27515 USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27515 USA. Wellcome Trust Sanger Inst, Cambridge, England. Brigham & Womens Hosp, Div Genet, Dept Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. Univ Tokyo, Lab Cellular Biochem, Tokyo, Japan. Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98104 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Natl Canc Ctr, Res Inst, Div Carcinogenesis, Tokyo 104, Japan. Albert Einstein Coll Med, Dept Med Hematol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. RP Greally, JM (reprint author), Albert Einstein Coll Med, Dept Med Hematol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jgreally@aecom.yu.edu OI Farnham, Peggy/0000-0003-4469-7914 FU NHGRI NIH HHS [R01 HG002966, R01 HG002966-03, R01 HG003420, R01 HG003420-02] NR 202 TC 36 Z9 37 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2006 VL 114 IS 1 BP 1 EP 15 DI 10.1159/000091922 PG 15 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 054PC UT WOS:000238390100001 PM 16717444 ER PT J AU Krause, DS von Andrian, UH van Etten, RA AF Krause, D. S. von Andrian, U. H. van Etten, R. A. TI Engraftment of BCR-ABL(+) leukemia-initiating cells is mediated by selectins and their ligands - A new strategy for autografting? SO CYTOTHERAPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. CBR Inst Biomed Res, Boston, MA USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 1 MA 254 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YB UT WOS:000239337600254 ER PT J AU Kramer, JH Nelson, A Johnson, JK Yaffe, K Glenn, S Rosen, HJ Miller, BL AF Kramer, Joel H. Nelson, Adam Johnson, Julene K. Yaffe, Kristine Glenn, Shenly Rosen, Howard J. Miller, Bruce L. TI Multiple cognitive deficits in amnestic mild cognitive impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE amnestic mild cognitive impairment; Alzheimer's disease; executive function; fluency ID ALZHEIMERS-DISEASE; EXECUTIVE DEFICITS; DEMENTIA; OUTCOMES; STAGE AB Objective: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). Methods: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease ( AD) patients on a battery of neuropsychological tests. Result: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group ( vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. Conclusions: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI. Copyright (C) 2006 S. Karger AG, Basel. C1 Univ Calif San Francisco, Med Clin, Mem & Aging Ctr, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Kramer, JH (reprint author), Univ Calif San Francisco, Med Clin, Mem & Aging Ctr, Box 1207,350 Parnassus,Suite 706, San Francisco, CA 94143 USA. EM kramer@itsa.ucsf.edu FU NIA NIH HHS [P50 AG005142, AG10129, AG16570, L30 AG024692, P30 AG010129, P50 AG016570, P50-AG05142, R01 AG022538, R01 AG022538-02] NR 32 TC 84 Z9 88 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2006 VL 22 IS 4 BP 306 EP 311 DI 10.1159/000095303 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 107JQ UT WOS:000242167400007 PM 16931884 ER PT J AU Yaffe, K Petersen, RC Lindquist, K Kramer, J Miller, B AF Yaffe, Kristine Petersen, Ron C. Lindquist, Karla Kramer, Joel Miller, Bruce TI Subtype of mild cognitive impairment and progression to dementia and death SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE mild cognitive impairment; mild cognitive impairment subtypes; risk of mortality ID ALZHEIMER-DISEASE; DECLINE AB Background: Mild cognitive impairment (MCI) represents a common cognitive state between normal cognitive aging and dementia. There is limited information about the heterogeneity of MCI and how this heterogeneity may influence the clinical course of MCI. We determined the longitudinal course of subtypes of MCI and assessed the rate of progression to dementia and to death. Methods: As part of the Alzheimer's Disease Research Centers of California, we studied 327 patients with MCI ( 250 with amnestic MCI, 34 with single nonmemory MCI, and 43 with multiple domain MCI) who were followed longitudinally. We determined if subtype of MCI was independently associated with time to dementia diagnosis and time to death using Cox proportional hazard models, and type of dementia using Fisher's exact test. Results: Mean age of the patients with MCI was 72.9 +/- 9.3 years and mean Mini-Mental State Examination score was 25.7 +/- 4.3. After a mean follow-up of 3.1 years, 199 (65%) progressed to dementia and 80 (24%) died. After multivariate adjustment, compared to those with amnestic MCI, patients with single nonmemory or multiple subtype MCI were less likely to receive a diagnosis of dementia (HR = 0.60; 95% CI 0.35 - 1.05 and HR = 0.71; 95% CI 0.44 - 1.14) but more likely to die HR = 2.57; 95% CI 1.13 - 5.84 and HR = 1.73; 95% CI 0.72 - 4.18), but these results were of borderline statistical significance. There were significant differences in the type of dementia diagnosed across MCI subtypes ( p = 0.006). Among the patients who progressed to Alzheimer's disease, 76% had prior amnestic MCI; of the patients who progressed to vascular dementia, 50% had prior amnestic MCI; all patients who progressed to a frontal dementia syndrome had single nonmemory MCI previously. Conclusions: The majority of patients with MCI progressed to dementia and a significant proportion died. Subtype of MCI may influence rates of progression to death and to dementia and has a major influence on subsequent type of dementia diagnosis. Copyright (C) 2006 S. Karger AG, Basel. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Mayo Clin, Dept Neurol, Rochester, MN USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU NIA NIH HHS [P01 AG019724, P50 AG023501, R01 AG021918] NR 20 TC 127 Z9 133 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2006 VL 22 IS 4 BP 312 EP 319 DI 10.1159/000095427 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 107JQ UT WOS:000242167400008 PM 16940725 ER PT J AU McMurtray, A Clark, DG Christine, D Mendez, MF AF McMurtray, A Clark, DG Christine, D Mendez, MF TI Early-onset dementia: Frequency and causes compared to late-onset dementia SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE dementia, early onset, late onset; Alzheimer's disease ID FRONTOTEMPORAL LOBAR DEGENERATION; PRESENILE-DEMENTIA; VASCULAR DEMENTIA; PREVALENCE; YOUNG; ASCERTAINMENT; POPULATION; MINNESOTA; ROCHESTER; SCOTLAND AB Background: Research on the epidemiology of dementia has focused on the elderly. Few investigations have studied differences in etiologic frequencies between early-onset dementia (EOD), with onset at an age of less than 65 years old, and the more common late-onset disorder. Objectives: To determine relative frequencies and characteristics of EOD versus late-onset dementia (LOD; age of onset 6 65 years) diagnosed in a large memory disorders program over a 4-year period. Methods: We reviewed medical records, including an extensive neurobehavioral and neurological evaluation, of all patients seen at a large Veteran's Affairs Medical Center Memory Disorders clinic between 2001 and 2004 and assessed demographic variables, final diagnoses, presence of dementia, and differential diagnosis of dementing illnesses. Results: Among 1,683 patients presenting for evaluation of an acquired decline in memory or cognition, 948 (56%) met established clinical criteria for a dementing illness. About 30% (n = 278) of these had an age of onset of <65 years, compared to 670 with LOD. Patients were predominantly male (98%). Compared to the late-onset group, the EOD patients were less severely impaired on presentation, but they did not differ in gender distribution or educational background. The EOD group had significantly more dementia attributed to traumatic brain injury, alcohol, human immunodeficiency virus (HIV), and frontotemporal lobar degeneration compared to the LOD patients. In contrast, the LOD group had significantly more Alzheimer's disease compared to the EOD group. Conclusions: This study, conducted at a Veterans Affairs Hospital, is the largest series to date on EOD, and found a previously unexpectedly large number of patients below the age of 65 with cognitive deficits and impaired functioning consequent to head trauma, alcohol abuse, and HIV. These findings highlight the differential distribution and importance of preventable causes of dementia in the young. Copyright (C) 2006 S. Karger AG, Basel. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. RP McMurtray, A (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit, 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM amcmurtray@mednet.ucla.edu NR 27 TC 71 Z9 76 U1 3 U2 17 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2006 VL 21 IS 2 BP 59 EP 64 DI 10.1159/000089546 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 002ZL UT WOS:000234651300001 PM 16276111 ER PT J AU Issa, AM Mojica, WA Morton, SC Traina, S Newberry, SJ Hilton, LG Garland, RH MacLean, CH AF Issa, AM Mojica, WA Morton, SC Traina, S Newberry, SJ Hilton, LG Garland, RH MacLean, CH TI The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: A systematic review SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE omega-3 fatty acids; treatment of dementia; Alzheimer's disease; cognitive function in normal aging ID ALZHEIMER-DISEASE; METHODOLOGICAL QUALITY; FATTY-ACIDS; RISK; FISH; CONSUMPTION; COHORT AB We systematically reviewed the published literature on the effects of omega - 3 fatty acids on measures of cognitive function in normal aging, incidence and treatment of dementia. Computerized databases were searched for published literature to identify potentially relevant studies with the intent to conduct a meta-analysis. We screened 5,865 titles, reviewed 497 studies of which 49 underwent a detailed review, and found 5 studies that pertained to our objectives. We included controlled clinical trials and observational studies, including prospective cohort, case-control, and case series designs; we excluded case reports. We had no language restrictions. We abstracted data on the effects of omega - 3 fatty acids and on study design, relevant outcomes, study population, source, type, amount, and duration of omega - 3 fatty acid consumption, and parameters of methodological quality. A single cohort study has assessed the effects of omega - 3 fatty acids on cognitive function with normal aging and found no association for fish or total omega - 3 consumption. In four studies that assessed the effects of omega - 3 fatty acids on incidence and treatment of dementia, a trend in favor of omega - 3 fatty acids (fish and total omega - 3 consumption) toward reducing risk of dementia and improving cognitive function was reported. The available data are insufficient to draw strong conclusions about the effects of omega - 3 fatty acids on cognitive function in normal aging or on the incidence or treatment of dementia. However, limited evidence suggests a possible association between omega - 3 fatty acids and reduced risk of dementia. Copyright (C) 2006 S. Karger AG, Basel. C1 RAND Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Issa, AM (reprint author), RAND Corp, Div Hlth, 1776 Main St, Santa Monica, CA 90401 USA. EM aissa1@ucla.edu NR 21 TC 49 Z9 50 U1 4 U2 22 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2006 VL 21 IS 2 BP 88 EP 96 DI 10.1159/000090224 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 002ZL UT WOS:000234651300005 PM 16340205 ER PT J AU Deckersbach, T Miller, KK Klibanski, A Fischman, A Dougherty, DD Blais, MA Herzog, DB Rauch, SL AF Deckersbach, T Miller, KK Klibanski, A Fischman, A Dougherty, DD Blais, MA Herzog, DB Rauch, SL TI Regional cerebral brain metabolism correlates of neuroticism and extraversion SO DEPRESSION AND ANXIETY LA English DT Article DE neuroimaging; personality; neuroticism; extraversion ID POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; ORBITOFRONTAL CORTEX; PERSONALITY-DISORDER; NEURAL ACTIVITY; AMYGDALA; RESPONSES; REWARD; FMRI; REPRESENTATION AB Factor-analytic approaches to human personality have consistently identified several core personality traits, such as Extraversion/Introversion, Neuroticism, Agreeableness, Consciousness, and Openness. There is an increasing recognition that certain personality traits may render individuals vulnerable to psychiatric disorders, including anxiety disorders and depression. Our purpose in this study was to explore correlates between the personality dimensions neuroticism and extraversion as assessed by the NEO Five-Factor Inventory (NEO-FFI) and resting regional cerebral glucose metabolism (rCMRglu) in healthy control subjects. Based oil the anxiety and depression literatures, we predicted correlations with a network of brain structures, including ventral and medial prefrontal cortex (encompassing anterior cingulate cortex and orbitofrontal cortex), insular cortex, anterior temporal pole, ventral striatum, and the anzygdala. Twenty healthy women completed an (18F)FDG (18F-fluorodeoxyglucose) positron emission tomography (PET) scan at rest and the NEO-FFI inventory. We investigated correlations between scores on NEO-FFI Neuroticism and Extraversion and rCMRglu using statistical parametric mapping (SPM99). Within a priori search territories, we found significant negative correlations between Neuroticism and rCMRglu in the insular cortex and positive correlations between Extraversion and rCMRglu in the orbitofrontal cortex. No significant correlations were found involving anterior cingulate, amygdala, or ventral striatum. Neuroticism and Extraversion are associated with activity in insular cortex and orbitofrontal cortex, respectively. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA USA. RP Deckersbach, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat Neurosci Div, Bldg 149,2611 13th St, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org NR 49 TC 65 Z9 65 U1 3 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2006 VL 23 IS 3 BP 133 EP 138 DI 10.1002/da.20152 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 041FG UT WOS:000237438800003 PM 16470804 ER PT J AU Dougherty, DD Bonab, AA Ottowitz, WE Livni, E Alpert, NM Rauch, SL Fava, M Fischman, AJ AF Dougherty, DD Bonab, AA Ottowitz, WE Livni, E Alpert, NM Rauch, SL Fava, M Fischman, AJ TI Decreased striatal D1 binding as measured using PET and [C-11]SCH 23,390 in patients with major depression with anger attacks SO DEPRESSION AND ANXIETY LA English DT Article; Proceedings Paper CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat ID RECEPTOR-BINDING; DOPAMINE; FLUOXETINE; SPECT AB This study assessed striatal dopamine 1 (D1) receptor binding in patients with major depressive disorder and anger attacks (MDD + A) and healthy volunteers. We used positron emission tomography with [C-11]SCH 23,390 to compare 10 patients with MDD+A to 10 healthy volunteers. [C-11]SCH 23,390 binding in bilateral striata was significantly lower in the MDD+A group when compared to healthy volunteers. These results implicate striatal D1 receptor dysfunction in MDD+A and further suggest an association between dopaminergic transmission and anger or aggression. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY-2612,Bldg 149,13th St, Boston, MA 02129 USA. EM ddougherty@partners.org FU NIMH NIH HHS [K23 MH001735] NR 18 TC 30 Z9 30 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2006 VL 23 IS 3 BP 175 EP 177 DI 10.1002/da.20168 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 041FG UT WOS:000237438800009 PM 16528700 ER PT J AU Papakostas, GI Worthington, JJ Iosifescu, DV Kinrys, G Burns, AM Fisher, LB Homberger, CH Mischoulon, D Fava, M AF Papakostas, GI Worthington, JJ Iosifescu, DV Kinrys, G Burns, AM Fisher, LB Homberger, CH Mischoulon, D Fava, M TI The combination of duloxetine and bupropion for treatment-resistant major depressive disorder SO DEPRESSION AND ANXIETY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; VENLAFAXINE; PAROXETINE; SR AB Our objective was to assess the effectiveness and safety of the combination of duloxetine and bupropion for treatment-resistant major depressive disorder (TRD). A retrospective chart review was conducted to identify patients with major depressive disorder (MDD) who had not experienced full remission of symptoms following an adequate trial of either duloxetine (n = 3) or bupropion (n = 7), and who then received the combination of these two antidepressants for TRD. Ten patients [37.2 +/- 11.3 years of age, five women, baseline Clinical Global Impressions (CGI) scale score 4.4 +/- 1.1], seven of whom, had not remitted following treatment with bupropion (330 +/- 67mg, 20.5 +/- 12.2 weeks), and three of whom bad not remitted following treatment with duloxetine (90 +/- 30 mg, 18 +/- 2 weeks) received at least 4 weeks of combination treatment. The CGI was administered when the combination was first prescribed, and following 8.8 +/- 4.0 (range, 4-16) weeks of treatment. There was a significant decrease in CGI-S (Severity) scores (4.4 +/- 1.1 to 2.1 +/- 0.9, P < .0001) following combination treatment. Three (30%) patients were remitters at follow-up, and six (60%) were responders who did not achieve full symptom remission. The mean maximum adjunctive duloxetine and bupropion doses were 60.0 +/- 17.3 mg and 175.0 +/- 114.5mg, respectively. Side effects reported during combination treatment were nausea (n = 2), dry month (n = 2), jitteriness/agitation (n = 2), fatigue/drowsiness (n = 2), increased blood pressure (n = 1), increased sweating (n = 1), insomnia (n = 1), pruritus (n = 1), headache (n = 1), sexual dysfunction (n = 1), and weight gain (n = 1). Although preliminary, these results suggest a possible role for the combination of duloxetine and bupropionfor TRD. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Anxiety Disorders Res Program, Cambridge Hlth Alliance, Cambridge, MA USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 7 TC 39 Z9 40 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2006 VL 23 IS 3 BP 178 EP 181 DI 10.1002/da.20181 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 041FG UT WOS:000237438800010 PM 16528701 ER PT J AU Monkul, ES Nicoletti, MA Spence, D Sassi, RB Axelson, D Brambilla, P Hatch, JP Keshavan, M Ryan, N Birmaher, B Soares, JC AF Monkul, E. Serap Nicoletti, Mark A. Spence, David Sassi, Roberto B. Axelson, David Brambilla, Paolo Hatch, John P. Keshavan, Matcheri Ryan, Neal Birmaher, Boris Soares, Jair C. TI MRI study of thalamus volumes in juvenile patients with bipolar disorder SO DEPRESSION AND ANXIETY LA English DT Article DE thalamus; bipolar disorder; mood disorders; affective disorders; neuroimaging; MRI; children ID ACETYL-L-ASPARTATE; MOOD DISORDERS; TRANSPORTER BINDING; HUMAN BRAIN; I DISORDER; SCHIZOPHRENIA; ABNORMALITIES; MATTER; MANIA; PET AB In vivo imaging studies suggest functional abnormalities of the thalamus in adult patients with bipolar disorder, but the presence of anatomical abnormalities is controversial. Our objective in this study was to compare the thalamus volumes of children and adolescents with bipolar disorder versus healthy controls to determine whether any morphological abnormalities exist early in illness course. We studied 16 patients with bipolar disorder according to DSM-IV criteria (mean age +/- SD = 15.5 +/- 3.4 years) and 21 healthy control subjects (mean age +/- SD = 16.9 +/- 3.8 years). Blinded examiners measured thalamic gray matter volumes with a semiautomated technique. Analysis of covariance, with age, gender, and intracranial brain volume as covariates, revealed no significant differences in left and right thalamic volumes between patients with bipolar disorder and healthy controls. Our findings indicate there are no significant differences in thalamus size between children and adolescents with bipolar disorder and healthy comparison subjects, in contrast to available findings for schizophrenia and first-break psychosis. Any differences in thalamus size that may exist between patients with bipolar disorder and healthy controls must amount to small effect sizes. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Progam, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Dept Psychiat, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Udine, Dept Pathol & Expt Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders,MOOD CNS Progam, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NCRR NIH HHS [RR 020571]; NIMH NIH HHS [MH 01736, MH 30915, MH 59929, MH55123] NR 35 TC 12 Z9 13 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2006 VL 23 IS 6 BP 347 EP 352 DI 10.1002/da.20161 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 091FM UT WOS:000241012200004 PM 16688738 ER PT J AU Simon, NM Zalta, AK Worthington, JJ Hoge, EA Christian, KM Stevens, JC Pollack, MH AF Simon, Naomi M. Zalta, Alyson K. Worthington, John J., III Hoge, Elizabeth A. Christian, Kelly M. Stevens, Julie C. Pollack, Mark H. TI Preliminary support for gender differences in response to fluoxetine for generalized anxiety disorder SO DEPRESSION AND ANXIETY LA English DT Article; Proceedings Paper CT 158th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 2005 CL Atlanta, GA SP Amer Psychiat Assoc DE gender; GAD; anxiety; fluoxetine; SSRI ID NATIONAL-COMORBIDITY-SURVEY; SERTRALINE TREATMENT; VENLAFAXINE; EFFICACY; STATES AB Women have a higher prevalence of generalized anxiety disorder (GAD) than do men, but few studies have assessed gender differences in response to pharmacotherapy. In this study we examined gender as a correlate of response to 6 weeks of open, prospective fluoxetine treatment in 23 men and 22 women with a primary diagnosis of GAD. There was no difference by gender in age or prevalence of mood and anxiety comorbidity; however, GAD onset occurred at a significantly younger age in women compared with men. Despite a lack of difference in baseline severity measures, women had a significantly poorer response to fluoxetine as measured by both the Hamilton Anxiety Rating Scale (HAM-A) and Clinician Global Impression-Severity Scale (CGI-S). In multivariate analyses, there was a significant interaction between age of onset and gender: mien with younger age of onset and women with older age of onset exhibited poorer response on the HAM-A. These data, though limited in sample size and by the post hoc nature of our analyses, offer preliminary support that women with GAD, particularly those with a later age of onset, may have a poorer response to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Larger placebo-controlled trials are needed to more definitively examine gender and treatment response in anxiety disorders. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Zalta, Alyson/0000-0002-5159-8431 NR 20 TC 23 Z9 23 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2006 VL 23 IS 6 BP 373 EP 376 DI 10.1002/da.20184 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 091FM UT WOS:000241012200007 PM 17068858 ER PT J AU Harley, R Petersen, T Scalia, M Papakostas, GI Farabaugh, A Fava, M AF Harley, Rebecca Petersen, Timothy Scalia, Margaret Papakostas, George I. Farabaugh, Amy Fava, Maurizio TI Problem-solving ability and comorbid personality disorders in depressed outpatients SO DEPRESSION AND ANXIETY LA English DT Article ID MAJOR DEPRESSION; COLLEGE POPULATION; SUICIDE IDEATION; HOPELESSNESS; APPRAISAL; SYMPTOMS; STRESS AB Major depressive disorder (MDD) is associated with poor problem-solving abilities. In addition, certain personality disorders (PDs) that are common among patients with MDD are also associated with limited problem-solving skills. Attempts to understand the relationship between PDs and problem solving can be complicated by the presence of acute MDD. Our objective in this study was to investigate the relationships between PDs, problem-solving skills, and response to treatment among outpatients with MDD. We enrolled 312 outpatients with MDD in an open, fixed-dose, 8-week fluoxetine trial. ID diagnoses were ascertained via structured clinical interview before and after fluoxetine treatment. Subjects completed the Problem-Solving Inventory (PSI) at both time points. We used analyses of covariance (ANCOVAs) to assess relationships between ID diagnoses and PSI scores prior to treatment. Subjects were divided into three groups: those with ID diagnoses that remained stable after fluoxetine treatment (N = 91), those who no longer met ID criteria after fluoxetine treatment (N = 119), and those who did not meet cliteria for a PD at any time point in the study (N = 95). We used multiple chi(2) analyses to compare rates of MDD response and remission between the three ID groups. ANCOVA was also used to compare posttreatment PSI scores between PD groups. Prior to fluoxetine treatment, patients with avoidant, dependent, narcissistic, and borderline PDs reported significantly worse problem-solving ability than did patients without any PDs. Only subjects with dependent ID remained associated with poorer baseline problem-solving reports after the effects of baseline depression severity were controlled. Patients with stable PD diagnoses bad significantly lower rates of MDD remission. Across ID groups, problem solving improved as MDD improved. No significant differences in posttreatment problem-solving were found between PD groups after controlling for baseline depression severity, baseline PSI score, and response to treatment. Treatment with fluoxetine is less likely to lead to remission of MDD inpatients with stable PDs. More study is needed to investigate causal links between PDs, problem solving, and MDD treatment response. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Harley, R (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rharley@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 25 TC 4 Z9 4 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2006 VL 23 IS 8 BP 496 EP 501 DI 10.1002/da.20194 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 113XH UT WOS:000242630800009 PM 16845662 ER PT J AU Perlis, CS Campbell, RM Perlis, RH Malik, M Dufresne, RG AF Perlis, CS Campbell, RM Perlis, RH Malik, M Dufresne, RG TI Incidence of and risk factors for medical malpractice lawsuits among Mohs surgeons SO DERMATOLOGIC SURGERY LA English DT Article ID CLAIMS; DERMATOLOGY; CARE AB BACKGROUND Despite rising medical malpractice costs, little is known about the factors associated with claims filed against Mohs surgeons. OBJECTIVE We sought to define the scope of medical malpractice claims filed against Mohs surgeons and to identify salient factors associated with the filing and disposition of those claims. METHODS A comprehensive survey was mailed to 599 physicians with US addresses listed in the 2003 directory of the American College of Mohs Micrographic Surgery and Cutaneous Oncology. RESULTS Of the 300 completed surveys returned, 33 (11%) reported ever having been sued. Physicians who practiced Mohs surgery for a longer period of time were more likely to have been sued for malpractice. Physicians reported the wrong site and functional outcome as the most frequent causes of malpractice lawsuits. C1 Rhode Isl Hosp, Dept Dermatol, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Perlis, CS (reprint author), Univ Dermatol, Rhode Isl Hosp, APC 10,593 Eddy St, Providence, RI 02903 USA. EM perlis@stanfordalumni.org NR 16 TC 25 Z9 25 U1 2 U2 3 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JAN PY 2006 VL 32 IS 1 BP 79 EP 83 DI 10.1111/j1524-4725.2006.32009 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 027JM UT WOS:000236411700012 PM 16393602 ER PT J AU Niendorf, KB Tsao, H AF Niendorf, KB Tsao, H TI Cutaneous melanoma: family screening and genetic testing SO DERMATOLOGIC THERAPY LA English DT Article DE cutaneous melanoma; dysplastic melanocytic nevi; genetic predisposition testing; hereditary cancer syndrome; melanoma; prevention ID CDKN2A GERMLINE MUTATIONS; MULTIPLE PRIMARY MELANOMAS; PANCREATIC-CANCER; PRONE FAMILIES; MALIGNANT-MELANOMA; SUSCEPTIBILITY LOCUS; HEREDITARY MELANOMA; OCULAR MELANOMA; VARIANT ALLELES; BRCA2 MUTATIONS AB The incidence of cutaneous melanoma (CM) has been steadily increasing in recent decades. Ultraviolet radiation (UVR) exposure, in the form of intermittent heavy exposure and severe sunburns in childhood, is believed to be the most important environmental contribution to CM risk. Genetic determinants also modulate CM risk, probably to a greater extent than environmental exposure. Certain heritable traits such as prominent numbers of common and atypical melanocytic nevi, skin type, dense UVR-induced freckling, and hair color are all known to be associated with increased CM risk. Very rarely, a heritable mutation in a high-risk gene renders the susceptible individual at extreme risk for CM. Families may carry one or more of the other high-risk phenotypic traits leading to uncertainty about how to quantify CM risk and provide management recommendations. Commercial genetic testing for the known high-risk inherited genetic mutations is available but is only relevant for those rare families likely to be carrying identifiable mutations. CM screening and risk intervention programs are being established internationally for families at markedly increased risk. Algorithms based on the level of risk are proposed. C1 Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc Risk Anal, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tsao, H (reprint author), Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 73 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD JAN-FEB PY 2006 VL 19 IS 1 BP 1 EP 8 DI 10.1111/j.1529-8019.2005.00050.x PG 8 WC Dermatology SC Dermatology GA 048WU UT WOS:000237978000001 PM 16405564 ER PT J AU Marenda, DR Vrailas, AD Rodrigues, AB Cook, S Powers, MA Lorenzen, JA Perkins, LA Moses, K AF Marenda, DR Vrailas, AD Rodrigues, AB Cook, S Powers, MA Lorenzen, JA Perkins, LA Moses, K TI MAP kinase subcellular localization controls both pattern and proliferation in the developing Drosophila wing SO DEVELOPMENT LA English DT Article DE Drosophila; moleskin; importin 7; wing; MAP kinase; cell cycle; translocation; ERK; Ras ID SIGNAL-TRANSDUCTION PATHWAY; ACTIVATED PROTEIN-KINASE; NUCLEAR TRANSLOCATION; VEIN DEVELOPMENT; EYE DEVELOPMENT; EGF RECEPTOR; ARGOS GENE; GROWTH; ERK; IMPORT AB Mitogen-activated protein kinases (MAPKs) phosphorylate target proteins in both the cytoplasm and nucleus, and a strong correlation exists between the subcellular localization of MAPK and resulting cellular responses. It was thought that MAPK phosphorylation was always followed by rapid nuclear translocation. However, we and others have found that MAPK phosphorylation is not always sufficient for nuclear translocation in vivo. in the developing Drosophila wing, MAPK-mediated signaling is required both for patterning and for cell proliferation, although the mechanism of this differential control is not fully understood. Here, we show that phosphorylated MAPK (pMAPK) is held in the cytoplasm in differentiating larval and pupal wing vein cells, and we show that this cytoplasmic hold is required for vein cell fate. At the same time, we show that MAPK does move into the nucleus of other wing cells where it promotes cell proliferation. We propose a novel Ras pathway bifurcation in Drosophila and our results suggest a mechanism by which MAPK phosphorylation can signal two different cellular outcomes (differentiation versus proliferation) based on the subcellular localization of MAPK. C1 Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. Med Coll Wisconsin, Dept Pediat Gastroenterol, Milwaukee, WI 53226 USA. RP Moses, K (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA USA. EM mosesk@hhmi.org FU NEI NIH HHS [R01 EY12537, R01 EY012537]; NICHD NIH HHS [P01 HD39942, P01 HD039942]; NIGMS NIH HHS [R01 GM061707, 1 F32 GM073608, R01 GM61707, T32 GM008490, F32 GM073608-01A1, F32 GM073608] NR 51 TC 33 Z9 35 U1 0 U2 3 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 JAN PY 2006 VL 133 IS 1 BP 43 EP 51 DI 10.1242/dev.02168 PG 9 WC Developmental Biology SC Developmental Biology GA 006ZK UT WOS:000234936400005 PM 16308331 ER PT J AU Harris, BS Spruill, L Edmonson, AM Rackley, MS Benson, DW O'Brien, TX Gourdie, RG AF Harris, BS Spruill, L Edmonson, AM Rackley, MS Benson, DW O'Brien, TX Gourdie, RG TI Differentiation of cardiac Purkinje fibers requires precise spatiotemporal regulation of Nkx2-5 expression SO DEVELOPMENTAL DYNAMICS LA English DT Article DE heart conduction system; Nkx2-5; Purkinje fibers; development; atrioventricular block ID CONGENITAL HEART-DISEASE; MYOSIN HEAVY-CHAIN; CONDUCTION SYSTEM; GENE-EXPRESSION; AVIAN HEART; MUTATIONS; LINEAGE; ADULT; MOUSE; CARDIOMYOCYTES AB Nkx2-5 gene mutations cause cardiac abnormalities, including deficits of function in the atrioventricular conduction system (AVCS). In the chick, Nkx2-5 is elevated in Purkinje fiber AVCS cells relative to working cardiomyocytes. Here, we show that Nkx2-5 expression rises to a peak as Purkinje fibers progressively differentiate. To disrupt this pattern, we overexpressed Nkx2-5 from embryonic day 10, as Purkinje fibers are recruited within developing chick hearts. Overexpression of Nkx2-5 caused inhibition of slow tonic myosin heavy chain protein (sMHC), a late Purkinje fiber marker but did not affect Cx40 levels. Working cardiomyocytes overexpressing Nkx2-5 in these hearts ectopically up-regulated Cx40 but not sMHC. Isolated embryonic cardiomyocytes overexpressing Nkx2-5 also displayed increased Cx40 and suppressed sMHC. By contrast, overexpression of a human NKX2-5 mutant did not effect these markers in vivo or in vitro, suggesting one possible mechanism for clinical phenotypes. We conclude that a prerequisite for normal Purkinje fiber maturation is precise regulation of Nkx2-5 levels. C1 Med Univ S Carolina, Dept Cell Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Anat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. Cincinnati Childrens Hosp, Med Ctr, Dept Mol & Cardiovasc Biol, Cincinnati, OH USA. RP Gourdie, RG (reprint author), Med Univ S Carolina, Dept Cell Biol & Anat, 171 Ashley Ave, Charleston, SC 29425 USA. EM gourdier@musc.edu FU NCRR NIH HHS [P20RR016434, P20 RR016434]; NHLBI NIH HHS [HL56728, P01 HL036059, HL36059, R01 HL056728, R01 HL056728-09]; NICHD NIH HHS [HD39946, P01 HD039946] NR 44 TC 17 Z9 18 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 2006 VL 235 IS 1 BP 38 EP 49 DI 10.1002/dvdy.20580 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 995AW UT WOS:000234073300006 PM 16245335 ER PT J AU Louvi, A Arboleda-Velasquez, JF Artavanis-Tsakonas, S AF Louvi, A Arboleda-Velasquez, JF Artavanis-Tsakonas, S TI CADASIL: A critical look at a Notch disease SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE CADASIL; central nervous system degenerative disorder; Notch 3 mutations ID AUTOSOMAL-DOMINANT ARTERIOPATHY; TRANSGENIC MOUSE MODEL; SUBCORTICAL INFARCTS; LEUKOENCEPHALOPATHY CADASIL; ALAGILLE-SYNDROME; SIGNALING PATHWAY; CELL FATE; NOTCH3-DEFICIENT MICE; SKIN BIOPSIES; HUMAN JAGGED1 AB Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a catastrophic late-onset syndrome which manifests itself mainly as a central nervous system degenerative disorder. CADASIL has been associated with mutations in the Notch 3 receptor which appear to cause, mainly, vascular abnormalities. Although more than a decade has passed since Notch 3 mutations were linked with this disease, we still do not have a good grasp on the molecular mechanisms underlying the CADASIL-associated Notch 3 receptor malfunction, nor do we understand many aspects of the CADASIL pathobiology. In this review, we discuss the CADASIL-related literature and attempt to evaluate the various experimental systems and approaches used to address what seems to be a paradigm for studying the pathobiology and genetics of vascular cognitive impairment. C1 Harvard Univ, Sch Med, Dept Cell Biol, Charlestown, MA 02129 USA. MGH Canc Ctr, Charlestown, MA USA. Coll France, F-75231 Paris, France. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM tsakonas@helix.mgh.harvard.edu NR 91 TC 45 Z9 45 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2006 VL 28 IS 1-2 BP 5 EP 12 DI 10.1159/000090748 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 018PB UT WOS:000235776200001 PM 16508299 ER PT J AU Levin, M Buznikov, GA Lauder, JM AF Levin, Michael Buznikov, Gennady A. Lauder, Jean M. TI Of minds and embryos: Left-right asymmetry and the serotonergic controls of pre-neural morphogenesis SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE serotonin; embryonic development; morphogenesis; asymmetry; craniofacial development ID LEFT-RIGHT AXIS; MEMBRANE H+-ATPASE; ENDOGENOUS ELECTRIC-FIELDS; AUXIN POLAR TRANSPORT; SEA-URCHIN EMBRYOS; GATED ION-CHANNEL; PLASMA-MEMBRANE; BINDING-PROTEIN; RETINOIC ACID; MOUSE EMBRYO AB Serotonin is a clinically important neurotransmitter regulating diverse aspects of cognitive function, sleep, mood, and appetite. Increasingly, it is becoming appreciated that serotonin signaling among non-neuronal cells is a novel patterning mechanism existing throughout diverse phyla. Here, we review the evidence implicating serotonergic signaling in embryonic morphogenesis, including gastrulation, craniofacial and bone patterning, and the generation of left-right asymmetry. We propose two models suggesting movement of neurotransmitter molecules as a novel mechanism for how bioelectrical events may couple to downstream signaling cascades and gene activation networks. The discovery of serotonin-dependent patterning events occurring long before the development of the nervous system opens exciting new avenues for future research in evolutionary, developmental, and clinical biology. Copyright (c) 2006 S. Karger AG, Basel. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCI NIH HHS [CO6RR11244]; NIDA NIH HHS [R21 DA018103-01]; NIDCR NIH HHS [DE13314-05]; NIGMS NIH HHS [1-R01-GM-06227]; NIMH NIH HHS [U54 MH66418] NR 192 TC 79 Z9 82 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2006 VL 28 IS 3 BP 171 EP 185 DI 10.1159/000091915 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 041RM UT WOS:000237473400001 PM 16679764 ER PT J AU Araki, KY Fujimura, S MacDonald, ME Bhide, PG AF Araki, Kiyorni Y. Fujimura, Satoshi MacDonald, Marcy E. Bhide, Pradeep G. TI Characterization of mouse striatal precursor cell lines expressing functional dopamine receptors SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE ganglionic eminence; dopamine; cell cycle; striatum; D-1 receptor; D-2 receptor ID ADENYLYL-CYCLASE; MESSENGER-RNA; ST14A CELLS; RAT-BRAIN; GLUTAMATE; NEURONS; D1; PROLIFERATION; DIFFERENTIATION; ACTIVATION AB Dopamine and its receptors appear in the developing brain early in the embryonic period and dopamine receptor activation influences proliferation and differentiation of neuroepithelial precursor cells. Since dopamine D-1 and D-2 receptor activation produces opposing effects on precursor cell activity, dopamine's overall effects may correlate with relative numbers and activity of each receptor subtype on the precursor cells. Dopamine receptor expression and activity in individual precursor cells in the intact brain are difficult to ascertain. Therefore, cell lines with known receptor expression profiles can be useful tools to study dopamine's influence on neuroepithelial cells. We report characterization of dopamine receptor expression and activity profiles in three mouse striatal precursor cell lines and suggest that these cell lines can be valuable tools to study dopamine's effects on striatal precursor cell proliferation and differentiation. Copyright (c) 2006 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, 149 13th St, Charlestown, MA 02129 USA. EM Bhide@helix.mgh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU NICHD NIH HHS [P01 HD005515, HD 05515]; NINDS NIH HHS [NS 43426, R01 NS043426] NR 30 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2006 VL 28 IS 6 BP 518 EP 527 DI 10.1159/000095114 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 094HB UT WOS:000241229400006 PM 17028429 ER PT J AU Matheson, SF Hu, KQ Brouns, MR Sordella, R VanderHeide, JD Settleman, J AF Matheson, Stephen F. Hu, Kang-Quan Brouns, Madeleine R. Sordella, Raffaella VanderHeide, John D. Settleman, Jeffrey TI Distinct but overlapping functions for the closely related p190 RhoGAPs in neural development SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Rho GTPases; axonal outgrowth; neuronal differentiation; p190 RhoGAP ID RHO-FAMILY GTPASES; ACTIVATING PROTEIN; SIGNALING PATHWAY; ADP-RIBOSYLATION; TYROSINE KINASE; CELLS; INHIBITION; MYOGENESIS; GAP; SRC AB The p190 RhoGAPs, p190A and p190B, are highly related GTPase-activating proteins for the Rho GTPases. Rho GTPases and p190A reportedly control various aspects of brain development, and we hypothesized that p190B would be likewise involved in neuronal development. We find that like p190A, p190B is prominently expressed in the developing and adult brain. Unlike p190A, p190B is not abundantly tyrosine phosphorylated. We further demonstrate, using p190B-deficient mice, that p190B is required for normal brain development. Mice lacking p190B display several major defects, including (1) deficits in the formation of major forebrain commissures, including the corpus callosum and anterior commissure, (2) dilation of the lateral ventricles, suggesting inhibition of neurogenesis and/or survival, (3) thinning of the neocortical intermediate zone, suggesting defects in neuronal differentiation and/or axonal outgrowth, and (4) impaired neuronal differentiation. These defects are similar to, but distinct from, those described in p190A-deficient mice. RNA interference-mediated knockdown of neither p190 protein results in significant inhibition of neurite outgrowth in neuroblastoma cells, despite an apparent increase in RhoA activity. We conclude that p190 RhoGAPs control pivotal aspects of neural development, including neuronal differentiation and process outgrowth, and that these effects are mediated by signaling systems that include, but are not limited to, RhoA. Copyright (c) 2006 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Calvin Coll, Dept Biol, Grand Rapids, MI 49506 USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu OI Matheson, Stephen/0000-0003-0561-8152 FU NCI NIH HHS [CA62142] NR 37 TC 16 Z9 16 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2006 VL 28 IS 6 BP 538 EP 550 DI 10.1159/000095116 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 094HB UT WOS:000241229400008 PM 17028431 ER PT J AU Florez, JC Wiltshire, S Agapakis, CM Burtt, NP de Bakker, PIW Almgren, P Bostrom, KB Tuomi, T Gaudet, D Daly, MJ Hirschhorn, JN McCarthy, MI Altshuler, D Groop, L AF Florez, JC Wiltshire, S Agapakis, CM Burtt, NP de Bakker, PIW Almgren, P Bostrom, KB Tuomi, T Gaudet, D Daly, MJ Hirschhorn, JN McCarthy, MI Altshuler, D Groop, L TI High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 people SO DIABETES LA English DT Article ID WHOLE-GENOME AMPLIFICATION; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY-GENE; ALZHEIMERS-DISEASE; MELLITUS; VARIANTS; SCAN; LOCI; POPULATION; PEDIGREES AB The insulin-degrading enzyme is responsible for the intracellular proteolysis of insulin. Its gene IDE is located on chromosome 10, in an area with suggestive linkage to type 2 diabetes and related phenotypes. Due to the impact of genetic variants of this gene in rodents and the function of its protein product, it has been proposed as a candidate gene for type 2 diabetes. Various groups have explored the role of the common genetic variation of IDE on insulin resistance and reported associations of various single nucleotide polymorphisms (SNPs) and haplotypes on both type 2 diabetes and glycemic traits. We sought to characterize the haplotype structure of IDE in detail and replicate the association of common variants with type 2 diabetes, fasting insulin, fasting glucose, and insulin resistance. We assessed linkage disequilibrium, selected single-marker and multimarker tags, and genotyped these markers in several case-control and family-based samples totalling 4,206 Caucasian individuals. We observed no statistically significant evidence of association between single-marker or multimarker tests in IDE and type 2 diabetes. Nominally significant differences in quantitative traits are consistent with statistical noise. We conclude that common genetic variation at, IDE is unlikely to confer clinically significant risk of type 2 diabetes in Caucasians. C1 Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Lund Univ, Univ Hosp MAS, Dept Clin Sci, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Univ Helsinki, Folkhalsan Genet inst, Folkhalsan Res Ctr, Helsinki, Finland. Univ Montreal, Community Genom Ctr, Chicoutinii Hosp, Quebec City, PQ, Canada. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 FU NIDDK NIH HHS [1K23 DK 65978-02] NR 30 TC 27 Z9 27 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2006 VL 55 IS 1 BP 128 EP 135 DI 10.2337/diabetes.55.01.06.db05-0954 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998WB UT WOS:000234349500016 PM 16380485 ER PT J AU Kershaw, EE Hamm, JK Verhagen, LAW Peroni, O Katic, M Flier, JS AF Kershaw, EE Hamm, JK Verhagen, LAW Peroni, O Katic, M Flier, JS TI Adipose triglyceride lipase - Function, regulation by insulin, and comparison with adiponutrin SO DIABETES LA English DT Article ID HORMONE-SENSITIVE LIPASE; MESSENGER-RNA EXPRESSION; ACYL-HYDROLASE; TUBER PROTEIN; PATATIN; POTATO; FAMILY; TISSUE; PURIFICATION; ADIPOCYTES AB Adipose triglyceride lipase (ATGL) is a recently described adipose-enriched protein with triglyceride-specific lipase activity. ATGL shares the greatest sequence homology with adiponutrin, a nutritionally regulated protein of unclear biological function. Here we present a functional analysis of ATGL and adiponutrin and describe their regulation by insulin. Retroviral-mediated overexpression of ATGL in 3T3-L1 adipocytes increased basal and isoproterenol-stimulated glycerol and nonesterified fatty acid (NEFA) release, whereas siRNA-mediated knockdown of ATGL had the opposite effect. In contrast, siRNA-mediated knockdown of adiponutrin in 3T3-L1 adipocytes had no effect on glycerol or NEFA release. In mice, both ATGL and adiponutrin are nutritionally regulated in adipose tissue, with ATGL being upregulated and adiponutrin being downregulated by fasting. In 3T3-L1 adipocytes, insulin decreased ATGL and increased adiponutrin expression in a dose- and time-dependent manner, suggesting that insulin directly mediates this nutritional regulation. In addition, adipose expression of ATGL was increased by insulin deficiency and decreased by insulin replacement in streptozotocin-induced diabetic mice and was increased in fat-specific insulin receptor knockout mice, whereas adiponutrin showed the opposite pattern. These data suggest that murine ATGL but not adiponutrin contributes to net adipocyte lipolysis and that ATGL and adiponutrin are oppositely regulated by insulin both in vitro and in vivo. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kershaw, EE (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol & Metab, 330 Brookline Ave, Boston, MA 02215 USA. EM ekershaw@bidmc.harvard.edu RI Kershaw, Erin/G-9587-2013 FU NIDDK NIH HHS [2P30 DK 057521-06, 4R37 DK 028082-24, 5K08 DK 065833-02, 5P30 DK 046200-13, K08 DK065833, K08 DK065833-03, P30 DK046200, R37 DK028082] NR 35 TC 214 Z9 234 U1 0 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2006 VL 55 IS 1 BP 148 EP 157 DI 10.2337/diabetes.55.01.06.db05-0982 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998WB UT WOS:000234349500019 PM 16380488 ER PT J AU Lara-Castro, C Luo, NL Wallace, P Klein, RL Garvey, WT AF Lara-Castro, C Luo, NL Wallace, P Klein, RL Garvey, WT TI Adiponectin multimeric complexes and the metabolic syndrome trait cluster SO DIABETES LA English DT Article ID PLASMA-PROTEIN ADIPONECTIN; NUCLEAR-MAGNETIC-RESONANCE; BODY-FAT DISTRIBUTION; INSULIN SENSITIVITY; ENERGY-EXPENDITURE; HUMANS; RESISTANCE; CELL; ACRP30/ADIPONECTIN; LEPTIN AB Adiponectin circulates in human plasma mainly as a 180-kDa low molecular weight (LMW) hexamer and a high molecular weight (HMW) multimer of similar to 360 kDa. We comprehensively examined the relationships between circulating levels of total adiponectin, adiponectin multimers, and the relative distribution (i.e., ratio) of multimeric forms with key features of the metabolic syndrome. Total adiponectin (r = 0.45), HMW (r = 0.47), LMW (r = 0.31), and HMW-to-total adiponectin ratio (r = 0.29) were significantly correlated with insulin-stimulated glucose disposal rate. Similarly, total (r = -0.30), HMW (r = -0.38), and HMW-to-total adiponectin ratio (r = -0.34) were correlated with central fat distribution but not with total fat mass or BMI. Regarding energy metabolism, although there were no effects on resting metabolic rate, total (r = 0.41) and HMW (r = 0.44) were associated with increasing rates of fat oxidation. HMW-to-total adiponectin ratio increased as a function of total adiponectin, and it was HMW quantity (not total or HMW-to-total adiponectin ratio or LMW) that was primarily responsible for all of these relationships. Impact on nuclear magnetic resonance lipoprotein subclasses was assessed. HMW and total adiponectin were correlated with decreases in large VLDL (r = -0.44 and -0.41); decreases in small LDL (r = -0.41 and -0.36) and increases in large LDL (r = 0.36 and 0.30) particle concentrations accompanied by increased LDL particle size (r = 0.47 and 0.39); and increases in large HDL (r = 0.45 and 0.37) and HDL particle size (r = 0.53 and 0.47). Most of these correlations persisted after adjustment for metabolic covariables. In conclusion, first, serum adiponectin is associated with increased insulin sensitivity, reduced abdominal fat, and high basal lipid oxidation; however, it is HAM quantity, not total or HMW-to-total adiponectin ratio, that is primarily responsible for these relationships. Second, reduced quantities of HMW independently recapitulate the lipoprotein subclass profile associated with insulin resistance after correcting for glucose disposal rate and BMI. Finally, HMW adiponectin is an important factor in explaining the metabolic syndrome. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Lara-Castro, C (reprint author), Univ Alabama, Dept Nutr Sci, 1675 Webb Nutr Sci Bldg,Room 244, Birmingham, AL 35294 USA. EM larac@uab.edu FU NCRR NIH HHS [M01 RR 00032]; NHLBI NIH HHS [P01 HL 55782]; NIDDK NIH HHS [DK 38765, P30 DK 56336] NR 35 TC 312 Z9 321 U1 2 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2006 VL 55 IS 1 BP 249 EP 259 DI 10.2337/diabetes.55.01.06.db05-1105 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998WB UT WOS:000234349500031 PM 16380500 ER PT J AU Garrow, D Egede, LE AF Garrow, D Egede, LE TI Association between complementary and alternative medicine use, preventive care practices, and use of conventional medical services among adults with diabetes SO DIABETES CARE LA English DT Article ID NATIONAL-SURVEY; UNITED-STATES; PREVALENCE; COSTS AB OBJECTIVE - To assess the association between complementary and alternative medicine (CAM) use, preventive care practices, and use of conventional medical services among adults with diabetes. RESEARCH DESIGN AND METHODS - We analyzed data on 2,474 adults with diabetes. We created an overall CAM-use category based on use of any of the following: diets, herbs, chiropractic care, yoga, relaxation, acupuncture, ayuverda, biofeedback, chelation, energy healing, Reiki therapy, hypnosis, massage, naturopathy, and homeopathy. We used multiple logistic regression to assess the effect of CAM use on preventive care practices (receipt of influenza and pneumonia vaccines) and use of conventional medical services (number of primary care and emergency department visits). STATA was used for statistical analysis to account for the complex survey design. RESULTS - A total of 48% of adults with diabetes used some form of CAM. CAM use was independently associated with receipt of pneumonia vaccination (odds ratio 1.56 [95% CI 1.26-1.94]) but not significantly associated with receipt of influenza vaccination (1.17 [0.921.48]). CAM use was independently associated with visiting the emergency department (1.34 [1.06-1.70]), having six or more primary care visits (1.44 [1.14-1.83]), and having eight or more primary care visits (1.66 [1.22-2.25]). CONCLUSIONS - in contrast to the findings of previous studies, CAM use appears to be associated with increased likelihood of receipt of preventive care services and increased emergency department and primary care visits. CAM use may not be a barrier to use of conventional medical services in adults with diabetes. C1 Med Univ S Carolina, Ctr Hlth Care Res, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Care Res, Dept Med, Div Gen Internal Med, 135 Cannon St,Suite 403, Charleston, SC 29425 USA. EM egedel@musc.edu NR 23 TC 50 Z9 50 U1 4 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2006 VL 29 IS 1 BP 15 EP 19 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998VZ UT WOS:000234349300003 PM 16373889 ER PT J AU Egede, LE Michel, Y AF Egede, LE Michel, Y TI Medical mistrust diabetes management, and glycemic indigent population with self control in an type 2 diabetes SO DIABETES CARE LA English DT Article ID AFRICAN-AMERICAN; PHYSICIAN SCALE; TRUST; CARE; RELIABILITY; VALIDATION; TESTS C1 Med Univ S Carolina, Div Gen Internal Med, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Dept Med, 135 Cannon St,Suite 403, Charleston, SC 29425 USA. EM egedel@musc.edu FU AHRQ HHS [5K08HS11418] NR 13 TC 10 Z9 10 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2006 VL 29 IS 1 BP 131 EP 132 DI 10.2337/diacare.29.01.06.dc05-1642 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998VZ UT WOS:000234349300022 PM 16373908 ER PT J AU Watson, GS Reger, MA Baker, LD McNeely, MJ Fujimoto, WY Kahn, SE Boyko, EJ Leonetti, DL Craft, S AF Watson, GS Reger, MA Baker, LD McNeely, MJ Fujimoto, WY Kahn, SE Boyko, EJ Leonetti, DL Craft, S TI Effects of exercise and nutrition on memory in Japanese Americans with impaired glucose tolerance SO DIABETES CARE LA English DT Article ID LIFE-STYLE; DIABETES-MELLITUS; GLYCEMIC CONTROL; INSULIN; DISEASE; RISK C1 Geriatr Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Watson, GS (reprint author), S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM gswatson@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR00037]; NIDDK NIH HHS [DK02654, DK17047, DK35816, DK48152] NR 13 TC 9 Z9 9 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2006 VL 29 IS 1 BP 135 EP 136 DI 10.2337/diacare.29.01.06.dc05-1889 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998VZ UT WOS:000234349300024 PM 16373910 ER PT J AU Garrison, MW AF Garrison, MW TI Pharmacodynamic assessment of the activity of high-dose (750 mg) levofloxacin, ciprofloxacin, and gatifloxacin against clinical strains of Pseudomonas aeruginosa SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE high-dose levofloxacin; pharmacodynamics; ciprofloxacin; gatifloxacin; P. aeruginosa ID COMMUNITY-ACQUIRED PNEUMONIA; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL SUSCEPTIBILITY; INTRAVENOUS CIPROFLOXACIN; NOSOCOMIAL PNEUMONIA; UNITED-STATES; US HOSPITALS; MODEL; PHARMACOKINETICS; RESISTANCE AB The objective of this study was to comparatively evaluate specific bacterial killing ability of high-dose (750 mg) levofloxacin, ciprofloxacin, and gatifloxacin against 2 clinical isolates of Pseudomonas aeruginosa (PA-21 and PA-2105). An in vitro pharmacodynamic modeling apparatus was used to expose the P aeruginosa isolates to total peak concentrations and elimination characteristics associated with each quinolone. All experiments were conducted over 24 h, and a subsequent dose of ciprofloxacin was given at 12 h to emulate twicedaily dosing. Respective 3-log reductions in PA-24 occurred after 0.6, 1.0, and 2.6 h for levofloxacin, ciprofloxacin, and gatifloxacin; regrowth was seen with all 3 agents, but was greatest with gatifloxacin. PA-2105 had 2- to 4-fold higher minimal inhibitory concentrations (MICs) than PA-24. Gatifloxacin failed to achieve a 3-log reduction. Levofloxacin and ciprofloxacin took roughly 3.5 h to decrease initial inoculum by 3 logs, but regrowth of PA-2105 followed. Simulated doses of levofloxacin and ciprofloxacin showed comparable activity against each study isolate; less activity was observed with gatifloxacin. Levofloxacin versus PA-24 was the only regimen that approached the desired AUC/MIC0-24 ratio of greater than 100-125 and achieved the targeted peak/MIC ratio of >= 8. Although quinolones are typically used in combination with other antibiotics for P. aeruginosa, differences in activity favor the use of levofloxacin or ciprofloxacin for the study isolates. Use of gatifloxacin may contribute to the increased rate of quinolone-resistant P aeruginosa. (c) 2006 Elsevier Inc. All rights reserved. C1 Washington State Univ, Coll Pharm, Dept Pharmacotherapy, Spokane, WA 99210 USA. Washington State Univ, Res Lab, Deaconess Med Ctr, Spokane, WA 99210 USA. RP Garrison, MW (reprint author), Washington State Univ, Coll Pharm, Dept Pharmacotherapy, POB 1495, Spokane, WA 99210 USA. EM garrism@wsu.edu NR 28 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JAN PY 2006 VL 54 IS 1 BP 51 EP 56 DI 10.1016/j.diagmicrobio.2005.08.010 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 004DZ UT WOS:000234733500008 PM 16368475 ER PT J AU Yao, JK Leonard, S Reddy, R AF Yao, Jeffrey K. Leonard, Sherry Reddy, Ravinder TI Altered glutathione redox state in schizophrenia SO DISEASE MARKERS LA English DT Article DE glutathione; glutathione disulfide; glutathione peroxidase; glutathione reductase; cigarette smoking; age; postmortem caudate; schizophrenia ID PERFORMANCE LIQUID-CHROMATOGRAPHY; INDUCED OXIDATIVE STRESS; CIGARETTE-SMOKE; NITRIC-OXIDE; BRAIN; PHASE; PEROXYNITRITE; QUANTITATION; DEPLETION; RADICALS AB Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH) redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG) through glutathione peroxidase (GPx), and converted back to GSH by glutathione reductase (GR). Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders). Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age-related decreases of GSSG and GR activities. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. VA Denver Hlth Care Syst, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Bldg 13,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU NIDA NIH HHS [DA09457]; NIMH NIH HHS [MH58141, MH64118] NR 44 TC 160 Z9 163 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2006 VL 22 IS 1-2 BP 83 EP 93 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 212GK UT WOS:000249581800007 PM 16410648 ER PT S AU Yang, XH Zou, L AF Yang, Xiaoijong Helena Zou, Lee BE Campbell, JL Modrich, P TI Recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes to DNA damage SO DNA REPAIR, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID REPLICATION PROTEIN-A; CHECKPOINT KINASE ATR; SINGLE-STRANDED-DNA; CELL-CYCLE; CHROMATIN ASSOCIATION; SLIDING CLAMP; IN-VITRO; S-PHASE; BINDING; CHK1 AB The ATR (ataxia-telangiectasia mutated and rad3-related)-ATRIP (ATR-interacting protein) kinase complex plays a central role in the checkpoint responses to a variety of types of DNA damage, especially those interfering with DNA replication. The checkpoint-signaling pathway activated by ATR-ATRIP regulates and coordinates cell-cycle progression, DNA replication, DNA repair, and many other cellular processes critical for genomic stability. Upon DNA damage or DNA replication interference, ATR-ATRIP and two of its key regulators, the Rad17 and the 9-1-1 complexes, are localized to sites of DNA damage and stalled replication forks. Recent biochemical and cell biological studies have revealed that RPA-coated single-stranded DNA, a common structure generated at sites of DNA damage and stalled replication forks, plays crucial roles in the recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes. The recruitment of ATR-ATRIP and its regulators to DNA damage is a key step for the recognition of DNA damage by the checkpoint, and is likely important for the regulation of ATR activity and/or function in response to DNA damage. The methods used to characterize the DNA association of ATR-ATRIP, Rad17, and 9-1-1 complexes have laid a foundation for further biochemical studies, which may ultimately lead us to understand the molecular mechanisms by which ATR-ATRIP monitors and protects genomic integrity. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Yang, XH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 31 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182814-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 409 BP 118 EP 131 DI 10.1016/S0076-6879(05)09007-5 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEN83 UT WOS:000238354800007 PM 16793398 ER PT S AU Wade, CM Karlsson, EK Mikkelsen, TS Zody, MC Lindblad-Toh, K AF Wade, Claire M. Karlsson, Elinor K. Mikkelsen, Tarjei S. Zody, Michael C. Lindblad-Toh, Kerstin BE Ostrander, EA Giger, U LindbladToh, K TI The Dog Genome: Sequence, Evolution, and Haplotype Structure SO DOG AND ITS GENOME SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID RECENT POSITIVE SELECTION; DOMESTIC DOG; MOLECULAR CLOCK; CANINE GENOME; LINKAGE DISEQUILIBRIUM; MAMMALIAN EVOLUTION; MOUSE GENOME; BODY-SIZE; GENE; PATTERNS C1 [Wade, Claire M.; Karlsson, Elinor K.; Mikkelsen, Tarjei S.; Zody, Michael C.; Lindblad-Toh, Kerstin] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA. [Wade, Claire M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Wade, CM (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02141 USA. NR 57 TC 0 Z9 0 U1 0 U2 1 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-781-5 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 44 BP 179 EP 207 PG 29 WC Genetics & Heredity; Veterinary Sciences SC Genetics & Heredity; Veterinary Sciences GA BNJ27 UT WOS:000274725700013 ER PT J AU Loftis, JM Matthews, AM Hauser, P AF Loftis, JM Matthews, AM Hauser, P TI Psychiatric and substance use disorders in individuals with hepatitis C - Epidemiology and management SO DRUGS LA English DT Review ID INTERFERON-ALPHA THERAPY; INJECTING DRUG-USERS; RIBAVIRIN COMBINATION THERAPY; CHRONIC VIRAL-HEPATITIS; VIRUS-INFECTION; LIVER-DISEASE; PLUS RIBAVIRIN; DEPRESSIVE SYMPTOMS; RATING-SCALE; FOLLOW-UP AB Hepatitis C virus (HCV) infection is a major health concern in the US strategies are complicated by the extremely high rate of psychiatric and substance use disorders in those who have HCV. The majority of new and existing cases of HCV are related to injection drug use and, in this population, the prevalence of psychiatric comorbidity is high. Optimally, all patients with HCV should be screened for psychiatric and substance use disorders before initiation of antiviral therapy. If a patient screens positive, he or she should be referred to a mental healthcare provider or addiction specialist, assessed for the presence of a psychiatric or substance use disorder, and appropriately treated prior to initiation of antiviral (i.e. interferon) therapy. Although interferon-based therapies can lead to severe neuropsychiatric adverse effects, including in rare instances suicide, evidence suggests that many patients with comorbid psychiatric and substance use diagnoses can be treated safely and effectively using comanagement strategies. However, most patients with HCV are not treated with antiviral therapy. Therefore, we must expand our definition of HCV 'treatment' to include treatment of the comorbid psychiatric and substance use disorders that accompany HCV infection and precede antiviral therapy. This paper reviews the epidemiology and management of psychiatric and substance use disorders in patients with HCV, the issue of psychiatric and substance use disorders as contraindications for antiviral therapy, and current treatment strategies for HCV patients with these comorbid conditions. C1 Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. Portland VAMC, Portland VA Mood Disorders Ctr, Oporto, Portugal. Portland VAMC, NW Hepatitis C Resource Ctr, Portland, OR USA. Portland VAMC, JENS Lab, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR USA. Oregon Hlth Sci Univ, Dept Internal Med, Portland, OR USA. RP Hauser, P (reprint author), Oregon Hlth Sci Univ, Dept Psychiat, 3710 SW US Vet Hosp Rd,P3MH Adm, Portland, OR 97239 USA. EM peter.hauser2@med.va.gov NR 156 TC 52 Z9 53 U1 0 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2006 VL 66 IS 2 BP 155 EP 174 DI 10.2165/00003495-200666020-00003 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 017OM UT WOS:000235702900003 PM 16451091 ER PT J AU Williams, ME AF Williams, Mark E. TI New potential agents in treating diabetic kidney disease - The fourth act SO DRUGS LA English DT Article ID PROTEIN-KINASE-C; GLYCATION END-PRODUCTS; STAGE RENAL-DISEASE; PKC-BETA INHIBITOR; OXIDATIVE STRESS; MESANGIAL CELLS; HIGH GLUCOSE; GLYCOSAMINOGLYCAN SULODEXIDE; MICROVASCULAR COMPLICATIONS; VASCULAR COMPLICATIONS AB Despite the worldwide epidemic of chronic kidney disease complicating diabetes mellitus, current therapies directed against nephroprogression are limited to angiotensin conversion or receptor blockade. Nonetheless, additional therapeutic possibilities are slowly emerging. The diversity of therapies currently in development reflects the pathogenic complexity of diabetic nephropathy. The three most important candidate drugs currently in development include a glycosaminoglycan, a protein kinase C (PKC) inhibitor and an inhibitor of advanced glycation. In targeting primary mechanisms by which hyperglycaemia contributes to diabetic complications, these drugs could provide risk reduction complementary to the partial reduction proven for ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers). Glycosaminoglycans act to restore glycoproteins present in reduced amounts in the glomerular basement membrane and mesangium of diabetic animal models. Components of the drug sulodexide prevent pathological changes and proteinuria in diabetic rats. Reductions in albuminuria, a hallmark of early diabetic kidney disease, have been reported in initial human trials. In the US, a multicentre phase II study has been completed, with an interim analysis indicating reduction in urinary albumin losses. Pivotal phase II trials have begun in patients with type 2 diabetes. A second metabolic pathway of diabetic complications is overexpression of PKC. Several activators of this family of intracellular kinases have been identified and PKC activation may result in tissue damage through a variety of mechanisms. In animal models, the inhibitor ruboxistaurin reduces albuminuria, diabetic histological changes and kidney injury. Like sulodexide, drug development of ruboxistaurin has reached completion of a phase II evaluation with mixed results. The third metabolic target is the nonenzymatic formulation of advanced glycation end-products (AGEs) through well described biochemical pathways. Multiple pathways lead to AGE accumulation in tissues in diabetes and diverse AGE products are formed. AGE deposition has been implicated in animal models of diabetic nephropathy. The leading AGE inhibitor currently in development is pyridoxamine, which has multiple actions that inhibit glycation. Pyridoxamine is an efficient AGE inhibitor in experimental diabetes. A phase II study in diabetic patients with nephropathy reported mixed efficacy results and a favourable safety profile. Phase III evaluation of pyridoxamine has not begun. C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 100 TC 20 Z9 28 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2006 VL 66 IS 18 BP 2287 EP 2298 DI 10.2165/00003495-200666180-00002 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 126CX UT WOS:000243490900001 PM 17181372 ER PT J AU Kaiser, RM Schmader, KE Pieper, CF Lindblad, CI Ruby, CM Hanlon, JT AF Kaiser, Robert M. Schmader, Kenneth E. Pieper, Carl F. Lindblad, Catherine I. Ruby, Christine M. Hanlon, Joseph T. TI Therapeutic failure-related hospitalisations in the frail elderly SO DRUGS & AGING LA English DT Article ID ADVERSE DRUG-REACTIONS; ADMISSIONS; EMERGENCY; EVENTS; DEFINITIONS; PREVENTION; MANAGEMENT AB Background and objective: Although therapeutic failure may be a common cause of drug-related morbidity in older adults, few studies have focused on this problem. The study objective was to determine the frequency and types of, and the factors associated with, therapeutic failure leading to hospitalisation in frail, elderly patients, using a new instrument named the Therapeutic Failure Questionnaire (TFQ). Methods: The sample included 106 frail, hospitalised elderly patients enrolled in a I-year-long health service intervention trial at I I Veterans Affairs Medical Centres. The TFQ was developed by a team of clinicial geriatricians and tested for reliability by two clinical pharmacists and a geriatrician on a sample of 32 patients. To establish validity, a geriatrician retrospectively reviewed the computerised medication records and clinical charts for these patients and applied the TFQ to determine probable therapeutic failures at the time of hospital admission. Results: Inter- and intra-rater reliability for the TFQ were very good (kappa = 0.82 for both). Overall, 11% of patients had one or more probable therapeutic failures (TFQ scores between 4 and 7) leading to hospitalisation. Cardiopulmonary disease was a common 'indicator' of therapeutic failure and was often the result of non-adherence. The only factor associated with therapeutic failure occurrence was severe chronic kidney disease (crude odds ratio 5.87; 95% CI 1.20, 28.69; p = 0.01). Conclusions: The TFQ was able to identify several cases of probable therapeutic failure leading to hospitalisation in frail, elderly patients. Non-adherence to effective therapies for chronic serious cardiopulmonary disease was a common cause of therapeutic failure and represents a target for interventions to reduce hospitalisation. Further research on the occurrence, risk factors for and types of therapeutic failure is needed in a larger cohort of older non-veterans. C1 Univ Pittsburgh, Dept Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. Univ Miami, Miller Sch Med, Div Gerontol & Geriatr Med, Miami, FL 33152 USA. Univ Miami, Geriatr Inst, Miami, FL 33152 USA. Miami VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Miami, FL USA. Duke Univ, Med Ctr, Aging Ctr, Durham, NC USA. Duke Univ, Med Ctr, Sch Med, Durham, NC 27710 USA. Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Minneapolis, MN USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Sch Med, Kaufman Med Bldg Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM hanlonj@dom.pitt.edu FU NIA NIH HHS [P30 AG024827, R01-AG-15432, P30-AG024827, R01-AG-14158]; NIAID NIH HHS [K24-AI-51324] NR 21 TC 17 Z9 19 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X EI 1179-1969 J9 DRUG AGING JI Drugs Aging PY 2006 VL 23 IS 7 BP 579 EP 586 DI 10.2165/00002512-200623070-00004 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 097YL UT WOS:000241485900004 PM 16930086 ER PT J AU Pugh, MJV Foreman, PJ Berlowitz, DR AF Pugh, Mary Jo V. Foreman, Perry J. Berlowitz, Dan R. TI Prescribing antiepileptics for the elderly - Differences between guideline recommendations and clinical practice SO DRUGS & AGING LA English DT Article ID NEWLY-DIAGNOSED EPILEPSY; NURSING-HOME RESIDENTS; TONIC CLONIC SEIZURES; DOUBLE-BLIND; DRUG-USE; LAMOTRIGINE MONOTHERAPY; UNTREATED EPILEPSY; CARBAMAZEPINE; THERAPY; AGE AB The incidence of epilepsy in patients aged > 60 years is higher than in any other period of life. Yet, until recently, what was known about the treatment of older patients with epilepsy has been inferred from studies in younger patients. A growing body of clinical evidence focused exclusively on the elderly suggests that, while some issues are similar for older and younger adults, older patients with epilepsy may require even more attention regarding antiepileptic drug (AED) selection than younger patients. This article reviews published guidelines and recommendations to identify explicit recommendations for use of specific AEDs in the elderly, and assesses the extent to which those recommendations have been adopted in clinical practice. We found that while one systematically derived guideline stated that lamotrigine may be a good choice for older patients because of its favourable adverse effect profile, only clinical recommendations based on expert opinion explicitly identified AEDs that are more and less appropriate for use in the elderly. Examination of published studies describing recent AED-prescribing patterns suggests that clinical recommendations have been, at best, slowly adopted. This observation is exemplified by the fact that older patients newly diagnosed with epilepsy are still prescribed phenobarbital - a drug identified as suboptimal in 1985. In order to better understand the delay in adopting clinical recommendations, we examine these findings in light of diffusion of innovations theory, a theory that has been used to understand dissemination of other new medical technologies. According to this theory, while it is too early to suggest that use of second-generation AEDs in the elderly has been delayed, the continued use of phenobarbital in older patients newly diagnosed with epilepsy represents a serious delay in adoption of recent guidelines. Delays may be related to lack of knowledge by primary care clinicians and emergency room physicians (who frequently treat older patients with epilepsy), lack of 'opinion leaders' in primary care and perhaps general neurology, clinicians' focus on seizure control as the primary endpoint in treating patients with epilepsy, and difficulties in changing long-standing prescribing patterns. Research targeting barriers to more appropriate prescribing is needed to determine appropriate strategies for changing AED prescribing practices in the elderly. C1 S Texas Vet Healthcare Syst, San Antonio, TX 78023 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. ENRM VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Pugh, MJV (reprint author), S Texas Vet Healthcare Syst, 7400 Merton Minter St, San Antonio, TX 78023 USA. EM pughm@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763 NR 73 TC 17 Z9 17 U1 5 U2 7 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2006 VL 23 IS 11 BP 861 EP 875 DI 10.2165/00002512-200623110-00002 PG 15 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 118SN UT WOS:000242962100002 PM 17109565 ER PT S AU Sharp, G Kandasamy, N AF Sharp, Gregory Kandasamy, Nagarajan GP IEEE TI A dependable system architecture for safety-critical respiratory-gated radiation therapy SO DSN 2006 INTERNATIONAL CONFERENCE ON DEPENDABLE SYSTEMS AND NETWORKS, PROCEEDINGS SE International Conference on Dependable Systems and Networks LA English DT Proceedings Paper CT International Conference on Dependable Systems and Networks CY JUN 25-28, 2006 CL Philadelphia, PA SP HP Invent, Raytheon Co, Google Inc, AVAYA Labs, Microsoft Res, AT& T ID TUMOR-TRACKING SYSTEM; RADIOTHERAPY; MOTION AB This experience report describes the design and implementation of safety-critical software and hardware for respiratory gating of a medical linear accelerator. Respiratory gating refers to a radiotherapy technique for treating cancer in the lung, liver, and abdomen, where tumors move while a patient breathes. A computer software program tracks the position of the tumor within the human body using x-ray fluoroscopy. When the tumor is in the correct position, the linear accelerator is triggered, delivering a beam of radiation toward the target. As part of the gating system, a comprehensive strategy for safety has been developed. This paper describes these safety features, focusing on the online monitoring techniques used to confirm the proper operation of the fluoroscopic imaging panels and the pattern recognition algorithms used for tumor identification. C1 [Sharp, Gregory] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kandasamy, Nagarajan] Drexel Univ, Dept Elect & Comp Engn, Philadelphia, PA 19104 USA. RP Sharp, G (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1530-0889 BN 0-7695-2607-1 J9 I C DEPEND SYS NETWO PY 2006 BP 55 EP 60 DI 10.1109/DSN.2006.3 PG 6 WC Computer Science, Hardware & Architecture; Computer Science, Theory & Methods SC Computer Science GA BEW96 UT WOS:000239916800007 ER PT J AU Jassal, DS Neilan, TG Hung, J AF Jassal, DS Neilan, TG Hung, J TI A continuous murmur SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE aortic dissection; fistula; echocardiography ID AORTIC DISSECTION; ASCENDING AORTA; ATRIAL FISTULA AB A 61-year-old male with a history of a mechanical Bjork-Shiley aortic valve replacement in 1977 and repair of an ascending aortic root dissection in 1993, presented with a 2-week history of fatigue and exertional dyspnea. Echocardiography confirmed the presence of an aortic pseudoaneurysm with a fistulous connection between the aorta and right atrium, which subsequently underwent successful repair. Although there have been several cases describing the development of an aortic pseudoaneurysm after aortic dissection repair, our case is the first to describe an aorta-atrial fistula as a long-term complication of a previous aortic dissection repair. C1 Massachusetts Gen Hosp, Dept Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Jassal, DS (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Cardiac Ultrasound Lab, VBK-508,55 Fruit St, Boston, MA 02114 USA. EM djassal@partners.org NR 4 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2006 VL 23 IS 1 BP 60 EP 61 DI 10.1111/j.1540-8175.2006.00112.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 999XU UT WOS:000234425800011 PM 16412186 ER PT J AU Canseven, AG Seyhan, N Mirshahidi, S Imir, T AF Canseven, AG Seyhan, N Mirshahidi, S Imir, T TI Suppression of natural killer cell activity on Candida stellatoidea by a 50 Hz magnetic field SO ELECTROMAGNETIC BIOLOGY AND MEDICINE LA English DT Article DE C. Stellatoidea; ELF magnetic field; environmental magnetic field; in vivo; NK cytotoxic activity ID MOUSE-SKIN MODEL; ELECTROMAGNETIC-FIELDS; CANCER PROMOTION; EXPOSURE; RATS; MODULATION; SYSTEM; MICE; NK AB Exposure to electromagnetic fields (EMF) is ubiquitous for almost all individuals living in industrialized countries. Epidemiological and laboratory studies suggest that exposure to Extremely Low Frequency (ELF) EMF increase cancer risk. The immune system functions as one of the body's main protective mechanisms, and Natural Killer (NK) cells are a subset of lymphocytes that can destroy several types of tumor cells. In this study, we investigated, NK cell activity after exposure to a 50 Hertz (Hz), 2 mT magnetic field generated by a Helmholtz Coil. Nineteen male, 10-12 week old guinea pigs were used, and NK cytotoxic activity of splenocytes was measured in vitro by natural anticandidial colorimetric index. The Mann-Whitney U test was applied for statistical analysis. NK cell cytotoxic activity was decreased in exposed compared to controls. Our data suggests that part of the immune system, the NK cell, can be suppressed by a 50 Hz magnetic field. C1 Gazi Univ, Tip Fak, Dept Biophys, TR-06510 Ankara, Turkey. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Gazi Univ, Tip Fak, Dept Med Microbiol, TR-06510 Ankara, Turkey. RP Canseven, AG (reprint author), Gazi Univ, Tip Fak, Dept Biophys, TR-06510 Ankara, Turkey. EM canseven@gazi.edu.tr NR 29 TC 7 Z9 7 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1536-8378 J9 ELECTROMAGN BIOL MED JI Electromagn. Biol. Med. PY 2006 VL 25 IS 2 BP 79 EP 85 DI 10.1080/15368370600697453 PG 7 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 051WN UT WOS:000238192500001 PM 16771296 ER PT S AU Priel, A Tuszynski, JA Cantiello, HF AF Priel, Avner Tuszynski, Jack A. Cantiello, Horacion F. BE Tuszynski, JA TI The Dendritic Cytoskeleton as a Computational Device: An Hypothesis SO EMERGING PHYSICS OF CONSCIOUSNESS SE Frontiers Collection LA English DT Article; Book Chapter ID LONG-TERM POTENTIATION; MICROTUBULE-ASSOCIATED PROTEINS; ACTIN-BASED PLASTICITY; DISPERSIVE TRANSMISSION-LINE; HIPPOCAMPAL PYRAMIDAL CELLS; INHIBITORY GUIDANCE CUE; GROWTH CONE MOTILITY; F-ACTIN; SYNAPTIC PLASTICITY; NEURITE INITIATION AB This chapter presents a, molecular-dynamical description of the functional role of cytoskeletal elements within the dendrites of a neuron. Our working hypothesis is that the dendritic cytoskeleton, including both microtubules (MTs) and actin filaments plays an active role in computations affecting neuronal function. These cytoskeletal elements are affected by, and in turn regulate, ion-channel activity, MAPs and other cytoskeletal proteins such as kinesin. A major hypothesis we advance here is that the C-termini protruding from the surface of a MT can exist in several conformational states, which lead to collective dynamical properties of the neuronal cytoskeleton. Further, these collective states of the C-termini on MTs have a significant effect. on the ionic condensation and ion-cloud propagation that have physical similarities to those recently found in actin filaments. Our objective is to provide an integrated view of these phenomena in a bottom-up scheme. We outline substantial evidence to support our model and contend that ionic wave propagation along cytoskeletal structures impact channel function, and thus the computational capabilities of the dendritic tree and neuronal function at large. C1 [Priel, Avner; Tuszynski, Jack A.] Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. [Cantiello, Horacion F.] Massachusetts Gen Hosp, Charlestown, MA USA. [Cantiello, Horacion F.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Priel, A (reprint author), Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. NR 144 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1612-3018 BN 978-3-540-23890-4 J9 FRONT COLLECT PY 2006 BP 293 EP 325 DI 10.1007/3-540-36723-3_8 D2 10.1007/3-540-36723-3 PG 33 WC History & Philosophy Of Science SC History & Philosophy of Science GA BJR75 UT WOS:000267050400008 ER PT J AU Leung, WK Chan, FKL Graham, DY AF Leung, WK Chan, FKL Graham, DY TI Ulcers and gastritis SO ENDOSCOPY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; MUCOSA; COHORT C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Chinese Univ Hong Kong, Prince Wales Hosp, Fac Med, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Prince Wales Hosp, Fac Med, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Rm 3A-320 111D,2002 Holocombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu RI Leung, Wai Keung/B-8140-2011; Chan, Francis K. L./F-4851-2010 OI Chan, Francis K. L./0000-0001-7388-2436 NR 12 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JAN PY 2006 VL 38 IS 1 BP 2 EP 4 DI 10.1055/s-2005-921129 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 003EF UT WOS:000234663700002 PM 16429346 ER PT J AU Rich, DQ Mittleman, MA Link, MS Schwartz, J Luttmann-Gibson, H Catalano, PJ Speizer, FE Gold, DR Dockery, DW AF Rich, DQ Mittleman, MA Link, MS Schwartz, J Luttmann-Gibson, H Catalano, PJ Speizer, FE Gold, DR Dockery, DW TI Increased risk of paroxysmal atrial fibrillation episodes associated with acute increases in ambient air pollution SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; arrhythmias; fibrillation; epidemiology; case-crossover; ozone ID ACUTE MYOCARDIAL-INFARCTION; CASE-CROSSOVER ANALYSIS; MANAGEMENT; EXERTION; DESIGN; STROKE; IMPACT; DEATH AB OBJECTIVES: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF. DESIGN: We performed a case-crossover study. PARTICIPANTS: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n = 203) were followed until July 2002. EVALUATIONS/MFASUREMENTS: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects. RESULTS: We found a statistically significant positive association between episodes of PAT and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio = 2.08; 95% confidence interval = 1.22, 3.54; p = 0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon. CONCLUSIONS: Increased ambient 03 pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Dockery, DW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Suite 415 W,401 Pk Dr, Boston, MA 02215 USA. EM ddockery@hsph.harvard.edu FU NIEHS NIH HHS [P30 ES000002, 5T32 ES007069, ES-09825, ES00002, P01 ES009825, T32 ES007069] NR 24 TC 66 Z9 67 U1 0 U2 4 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 JAN PY 2006 VL 114 IS 1 BP 120 EP 123 DI 10.1289/ehp.8371 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 999NR UT WOS:000234396800048 PM 16393668 ER PT J AU Gillman, MW Rifas-Shiman, SL Berkey, CS Frazier, AL Rockett, HRH Camargo, CA Field, AE Colditz, GA AF Gillman, MW Rifas-Shiman, SL Berkey, CS Frazier, AL Rockett, HRH Camargo, CA Field, AE Colditz, GA TI Breast-feeding and overweight in adolescence SO EPIDEMIOLOGY LA English DT Article ID OBESITY; CHILDREN; ASSOCIATION; CHILDHOOD; RISK AB Background: Previous reports have found associations between having been breast-fed and a reduced risk of being overweight. These associations may be confounded by sociocultural determinants of both breast-feeding and obesity. We addressed this possibility by assessing the association of breast-feeding duration with adolescent obesity within sibling sets. Methods: We surveyed 5614 siblings age 9 to 14 years and their mothers. These children were a subset of participants in the Growing Up Today Study, in which we had previously reported an inverse association of breast-feeding duration with overweight. We compared the prevalence of overweight (body mass index exceeding the age-sex-specific 85th percentile) in siblings who were breast-fed longer than the mean duration of their sibship with those who were breast-fed for a shorter period. Then we compared odds ratios from this within-family analysis with odds ratios from an overall (ie, not within-family) analysis. Results: Mean +/- standard deviation breast-feeding duration was 6.4 +/- 4.0 months, and crude prevalence of overweight was 19%. On average, siblings who were breast-fed longer than their family mean had breast-feeding duration 3.7 months longer than their shorter-duration siblings. The adjusted odds ratio (OR) for overweight among siblings with longer breast-feeding duration, compared with shorter duration, was 0.92 (95% confidence interval = 0.76-1.11). In overall analyses, the adjusted OR was 0.94 (0.88-1.00) for each 3.7-month increment in breast-feeding duration. Conclusion: The estimated OR for the within-family analysis was close to the overall estimate, suggesting that the apparent protective effect of breast-feeding on later obesity was not highly confounded by unmeasured sociocultural factors. A larger study of siblings, however, would be needed to confirm this conclusion. C1 HMS, HPHC, DACP, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Gillman, MW (reprint author), HMS, HPHC, DACP, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM matthew_gillman@hms.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL 68041, K24 HL068041, K24 HL068041-03]; NIDDK NIH HHS [R01 DK046834, DK 46200, P30 DK040561, P30 DK040561-11, P30 DK046200, R01 DK046834-04] NR 18 TC 50 Z9 51 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2006 VL 17 IS 1 BP 112 EP 114 DI 10.1097/01.ede.0000181629.59452.95 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 996SQ UT WOS:000234195400020 PM 16357604 ER PT J AU Camposano, SE Lyczkowski, DA Rakowski, SK Thiele, EA AF Camposano, Susana E. Lyczkowski, David A. Rakowski, Sonja K. Thiele, Elizabeth A. TI Epilepsy in tuberous sclerosis complex (TSC): A retrospective population based study SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Massachusetts Gen Hosp, Herscot Ctr TSC, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 2 EP 2 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500005 ER PT J AU Licht, EA McMurtray, AM Wallis, RA Panizzon, K Saul, RE Fujikawa, DG Mendez, MF AF Licht, Eliot A. McMurtray, Aaron M. Wallis, Roi Ann Panizzon, Kimberley Saul, Ron E. Fujikawa, Denson G. Mendez, Mario F. TI MRI abnormalities as markers for epileptiform activity in cognitively impaired and demented patients SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 50 EP 50 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500140 ER PT J AU Andermann, E Jansen, A Sancak, O D'Agostino, M Badhwar, A Roberts, P Wilkinson, R Melanson, D Tampieri, D Maat-Kievit, A Goedbloed, M Van den Ouweland, A Nellist, M Pandolfo, M Sims, K Thiele, E Dubeau, F Andermann, F Kwiatkowski, D Halley, D AF Andermann, E. Jansen, A. Sancak, O. D'Agostino, M. Badhwar, A. Roberts, P. Wilkinson, R. Melanson, D. Tampieri, D. Maat-Kievit, A. Goedbloed, M. Van den Ouweland, A. Nellist, M. Pandolfo, M. Sims, K. Thiele, E. Dubeau, F. Andermann, F. Kwiatkowski, D. Halley, D. TI Mild phenotype in tuberous sclerosis patients with codon 905 missense mutations in the TSC2 gene SO EPILEPSIA LA English DT Meeting Abstract CT 7th European Congress on Epileptology CY JUL 02-06, 2006 CL Helsinki, FINLAND C1 Montreal Neurol Hosp & Inst, Neurogenet Unit, Montreal, PQ, Canada. McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. McGill Univ, Dept Dermatol, Montreal, PQ, Canada. McGill Univ, Dept Radiol, Montreal, PQ, Canada. Free Univ Brussels, Dept Neurol, Brussels, Belgium. Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Pediat Neurol, Boston, MA USA. RI maat-kievit, anneke/C-7483-2013; Kievit, Anneke/O-8830-2014; Jansen, Anna/P-3121-2014 OI Jansen, Anna/0000-0002-3835-2824 NR 0 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 3 BP 85 EP 85 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 119OO UT WOS:000243021800324 ER PT J AU Kustra, R Morrell, M Hayes, F Sluss, P Warnock, C Conklin, H Isojarvi, J AF Kustra, R. Morrell, M. Hayes, F. Sluss, P. Warnock, C. Conklin, H. Isojarvi, J. TI The incidence of components of polycystic ovary syndrome is higher in young women with epilepsy treated with valproate versus lamotrigine SO EPILEPSIA LA English DT Meeting Abstract CT 7th European Congress on Epileptology CY JUL 02-06, 2006 CL Helsinki, FINLAND C1 GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Stanford Univ, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 3 BP 124 EP 124 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 119OO UT WOS:000243021800477 ER PT J AU Bruno, PL Lyczkowski, DA Sedgewick, AE Thiele, EA AF Bruno, Patricia L. Lyczkowski, David A. Sedgewick, Allison E. Thiele, Elizabeth A. TI Safety and efficacy of felbamate treatment in pediatric epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 177 EP 178 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500503 ER PT J AU Rowan, AJ Ramsay, RE Macias, F AF Rowan, A. James Ramsay, R. Eugene Macias, Flavia CA VA Cooperative Study 428 Study G TI In the elderly, seizure control and antiepileptic drug tolerance decrease with increasing age SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Bronx Vet Adm Med Ctr, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. VA Med Ctr, Miami, FL USA. Univ Miami, Sch Med, Miami, FL USA. RI Ramsay, R. Eugene/D-4491-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 198 EP 198 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501036 ER PT J AU Cash, SS Meng, N Melinosky, C Ulbert, I Devinsky, O Doyle, W Mehta, A Wang, C Bromfield, E Madsen, J Halgren, E AF Cash, S. S. Meng, N. Melinosky, C. Ulbert, I. Devinsky, O. Doyle, W. Mehta, A. Wang, C. Bromfield, E. Madsen, J. Halgren, E. TI Macro- and microelectrode recordings show complex spatiotemporal evolution of focal seizures in human epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. NYU, Med Ctr, New York, NY 10016 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 208 EP 208 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501064 ER PT J AU Higgs, MH Robbins, CA Spain, WJ AF Higgs, Matthew H. Robbins, Carol A. Spain, William J. TI Stochastic bursting in neocortical layer 2/3 pyramidal neurons SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 216 EP 216 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501088 ER PT J AU Niquet, J Lopez-Meraz, ML Wasterlain, C Suchomelova, L AF Niquet, Jerome Lopez-Meraz, Maria-Leonor Wasterlain, Claude Suchomelova, Lucie TI Hyperthermia aggravates status epilepticus induced-neuronal injury in the immature brain SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 224 EP 225 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501113 ER PT J AU Peng, ZC Huang, CS Houser, CR AF Peng, Zechun Huang, Christine S. Houser, Carolyn R. TI Transitory activation of extracellular signal-regulated kinase (ERK) by spontaneous seizures in a mouse model of temporal lobe epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 231 EP 231 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501133 ER PT J AU Wallis, RA Panizzon, KL AF Wallis, Roi Ann Panizzon, Kimberly L. TI Neuroprotective efficacy of the mitochondrial ATP-sensitive potassium channel opener, chromakalim against depolarization injury to Ca1 pyramidal neurons in rat hippocampal slices SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 238 EP 238 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501151 ER PT J AU Zhao, SP Shinmei, SS Aviles, ER Fujikawa, DG AF Zhao, Shuangping Shinmei, Steve S. Aviles, Ernesto R., Jr. Fujikawa, Denson G. TI Translocation of mitochondrial cytochrome C, apoptosis-inducing factor and endonuclease G to the nuclei of seizure-induced necrotic neurons SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 242 EP 242 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501164 ER PT J AU Pugh, MJV Knoefel, JE Cramer, JA Berlowitz, DR AF Pugh, Mary Jo V. Knoefel, Jan E. Cramer, Joyce A. Berlowitz, Dan R. TI Profound comorbidity in older patients with epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Vet Healthcare Syst New Mexico, Albuquerque, NM USA. S Texas Vet Healthcare Syst, VERDICT, San Antonio, TX USA. Yale Univ, New Haven, CT USA. Bedford VA Hosp, CHQOER, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 281 EP 282 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501279 ER PT J AU Besio, WG Koka, K Cole, AJ Zhu, F AF Besio, Walter G. Koka, Kanthaiah Cole, Andrew J. Zhu, Fei TI Feasibility of modulating pilocarpine-induced status epilepticus in rats via concentric ring electrode transcutaneous electrical stimulation SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Louisiana Tech Univ, Ruston, LA 71270 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 299 EP 300 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501330 ER PT J AU Bower, CM Cheng, EM Spencer, SS Vassar, S Vickrey, BG AF Bower, Christine M. Cheng, Eric M. Spencer, Susan S. Vassar, Stefanie Vickrey, Barbara G. TI Preoperative expectations for resective epilepsy surgery SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Greater Los Angeles VA Med Ctr, Dept Neurol, Los Angeles, CA USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 340 EP 340 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501444 ER PT S AU Offner, H Polanczyk, M AF Offner, Halina Polanczyk, Magdalena BE Bradlow, HL Carruba, G TI A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis SO ESTROGENS AND HUMAN DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Estrogens and Human Diseases CY MAY 15-21, 2006 CL Erice, ITALY SP Ettore Majorana Fdn, Ctr Sci Culture DE estrogen; estrogen receptors; Treg; FoxP3; immunoregulation; neuroprotection; EAE; multiple sclerosis ID REGULATORY T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; IMMUNOLOGICAL SELF-TOLERANCE; CENTRAL-NERVOUS-SYSTEM; MYELIN PROTEOLIPID PROTEIN; BV8S2 TRANSGENIC MICE; RECEPTOR-ALPHA; GENE-EXPRESSION; FEMALE MICE; GENDER DIFFERENCES AB The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17-beta estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. The E2 mediates inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE are mediated through Esr-1 (alpha receptor for E2) but not Esr-2 (beta receptor for E2), as are its anti-inflammatory and neuroprotective effects. A novel finding is that E2 upregulated the expression of FoxP3 that contributes to the activity of CD4 + CD25 + T regulatory cells (Treg). The protective effects of E2 in EAE suggest its use as a therapy for multiple sclerosis (MS). Possible risks may be minimized by using sub-pregnancy levels of exogenous E2 that produced synergistic effects when used in combination with another immunoregulatory therapy. Alternatively, one might envision using E2 derivatives alone or in combination therapies in both male and female MS patients. C1 Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu NR 113 TC 52 Z9 57 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-669-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1089 BP 343 EP 372 DI 10.1196/annals.1386.021 PG 30 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFU92 UT WOS:000244736800029 PM 17261780 ER PT J AU Ellinor, PT Low, AF MacRae, CA AF Ellinor, PT Low, AF MacRae, CA TI Reduced apelin levels in lone atrial fibrillation SO EUROPEAN HEART JOURNAL LA English DT Article DE atrial fibrillation; arrhythmia; peptides; diagnosis ID CONGESTIVE-HEART-FAILURE; NATRIURETIC PEPTIDE LEVELS; ORPHAN RECEPTOR APJ; SINUS RHYTHM; ENDOGENOUS LIGAND; BLOOD-PRESSURE; PERSISTENT; ENALAPRIL AB Aims Apelin is an endogenous peptide hormone that appears to have a physiological role in counter-regulation of the angiotensin and vasopressin systems. This peptide has been reported to be down-regulated in subjects with acute heart failure, but has not been studied in other cardiovascular conditions. We studied apelin levels in 73 subjects with lone atrial fibrillation (AF). Methods and results Study subjects had electrocardiographic evidence of paroxysmal or chronic AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of coronary artery disease, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or antecedent hypertension. Controls were recruited from a healthy outpatient population. Plasma apelin levels were determined using a commercially available immunoassay. Seventy-three subjects with lone AF and 73 healthy controls were enrolled and studied. Mean levels of apelin were significantly lower in subjects with lone AF when compared with controls (307 vs. 648 pg/mL, P < 0.00005). Conclusion Reduced apelin levels were observed in this homogenous population of lone AF subjects and may represent an underlying diathesis predisposing to this common arrhythmia. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 149 13th St, Boston, MA 02114 USA. EM cmacrae@partners.org FU NHLBI NIH HHS [HL71632, R01 HL075431, HL075431] NR 34 TC 42 Z9 54 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2006 VL 27 IS 2 BP 222 EP 226 DI 10.1093/eurheartj/ehi648 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000BV UT WOS:000234436800020 PM 16278229 ER PT J AU Ramaswamy, S AF Ramaswamy, S TI Modeling metastasis SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID BREAST-CANCER METASTASIS; SIGNATURE; TUMORS; GENES C1 Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, 185 Cambridge St,CPZN 4200, Boston, MA 02114 USA. EM sridhar@mgh.harvard.edu FU NCI NIH HHS [K08 CA100339-04, K08 CA100339] NR 11 TC 1 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2006 VL 14 IS 1 BP 1 EP 2 DI 10.1038/sj.ejhg.5201525 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 995MA UT WOS:000234103200001 PM 16288308 ER PT J AU Liang, SC Greenwald, RJ Latchman, YE Rosas, L Satoskar, A Freeman, GJ Sharpe, AH AF Liang, SC Greenwald, RJ Latchman, YE Rosas, L Satoskar, A Freeman, GJ Sharpe, AH TI PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE costimulation; infection; lelshmania; PD-1; Th1/Th2 ID RECEPTOR-DEFICIENT MICE; T-CELL-ACTIVATION; B7 FAMILY; TH1 RESPONSE; BALB/C MICE; INFECTION; MEXICANA; DISRUPTION; EXPRESSION; MEMBER AB To compare the roles of programmed death 1 ligand 1 (PD-L1) and PD-L2 in regulating immunity to infection, we investigated responses of mice lacking PD-L1 or PD-L2 to infection with Leishmania mexicana. PD-L1(-/-) and PD-L2(-/-) mice exhibited distinct disease outcomes following infection with L. mexicana. In comparison to susceptible WT mice, PD-L1(-/-) mice showed resistance to L. mexicana, as demonstrated by reduced growth of cutaneous lesions and parasite burden. In contrast, PD-L2-/- mice developed exacerbated disease with increased parasite burden. Host resistance to L. mexicana is partly associated with the development of a Th1 response and down-regulation of the Th2 response. Both PD-L1(-/-) and PD-L2(-/-) mice produced levels of IFN-gamma similar to WT mice. However, the development of IL-4-producing cells was reduced in PD-L1(-/-) mice, demonstrating a role for PD-L1 in regulating Th cell differentiation. This inadequate Th2 response may explain the increased resistance of PD-L1(-/-) mice. Although no alterations in Th1/Th2 skewing were observed in PD-L2-/- mice, PD-L2-/- mice exhibited a marked increase in L. mexicana-specific antibody production. Increased Leishmania-specific IgG production may suppress the healing response through Fc gamma R ligation on macrophages. Taken together, our results demonstrate that PD-L1 and PD-L2 have distinct roles in regulating the immune response to L. mexicana. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur,NRB 837, Boston, MA 02115 USA. EM asharpe@rics.bwh.harvard.edu FU Wellcome Trust NR 25 TC 40 Z9 44 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2006 VL 36 IS 1 BP 58 EP 64 DI 10.1002/eji.200535458 PG 7 WC Immunology SC Immunology GA 002NF UT WOS:000234617500007 PM 16358363 ER PT J AU Barton, JJS Greenzang, C Hefter, R Edelman, J Manoach, DS AF Barton, JJS Greenzang, C Hefter, R Edelman, J Manoach, DS TI Switching, plasticity, and prediction in a saccadic task-switch paradigm SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE task switch; prediction; foreknowledge; reconfiguration; antisaccade ID ANTI-SACCADES; PRO-SACCADES; EYE-MOVEMENT; SET; RECONFIGURATION; COSTS; PERFORMANCE; INHIBITION AB Several cognitive processes are involved in task-switching. Using a prosaccade/antisaccade paradigm, we manipulated both the interval available for preparation between the cue and the target and the predictability of trial sequences, to isolate the contributions of foreknowledge, an active switching (reconfiguration) process, and passive inhibitory effects persisting from the prior trial. We tested 15 subjects with both a random and a regularly alternating trial sequence. Half of the trials had a short cue-target interval of 200 ms, and half a longer cue-target interval of 2,000 ms. When there was only a short preparatory interval, switching increased the latencies for both prosaccades and antisaccades. With a long preparatory interval, switching was associated with a smaller latency increase for prosaccades and, importantly, a paradoxical reduction in latency for antisaccades. Foreknowledge of a predictable sequence did not allow subjects to reduce switch costs in the manner that a long preparatory cue-target interval did. In the trials with short preparatory intervals, the effects on latency attributable to active reconfiguration processes were similar for prosaccades and antisaccades. We propose a model in which the passive inhibitory effects that persist from the prior saccadic trial are due not to task-set inertia, in which one task-set inhibits the opposite task-set, but to inhibition of the saccadic response-system by the antisaccade task, to account for the paradoxical set-switch benefit for antisaccades at long cue-target intervals. Our findings regarding foreknowledge show that previous studies used to support task-set inertia may have conflated the effects of both active reconfiguration and passive inhibitory processes on latency. While our model of response-system plasticity can explain a number of effects of dominance asymmetry in switching, other models fail to account for the paradoxical set-switch benefit for antisaccades. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Med Ctr, Boston, MA USA. Boston Univ, Dept Bioengn, Boston, MA USA. Harvard Univ, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr, Boston, MA 02115 USA. RP Barton, JJS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. EM jasonbarton@shaw.ca RI Barton, Jason/A-6362-2012 NR 27 TC 46 Z9 48 U1 6 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2006 VL 168 IS 1-2 BP 76 EP 87 DI 10.1007/s00221-005-0091-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 991OG UT WOS:000233822700008 PM 16096781 ER PT J AU Marklund, N Fulp, CT Shimizu, S Puri, R McMillan, A Strittmatter, SM McIntosh, TK AF Marklund, N Fulp, CT Shimizu, S Puri, R McMillan, A Strittmatter, SM McIntosh, TK TI Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Nogo-A; Nogo-66 receptor; small proline-rich repeat protein 1A (SPRR1A); traumatic brain injury; oligodendrocytes ID CENTRAL-NERVOUS-SYSTEM; LATERAL FLUID-PERCUSSION; SPINAL-CORD-INJURY; MYELIN-ASSOCIATED GLYCOPROTEIN; MESSENGER-RNA EXPRESSION; OLIGODENDROCYTE PRECURSOR CELLS; INHIBITS NEURITE OUTGROWTH; RETINAL GANGLION-CELLS; AXON REGENERATION; WHITE-MATTER AB Axons show a poor regenerative capacity following traumatic central nervous system (CNS) injury, partly due to the expression of inhibitors of axonal outgrowth, of which Nogo-A is considered the most important. We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats. Immunoflourescence with antibodies against Nogo-A, NgR and SPRR1A was combined with antibodies against the neuronal markets NeuN and microtubule-associated protein (MAP)-2 and the oligodendrocyte market RIP, while Western blot analysis was performed for Nogo-A and NgR. Brain injury produced a significant increase in Nogo-A expression in injured cortex, ipsilateral external capsule and reticular thalamus from days 1-7 post-injury (P < 0.05) compared to controls. Increased expression of Nogo-A was observed in both RIP- and NeuN positive (+) cells in the ipsilateral cortex, in NeuN (+) cells in the CA3 region of the hippocampus and reticular thalamus and in RIP (+) cells in white matter tracts. Alterations in NgR expression were not observed following traumatic brain injury (TBI). Brain injury increased the extent of SPRR1A expression in the ipsilateral cortex and the CA3 at all post-injury time-points in NeuN (+) cells. The marked increases in Nogo-A and SPRR1A in several important brain regions suggest that although inhibitors of axonal growth may be upregulated, the injured brain is also capable of expressing proteins promoting axonal outgrowth following TBI. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, Dept Neurosurg, Traumat Brain Injury Lab, Philadelphia, PA 19104 USA. Univ Uppsala Hosp, Dept Neurosurg, SE-75185 Uppsala, Sweden. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. RP Marklund, N (reprint author), Univ Uppsala Hosp, Dept Neurosurg, SE-75685 Uppsala, Sweden. EM niklas.marklund@neurokir.uu.se; ss4662@drexel.edu; Stephen.Strittmatter@yale.edu; tkm53@comcast.net RI Strittmatter, Stephen/F-5739-2011 OI Strittmatter, Stephen/0000-0001-8188-3092 FU NIMH NIH HHS [MH T32-17168]; NINDS NIH HHS [R01 NS039962-10, NS P50-08803, NS R01-40978, R01 NS039962, R01 NS042304, R01 NS042304-08, R01 NS056485, R01 NS056485-04, R37 NS033020, R37 NS033020-15] NR 110 TC 36 Z9 38 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2006 VL 197 IS 1 BP 70 EP 83 DI 10.1016/j.expneurol.2005.08.029 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 001LI UT WOS:000234534200008 PM 16321384 ER PT J AU Topcuoglu, MA Singhal, AB AF Topcuoglu, MA Singhal, AB TI Effects of common medications on cerebral vasospasm after subarachnoid haemorrhage SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE angiotensin-converting enzyme inhibitor; aspirin; calcium channel blocker; HMG-coenzyme A reductase inhibitor; nitric oxide (NO); selective serotonin re-uptake inhibitor (SSRI); statin; subarachnoid haemorrhage (SAH); sympathomimetics; vasospasm ID PROTEIN-KINASE-C; RENIN-ANGIOTENSIN SYSTEM; CONVERTING ENZYME-INHIBITOR; DELAYED ISCHEMIC DEFICITS; SMOOTH-MUSCLE CELLS; NITRIC-OXIDE; TRANSDERMAL NITROGLYCERIN; SIGNALING MECHANISMS; BLOOD-PRESSURE; VASCULAR-TONE AB Cerebral vasospasm is a common and serious complication of aneurysmal subarachnoid haemorrhage (SAH). At present, no consistently effective preventative and therapeutic measures are available, perhaps because of incomplete understanding of the pathogenesis of vasospasm. Experimental studies provide evidence that the incidence and severity of vasospasm after SAH can be modulated by drugs that affect neurotransmitter levels, intracellular signalling mechanisms, vascular smooth muscle function, inflammation and cellular proliferation, and the concentration of 'spasmogenic' factors. Preliminary clinical studies indicate that some illicit drugs and common prescription medications can have similar effects in humans. Recognition of these pharmacological effects is important because medications that can worsen or alleviate vasospasm are frequently administered to SAH patients to treat coincident medical problems. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Akdeniz Univ Hosp, Dept Neurol, TR-07059 Antalya, Turkey. RP Topcuoglu, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, VBK-802, Boston, MA 02114 USA. EM matopcuoglu@yahoo.com; asinghal@partners.org NR 68 TC 1 Z9 3 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD JAN PY 2006 VL 5 IS 1 BP 57 EP 65 DI 10.1517/14740338.5.1.57 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 034RK UT WOS:000236948100011 PM 16370956 ER PT J AU Clark, JW AF Clark, JW TI Rubitecan SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE camptothecin; oral; pancreatic cancer; rubitecan; topoisomerase I ID PHASE-II TRIAL; CELL LUNG-CANCER; SOLID TUMORS; 9-NITROCAMPTOTHECIN RFS-2000; CAMPTOTHECIN ANALOG; PANCREATIC-CANCER; ORAL 9-NITROCAMPTOTHECIN; PRECLINICAL EVALUATION; ADVANCED MALIGNANCIES; LIPOSOME AEROSOL AB The only approved camptothecins for use in patients to date (topotecan and irinotecan) are delivered intravenously. Thus, an oral camptothecin analogue that would provide the convenience of oral delivery with the flexibility for a variety of prolonged treatment schedules would be advantageous. Rubitecan is an orally available camptothecin analogue that also has potential for delivery transdermally or by inhalation. Like all of the camptothecins, its antitumour activity is mediated through the inhibition of DNA topoisomerase 1, which is involved in relaxing supercoiled DNA, which is important for the process of DNA replication and RNA transcription. Rubitecan exists in equilibrium as 9-nitro-camptothecin (9-NC) and 9-amino-camptothecin (9-AC), a metabolite that is thought to be active although it failed in clinical trials. Both 9-NC and 9-AC contain a lactone ring that is required for optimal activity with the carboxylic acid (open ring) forms being significantly less active or inactive. A more acidic environment favours the lactone ring structure, whereas neutral or basic conditions favour the conversion to the carboxylic acid form. in addition to issues of lactone ring stability at physiological pH (true for all of the camptothecin analogues), there is pharmacolkinetic variability that has had to be dealt with during the development of rubitecan. Preclinically, rubitecan has shown activity against a broad spectrum of tumour types in in vitro and in vivo human tumour xenograft models. Frustratingly, the level of activity of an agent in preclinical models has not always translated into similar activity against human tumours in clinical trials. To date, with the exception of pancreatic and possibly ovarian cancer, rubitecan has had disappointing activity against a number of other solid turnours in relatively small Phase I/II trials; however, it has shown sufficient activity against pancreatic cancer, a malignancy that remains difficult to treat, to continue to be evaluated in clinical trials for this indication. Results of clinical trials in the next few years should determine whether rubitecan can find a role in cancer therapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Clark, JW (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM jclark@partners.org NR 59 TC 17 Z9 21 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JAN PY 2006 VL 15 IS 1 BP 71 EP 79 DI 10.1517/13543784.15.1.71 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 999WF UT WOS:000234421000007 PM 16370935 ER PT J AU Kligler, B Ulbricht, C Basch, E Kirkwood, CD Abrams, TR Miranda, M Khalsa, KPS Giles, M Boon, H Woods, J AF Kligler, B Ulbricht, C Basch, E Kirkwood, CD Abrams, TR Miranda, M Khalsa, KPS Giles, M Boon, H Woods, J TI Andrographis paniculata for the treatment of upper respiratory infection: A systematic review by the natural standard research collaboration SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Review ID COMBINATION KAN-JANG; DOUBLE-BLIND; FIXED COMBINATION; TRACT INFECTIONS; EXTRACT SHA-10; COMMON COLDS; PLACEBO; PILOT; TRIAL; SYMPTOMS C1 Continum Ctr Hlth & Healing, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Rhode Isl, Kingston, RI 02881 USA. Bastyr Univ, Seattle, WA USA. Univ Toronto, Toronto, ON, Canada. Northeastern Univ, Boston, MA 02115 USA. RP Kligler, B (reprint author), Beth Israel Ctr Hlth & Healing, 245 5th Ave, New York, NY 10015 USA. EM bkligler@bethisraelny.org NR 22 TC 17 Z9 20 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD JAN PY 2006 VL 2 IS 1 BP 25 EP 29 DI 10.1016/j.explore.2005.08.008 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 010PC UT WOS:000235205600016 PM 16781605 ER PT J AU Goodwin, SC Bradley, LD Lipman, JC Stewart, EA Nosher, JL Sterling, KM Barth, MH Siskin, GP Shlansky-Goldberg, RD AF Goodwin, SC Bradley, LD Lipman, JC Stewart, EA Nosher, JL Sterling, KM Barth, MH Siskin, GP Shlansky-Goldberg, RD CA UAE versus Myomectomy Study Grp TI Uterine artery embolization versus myomectomy: a multicenter comparative study SO FERTILITY AND STERILITY LA English DT Article DE embolization; fibroid; leiomyoma ID FIBROID EMBOLIZATION; ABDOMINAL MYOMECTOMY; SYMPTOMATIC LEIOMYOMATA; TRIAL; HYSTERECTOMY; MENORRHAGIA; REDUCTION; SUCCESS AB Objective: To determine whether there is significant quality of life score improvement after uterine artery embolization (UAE) and to compare UAE and myomectomy outcomes. Design: Prospective cohort controlled study. Setting: Sixteen medical centers in the United States. Patient(s): One hundred forty-nine UAE patients and 6.0 myomectomy patients. Patients were assigned to myomectomy or UAE on the basis of a best treatment decision made by the patient and her physician. All patients were observed for 6 months. The UAE patients also had follow-up examinations at 1 year. Intervention(s): Myomectomy or UAE. Main Outcome Measure(s): Quality of life score changes, menstrual bleeding score changes, uterine size differences, time off, and adverse events. Result(s): Both groups experienced statistically significant improvements in the uterine fibroid quality of life score, menstrual bleeding, uterine volume, and overall postoperative quality of life. The mean hospital stay was 1 day for the UAE patients, compared with 2.5 days for the myomectomy patients. The UAE and myomectomy patients returned to their normal activities in 15 days and 44 days, respectively, and returned to work in 10 days and 37 days, respectively. At least one adverse event occurred in 40.1% of the myomectomy patients, compared with 22.1% in the UAE group. Conclusion(s): The uterine fibroid quality of life score was significantly improved in both groups. No significant differences were observed in bleeding improvement, uterine volume reduction, uterine fibroid quality of life score improvement, and overall quality of life score improvement between groups. Patients receiving UAE required fewer days off work, fewer hospital days, and experienced fewer adverse events. C1 Dept Vet Affairs, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Cleveland Clin Fdn, Dept Gynecol, Cleveland, OH 44195 USA. Radiol Associates Atlanta, Atlanta, GA USA. Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Robert Wood Johnson Med Ctr, Dept Radiol, New Brunswick, NJ USA. Inova Alexandria Hosp, Dept Radiol, Alexandria, VA USA. Methodist Hosp, Dept Radiol, Houston, TX 77030 USA. Albany Med Ctr, Albany, NY USA. Hosp Univ Penn, Div Intervent Radiol, Philadelphia, PA 19104 USA. RP Goodwin, SC (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Imaging Serv, 11301 Wilshire Blvd,Mail Code 114, Los Angeles, CA 90073 USA. EM scott.goodwin@med.va.gov OI Shlansky-Goldberg, Richard/0000-0003-3371-0570 NR 37 TC 63 Z9 72 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2006 VL 85 IS 1 BP 14 EP 21 DI 10.1016/j.fertnstert.2005.05.074 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 006QX UT WOS:000234913100003 PM 16412720 ER PT J AU Goodwin, SC AF Goodwin, SC TI Uterine artery embolization: a legitimate option for the treatment of uterine fibroids SO FERTILITY AND STERILITY LA English DT Editorial Material ID LEIOMYOMAS; MANAGEMENT AB As compared with hysterectomy and myomectomy, uterine artery embolization is a safe and efficacious therapy. It should be offered as a legitimate alternative for the treatment of symptomatic fibroids. C1 Vet Adm Greater Los Angeles Hlth Care Syst, Imaging Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA USA. RP Goodwin, SC (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Imaging Serv, 11301 Wilshire Blvd,Mail Code 114, Los Angeles, CA 90073 USA. EM scott.goodwin@med.va.gov NR 9 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2006 VL 85 IS 1 BP 48 EP 48 DI 10.1016/j.fertnstert.2005.09.009 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 006QX UT WOS:000234913100010 ER PT J AU Hess, MM Mueller, F Kobler, JB Zeitels, SM Goodyer, E AF Hess, Markus M. Mueller, Frank Kobler, James B. Zeitels, Steven M. Goodyer, Eric TI Measurements of vocal fold elasticity using the linear skin rheometer SO FOLIA PHONIATRICA ET LOGOPAEDICA LA English DT Article DE vocal fold elasticity; linear skin rheometer; dynamic spring rate ID VISCOELASTIC SHEAR PROPERTIES; HYALURONIC-ACID; INTRAOPERATIVE MEASUREMENT; MECHANICAL-PROPERTIES; STRESS-STRAIN; MUCOSA; MODULUS; BIOMECHANICS; TISSUES AB Objective: The linear skin rheometer (LSR), which measures skin visco-elasticity, was adapted for measurements of vocal fold properties. A series of studies was performed on animal and human excised larynges to determine if the LSR technique can be applied to the vocal fold. Methods: In excised larynges, small patches of mucosa were driven sinusoidally at 0.3 Hz over distances of 1-2 mm using a small probe. Forces in the order of 1 g equivalent gave optimal measurements. Stiffness and viscosity values were derived from stress/strain data. Results: The instrument was able to measure the visco-elasticity of the tissue in a repeatable manner and it could detect areas where the tissue was artificially stiffened. Two-dimensional maps of the mechanical properties of the laryngeal mucosa were obtained showing local variations in elasticity both parallel and perpendicular to the vocal fold edge. Initial studies were undertaken using animal tissue; more recently, the LSR has been successfully used to obtain similar data from human tissue. Conclusion: The LSR was been demonstrated to be capable of measuring the elastic properties of the vocal fold in a repeatable and reliable manner. Further studies will now be undertaken to obtain data from a larger sample of human tissue. Copyright (c) 2006 S. Karger AG, Basel. C1 Univ Hamburg, Ctr Med, Dept Phoniatr & Pediat Audiol, Hamburg, Germany. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. De Montfort Univ, Dept Comp Sci & Engn, Leicester LE1 9BH, Leics, England. RP Hess, MM (reprint author), Univ Klinikum Hamburg, Poliklin Hor Stimm & Sprachheilkunde, Martinistr 52, DE-20246 Hamburg, Germany. EM hess@uke.uni-hamburg.de RI goodyer, eric/G-9191-2012; OI goodyer, eric/0000-0002-4414-0860; Muller, Frank/0000-0003-0566-3076 NR 24 TC 29 Z9 29 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7762 J9 FOLIA PHONIATR LOGO JI Folia Phoniatr. Logop. PY 2006 VL 58 IS 3 BP 207 EP 216 DI 10.1159/000091734 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology; Rehabilitation SC Audiology & Speech-Language Pathology; Otorhinolaryngology; Rehabilitation GA 107IV UT WOS:000242165300006 PM 16636568 ER PT J AU Kochevar, IE Valencia, A AF Kochevar, Irene E. Valencia, Antonio TI Nox1-containing NADPH oxidase is the major source of UVA-induced reactive oxygen species in human keratinocytes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S71 EP S72 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600197 ER PT J AU Reusch, JE Gliwa, C Gunther, J Pedler, M Mcdonald, T O'Brien, K Schauer, I AF Reusch, Jane E. B. Gliwa, Catherine Gunther, Jodean Pedler, Michelle Mcdonald, Tom O'Brien, Kevin Schauer, Irene TI Divergent impact of LDL and oxidized LDL on CREB activation and downregulation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 Denver VAMC, Denver, CO USA. Univ Colorado, Boulder, CO 80309 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S42 EP S42 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600119 ER PT J AU Richardson, A AF Richardson, A. TI Quantitative assessment of the post-translational modification of proteins in aging SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int C1 Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2006 VL 40 SU 1 BP S49 EP S49 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086EG UT WOS:000240656000056 ER PT J AU Zheng, Z Yenari, MA AF Zheng, Z Yenari, MA TI The application of HSP70 as a target for gene therapy SO FRONTIERS IN BIOSCIENCE LA English DT Review DE cerebral ischemia; heat shock protein; gene therapy; HSP70; stroke ID HEAT-SHOCK PROTEINS; FOCAL CEREBRAL-ISCHEMIA; ALPHA-SYNUCLEIN AGGREGATION; PEPTIDE-BINDING DOMAIN; SIMPLEX-VIRUS VECTORS; TRANSCRIPTION FACTOR; IN-VIVO; TRANSGENIC MICE; KINASE-C; RAT HEAT-SHOCK-PROTEIN-70 AB The 70-kDa heat shock proteins (HSP70s) are well-studied and characterized heat shock proteins (HSPs). They constitute essential components of a quality control system of protein synthesis, and function as molecular chaperones to prevent proteins from misfolding and aggregating during both de novo synthesis and under conditions of stress. Moreover, it is now well established that HSP70s play important cytoprotective roles in various pathological settings. Recognition of molecular chaperone and cytoprotective functions of HSP70s is fostering active investigations into the potential of HSP70s as therapeutic targets at the laboratory level. Gaining insight into these recent advances may have profound implications in the development of HSP70-based clinical studies. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94131 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA 94131 USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94131 USA. EM yenari@alum.mit.edu FU NINDS NIH HHS [NS40516] NR 117 TC 12 Z9 13 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 699 EP 707 DI 10.2741/1828 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000054 PM 16146762 ER PT J AU Braun, SE Johnson, RP AF Braun, SE Johnson, RP TI Setting the stage for bench-to-bedside movement of anti-HIV RNA inhibitors-gene therapy for AIDS in macaques SO FRONTIERS IN BIOSCIENCE LA English DT Review DE AIDS; gene therapy; nonhuman primates; animal models; simian immunodeficiency virus; adoptive T cell therapy; hematopoietic stem cell gene therapy; review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC PROGENITOR CELLS; ACTIVE ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE INHIBITORS; IN-VIVO; REPOPULATING CELLS; STEM-CELLS; TYPE-1 REPLICATION; NONHUMAN-PRIMATES; RHESUS MACAQUES AB Despite significant progress over the last two decades, treatment of HIV infection remains a tremendous challenge. Although antiretroviral therapy has proved quite effective in most HIV-infected patients, increasing recognition of toxicity and the emergence of multidrug resistant HIV strains has fueled the development of alternative therapeutic approaches. Introduction of genes to inhibit HIV replication into CD4+ T lymphocytes or hematopoietic stem cells represents a potentially attractive but still unproven strategy. Despite the availability of a diverse range of molecular strategies that are able to provide potent inhibition of HIV replication in the laboratory, translation of these in vitro successes to in vivo therapies has been difficult. Fundamental challenges facing AIDS gene therapy at the present time includes the need to increase the efficiency of gene transfer in vivo, to confer upon genetically-modified T cells the ability to have a selective growth advantage in vivo, and the development of additional techniques to decrease the probability of emergence of resistant viruses. As one of the leading animal models for AIDS and for hematopoietic stem cell gene therapy, nonhuman primates are ideally suited to help address many of these basic questions. This review will provide a general overview of RNA-based genetic strategies for inhibition of HIV and SIV replication, criteria to be considered in the selection of promising inhibitory strategies for in vivo use, and key questions that can be addressed in the macaque model. C1 Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Unit, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU NCI NIH HHS [CA 73473]; NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI 61797, P30 AI 42851] NR 109 TC 9 Z9 10 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 838 EP 851 DI 10.2741/1841 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000067 PM 16146775 ER PT J AU Kabbarah, O Chin, L AF Kabbarah, O Chin, L TI Advances in malignant melanoma: genetic insights from mouse and man SO FRONTIERS IN BIOSCIENCE LA English DT Review DE tumor; cancer; neoplasia; melanoma; melanocyte; genetics; mouse model; review ID HEPATOCYTE GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; SPORADIC PRIMARY MELANOMAS; RECEPTOR MC1R GENE; ULTRAVIOLET-RADIATION; CUTANEOUS MELANOMA; GERMLINE MUTATIONS; RED HAIR; C-MET AB Notorious for its proclivity for metastases and resistance to known therapies, malignant melanoma represents a major health concern. Genetic, epidemiological and genomic investigations are highlighting a repertoire of stereotypical mutations that are associated with human melanoma genesis. The functional significance of many of these genetic alterations is being ascertained through the use of in vivo mouse models. Insights from human and mouse studies, coupled with the development of novel tools for high-resolution characterization of the melanoma genome, hold promise for the identification of better diagnostic markers and potential therapeutic targets. With the rapid improvements in drug design, these recent advances are generating optimism for the development of better therapeutic options for melanoma patients. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Dermatol, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Dermatol, Boston, MA 02115 USA. EM Lynda_Chin@dfci.harvard.edu FU NCI NIH HHS [R01 CA93947, U01 CA84313]; NIAMS NIH HHS [T32 AR07098] NR 161 TC 7 Z9 7 U1 2 U2 5 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2006 VL 11 BP 928 EP 942 DI 10.2741/1849 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973MX UT WOS:000232528000075 PM 16146783 ER PT J AU Wong, P Verselis, SJ Garber, JE Schneider, K Digianni, L Stockwell, DH Li, FP Syngal, S AF Wong, P Verselis, SJ Garber, JE Schneider, K Digianni, L Stockwell, DH Li, FP Syngal, S TI Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome SO GASTROENTEROLOGY LA English DT Article ID NONPOLYPOSIS COLON-CANCER; P53 MUTATIONS; FAMILIAL SYNDROME; BREAST-CANCER; GENE; HOMOLOG; DATABASE; CHROMOSOME-5Q21; IDENTIFICATION; NEOPLASMS AB Background & Aims: Hereditary colorectal cancer is associated most commonly with the hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndromes. We investigated the prevalence of early onset colorectal cancer and the frequency of p53 germline mutations in 64 families from a Li-Fraumeni syndrome (LFS) registry. Methods: Patients with documented colorectal cancer and a diagnosis at or before age 50 were included. P53 analyses were performed through germline mutational analyses using standard molecular techniques. Results: Among the 397 patients and 64 families in the classic LFS registry, a total of 11 patients (2.8%) from 10 different families (15.6%) met criteria for classic LFS and had documented colorectal cancer at less than 50 years of age. The mean age at diagnosis in this group was 33 years and of these patients 4 developed colorectal cancer before age 21 (ages, 9, 11, 15, and 20 y). All families that were tested for p53 mutations (8 of 10) had evidence of germline mutations by sequence analysis; therefore, 12.5% of the total number of families in the registry had colorectal cancer at age less than 50 years and a documented germline p53 mutation. Mutations primarily were missense or nonsense and were located between exons 4-10. Conclusions: LFS patients with germline p53 mutations may have an increased susceptibility to colorectal cancer and present up to several decades earlier than the general population. LFS should be considered when a young patient presents with colorectal cancer. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org FU NCI NIH HHS [K24 CA113433] NR 32 TC 49 Z9 50 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2006 VL 130 IS 1 BP 73 EP 79 DI 10.1053/j.gastro.2005.10.014 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 001HW UT WOS:000234525200013 PM 16401470 ER PT J AU Dienstag, JL McHutchison, JG AF Dienstag, JL McHutchison, JG TI American Gastroenterological Association technical review on the management of hepatitis C SO GASTROENTEROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-ALPHA THERAPY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; NON-B-HEPATITIS; SUSTAINED VIROLOGICAL RESPONSE; LIVER FIBROSIS PROGRESSION; INDIVIDUAL PATIENT DATA; HIV-INFECTED PATIENTS; LONG-TERM EFFICACY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Med Serv,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Med Serv,Off Dean Med Educ, Boston, MA 02115 USA. Duke Univ, Ctr Med, Duke Clin Res Inst, Div Gastroenterol, Durham, NC USA. RP Dienstag, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Med Serv,Dept Med, Boston, MA 02115 USA. NR 375 TC 276 Z9 285 U1 3 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2006 VL 130 IS 1 BP 231 EP 264 DI 10.1053/j.gastro.2005.11.010 PG 34 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 001HW UT WOS:000234525200029 PM 16401486 ER PT J AU Naliboff, BD Mayer, EA AF Naliboff, BD Mayer, EA TI Brain imaging in IBS: Drawing the line between cognitive and non-cognitive processes SO GASTROENTEROLOGY LA English DT Editorial Material ID IRRITABLE-BOWEL-SYNDROME; PAIN; ACTIVATION; PERCEPTION; RESPONSES; PLACEBO; FIBROMYALGIA; STIMULATION; MECHANISMS; SYSTEM C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Physiol, Los Angeles, CA USA. RP Naliboff, BD (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles,Bldg 115,Room 223,11301 Wilshire Bl, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu NR 27 TC 20 Z9 22 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2006 VL 130 IS 1 BP 267 EP 270 DI 10.1053/j.gastro.2005.1.1.034 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 001HW UT WOS:000234525200031 PM 16401488 ER PT J AU Broekaert, IJ Walker, WA AF Broekaert, IJ Walker, WA TI Probiotics as flourishing benefactors for the human body SO GASTROENTEROLOGY NURSING LA English DT Article ID PLACEBO-CONTROLLED TRIAL; LACTOBACILLUS-RHAMNOSUS GG; MUCIN GENE-EXPRESSION; LONG-TERM CONSUMPTION; LACTIC-ACID BACTERIA; ATOPIC DISEASE; KAPPA-B; NECROTIZING ENTEROCOLITIS; SACCHAROMYCES-BOULARDII; HELICOBACTER-PYLORI AB This article provides a comprehensive review of the beneficial effects of various strains of probiotics in preventing and treating certain diseases. I Currently, changed lifestyles as well as the increased use of antibiotics are significant factors challenging the preservation of a healthy intestinal microflora. The concept of probiotics is to restore and uphold a microflora advantageous for the human body. Probiotics are found in a number of fermented dairy products, infant formula, and dietary supplements. In the presence of prebiotics, which are nondigestible food ingredients favorable for probiotic growth, their survival in the intestine is ameliorated. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 114 16th St, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NICHD NIH HHS [R37 HD12437]; NIDDK NIH HHS [P30 DK040561, P30 DK40561, P30 DK040561-11, P01 DK33506] NR 60 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1042-895X J9 GASTROENTEROL NURS JI Gastroenterol. Nurs. PD JAN-FEB PY 2006 VL 29 IS 1 BP 26 EP 34 DI 10.1097/00001610-200601000-00005 PG 9 WC Gastroenterology & Hepatology; Nursing SC Gastroenterology & Hepatology; Nursing GA 044NM UT WOS:000237679300004 PM 16552297 ER PT J AU Seltman, AK Kahrilas, PJ Chang, EY Mori, M Hunter, JG Jobe, BA AF Seltman, AK Kahrilas, PJ Chang, EY Mori, M Hunter, JG Jobe, BA TI Endoscopic measurement of cardia circumference as an indicator of GERD SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID LOWER ESOPHAGEAL SPHINCTER; GASTROESOPHAGEAL-REFLUX DISEASE; HIATAL-HERNIA; GASTRIC DISTENSION; RELAXATION; COMPETENCE; MECHANISM; VALVE; LENGTH AB Background: It is theorized that repeated gastric distention leads to dilatation of the cardia and the development of GERD. We hypothesize that cardia circumference correlates with the presence and the severity of GERD, and we developed software to measure cardia circumference from static endoscopic images. Our aims were to validate the software and to quantify cardia circumference along the spectrum of GERD. Methods: Software-based measurements were compared with actual measurements in animal and mechanical models. A retrospective review of an endoscopic database and patient charts produced 273 subjects, grouped as follows: controls, GERD, <= 3-cm Barrett's esophagus, or > 3-cm Barrett's esophagus. A blinded abstractor measured cardia circumference by using images from the database. Results: Software and actual measurements correlated closely and were reproducible among observers. Median cardia circumference for each group was the following: control, 31.8 mm; GERD, 37.8 mm; <= 3-cm Barrett's esophagus, 38.4 mm; and > 3-cm Barren's esophagus, 45.0 mm (p < 0.001). By using 34.3 mm as a cutoff, cardia circumference was 85.3% sensitive and 89.6% specific for the diagnosis of GERD. Conclusions: There was a direct relationship between cardia circumference and the presence of GERD. This finding augments our understanding of the anatomic contributions of the esophagogastric junction in the pathogenesis of GERD. Cardia measurement may prove to be a useful diagnostic tool. C1 Portland VA Med Ctr, Surg Serv, Portland, OR 97207 USA. RP Jobe, BA (reprint author), Portland VA Med Ctr, Surg Serv, P3Surg,POB 1034, Portland, OR 97207 USA. FU NCI NIH HHS [5P30 CA69533-04, R03 CA150959-01]; NIDCD NIH HHS [R01 DC00646]; NIDDK NIH HHS [2U01DK057132-06A1, K23 DK066165-01] NR 35 TC 14 Z9 14 U1 0 U2 1 PU MOSBY, 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 JAN PY 2006 VL 63 IS 1 BP 22 EP 31 DI 10.1016/j.gie.2005.07.030 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 999UC UT WOS:000234415000005 PM 16377311 ER PT J AU Gopal, DV Chang, EY Kim, CY Sandone, C Pfau, PR Frick, TJ Hunter, JG Kahrilas, PJ Jobe, BA AF Gopal, DV Chang, EY Kim, CY Sandone, C Pfau, PR Frick, TJ Hunter, JG Kahrilas, PJ Jobe, BA TI EUS characteristics of Nissen fundoplication: normal appearance and mechanisms of failure SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 14th World Congress of the International-Association-of-Surgeons-and-Gastroenterologists CY SEP 09-12, 2004 CL Zurich, SWITZERLAND SP Int Assoc Surg & Gastroenterologists ID GASTROESOPHAGEAL-REFLUX DISEASE; LAPAROSCOPIC ANTIREFLUX SURGERY; FOLLOW-UP; MANAGEMENT; COMPLICATIONS; OPERATIONS; APPRAISAL; SYMPTOMS AB Background: In patients who develop symptoms after Nissen fundoplication, the precise mechanism of failure can be difficult to determine. Current testing modalities do not demonstrate sufficient anatomic detail to definitively determine the mechanism. This observational study establishes that EUS can determine fundoplication integrity and hiatal anatomic relationships after Nissen fundoplication. Methods: EUS was performed on the native esophagogastric junction and after Nissen fundoplication in two swine. The EUS characteristics of a properly performed fundoplication were determined. Subsequently; complications of Nissen fundoplication were created, and EUS was performed on each. The EUS criteria of each mechanism of failure were defined. Results: EUS provided sufficient axial resolution to distinguish the esophagus, the fundoplication, and the surrounding hiatal structures within a single image. US of the native esophagogastric junction discerned the length of intra-abdominal esophagus, esophagogastric junction, crura, and anterior hiatus, and, thus; the point of entry into the abdominal cavity. EUS of Nissen fundoplication revealed a 5-layered pattern in a 360 degrees configuration. These layers represent the following: (1) the esophageal wall, (2) the space between the esophagus and the fundoplication, (3) the inner gastric wall of the fundoplication, (4) the gastric lumen, and (5) the outer gastric wall of the fundoplication. A slipped repair was identified by the presence of an echogenic gastric serosa within the fundoplication. A tight fundoplication results in attenuation of the gastric walls, thickening of the esophageal wall, and loss of the 5-layer pattern secondary to obliteration of the potential spaces of the gastric lumen. Dehiscence of the fundoplication was evidenced by a less than 360 degrees 5-layer pattern. Conclusions: EUS of hiatal anatomic relationships is feasible and provides detailed information regarding the integrity and the position of a Nissen fundoplication. EUS may enable a precise determination of the anatomic causes of failure after antireflux surgery. C1 Portland VA Med Ctr, Surg Serv, Portland, OR 97207 USA. RP Jobe, BA (reprint author), Portland VA Med Ctr, Surg Serv, P3Surg,POB 1034, Portland, OR 97207 USA. FU NCI NIH HHS [R03 CA105959-01]; NIDCD NIH HHS [R01 DC00646]; NIDDK NIH HHS [K23 DK066165-01] NR 23 TC 6 Z9 6 U1 0 U2 2 PU MOSBY, 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 JAN PY 2006 VL 63 IS 1 BP 35 EP 44 DI 10.1016/j.gie.2005.08.044 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 999UC UT WOS:000234415000007 PM 16377313 ER PT J AU Ciechanowski, P Russo, J Katon, W Simon, G Ludman, E Von Korff, M Young, B Lin, E AF Ciechanowski, P Russo, J Katon, W Simon, G Ludman, E Von Korff, M Young, B Lin, E TI Where is the patient? The association of psychosocial factors and missed primary care appointments in patients with diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE attachment theory; attachment style; depression; health care utilization; missed appointment; no-show appointments ID CORONARY-HEART-DISEASE; HEALTH-CARE; ATTACHMENT THEORY; ADULT ATTACHMENT; SELF-CARE; DEPRESSIVE SYMPTOMS; MAJOR DEPRESSION; GLYCEMIC CONTROL; NON-ATTENDANCE; ADHERENCE AB Objective: Missed appointments are associated with poorer health outcomes. We predicted that compared to secure attachment style, fearful and dismissing attachment styles would be associated with greater number of missed primary care visits in patients with diabetes. Methods: In patients with diabetes from nine health maintenance organization primary care clinics, we collected data on attachment style and major depression status, and determined the number of missed primary care appointments from automated data. We used Poisson and logistic regression analyses to determine if attachment style was associated with the number of missed primary care same day appointments, scheduled office visits and scheduled preventive care visits, after adjusting for demographics, clinical characteristics, appointment frequency and clustering by clinic. We included major depression as a potential effect modifier. Results: Among 3923 patients with diabetes, prevalence rates of attachment styles were 43.9% for secure, 35.8% for dismissing, 8.1% for preoccupied and 12.2% for fearful attachment style. Major depression was present in 12.4% of patients. Among patients without major depression, there were more missed scheduled office visits (RR= 1.46, 95% CI = 1.18-1.81) among those with dismissing compared to secure attachment style. The likelihood ofhaving missed same day appointments was lower for those with fearful attachment style relative to those with secure attachment style in nondepressed patients compared to patients with fearful and secure attachment style with major depression ( P < .01). Conclusions: Attachment styles characterized by low levels of collaboration are associated with more missed primary care appointments compared to secure attachment style in patients with diabetes. These associations are moderated by depression status. (c) 2006 Elsevier Inc. All tights reserved. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. RP Ciechanowski, P (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM pavelcie@u.washington.edu FU NIDDK NIH HHS [K23 DK60652-01]; NIMH NIH HHS [MH 016473, MH 4-1739] NR 50 TC 36 Z9 36 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2006 VL 28 IS 1 BP 9 EP 17 DI 10.1016/j.genhosppsych.2005.07.004 PG 9 WC Psychiatry SC Psychiatry GA 006YT UT WOS:000234934600003 PM 16377360 ER PT J AU Greenberg, RA Sobhian, B Pathania, S Cantor, SB Nakatani, Y Livingston, DM AF Greenberg, RA Sobhian, B Pathania, S Cantor, SB Nakatani, Y Livingston, DM TI Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes SO GENES & DEVELOPMENT LA English DT Article DE BACH1; BARD1; BRCA1; CtIP; M/R/N; TopBP1 ID S-PHASE CHECKPOINT; CELL-CYCLE CHECKPOINT; DOUBLE-STRAND BREAKS; IONIZING IRRADIATION; RADIOSENSITIZING AGENT; CHK2 PHOSPHORYLATION; FANCONI-ANEMIA; MEIOTIC CELLS; HISTONE H2AX; BRCA1 AB The BRCA1 gene product and its stoichiometric binding partner, BARD1, play a vital role in the cellular response to DNA damage. However, how they acquire specific biochemical functions after DNA damage is poorly understood. Following exposure to genotoxic stress, DNA damage-specific interactions were observed between BRCA1/BARD1 and the DNA damage-response proteins, TopBP1 and Mre11/Rad50/NBS1. Two distinct DNA damage-dependent super complexes emerged; their activation was dependent, in part, on the actions of specific checkpoint kinases, and each super complex contributed to a distinctive aspect of the DNA damage response. The results support a new, multifactorial model that describes how genotoxic stress enables BRCA1 to execute a diverse set of DNA damage-response functions. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biochem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu NR 61 TC 168 Z9 178 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2006 VL 20 IS 1 BP 34 EP 46 DI 10.1101/gad.1381306 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 010AG UT WOS:000235154600005 PM 16391231 ER PT J AU Lee, DG Urbach, JM Wu, G Liberati, NT Feinbaum, RL Miyata, S Diggins, LT He, JX Saucier, M Deziel, E Friedman, L Li, L Grills, G Montgomery, K Kucherlapati, R Rahme, LG Ausubel, FM AF Lee, Daniel G. Urbach, Jonathan M. Wu, Gang Liberati, Nicole T. Feinbaum, Rhonda L. Miyata, Sachiko Diggins, Lenard T. He, Jianxin Saucier, Maude Deziel, Eric Friedman, Lisa Li, Li Grills, George Montgomery, Kate Kucherlapati, Raju Rahme, Laurence G. Ausubel, Frederick M. TI Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial SO GENOME BIOLOGY LA English DT Article ID MICROBIAL GENE IDENTIFICATION; CYSTIC-FIBROSIS PATIENTS; CAENORHABDITIS-ELEGANS; CRYPTOCOCCUS-NEOFORMANS; PATHOGENICITY ISLANDS; MODEL; PATHOGENESIS; SEQUENCE; STRAIN; MAINTENANCE AB Background: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. Results: The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. Conclusion: Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Envivo Pharmaceut Inc, Watertown, MA 02472 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02139 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Cambridge St, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu RI Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 FU NHLBI NIH HHS [U01 HL066678, U01 HL66678]; NIAID NIH HHS [R01 AI064332]; NIDDK NIH HHS [P30 DK040561-11, P30 DK040561] NR 40 TC 219 Z9 588 U1 1 U2 38 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 10 AR R90 DI 10.1186/gb-2006-7-10-r90 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 112HJ UT WOS:000242516200008 PM 17038190 ER PT J AU Mar, JC Rubio, R Quackenbush, J AF Mar, Jessica C. Rubio, Renee Quackenbush, John TI Inferring steady state single-cell gene expression distributions from analysis of mesoscopic samples SO GENOME BIOLOGY LA English DT Article ID NOISE; LEVEL AB Background: A great deal of interest has been generated by systems biology approaches that attempt to develop quantitative, predictive models of cellular processes. However, the starting point for all cellular gene expression, the transcription of RNA, has not been described and measured in a population of living cells. Results: Here we present a simple model for transcript levels based on Poisson statistics and provide supporting experimental evidence for genes known to be expressed at high, moderate, and low levels. Conclusion: Although the model describes a microscopic process occurring at the level of an individual cell, the supporting data we provide uses a small number of cells where the echoes of the underlying stochastic processes can be seen. Not only do these data confirm our model, but this general strategy opens up a potential new approach, Mesoscopic Biology, that can be used to assess the natural variability of processes occurring at the cellular level in biological systems. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Huntington Ave, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu NR 11 TC 8 Z9 8 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 12 AR R119 DI 10.1186/gb-20067-12-r119 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132UG UT WOS:000243967100013 PM 17169148 ER PT J AU Monticelli, S Sharma, S Rao, A AF Monticelli, Silvia Sharma, Sonia Rao, Anjana TI Immunological applications of genomics SO GENOME BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Monticelli, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM monticel@cbr.med.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 7 AR 321 DI 10.1186/gb-2006-7-7-321 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QM UT WOS:000241322700007 PM 16879724 ER PT J AU Peck, D Crawford, ED Ross, KN Stegmaier, K Golub, TR Lamb, J AF Peck, David D Crawford, Emily Ross, Kenneth N. Stegmaier, Kimberly Golub, Todd R. Lamb, Justin TI A method for high-throughput gene expression signature analysis SO GENOME BIOLOGY LA English DT Article ID LIGATION; CANCER; ASSAY AB Genome-wide transcriptional profiling has shown that different biologic states (for instance, disease and response to pharmacologic manipulation) can be recognized by the expression pattern of relatively small numbers of genes. However, the lack of a practical and cost-effective technology for detection of these gene expression 'signatures' in large numbers of samples has severely limited their exploitation in important medical and pharmaceutical discovery applications. Here, we describe a solution based on the combination of ligation-mediated amplification with an optically addressed microsphere and flow cytometric detection system. C1 MIT, Broad Inst, Cambridge, MA 02142 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lamb, J (reprint author), MIT, Broad Inst, Cambridge, MA 02142 USA. EM justin@broad.mit.edu NR 11 TC 86 Z9 89 U1 3 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 7 AR R61 DI 10.1186/gb-2006-7-7-r61 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QM UT WOS:000241322700018 PM 16859521 ER PT J AU Rao, S Orkin, SH AF Rao, Sridhar Orkin, Stuart H. TI Unraveling the transcriptional network controlling ES cell pluripotency SO GENOME BIOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; SELF-RENEWAL; MAMMALIAN EMBRYO; NANOG; STAT3; OCT4; DIFFERENTIATION; EXPRESSION; INDUCTION; FUSION AB Embryonic stem cells (ES cells) are powerful tools for genetic engineering and hold significant potential for regenerative medicine. Recent work provides new insights into ES cell pluripotency and delineates separate transcriptional pathways in ES cells for maintenance of the undifferentiated state and for self-renewal. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 18 TC 27 Z9 30 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 8 AR 230 DI 10.1186/gb-2006-7-8-230 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QN UT WOS:000241322800004 PM 16942632 ER PT J AU Wang, QF Prabhakar, S Wang, QB Moses, AM Chanan, S Brown, M Eisen, MB Cheng, JF Rubin, EM Boffelli, D AF Wang, Qian-fei Prabhakar, Shyam Wang, Qianben Moses, Alan M. Chanan, Sumita Brown, Myles Eisen, Michael B. Cheng, Jan-Fang Rubin, Edward M. Boffelli, Dario TI Primate-specific evolution of an LDLR enhancer SO GENOME BIOLOGY LA English DT Article ID STEROL REGULATORY ELEMENT; LIPOPROTEIN RECEPTOR GENE; FATTY-ACID SYNTHESIS; COMPARATIVE GENOMICS; POSITIVE SELECTION; CHOLESTEROL; SEQUENCE; HUMANS; VERTEBRATE; BINDING AB Background: Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. Results: In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Conclusion: Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human. C1 Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA. Joint Genome Inst, US DOE, Walnut Creek, CA 94598 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rubin, EM (reprint author), Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA. EM EMRubin@lbl.gov RI Wang, Qianben/E-4267-2011; OI Brown, Myles/0000-0002-8213-1658; Eisen, Michael/0000-0002-7528-738X FU NHLBI NIH HHS [T32 HL007279, U01 HL066681, U1HL66681B]; PHS HHS [THL007279F] NR 37 TC 10 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 8 AR R68 DI 10.1186/gb-2006-7-8-r68 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QN UT WOS:000241322800013 PM 16884525 ER PT J AU Zhang, H Loriaux, P Eng, J Campbell, D Keller, A Moss, P Bonneau, R Zhang, N Zhou, Y Wollscheid, B Cooke, K Yi, EC Lee, H Peskind, ER Zhang, J D Smith, R Aebersold, R AF Zhang, Hui Loriaux, Paul Eng, Jimmy Campbell, David Keller, Andrew Moss, Pat Bonneau, Richard Zhang, Ning Zhou, Yong Wollscheid, Bernd Cooke, Kelly Yi, Eugene C. Lee, Hookeun Peskind, Elaine R. Zhang, Jing D Smith, Richard Aebersold, Ruedi TI UniPep - a database for human N-linked glycosites: a resource for biomarker discovery SO GENOME BIOLOGY LA English DT Article ID HUMAN PLASMA PROTEOME; TANDEM MASS-SPECTROMETRY; IMMUNOAFFINITY SUBTRACTION; QUANTITATIVE-ANALYSIS; HYDRAZIDE CHEMISTRY; SERUM PROTEOME; ACCURATE MASS; SPECTRAL DATA; PROTEINS; CANCER AB There has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N- linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep http://www.unipep.org-a database of human N-linked glycosites - as a resource for biomarker discovery. C1 Inst Syst Biol, Seattle, WA 98103 USA. NYU, Ctr Comparat Funct Genom, New York, NY USA. Univ Zurich, ETH, Inst Mol Syst Biol, CH-8006 Zurich, Switzerland. Univ Zurich, Fac Sci, CH-8006 Zurich, Switzerland. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Harborview Med Ctr, Seattle, WA 98104 USA. Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. RP Zhang, H (reprint author), Inst Syst Biol, Seattle, WA 98103 USA. EM hzhang@systemsbiology.org RI Eng, Jimmy/I-4202-2012; Smith, Richard/J-3664-2012; Wollscheid, Bernd/E-8909-2010; Eng, Jimmy/C-6556-2017; OI Eng, Jimmy/0000-0001-6352-6737; Smith, Richard/0000-0002-2381-2349; Wollscheid, Bernd/0000-0002-3923-1610; Eng, Jimmy/0000-0001-6352-6737; Lee, Hookeun/0000-0002-0696-8421 FU NCI NIH HHS [R21 CA114852, R21-CA-114852, U01 CA111244, U01-CA-111244]; NCRR NIH HHS [P41 RR018522, RR18522]; NHLBI NIH HHS [N01-HV-28179, N01HV28179] NR 46 TC 69 Z9 70 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2006 VL 7 IS 8 AR r73 DI 10.1186/gb-2006-7-8-r73 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 095QN UT WOS:000241322800018 PM 16901351 ER PT J AU Crawford, GE Holt, IE Whittle, J Webb, BD Tai, D Davis, S Margulies, EH Chen, YD Bernat, JA Ginsburg, D Zhou, DX Luo, SJ Vasicek, TJ Daly, MJ Wolfsberg, TG Collins, FS AF Crawford, GE Holt, IE Whittle, J Webb, BD Tai, D Davis, S Margulies, EH Chen, YD Bernat, JA Ginsburg, D Zhou, DX Luo, SJ Vasicek, TJ Daly, MJ Wolfsberg, TG Collins, FS TI Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS) SO GENOME RESEARCH LA English DT Article ID IDENTIFICATION; CHROMATIN; PROMOTERS; ELEMENTS; GENES AB A major goal in genomics is to Understand how genes are regulated in different tissues, stages of development, diseases, and species. Mapping DNase I hypersensitive (HS) sites within nuclear chromatin is a powerful and well-established method of identifying many different types of regulatory elements, but ill the past it has been limited to analysis of single loci. We have recently described a protocol to generate a genome-wide library of DNase HS sites. Here, we report high-throughput analysis, Using massively parallel signature sequencing (MPSS), of 230,000 tags from a DNase library generated from quiescent human CD4(+) T cells. Of the tags that uniquely map to the genome, we identified 14,190 clusters of sequences that group Within close proximity to each other. By using a real-time PCR strategy, we determined that the majority of these clusters represent valid DNase HS sites. Approximately 80% of these DNase HS Sites uniquely map within one or more annotated regions of the genome believed to contain regulatory elements, including regions 2 kb upstream of genes, CpG islands, and highly conserved sequences. Most DNase HS sites identified in CD4(+) T cells are also HS in CD8(+) T cells, B cells, hepatocytes, human umbilical vein endothelial cells (HUVECs), and HeLa cells. However, similar to 10% of the DNase HS sites are lymphocyte specific, indicating that this procedure call identify gene regulatory elements that control cell type specificity. This strategy, which call be applied to any cell line or tissue, will enable a better Understanding of how chromatin structure dictates cell function and fate. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Solexa Inc, Hayward, CA 94545 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM francisc@exchange.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Intramural NIH HHS; NHLBI NIH HHS [HL39639] NR 19 TC 237 Z9 245 U1 2 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2006 VL 16 IS 1 BP 123 EP 131 DI 10.1101/gr.4074106 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 016CJ UT WOS:000235598000014 PM 16344561 ER PT J AU Rubin, RT Miller, TH Rhodes, ME Czambel, RK AF Rubin, RT Miller, TH Rhodes, ME Czambel, RK TI Growth hormone responses to low-dose physostigmine in elderly vs. young women and men SO GERONTOLOGY LA English DT Article DE growth hormone; cholinergic; physostigmine; aging; cortisol; sexual diergism ID ADRENAL CORTICAL RESPONSES; ADRENOCORTICAL AXIS RESPONSES; ALZHEIMERS-DISEASE; SEXUAL DIERGISM; GH SECRETION; CHOLINERGIC SYSTEM; MAJOR DEPRESSIVES; PYRIDOSTIGMINE; AGE; RELEASE AB Background: Growth hormone (GH) secretion is a sensitive measure of CNS cholinergic neurotransmission, and GH decreases considerably with age. Cholinesterase inhibitors, which increase acetylcholine concentrations, have been used in elderly subjects to investigate the neuroendocrine effects of aging and Alzheimer's disease. However, there have been only a few studies of a potential sex difference in GH responses to cholinesterase inhibitors in elderly subjects, with mixed results. Objective: We therefore administered low-dose physostigmine (PHYSO), a cholinesterase inhibitor, to normal, non-hormone-replaced, elderly women and men, to ascertain a potential sex difference in GH response. We hypothesized: ( 1) elderly women and men would have similar hormone responses, because of relatively low circulating estrogen in the women, and ( 2) the elderly women would have significantly lower baseline GH and GH responses to cholinergic challenge than the young women we studied previously. Methods: Normal elderly women and men >= 65 years of age meeting stringent inclusion and exclusion criteria were studied on three test days, 4 - 7 days apart, by serial blood sampling for several hours for baseline GH, followed by administration of low-dose PHYSO ( first and third days) or saline (second day) at 18: 00 h. Frequent blood sampling was continued for several hours. Plasma GH and hypothalamo-pituitaryadrenal cortical hormones were measured in each sample. Results: PHYSO administration produced no side effects in about half the elderly subjects and mild side effects in the other half, with no significant female-male differences and no significant relationship between the presence or absence of side effects and GH response. PHYSO significantly increased GH compared to saline, to a similar degree in the elderly women and men. The elderly women had a significantly greater GH response to PHYSO than did the young women, whereas GH responses were similar in the elderly and young men. Conclusions: These results indicate similar GH responses to low-dose PHYSO in elderly women compared to elderly men, and a significantly greater GH response in elderly women compared to young women. A likely mechanism is increased sensitivity of central cholinergic systems that inhibit somatostatin and/or enhance GHRH release from the hypothalamus. Copyright (c) 2006 S. Karger AG, Basel. C1 VA Greater LA Healthcare Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA 90073 USA. Drexel Univ, Allegheny Gen Hosp, Coll Med, Ctr Res Neurosci, Pittsburgh, PA USA. RP Rubin, RT (reprint author), VA Greater LA Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM robert.rubin@med.va.gov FU NIMH NIH HHS [MH28380] NR 47 TC 2 Z9 4 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PY 2006 VL 52 IS 2 BP 76 EP 84 DI 10.1159/000090952 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 018PA UT WOS:000235776100002 PM 16508314 ER PT J AU Bichara, M Attmane-Elakeb, A Brown, D Essig, M Karim, Z Muffat-Joly, M Micheli, L Eude-Le Parco, I Cluzeaud, F Peuchmaur, M Bonvalet, JP Poirier, F Farman, N AF Bichara, M Attmane-Elakeb, A Brown, D Essig, M Karim, Z Muffat-Joly, M Micheli, L Eude-Le Parco, I Cluzeaud, F Peuchmaur, M Bonvalet, JP Poirier, F Farman, N TI Exploring the role of galectin 3 in kidney function: a genetic approach SO GLYCOBIOLOGY LA English DT Article DE blood pressure; body fluid volumes; hyperfiltration; Bartter's like syndrome; null mutant mouse ID TERMINAL DIFFERENTIATION; COLLECTING DUCTS; MUTANT MICE; MOUSE; FAMILY; CELLS; RAT; HETEROGENEITY; HYPERTENSION; BIOIMPEDANCE AB Galectin 3 belongs to a family of glycoconjugate-binding proteins that participate in cellular homeostasis by modulating cell growth, adhesion, and signaling. We studied adult galectin 3 null mutant ( Gal 3(-/-))and wild-type (WT) mice to gain insights into the role of galectin 3 in the kidney. By immunofluorescence, galectin 3 was found in collecting duct ( CD) principal and intercalated cells in some regions of the kidney, as well as in the thick ascending limbs at lower levels. Compared to WT mice, Gal 3(-/-) mice had similar to 11% fewer glomeruli ( p < 0.04), associated with kidney hypertrophy ( p < 0.006). In clearance experiments, urinary chloride excretion was found to be higher in Gal 3(-/-) than in WT mice ( p < 0.04), but there was no difference in urinary bicarbonate excretion, in glomerular filtration, or urinary flow rates. Under chronic low sodium diet, Gal 3(-/-) mice had lower extracellular fluid (ECF) volume than WT mice ( p < 0.05). Plasma aldosterone concentration was higher in Gal 3(-/-) than in WT mice ( p < 0.04), which probably caused the observed increase in alpha-epithelial sodium channel (alpha-ENaC) protein abundance in the mutant mice ( p < 0.001). Chronic high sodium diet resulted paradoxically in lower blood pressure ( p < 0.01) in Gal 3(-/-) than in WT. We conclude that Gal 3(-/-) mice have mild renal chloride loss, which causes chronic ECF volume contraction and reduced blood pressure levels. C1 Univ Paris 06, CNRS, Inst Jacques Monod, UMR 7592, F-75251 Paris, France. Univ Paris 07, CNRS, Inst Jacques Monod, UMR 7592, F-75251 Paris, France. INSERM, U426, F-75870 Paris, France. IFR 2 Claude Bernard, F-75870 Paris, France. Univ Paris 07, F-75005 Paris, France. Massachusetts Gen Hosp, Program Membrane Biol, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hop Xavier Bichat, Serv Nephrol, F-75870 Paris, France. IFR 2 Claude Bernard, Ctr Explorat Fonct Integrees, F-75870 Paris, France. Assoc Claude Bernard, Ctr Rech Genet & Pathol Mol Hematopoiese, F-75870 Paris, France. INSERM, U478, F-75870 Paris, France. Hop Robert Debre, Equipe EA 3102, Serv Anatomopathol, F-75019 Paris, France. RP Poirier, F (reprint author), Univ Paris 06, CNRS, Inst Jacques Monod, UMR 7592, 2 Pl Jussieu, F-75251 Paris, France. EM poirier@ijm.jussieu.fr RI Essig, Marie/Q-5770-2016 OI Essig, Marie/0000-0002-2030-5616 NR 32 TC 22 Z9 22 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD JAN PY 2006 VL 16 IS 1 BP 36 EP 45 DI 10.1093/glycob/cwj035 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XC UT WOS:000233989700006 PM 16166603 ER PT S AU Hitchcock, AL Kahana, JA Silver, PA AF Hitchcock, Amy L. Kahana, Jason A. Silver, Pamela A. BE Chalfie, M Kain, SR TI THE USES OF GREEN FLUORESCENT PROTEIN IN YEASTS SO GREEN FLUORESCENT PROTEIN: PROPERTIES, APPLICATIONS, AND PROTOCOLS, 2ND EDITION SE Methods of Biochemical Analysis LA English DT Article; Book Chapter ID NUCLEAR-PORE COMPLEX; MESSENGER-RNA LOCALIZATION; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; SCHIZOSACCHAROMYCES-POMBE; FISSION YEAST; IN-VIVO; BUDDING YEAST; LIVING CELLS; CHROMOSOME DYNAMICS C1 [Hitchcock, Amy L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Kahana, Jason A.] Merck Res Labs, Dept Alzheimers Res, West Point, PA USA. [Silver, Pamela A.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Silver, Pamela A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Hitchcock, Amy L.] Harvard Univ, Dept Mol & Celluar Biol, Cambridge, MA 02138 USA. [Kahana, Jason A.] Merck Res Labs, Dept Alzheimers, West Point, PA USA. RP Hitchcock, AL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NR 92 TC 6 Z9 6 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0076-6941 BN 978-0-471-73949-4 J9 METHOD BIOCHEM ANAL PY 2006 VL 47 BP 179 EP 201 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYB77 UT WOS:000297845600011 PM 16335714 ER PT J AU Mora, JR von Andrian, UH AF Mora, J. Rodrigo von Andrian, U. H. TI Specificity and plasticity of memory lymphocyte migration SO GUT-ASSOCIATED LYMPHOID TISSUES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID CD8(+) T-CELLS; ANTIBODY-SECRETING CELLS; THYMUS-EXPRESSED CHEMOKINE; INTESTINAL HOMING RECEPTOR; VERSUS-HOST-DISEASE; LEUKOCYTE ADHESION DEFICIENCY; HIGH ENDOTHELIAL VENULES; PATCH DENDRITIC CELLS; MUCOSAL VASCULAR ADDRESSIN; ACTIVE CROHNS-DISEASE AB To exert immunological activity, T and B cells must leave the blood and enter different extravascular compartments in the body. An essential step in this process is their adhesion to microvascular endothelium and subsequent diapedesis into a target tissue. Naive and effector/memory T and B cells possess distinct repertoires of traffic molecules that restrict their ability to interact with specialized microvessels in different anatomic compartments and thus exhibit distinct patterns of migration. In addition, antigen-experienced lymphocytes are subdivided into different subsets based on their expression of characteristic sets of adhesion receptors that favor their accumulation in certain target organs, such as the skin and the gut. This article focuses on recent discoveries that have broadened our understanding of the "imprinting" mechanisms responsible for the generation of tissue-specific effector/memory lymphocytes, especially in the intestine., We discuss how gut-specific homing is acquired, maintained, and modulated and how these mechanisms might be harnessed to develop improved vaccine protocols and treatments for intestinal autoimmune diseases. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL-54936, HL-56949, HL-62524]; NIAID NIH HHS [AI-061663] NR 182 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 308 BP 83 EP 116 PG 34 WC Immunology; Microbiology SC Immunology; Microbiology GA BFD70 UT WOS:000241213500004 PM 16922087 ER PT J AU Casola, S Rajewsky, K AF Casola, S. Rajewsky, K. TI B cell recruitment and selection in mouse GALT germinal centers SO GUT-ASSOCIATED LYMPHOID TISSUES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID EPSTEIN-BARR-VIRUS; COMMENSAL BACTERIA; LYMPHOID-TISSUES; GENE CONVERSION; SOMATIC DIVERSIFICATION; ANTIBODY REPERTOIRE; IMMUNE-RESPONSES; PEYERS-PATCHES; LAMINA PROPRIA; NKT CELLS AB In conventionally reared mice germinal centers (GCs) are chronically induced in Peyer's patches (PP), mesenteric lymph node (MLN), and isolated lymphoid follicles (ILF) of gut-associated lymphoid tissues (GALT), as a result of continuous B cell stimulation by commensal bacteria. It is generally thought that BCR-mediated antigen recognition controls the recruitment and thus selection of B cells within GALT GCs. However, recent results challenge this view and suggest that engagement of innate immune receptors by microbial antigens promotes B cell recruitment to, and maintenance within, the GC, irrespective of BCR specificity. We propose a scenario in which microbial determinants presented by follicular dendritic cells (FDCs) to innate receptors on B cells within the GC support the survival and concomitant expansion of somatically mutated, IgA-class-switched B cell clones expressing a variety of BCR specificities. From this pool, B cell mutants recognizing gut-derived antigens through their BCR are either, in GCs, drawn into the process of affinity maturation, or, in the lamina propria (LP) of the gut, locally selected to differentiate into plasmablasts, thus contributing to the continuous production of IgA antibodies required for an efficient protection against commensal and pathogenic microorganisms. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Casola, S (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM stefan.casola@ifom-ieo-campus.it FU NCI NIH HHS [R01-CA 098285001A1]; PHS HHS [R01-A1054636-01] NR 55 TC 29 Z9 29 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 308 BP 155 EP 171 PG 17 WC Immunology; Microbiology SC Immunology; Microbiology GA BFD70 UT WOS:000241213500007 PM 16922090 ER PT B AU Podolsky, DK AF Podolsky, DK BE Blumberg, RS Gangl, A Manns, MP Tilg, H Zeitz, M TI The intestinal epithelium and inflammatory bowel disease SO Gut-Liver Interactions: Basic and Clinical Concepts SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 146 on Gut-Liver Interactions - Basic and Clinical Concepts CY MAR 11-12, 2005 CL Innsbruck, AUSTRIA C1 Massachusetts Gen Hosp, Sch Med, GI Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Sch Med, GI Unit, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-4143-8 J9 FALK SYMP PY 2006 VL 146 BP 46 EP 50 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BDS32 UT WOS:000235163500005 ER PT J AU Klein, A He, XY Roche, M Mallett, A Duska, L Supko, JG Seiden, MV AF Klein, A He, XY Roche, M Mallett, A Duska, L Supko, JG Seiden, MV TI Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; platinum-resistance; alternative therapies; genistein ID UNCONVENTIONAL MEDICINE; DIETARY PHYTOESTROGENS; PHASE-III; GENISTEIN; DAIDZEIN; ISOFLAVONES; CELLS; CARCINOMA; ONCOLOGY; GROWTH AB Background. Women with ovarian cancer who experience disease progression during or within 6 months of first-line treatment with platinum-based anticancer drugs are considered to have platinum-resistant tumors. These patients have ail unfavorable prognosis, and they frequently seek complementary and alternative therapies (CAM). Historically, this represents ail understudied and underreported component of ovarian cancer treatment. Case. This report describes the case of a woman with rapidly progressive, platinum-resistant ovarian cancer. Upon initiating self-directed treatment with Haelan951 (R), a commercially available fermented soy beverage, she entered into a phase of prolonged disease stabilization including improvement in the serum tumor marker CA-125. Conclusion. Fermented soy products are known to contain high concentrations of the isoflavone, genistein, and other compounds that exhibit anticancer activity in preclinical models. This case report supports the prospective evaluation of alternative therapies such as these in patients with platinum-refractory ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Med Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM mseiden@partners.org FU NCI NIH HHS [P30 CA0516] NR 24 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2006 VL 100 IS 1 BP 205 EP 209 DI 10.1016/j.ygyno.2005.08.006 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 999UX UT WOS:000234417200038 PM 16171852 ER PT J AU Pekary, AE AF Pekary, Albert Eugene BE Kastin, AJ TI Thyrotrophin-Releasing Hormone: New Functions for an Ancient Peptide SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID GLYCOGEN-SYNTHASE KINASE-3-BETA; XENOPUS-LAEVIS; TRH RECEPTORS; RAT-BRAIN; CLONING; CDNA; EXPRESSION; SUBTYPE; INHIBITOR; NEURONS AB Thyrotrophin-releasing hormone (TRH) was the first of the hypothalamic releasing factors to be fully characterized. It consists of the tripeptide pGlu-His-Pro-NH2 that is derived from a precursor protein with multiple copies of the precursor sequence Lys-Arg-Gln-His-Pro-Gly-(Lys/Arg)-Arg. Pre-proTRH is distributed throughout the animal kingdom, occurring in species lacking a pituitary. In addition to its neuroendocrine release from the hypothalamus of mammals, resulting in secretion of TSH and PRL from the anterior pituitary, it functions as a neurotransmitter, neuromodulator, and neuroprotective agent in the central and peripheral nervous systems. Unlike hypothalamic preproTRH mRNA levels and TRH content that are subject to thyroid hormone negative feedback inhibition, extrahypothalamic brain TRH biosynthesis and release are unresponsive to thyroid hormone status. TRH suppresses glycogen synthase kinase-3 beta (GSK-3 beta) expression, a process that may lead to treatments for Alzheimer's disease, depression, bipolar disorder, and diabetes. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 114,Rm 229, Los Angeles, CA 90073 USA. NR 42 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 629 EP 634 DI 10.1016/B978-012369442-3/50092-1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400091 ER PT J AU Martinez, V Tache, Y AF Martinez, Vicente Tache, Yvette BE Kastin, AJ TI Calcitonin Gene-Related Peptide and Gastrointestinal Function SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID CGRP ANTAGONISTS; GASTRIC-MUCOSA; BINDING-SITES; DIABETIC-RATS; SUBSTANCE-P; CAPSAICIN; RECEPTOR; AFFERENTS; LOCALIZATION; INFLAMMATION AB Calcitonin gene-related peptide (CGRP) is a 37-amino-acid peptide present in nerve terminals of extrinsic afferents and in intrinsic enteric neurons throughout the gastrointestinal tract. Following its release, the peptide acts locally on specific receptors (CGRP(1)) located in enteric neurons, smooth muscle, endocrine cells, and vascular structures. The stimulation of CGRP(1) receptors elicits wide-ranging effects on gut function, including inhibition of gastric acid secretion and gut motility, increased gastric mucosal blood flow and mucosal resistance to injury, and modulation of visceral nociception. These observations suggest that CGRP plays an important role in the maintenance of gastrointestinal homeostasis and might be involved in pathophysiological alterations associated with secretory, motor, inflammatory, and sensory disturbances. C1 [Martinez, Vicente] AstraZeneca R&D, Integrat Pharmacol GI Biol, SE-43183 Molndal, Sweden. [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. RP Martinez, V (reprint author), AstraZeneca R&D, Integrat Pharmacol GI Biol, SE-43183 Molndal, Sweden. RI Martinez, Vicente/N-1189-2014 NR 34 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 1005 EP 1011 DI 10.1016/B978-012369442-3/50141-0 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400140 ER PT J AU Germano, PM Pisegna, JR AF Germano, Patrizia M. Pisegna, Joseph R. BE Kastin, AJ TI Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) SO HANDBOOK OF BIOLOGICALLY ACTIVE PEPTIDES LA English DT Article; Book Chapter ID VASOACTIVE-INTESTINAL-PEPTIDE; DESCENDING RELAXATION PHASE; GUINEA-PIG; SIGNAL-TRANSDUCTION; I RECEPTOR; HYPOTHALAMIC POLYPEPTIDE; PERISTALTIC REFLEX; CIRCULAR MUSCLE; SPLICE VARIANTS; BINDING-SITES AB Pituitary adenylate cyclase activating polypeptide (PACAP) is expressed in the enteric nervous system of the gastrointestinal tract, where it functions to increase secretory activity and motility. Studies focusing on the role of PACAP in the gastrointestinal (GI) tract have identified it is as a key regulator in gastric acid secretion. Receptors for PACAP (PAC1) are expressed on the enterochromaffinlike (ECL) cells of the gastric corpus, where they regulate the release of histamine. PACAP is expressed in both gastric and colonic neurons, where it regulates gastrointestinal physiology. PACAP has also been demonstrated to regulate immune function in the GI tract and may be a key regulator of the inflammatory response associated with conditions such as inflammatory bowel disease. Receptors for PACAP have been discovered on tumors of the GI tract, and their stimulation is involved with growth of colonic tumors. C1 [Germano, Patrizia M.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Pisegna, Joseph R.] Univ Calif Los Angeles, Div Gastroenterol & Hepatol, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Germano, PM (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Los Angeles, CA 90073 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046379-7 PY 2006 BP 1091 EP 1096 DI 10.1016/B978-012369442-3/50153-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR53 UT WOS:000311102400152 ER PT B AU Link, JM Jones, RE Offner, H Vandenbark, AA AF Link, Jason M. Jones, Richard E. Offner, Halina Vandenbark, Arthur A. BE Tatlisumak, T Fisher, M TI Experimental models for demyelinating diseases SO HANDBOOK OF EXPERIMENTAL NEUROLOGY: METHODS AND TECHNIQUES IN ANIMAL RESEARCH LA English DT Article; Book Chapter ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; T-CELL-RECEPTOR; CENTRAL-NERVOUS-SYSTEM; INCOMPLETE FREUNDS-ADJUVANT; LYMPH-NODE CELLS; PROTEOLIPID PROTEIN; MULTIPLE-SCLEROSIS; LEWIS RATS C1 [Link, Jason M.; Jones, Richard E.; Offner, Halina] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Tykeson Multiple Sclerosis Res Lab, Dept Neurol, Portland, OR 97239 USA. RP Link, JM (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 74 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-83814-6 PY 2006 BP 393 EP 410 DI 10.1017/CBO9780511541742.023 D2 10.1017/CBO9780511541742 PG 18 WC Neurosciences; Veterinary Sciences SC Neurosciences & Neurology; Veterinary Sciences GA BXT09 UT WOS:000297007700023 ER PT J AU Ramanadhan, S Viswanath, K AF Ramanadhan, Shoba Viswanath, K. TI Health and the information nonseeker: A profile SO HEALTH COMMUNICATION LA English DT Article; Proceedings Paper CT Kentucky Conference on Health Communication CY APR 20-22, 2006 CL Univ Kentucky, Lexington, KY HO Univ Kentucky ID TREATMENT DECISION-MAKING; CANCER-PATIENTS; BREAST-CANCER; NEEDS; SEEKING; PATIENT; WOMEN; PARTICIPATION; DETERMINANTS; PREFERENCES AB Despite increased information-seeking by the public, a significant percentage of those diagnosed with a serious disease such as cancer report that they do not seek or receive health information beyond that given by health care providers. This study attempts to profile these nonseekers and study possible determinants of nonseeking behaviors. Data come from the 2003 Health Information National Trends Survey, a national survey of American adults conducted by the National Cancer Institute (N = 6,133; Nelson et al., 2004. Individuals were categorized as nonseekers or seekers and then further classified based on cancer history to yield four groups: nonseeker patients, the nonseeker public, seeker patients, and the seeker public. Compared to other groups, nonseeker patients came from the lowest income and education groups, and scored lower on attention to health in the media and trust in mass media health information. Nonseekers also scored lower on preventative health behaviors. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Med Oncol,Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Viswanath, K (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Med Oncol,Dept Soc Human Dev & Hlth, SM 251,44 Binney St, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu NR 56 TC 103 Z9 104 U1 1 U2 14 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2006 VL 20 IS 2 BP 131 EP 139 DI 10.1207/s15327027hc2002_4 PG 9 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 094ZC UT WOS:000241276900004 PM 16965250 ER PT J AU Young, AJ Rodriguez, KL AF Young, AJ Rodriguez, KL TI The role of narrative in discussing end-of-life care: Eliciting values and goals from text, context, and subtext SO HEALTH COMMUNICATION LA English DT Article ID PATIENT AB This article reports a qualitative study of elderly veterans' perceptions of and preferences for end-of-life care. At a large urban Veterans Affairs (VA) hospital, we asked 30 veterans and 30 health care providers to define 4 terms in the VA form of the advance directive: life-sustaining treatment, terminal condition, state of permanent unconsciousness, and decision-making capacity. The veterans commonly used narratives to construct meaning, and analysis showed that the resulting texts had both a subtext (the values and goals driving the narrative) and a context (life experiences that filter and shape the current interpretation). We found that all 3 components-text, subtext, and context-are crucial to understanding the central theme of an individual's narrative and the decision-making processes associated with it. In this article we examine 1 lengthy narrative using Chafe's (1994) notion of intonation units. We then present a series of short narratives to demonstrate 3 subthemes that emerged from the data: quality of life versus quantity of life, benefit of treatment versus cost of treatment, and, most common, control versus lack of control. Our goal was to demonstrate the centrality and usefulness of storytelling in the patient-provider interaction when listeners are willing to consider the subtext and context of the story and its role in the decision-making process. As demonstrated in this study, deciphering people's stories gives us insight into their values, the mental constructs that drive their decision making, and the goals that they have for their own health care. C1 Univ Memphis, Dept Commun, Memphis, TN 38152 USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Young, AJ (reprint author), Univ Memphis, Dept Commun, 143 Theatre & Commun Bldg, Memphis, TN 38152 USA. EM aj.young@memphis.edu NR 15 TC 10 Z9 10 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2006 VL 19 IS 1 BP 49 EP 59 DI 10.1207/s15327027hc1901_6 PG 11 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 010AJ UT WOS:000235154900006 PM 16519592 ER PT J AU Dukkipati, S Holmvang, G Ruskin, J Mansour, M AF Dukkipati, S Holmvang, G Ruskin, J Mansour, M TI Ablation of mitral isthmus-dependent atrial flutter using integration of real-time electroanatomic mapping with three-dimensional computed tomography SO HEART RHYTHM LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2006 VL 3 IS 1 BP 124 EP 124 DI 10.1016/j.hrthm.2005.06.024 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 001ZP UT WOS:000234581500025 PM 16399068 ER PT J AU Musani, SK Zhang, HG Hsu, HC Yi, NJ Gorman, BS Allison, DB Mountz, JD AF Musani, Solomon K. Zhang, Huang-Ge Hsu, Hui-Chen Yi, Nengjun Gorman, Bernard S. Allison, David B. Mountz, John D. TI Principal component analysis of quantitative trait loci for immune response to adenovirus in mice SO HEREDITAS LA English DT Article ID MEDIATED GENE-TRANSFER; NECROSIS-FACTOR-ALPHA; TRANSGENE EXPRESSION; IL-10-DEFICIENT MICE; KUPFFER CELLS; THERAPY; TUMOR; VECTORS; INTERLEUKIN-12; ACTIVATION AB Data on the duration of transgene expression in the liver, the presence of cytotoxic T lymphocytes (CTLs) against adenovirus, and serum cytokines from 18 strains of C57BL/6xDBA/2 (BxD) recombinant inbred mice were analyzed. Our aim was to detect quantitative trait loci (QTLs) that may have causal relationship with the duration of adenovirus-mediated transgene expression in the liver. Information from beta-galactosidase (LacZ) expression; CTL production; and serum levels of gamma interferon, tumor necrosis factor-alpha, and interleukin-6 30 days after intravenous injection of liver LacZ were summarized by principal component analysis and analyzed using maximum likelihood interval mapping implemented in the QTL cartographer software. Two principal component (PC) scores explained 82.5% of the phenotypic variance in the original variables and identified QTLs not identified by analysis of individual traits. The distribution of original variables among PCs was such that variables in PC1 were predominantly cytokines with little CTL response whereas LacZ and CTL were the predominant contributors to PC2 with practically no contribution from cytokines. PC1 was significantly associated with two QTLs on chromosomes 7 and 9 located at 57.5 cM and 41.01 cM, respectively. Five QTLs were significantly associated with PC2 on chromosomes 12 (23.01 and 31.01 cM) and 15 (29.21, 36.01, and 56.31 cM). These results illustrate the use of principal component analysis in mapping QTLs using multiple correlated traits. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. Nassau Community Coll, Garden City, NY 11530 USA. Univ Alabama, Dept Nutr Sci, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 701 S 19th St,Room 473,LHRB Birmingham, Birmingham, AL 35294 USA. EM jdmountz@.uab.edu OI Allison, David/0000-0003-3566-9399 FU NHLBI NIH HHS [1T32HL072757-01]; NIA NIH HHS [R01-AG11653]; NIAID NIH HHS [R01-AI42900]; NIDDK NIH HHS [5 P30 DK56336-04]; NIEHS NIH HHS [5R01ES009912-05] NR 48 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0018-0661 J9 HEREDITAS JI Hereditas PY 2006 VL 143 IS 1 BP 189 EP 197 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 125WO UT WOS:000243474400027 PM 17362354 ER PT B AU Lieberman, D AF Lieberman, D. BE VanCutsem, E Schmiegel, W Rustgi, AK Zeitz, M TI Colorectal cancer screening: cost-effectiveness and adverse events SO Highlights in Gastrointestinal Oncology SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 149 on Highlights in Gastrointestinal Oncology CY OCT 01-02, 2005 CL Berlin, GERMANY ID FECAL-OCCULT-BLOOD; COMPUTED TOMOGRAPHIC COLONOGRAPHY; CONTRAST BARIUM ENEMA; AVERAGE-RISK; ASYMPTOMATIC ADULTS; FLEXIBLE SIGMOIDOSCOPY; VIRTUAL COLONOSCOPY; NATIONAL-SURVEY; TASK-FORCE; RECOMMENDATIONS C1 Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97239 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-G1,POB 1034, Portland, OR 97239 USA. NR 46 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-5108-5 J9 FALK SYMP PY 2006 VL 149 BP 91 EP 103 PG 13 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BFB98 UT WOS:000240945400010 ER PT J AU Nichols, EA Kao, YC Verfaellie, M Gabrieli, JDE AF Nichols, Elizabeth A. Kao, Yun-Ching Verfaellie, Mieke Gabrieli, John D. E. TI Working memory and long-term memory for faces: Evidence from fMRI and global amnesia for involvement of the medial temporal lobes SO HIPPOCAMPUS LA English DT Article DE hippocampus; neuroimaging; lesion; subsequent memory; Korsakoff's syndrome ID BILATERAL HIPPOCAMPAL LESIONS; WERNICKE-KORSAKOFF-SYNDROME; DIENCEPHALIC AMNESIA; RECOGNITION MEMORY; VISUAL RECOGNITION; SUBSEQUENT MEMORY; IMMEDIATE MEMORY; BRAIN ACTIVITY; VERBAL MEMORY; MONKEYS AB Behavioral studies with amnesic patients and imaging studies with healthy adults have suggested that medial temporal lobe (MTL) structures known to be essential for long-term declarative memory (LTM) may also be involved in the maintenance of information in working memory (WM). To examine whether MTL structures are involved in WM maintenance for faces, and the nature of that involvement, WM and LTM for faces were examined in normal participants via functional magnetic resonance imaging (fMRI) and in amnesic patients behaviorally. In Experiment 1, participants were scanned while performing a WM task in which they determined if two novel faces, presented 7 s apart, were the same or different. Later, participants' LTM for the faces they saw during the WM task was measured in an unexpected recognition test. During WM maintenance, the hippocampus was activated bilaterally, and there was greater activation during maintenance for faces that were later remembered than faces later forgotten. A conjunction analysis revealed overlap in hippocampal activations across WM maintenance and LTM contrasts, which suggested that the same regions were recruited for WM maintenance and LTM encoding. In Experiment 2, amnesic and control participants were tested on similar WM and LTM tasks. Amnesic patients, as a group, had intact performance with a 1-s maintenance period, but were impaired after a 7-s WM maintenance period and on the LTM task. Thus, parallel neuroimaging and lesion designs suggest that the same hippocampal processes support WM maintenance, for intervals as short as 7 s, and LTM for faces. (c) 2006 Wiley-Liss, Inc. C1 Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Nichols, EA (reprint author), Stanford Univ, Dept Psychol, Jordan Hall,Bldg 420,Room 478, Stanford, CA 94305 USA. EM bnichols@psych.stanford.edu OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIA NIH HHS [AG12995, R01 AG012995]; NIMH NIH HHS [MH57681, MH59940, R01 MH057681, R01 MH059940]; NINDS NIH HHS [NS 26985, P50 NS026985] NR 63 TC 104 Z9 106 U1 2 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2006 VL 16 IS 7 BP 604 EP 616 DI 10.1002/hipo.20190 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 063JY UT WOS:000239015700005 PM 16770797 ER PT S AU Nakatani, Y Tagami, H Shestakova, E AF Nakatani, Y. Tagami, H. Shestakova, E. BE Berger, SL Nakanishi, O Haendler, B TI How is epigenetic information on chromatin inherited after DNA replication? SO HISTONE CODE AND BEYOND: NEW APPROACHES TO CANCER THERAPY SE Ernst Schering Research Foundation Workshop LA English DT Proceedings Paper CT 57th Ernst-Schering-Research-Foundation Workshop CY MAR 09-11, 2005 CL Berlin, GERMANY SP Ernst Schering Res Fdn ID HISTONE CODE; CELL-CYCLE; HUMAN ASF1; SEGREGATION; PROTEIN; IDENTIFICATION; PURIFICATION; NUCLEOSOMES; CAF-1; FORK AB Although most somatic cells have identical genetic information, gene expression profiles are quite distinct in each cell type. The gene expression profiles are considered to be determined mainly by chromatin-encoded epigenetic information that includes histone modifications, histone variants, and factors such as HP1 and polycomb group proteins that organize higher-ordered chromatin structures. To gain insights into how such epigenetic information on chromatin is inherited on daughter DNA strands after DNA replication, we have purified the preassembled form of histone H3 by immunoaffinity purification. The histone H3 complex contains the two histone H3-H4 chaperones CAF1 and ASF1 Surprisingly, the H3 complex also contains a pair of H3-H4 dimers. This observation is striking because histones H3-H4 are known to exist as tetramers in solution. Since histones H3-H4 in the predeposition complex exist as a dimer, this raises the possibility that the H3-H4 dimer in the complex pairs with a parental H3-H4 dimer, assembling the de novo-synthesized and parental H3-H4 dimers in the same nucleosome. Based on these results, we propose a semi-conservative model of nucleosome duplication, which allows for segregation of parental H3-H4 dimers with encoded epigenetic information evenly to daughter DNA strands. C1 [Nakatani, Y.; Shestakova, E.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tagami, H.] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Nagoya, Aichi, Japan. RP Nakatani, Y (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. EM yoshihiro_nakatani@dfci.harvard.edu FU NIH [GM065939-02] FX Y.N. is in part supported by grants from NIH (GM065939-02). NR 22 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-27857-5 J9 E SCHERING RES FDN W JI E Schering Res. Fdn. Workshop PY 2006 VL 57 BP 89 EP + PG 4 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BEH85 UT WOS:000237285700005 ER PT J AU Page-Wilson, G Smith, PC Welt, CK AF Page-Wilson, G Smith, PC Welt, CK TI Prolactin suppresses GnRH but not TSH secretion SO HORMONE RESEARCH LA English DT Article DE menstrual cycle; hyperprolactinemia; amenorrhea; hypothalamus; gonadotropin-releasing hormone ID LUTEINIZING-HORMONE SECRETION; FOLLICLE-STIMULATING-HORMONE; SULPIRIDE-INDUCED HYPERPROLACTINEMIA; GONADOTROPIN-RELEASING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; PULSATILE SECRETION; NORMAL WOMEN; PATHOLOGICAL HYPERPROLACTINEMIA; THYROTROPIN SECRETION; BROMOCRIPTINE THERAPY AB Background/Aims: In animal models, prolactin increases tuberoinfundibular dopamine turnover, which has been demonstrated to suppress both hypothalamic GnRH and pituitary TSH secretion. To test the hypothesis that prolactin suppresses GnRH and TSH secretion in women, as preliminary evidence that a short-feedback dopamine loop also operates in the human, the effect of hyperprolactinemia on GnRH and TSH secretion was examined. Methods: Subjects (n = 6) underwent blood sampling every 10 min in the follicular phase of a control cycle and during a 12-hour recombinant human prolactin (r-hPRL) infusion preceded by 7 days of twice-daily subcutaneous r-hPRL injections. LH and TSH pulse patterns and menstrual cycle parameters were measured. Results: During the 7 days of r-hPRL administration, baseline prolactin increased from 16.0 +/- 3.0 to 101.6 +/- 11.6 mu g/l, with a further increase to 253.7 +/- 27.7 mu g/l during the 12-hour infusion. LH pulse frequency decreased (8.7 +/- 1.0 to 6.0 +/- 1.0 pulses/12 h; p < 0.05) with r-hPRL administration, but there were no changes in LH pulse amplitude or mean LH levels. There were also no changes in TSH pulse frequency, mean or peak TSH. The decreased LH pulse frequency did not affect estradiol, inhibin A or B concentrations, or menstrual cycle length. Conclusion: These studies demonstrate that hyperprolactinemia suppresses pulsatile LH secretion but not TSH secretion and suggest that GnRH secretion is sensitive to hyperprolactinemia, but that TSH secretion is not. These data further suggest that the degree of GnRH disruption after 7 days of hyperprolactinemia is insufficient to disrupt menstrual cyclicity. C1 Massachusetts Gen Hosp, BHX 511, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, BHX 511, Dept Med, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066] NR 60 TC 8 Z9 10 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2006 VL 65 IS 1 BP 31 EP 38 DI 10.1159/000090377 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 008HZ UT WOS:000235032100006 PM 16357488 ER PT J AU Lin, FH Belliveau, JW Dale, AM Hamalainen, MS AF Lin, FH Belliveau, JW Dale, AM Hamalainen, MS TI Distributed current estimates using cortical orientation constraints SO HUMAN BRAIN MAPPING LA English DT Article DE inverse; MEG; cortical constraints; NINE; MCE; minimum norm; brain ID HUMAN BRAIN; MEG; MAGNETOENCEPHALOGRAPHY; LOCALIZATION; EEG AB Distributed source models of magnetoencephalographic (MEG) and electroencephalographic (EEG) data employ dense distributions of current sources in a volume or on a surface. Previously, anatomical magnetic resonance imaging (MRI) data have been used to constrain locations and orientations based on cortical geometry extracted from anatomical MRI data. We extended this approach by first calculating cortical patch statistics (CPS), which for each patch corresponding to a current source location on the cortex comprise the area of the patch, the average normal direction, and the average deviation of the surface normal from its average. The patch areas were then incorporated in the forward model to yield estimates of the surface current density instead of dipole amplitudes at the current locations. The surface normal data were employed in a loose orientation constraint (LOC), which allows some variation of the current direction from the average normal. We employed this approach both in the l(2) minimum-norm estimates (MNE) and in the more focal l(1) minimum-norm solutions, the minimum-current estimate (MCE). Simulations in auditory and somatosensory areas with current dipoles and 10- or 20-mm diameter cortical patches as test sources showed that applying the LOC can increase localization accuracy. We also applied the method to in vivo auditory and somatosensory data. C1 Massachusetts Gen Hosp, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Lin, FH (reprint author), Massachusetts Gen Hosp, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fhlin@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Hamalainen, Matti/C-8507-2013; Lin, Fa-Hsuan/G-6988-2012 OI Lin, Fa-Hsuan/0000-0002-9539-1731 FU NCRR NIH HHS [P41 RR14075]; NIBIB NIH HHS [1R21EB004965-01]; NICHD NIH HHS [R01 HD040712]; NINDS NIH HHS [R01 NS037462] NR 20 TC 142 Z9 142 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2006 VL 27 IS 1 BP 1 EP 13 DI 10.1002/hbm.20155 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001RJ UT WOS:000234553700001 PM 16082624 ER PT J AU Spiridon, M Fischl, B Kanwisher, N AF Spiridon, M Fischl, B Kanwisher, N TI Location and spatial profile of category-specific regions in human extrastriate cortex SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; extrastriate cortex; face recognition; object recognition; brain mapping ID HUMAN VISUAL-CORTEX; FACE-SPECIFIC POTENTIALS; HUMAN CEREBRAL-CORTEX; OCCIPITOTEMPORAL CORTEX; RESPONSE PROPERTIES; OBJECT PERCEPTION; COORDINATE SYSTEM; CORTICAL SURFACE; AREAS; REPRESENTATIONS AB Subjects were scanned in a single functional MRI (fMRI) experiment that enabled us to localize cortical regions in each subject in the occipital and temporal lobes that responded significantly in a variety of contrasts: faces > objects, body parts > objects, scenes > objects, objects > scrambled objects, and Moving > stationary stimuli. The resulting activation maps were coregistered across subjects using spherical surface coordinates [Fischl et al., Hum Brain Mapp 1999;8:272-284] to produce a "percentage overlap map" indicating the percentage of subjects who showed a significant response for each contrast at each point on the surface. Prominent among the overlapping activations in these contrasts were the fusiform face area (FFA), extrastriate body area (EBA), parahippocampal place area (PPA), lateral occipital complex (LOC), and MT+/V5; only a few other areas responded consistently across subjects in these contrasts. Another analysis showed that the spatial profile of the selective response drops off quite sharply outside the standard borders of the FFA and PPA (less so for the EBA and MT+/V5), indicating that these regions are not simply peaks of very broad selectivities spanning centimeters of cortex, but fairly discrete regions of cortex with distinctive functional profiles. The data also yielded a surprise that challenges our understanding of the function of area MT+: a higher response to body parts than to objects. The anatomical consistency of each of our functionally defined regions across subjects and the spatial sharpness of their activation profiles within subjects highlight the fact that these regions constitute replicable and distinctive landmarks in the functional organization of the human brain. C1 Univ Geneva, Ctr Med, Neurol & Imaging Cognit Lab, Dept Neurosci, CH-1211 Geneva 4, Switzerland. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. McGovern Inst Brain Res, Cambridge, MA USA. RP Spiridon, M (reprint author), Univ Geneva, Ctr Med, Neurol & Imaging Cognit Lab, Dept Neurosci, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM mojia.spiridon@medecine.unige.ch FU NCRR NIH HHS [R01 RR016594, U24 RR021382, P41 RR014075]; NEI NIH HHS [R21 EY016231, R01 EY013455, R21 EY016231-01] NR 51 TC 137 Z9 139 U1 0 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2006 VL 27 IS 1 BP 77 EP 89 DI 10.1002/hbm.20169 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001RJ UT WOS:000234553700007 PM 15966002 ER PT J AU Messerli, SM Prabhakar, S Tang, Y Mahmood, U Weissleder, R Bronson, R Martuza, R Rabkin, S Breakefield, XO AF Messerli, SM Prabhakar, S Tang, Y Mahmood, U Weissleder, R Bronson, R Martuza, R Rabkin, S Breakefield, XO TI Treatment of schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2 SO HUMAN GENE THERAPY LA English DT Article ID REPLICATION-CONDITIONAL HSV; ANTIGEN PRESENTATION; SAFETY EVALUATION; BRAIN-TUMORS; THERAPEUTIC-EFFICACY; CANCER VACCINATION; ANTITUMOR IMMUNITY; NONHUMAN-PRIMATES; PROTEIN-SYNTHESIS; TRANSGENIC MICE AB Gene therapy for schwannomas was evaluated in two mouse models of neurofibromatosis type 2 ( NF2): ( 1) a transgenic model in which mice express a dominant mutant form of merlin and spontaneously develop schwannomas, and ( 2) a xenograft model in which human schwannoma tissue is implanted subcutaneously into immune-compromised mice. In both models, schwannoma volumes were monitored by magnetic resonance imaging ( MRI) and showed strong gadolinium enhancement typical of these tumors in humans. Both types of tumor were positive for the Schwann cell marker S100, and highly infectable with herpes simplex virus ( HSV) vectors. Schwannomas were injected with an oncolytic HSV-1 recombinant virus vector, G47 Delta, which has deletions in genes for ribonucleotide reductase ( ICP6), gamma 34.5, and ICP47. In the NF2 transgenic model, schwannomas were reduced by more than half their original size by 10 days after infection. In the case of subcutaneous schwannoma xenografts, reduction in size after infection occurred more slowly, with a mean reduction of one-third by 42 days after treatment. Schwannomas injected with control vehicles continued to grow slowly over time in both schwannoma models. These studies demonstrate the ability of an oncolytic recombinant HSV vector to reduce the volume of schwannoma tumors in NF2 tumor models in mice and extend the possible therapeutic applications of oncolytic vectors for benign tumors to reduce mass while minimizing nerve damage. C1 Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Rodent Histopathol Core Facil, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, E 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 51 TC 19 Z9 19 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2006 VL 17 IS 1 BP 20 EP 30 DI 10.1089/hum.2006.17.20 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 003YY UT WOS:000234720400003 PM 16409122 ER PT J AU Seddon, JM George, S Rosner, B Klein, ML AF Seddon, Johanna M. George, Sarah Rosner, Bernard Klein, Michael L. TI CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration SO HUMAN HEREDITY LA English DT Article DE case-control association analysis; environmental risk factor; epidemiologic approaches; gene-environment interaction; genotype; macular degeneration ID COMPLEMENT FACTOR-H; C-REACTIVE PROTEIN; RISK-FACTORS; FAMILIAL AGGREGATION; MACULOPATHY; POLYMORPHISM; DIETARY; EYE; CAROTENOIDS; POPULATION AB Objectives: We tested the hypothesis that modifiable lifestyle factors alter the genetic susceptibility associated with a common coding variant in the complement factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly, age-related macular degeneration (AMD). Methods: In this case-control association analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated. AMD status was determined by grading of fundus photographs. Risk factors including cigarette smoking and body mass index (BMI) were assessed and DNA specimens were genotyped for the variant in the CFH gene. Unconditional logistic regression analyses were performed. Attributable risks and multivariable AMD risk scores were calculated. Results:The number of risk alleles for Y402H was associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence interval (CI) 1.8-3.8) for the CT heterozygous genotype and OR 7.4 (4.7-11.8) for the homozygous CC risk genotype, after controlling for demographic and behavioral risk factors. Current cigarette smoking (OR 5.1) and high BMI >= 30 (OR 2.1) were independently related to AMD, controlling for genotype. The association between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR 10.2) conferred the greatest risks. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70-0.75. Conclusions: Genetic and environmental factors are independently related to advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk score identifies a highly susceptible population. Copyright (c) 2006 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Devers Eye Inst, Macular Degenerat Ctr, Casey Eye Inst, Portland, OR 97201 USA. RP Seddon, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Epidemiol Unit,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Johanna_Seddon@meei.harvard.edu FU NCRR NIH HHS [U54 RR 020278]; NEI NIH HHS [R01 EY 12203, R01 EY 11309] NR 34 TC 104 Z9 107 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2006 VL 61 IS 3 BP 157 EP 165 DI 10.1159/000094141 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 075ZQ UT WOS:000239927200004 PM 16816528 ER EF