FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gilliland, DG Gribben, JG AF Gilliland, DG Gribben, JG TI Evaluation of the risk of therapy-related MDS/AML after autologous stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE therapy-related MDS/AML; autologous stem cell transplantation; non-Hodgkin's lymphoma; cytogenetics; interphase FISH; loss of heterozygosity; point mutation; X-activation-based clonality assays ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; ACUTE MYELOID-LEUKEMIA; HIGH-DOSE THERAPY; MYELODYSPLASTIC SYNDROME; TRANSGENIC MICE; FOLLICULAR LYMPHOMA; NORMAL INDIVIDUALS; LATE COMPLICATION; FUSION GENE AB A major complication of autologous stem cell transplantation (ASCT) is the development of therapy-related myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). This complication likely results from previous exposure of the autologous stem cells to chemotherapy as well as to the high doses of chemotherapy and radiation therapy that are used as part of the conditioning regimen. A number of centers are reporting that, second to disease relapse, therapy-related MDS and AML are, among the major causes of morbidity and mortality after ASCT. There is abundant evidence that therapy-related MDS and AML are clonal hemopathies that are the consequence of an acquired somatic mutation that confers a proliferative and/or survival advantage to hematopoietic progenitors. However, no single mutation or gene rearrangement is sufficient for the development of therapy-related AML, and the identification of a single gene rearrangement or point mutation may not necessarily be predictive of the development of therapy-related AML in the post-ASCT setting, a caveat that must be kept in mind when risk is assessed. There are at least 5 methods for assessing risk based on the presence of clonal abnormalities in hematopoietic cells, including standard cytogenetics, interphase fluorescence in situ hybridization, analysis for loss of hererozygosity, polymerase chain reaction for point mutations, and X-inactivation-based clonality assays. Each of these approaches has strengths and weaknesses that are discussed here in detail. C1 Harvard Univ, Inst Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Inst Med, Howard Hughes Med Inst, 4 Blackfan Cir,Rm 418, Boston, MA 02115 USA. NR 39 TC 24 Z9 24 U1 0 U2 1 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. PY 2002 VL 8 IS 1 BP 9 EP 16 DI 10.1053/bbmt.2002.v8.pm11846355 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 517CV UT WOS:000173594300002 PM 11846355 ER PT J AU Lee, SJ Vogelsang, G Gilman, A Weisdorf, DJ Pavletic, S Antin, JH Horowitz, MM Akpek, G Flowers, ME Couriel, D Martin, PJ AF Lee, SJ Vogelsang, G Gilman, A Weisdorf, DJ Pavletic, S Antin, JH Horowitz, MM Akpek, G Flowers, ME Couriel, D Martin, PJ TI A survey of diagnosis, management, and grading of chronic GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE chronic graft-versus-host disease; allogeneic stem cell transplantation ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; PREDNISONE; PREDICTORS AB Chronic GVHD (cGVHD) is a potentially devastating late complication of allogeneic stem cell transplantation. To better understand current diagnostic and treatment practices regarding this complication, we mailed a self-administered survey to 188 adult and pediatric transplantation programs. The survey collected data on experience with therapies for cGVHD and presented 6 vignettes to assess agreement about the diagnosis, clinical management, grading, and prognosis of patients with symptoms of cGVHD. Response rate to the survey was 51%. Of the respondents, 28% felt they had "great success" in treating patients with systemic corticosteroids, and 13% had similar success with cyclosporine or mycophenolate mofetil; less success and experience were reported with other agents. Respondents estimated an average 3-year, nonrelapse mortality of 16% (95% CI, 14%-19%) for patients assessed to have limited disease and 39% (95% CI, 36%-43%) for extensive disease. Analysis of responses to the 6 vignettes showed that agreement was greatest for supportive care issues, willingness to enroll patients in clinical trials, and use of systemic immunosuppression for symptomatic cGVHD. Less agreement was seen for diagnosis and management when cGVHD manifestations were atypical or less severe, the decision of whether to taper immunosuppression in the face of stable symptoms, and for assignment of mild, moderate, or severe cGVHD grades. Most respondents were willing to use systemic immunosuppression to treat symptoms that they believed to be caused by cGVHD, but differences of opinion about cGVHD diagnosis and disease activity resulted in significant practice variation. Low estimates of treatment success were noted and reflected an overall pessimism about the success of therapy for cGVHD. We conclude that studies defining appropriate diagnostic pathways, criteria for disease activity, and prognosis could help standardize management of cGVHD. There is an urgent need to develop and test new approaches to treat cGVHD. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Nebraska, Med Ctr, Omaha, NE 68198 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. NR 9 TC 53 Z9 55 U1 0 U2 2 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. PY 2002 VL 8 IS 1 BP 32 EP 39 DI 10.1053/bbmt.2002.v8.pm11846354 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 517CV UT WOS:000173594300005 PM 11846354 ER PT J AU Alyea, E Neuberg, D Mauch, P Marcus, K Freedman, A Webb, I Anderson, K Schlossman, R Fisher, D Gribben, J Ritz, J Soiffer, R AF Alyea, E Neuberg, D Mauch, P Marcus, K Freedman, A Webb, I Anderson, K Schlossman, R Fisher, D Gribben, J Ritz, J Soiffer, R TI Effect of total body irradiation dose escalation on outcome following T-cell-depleted allogeneic bone marrow transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE total body irradiation; T-cell depletion; bone marrow transplantation ID VERSUS-HOST DISEASE; ACUTE MYELOID-LEUKEMIA; RANDOMIZED TRIAL; MYELOGENOUS LEUKEMIA; 1ST REMISSION; CHRONIC PHASE; REGIMENS; THERAPY; CHEMOTHERAPY; MALIGNANCIES AB Prior studies of non-T-cell-depleted (TCD) transplantation have demonstrated a reduction in relapse in patients receiving escalated doses of TBI; however, overall survival in these studies was not significantly improved due to increased treatment-related toxicity seen at the higher doses of irradiation. Toxicity was in part related to an increased incidence of GVHD. Because T-cell. depletion of donor bone marrow reduces the incidence of GVHD and other treatment-related complications after allogeneic bone marrow transplantation, it was postulated that TBI dose may be safely escalated in this setting and may decrease the risk of relapse following TCD BMT. Herein, we report the results of a trial assessing the safety and impact of escalated doses of TBI after TCD BMT. Two hundred adults with hematologic malignancies were treated in consecutive cohorts defined by increasing doses of TBI (1400, 1480, and 1560 cGy) in combination with cyclophosphamide. In vitro T-cell depletion using anti-CD6 monoclonal antibody was used for GVHD prophylaxis. The incidence of grade H or greater acute GVHD in patients receiving 1560 cGy (36%) was significantly higher than in patients receiving 1400 cGy (18%) (P=.04) or 1480 cGy (13%) (P=.01). Two-year treatment-related mortality was significantly higher in patients who received 1560 cGy of TBI (33%) than in those who received 1400 cGy (20%) (P=.04) or 1 480 cGy (19%) (P=.05). The increased dose of TBI did not reduce the rates of relapse, with the estimated 2-year risk of relapse being 24% (1400 cGy), 24% (1480 cGy), and 31% (1560 cGy) for the 3 cohorts of patients. Overall survival at 2 years was inferior for patients receiving 1560 cGy of TBI (36%) compared with those who received 1400 cGy (55%) or 1480 cGy (58%) (P=.01). We conclude that dose escalation of TBI is associated with increased GVHD and inferior survival following TCD BAIT. Future efforts to reduce the risk of relapse after TCD BMT should focus on immunologic methods to induce the graft-versus-leukemia effect after BMT rather than intensification of the ablative regimen by escalation of irradiation dose. C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Alyea, E (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 19 TC 16 Z9 17 U1 1 U2 1 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. PY 2002 VL 8 IS 3 BP 139 EP 144 DI 10.1053/bbmt.2002.v8.pm11939603 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 536VD UT WOS:000174721800003 PM 11939603 ER PT J AU Elias, AD Ibrahim, J Richardson, P Avigan, D Joyce, R Reich, E McCauley, M Wheeler, C Frei, E AF Elias, AD Ibrahim, J Richardson, P Avigan, D Joyce, R Reich, E McCauley, M Wheeler, C Frei, E TI The impact of induction duration and the number of high-dose cycles on the long-term survival of women with metastatic breast cancer treated with high-dose chemotherapy with stem cell rescue: An analysis of sequential phase I/II trials from the Dana-Farber/Beth Israel STAMP program SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE metastatic breast cancer; hematopoietic stem cell support; double transplantation ID PROGRESSION-FREE SURVIVAL; INTENSIVE CHEMOTHERAPY; 2 CYCLES; SUPPORT; DOXORUBICIN; RESISTANT; SELECTION; CARCINOMA; DAMAGE; LINES AB Although high-dose chemotherapy (HDC) with stem cell rescue for the treatment of women with metastatic breast cancer (MBC) is currently a controversial strategy, we report the long-term outcomes of women undergoing high-dose therapy for MBC over the past 12 years while participating in a sequence of research studies transitioning between a single to a double intensification approach. Univariate and multivariate analyses provide a framework to understand the prognostic factors important for event-free and overall survival. Between May 1988 and April 1998, we enrolled 188 women with MBC into 3 trials of previously reported sequential transplantation strategies. Trial I (long induction/single transplantation) accepted 62 women in partial or complete response to an unspecified induction therapy and treated them with high-dose CTCb (cyclophosphamide, thiotepa, and carboplatin) supported by marrow or peripheral blood progenitor cells (PBPC). Trial II (long induction/double transplantation) accepted 68 women in partial or complete response to an unspecified induction therapy, and mobilized stem cells with 2 cycles of AF (doxorubicin and 5-fluorouracil) with granulocyte colony-stimulating factor (G-CSF). These women then received I cycle of high-dose single-agent melphalan followed 3 to 5 weeks later by CTCb, each with marrow or PBPC support Trial III (short induction/double transplantation) enrolled 58 women prior to chemotherapy treatment for metastatic disease. Induction/mobilization consisted of 2 cycles given 14 days apart of doxorubicin and G-CSE In contrast to trials I and H, patients with stable disease or better response to induction were eligible to proceed ahead with 2 cycles of HDC, I being CTCb and the other being dose escalated paclitaxel together with high-dose melphalan (TxM). These 2 HDC regimens were administered 5 weeks apart. TxM was given first in 32 patients and CTCb was given first in 26 patients. The median follow-up periods for trials 1, 11, and III were 98, 62, and 39 months from the initiation of induction chemotherapy and 92, 55, and 36 months from last high-dose therapy, respectively. The patient characteristics upon entry into these trials were similar. Important differences were that only those patients achieving a partial response or better to induction therapy were enrolled and analyzed for trials I and H, but all patients were analyzed on an intent-to-treat basis for trial 111, including those who did not receive intensification. The median event-free survival (EFS) times from induction chemotherapy were 13, 19, and 27 months for trials I, II, and M. respectively (III versus I + II, P = .0004; III versus I, P = .003; III versus II, P = .005; II versus I, P = .25). The median overall survival (OS) times from induction chemotherapy were 30, 29, and 57 months for trials I, H, and 111, respectively (III versus I + II, P = .002; III versus I, P = .003; III versus II, P = .009; II versus I, P = .47). By multivariate Cox regression, participation in the short induction/double transplantation trial III and having no prior adjuvant chemotherapy remained favorable prognostic factors for both EFS and OS. The presence of visceral disease shortened EFS, and hormone sensitivity was of borderline significance. No substantive differences in the characteristics of the patient populations between the 3 trials appeared to interact with outcomes. In conclusion, we found that single transplantation in responding patients after long induction achieves a small cohort of long-term survivors, similar to the results reported by other transplantation centers. Adding a cycle of single-agent high-dose melphalan in this context delayed median time to relapse but did not affect long-term EFS or OS. The double transplantation approach using CTCb and TxM early in the course of treatment was associated with the best EFS and overall survival and was safe, feasible, and tolerable. Treatment duration was only 14 weeks, and this treatment option eliminated lengthy induction chemotherapy. Although selection biases may have in part contributed to this effect, a randomized comparison of standard therapy versus short induction/double transplantation is warranted. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Elias, AD (reprint author), Univ Colorado, Hlth Sci Ctr, Breast Canc Program, POB 6510 Mailstop F-724 1635 N Ursula St, Aurora, CO 80010 USA. FU NCI NIH HHS [CA13849] NR 35 TC 10 Z9 10 U1 0 U2 2 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. PY 2002 VL 8 IS 4 BP 198 EP 205 DI 10.1053/bbmt.2002.v8.pm12017145 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 546NC UT WOS:000175279300003 PM 12017145 ER PT J AU Martin, PJ Antin, JH Weisdorf, DJ Paton, V Horowitz, MM AF Martin, PJ Antin, JH Weisdorf, DJ Paton, V Horowitz, MM TI Reporting of adverse event data in hematopoietic stem cell transplantation clinical trials involving investigational new drugs or devices: A report from the William Guy Forbeck Foundation 2001 Focus Meeting on clinical stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE hematopoietic stem cell transplantation; adverse events; monitoring AB The William Guy Forbeck Foundation was established in 1984 in memory of William Guy Forbeck, an 11-year-old boy who died of neuroblastoma. The objectives of the Forbeck Foundation are to promote advances and shorten the research timetable in the field of oncology, particularly pediatric oncology. The Foundation's centerpiece activity is an annual scientific forum held at Hilton Head Island, South Carolina, where 12 to 15 leading scientists from a variety of disciplines associated with a specific topic are invited to participate in a private "think tank" environment, where they can freely exchange ideas in the hope of building on each other's knowledge and experience. Additionally, the Foundation sponsors grants for Focus Meetings, which are designed to give other researchers an opportunity to conduct their own meetings along the lines of the Foundation's annual forum. The idea for this Focus Meeting was born during the 2000 Annual Forbeck Forum in South Carolina, which considered the current status of allogeneic hematopoietic stem cell transplantation (HSCT). Participants considered various obstacles to conducting clinical trials in this area and decided to bring together experts from academia, industry, and government to discuss ways in which these obstacles might be overcome. Topics included efficient clinical trial designs, issues of monitoring and reporting adverse events, and appropriate definitions and grading systems for transplantation-specific outcomes. This article summarizes the issue of adverse event reporting in HSCT. C1 Fred Hutchinson Canc Res Ctr D2 100, Seattle, WA 98109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN USA. Cerus Corp, Concord, CA USA. Int Bone Marrow Transplant Registry, Milwaukee, WI USA. RP Martin, PJ (reprint author), Fred Hutchinson Canc Res Ctr D2 100, POB 19024, Seattle, WA 98109 USA. NR 8 TC 8 Z9 8 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. PY 2002 VL 8 IS 6 BP 295 EP 302 DI 10.1053/bbmt.2002.v8.pm12108915 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 570LB UT WOS:000176658800002 PM 12108915 ER PT J AU Elias, AD Skarin, AT Richardson, P Ibrahim, J McCauley, M Frei, E AF Elias, AD Skarin, AT Richardson, P Ibrahim, J McCauley, M Frei, E TI Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: Long-term outcome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE small cell lung cancer; hematopoietic stem cell support; phase II ID BONE-MARROW METASTASES; BRONCHOGENIC-CARCINOMA; MONOCLONAL-ANTIBODIES; PROGENITOR CELLS; PERIPHERAL-BLOOD; RANDOMIZED TRIAL; CHEMOTHERAPY; ETOPOSIDE; CARBOPLATIN; IFOSFAMIDE AB Treatment for extensive-stage small cell lung cancer (ES SCLC) or extrapulmonary small cell carcinoma (EPSC) is typically palliative. We set out to determine progression-free survival (PFS) and overall long-term survival of ES SCLC and EPSC patients, physiologically aged : 60 years, responding to first-line chemotherapy followed by high-dose combination alkylating agents with hematologic stem cell support. Patients in first-line chemotherapy response underwent stem cell collection (marrow, peripheral blood progenitor cells, or both) followed by high-dose therapy with 1 of 2 regimens: CBP (cyclophosphamide, cisplatin, and carmustine) or ICE (ifosfamide, carboplatin, and etoposide) with or without etanidazole. Involved-field radiotherapy was given to selected patients with oligometastatic disease distributed in sites allowing for reasonable radiation ports, and prophylactic cranial radiotherapy was given upon recovery to patients in complete response (CR) or near-CR. A total of 36 patients were treated. Of 29 patients with ES SCLC, 6 (21%) had achieved CR, 18 near-CR, and 5 partial response prior to high-dose therapy. Of 7 patients with EPSC, 3 (43%) had achieved CR, 3 had achieved near-CR, and 1 had progression of disease prior to high-dose therapy. Thirteen ES SCLC patients received high-dose CBP. Of the remaining 23 patients with SCLC or EPSC, 17 were treated with ICE and 6 with ICE plus etanidazole, a hypoxic cell sensitizer. Treatment-related mortality was 11% (4 of 36 patients). For all patients, the median event-free survival (EFS) was 5 months. The 2- and 5-year survivals after intensification were 12% (95% confidence interval [CI], 5%-31%) and 9% (95% CI, 3%-27%), respectively. Of the 30 patients in or near CR prior to high-dose therapy, 5 remain continuously progression-free (2 ES SCLC, 3 EPSC) for a median of 55 months (range, 1-96 months) after high-dose therapy. By multivariate analysis, factors associated with more favorable EFS were the use of a more aggressive induction regimen (ICE), and the EPSC histology. These factors were also associated with more favorable overall survival. Other factors associated with more favorable overall survival were the use of short induction therapy (: 4 cycles) and younger age (<50 years). Except for high-dose ICE with etanidazole, the use of high-dose systemic therapy in ES SCLC and EPSC was associated with low treatment-related morbidity and mortality over the past 5 years. Late complications were infrequent, and most patients returned to full-time work and activity, barring disease recurrence. Nonetheless, few patients with ES SCLC have progression-free long-term survival. We conclude that high-dose therapy is not indicated as an approach for ES SCLC, except as part of an investigative trial. Conversely, 3 of the 7 patients with EPSC remain relapse-free (range, 1-96 months), warranting further phase II evaluation of this approach in this population. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Elias, AD (reprint author), Univ Colorado, Hlth Sci Ctr, 1635 N Ursula St, Aurora, CO 80010 USA. FU NCI NIH HHS [CA13849] NR 38 TC 4 Z9 4 U1 0 U2 1 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. PY 2002 VL 8 IS 6 BP 326 EP 333 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 570LB UT WOS:000176658800005 PM 12108918 ER PT J AU Webb, IJ Friedberg, JW Gribben, JG Fisher, DC Spitzer, T Neuberg, D Fallow, H Kim, H Houde, H Monroy, R Schmittling, R Freedman, AS AF Webb, IJ Friedberg, JW Gribben, JG Fisher, DC Spitzer, T Neuberg, D Fallow, H Kim, H Houde, H Monroy, R Schmittling, R Freedman, AS TI Effective purging of autologous hematopoietic stem cells using anti-B-cell monoclonal antibody-coated high-density microparticles prior to high-dose therapy for patients with non-Hodgkin's lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE autologous transplant; B-cell lymphoma; purging ID BONE-MARROW TRANSPLANTATION; POLYMERASE CHAIN-REACTION; FOLLICULAR LYMPHOMA; FIRST REMISSION; BLOOD; CHEMOTHERAPY; ELIMINATION; DISEASE; TRIAL; AMPLIFICATION AB Contamination of hematopoietic stem cells (HSCs) with tumor cells has been associated with increased incidence of relapse in patients with non-Hodgkin's lymphoma following autologous HSC transplantation. Effective purging of tumor cells may improve the results of HSC transplantation, but current methods of purging are technically difficult to perform with large numbers of cells and do not consistently remove all detectable cells. We report a pilot clinical trial in which 10 patients with relapsed B-cell non-Hodgkin's lymphoma received high-dose chemotherapy followed by infusion of autologous HSCs depleted of B-cells by high-density microparticles (HDM) coated with anti-CD19 and anti-CD20 monoclonal antibodies (BCell-HDM). HSCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. In 6 of the 10 patients, B-cells were detectable by immunocytochemical analysis of the apheresis products prior to treatment. Following treatment with the BCell-HDM, no B-cells were detected in the products from 5 of these patients, a result representing a median depletion of >2.2 logs (range, >0.4 to >5.1 logs). The median recovery of nontarget cells postdepletion was 73% for CD34(+) cells and 78% for CD3(+) cells. All patients received high-dose cyclophosphamide, BCNU (carmustine), and etoposide prior to reinfusion of their B-cell-depleted autologous HSCs. The median number of CD34(+) cells cryopreserved was 3.6 x 10(6) cells/kg (range, 2.2-10.1 X 10(6) cells/kg). Engraftment was rapid in all cases, with a median time to achieve an absolute neutrophil count of 0.5 x 10(9)/L of 10 days (range, 8-11 days). The median time to achieve a platelet count of 20 x 10(9)/L unsupported by platelet transfusion was 11.5 days (range, 8-17 days). This nonmagnetic negative-depletion technology is simple, rapid, and effective in depleting target cells to undetectable levels, with excellent recovery of nontarget cells. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol Oncol, Cell Manipulat Core Facil, Joint Program Tranfus Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Eligix Inc, Medford, MA USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 66996] NR 46 TC 7 Z9 7 U1 0 U2 1 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. PY 2002 VL 8 IS 8 BP 429 EP 434 DI 10.1053/bbmt.2002.v8.pm12234168 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 590FL UT WOS:000177807600004 PM 12234168 ER PT J AU Lee, SJ Cook, EF Soiffer, R Antin, JH AF Lee, SJ Cook, EF Soiffer, R Antin, JH TI Development and validation of a scale to measure symptoms of chronic graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE chronic graft-versus-host disease; stem-cell transplantation; quality of life; outcomes research ID BONE-MARROW TRANSPLANTATION; PROGENITOR-CELL TRANSPLANTATION; BLOOD STEM-CELL; HEMATOLOGIC MALIGNANCIES; HIGH-RISK; HEALTH; PREDNISONE; PREDICTORS; LEUKEMIA; SURVIVAL AB Chronic GVHD (cGVHD) affects 30% to 90% of surviving allogeneic transplant recipients. Thus far, no quality-of-life instruments have been developed to measure the effect of this common complication of allogeneic transplantation on patients' functioning and well-being. Using a prospective cohort of 107 patients with active cGVHD who completed the symptom scale at enrollment and at intervals of 3 and 6 months, we developed a 30-item symptom scale with 7 subscales to capture the cGVHD-specific symptom burden. The symptom scale correlated highly with patients' self-assessed mild, moderate, and severe cGVHD manifestations in cross-sectional analysis. Reliability (Cronbach's alpha = 0.79-0.90), test-retest (r(2) = 0.28-0.93), and convergent and discriminant validity compared to the Medical Outcomes Study Short Form 36 (SF-36) and Functional Assessment of Chronic Illness Therapy with BAIT subscale (FACT-BMT) were assessed and found to be adequate. Longitudinal assessments showed that changes in overall health status correlated best with changes in quality of life as measured by the SF-36 and FACT-BAIT. In contrast, changes in cGVHD severity were best detected by changes in the symptom scale. We recommend that either the SF-36 or the FACT-BMT be combined with a cGVHD-specific symptom scale to measure the impact of cGVHD on patients' quality of life and that this endpoint be included in clinical trials testing cGVHD interventions. The cGVHD symptom scale is a short, simple, and valid measure of cGVHD manifestations and can be used to follow complication-specific symptoms using patient self-administered questionnaires. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75267-04] NR 31 TC 91 Z9 92 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. PY 2002 VL 8 IS 8 BP 444 EP 452 DI 10.1053/bbmt.2002.v8.pm12234170 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 590FL UT WOS:000177807600006 PM 12234170 ER PT J AU Jiang, Z Adams, GB Hanash, AM Scadden, DT Levy, RB AF Jiang, Z Adams, GB Hanash, AM Scadden, DT Levy, RB TI The contribution of cytotoxic and noncytotoxic function by donor T-cells that support engraftment after allogeneic bone marrow transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE CD8(+) T-cell cytotoxicity; engraftment; facilitation; bone marrow transplantation ID HEMATOPOIETIC STEM-CELLS; NATURAL-KILLER-CELLS; TERM REPOPULATING ABILITY; VERSUS-HOST DISEASE; LONG-TERM; GRAFT-REJECTION; RISK-FACTORS; MICE; FAILURE; ALLOGRAFTS AB The present studies were designed for investigation of the requirements for cytotoxic function in donor T-cells transplanted to support engraftment after infusion of allogeneic bone marrow. The experiments examined the capacity of donor CD8(+) T-cells lacking Fas ligand and/or perforin function to facilitate donor B6 congenic (B6-Ly5.1) BM engraftment across major histocompatibility complex class I/II barriers after transplantation. T-cell-depleted BM cells from B6-Ly5.1 donors were transplanted into sublethally irradiated (5.5 Gy) BALB/c recipients together with different lymphocyte populations from wild-type B6 (B6-wt) donors or donors lacking functional cytotoxic pathways. Early presence of lineage-committed donor progenitor cells was assessed by the presence of day 5 splenic colony-forming units-granulocyte-macrophage (CFU-GM). Recipients of BMT without donor T-cens did not demonstrate significant CFU-GM activity 5 days post-BAIT. Lineage-committed progenitor cells in recipient spleens could be supported by addition to the BM of wild-type (B6-wt) and cytotoxically single- (perforin, B6-pko or FasL, B6-gld) or double-deficient (B6-cdd) CD8(+) T-cells. However, B220(+)-enriched B-cells could not support the presence of day 5 donor CFU-GM. For further assessment of the capacity of cytotoxically impaired T-cells to participate in the engraftment process, the ability of these and normal CD8 cells to support the homing of donor cells to the BM was examined after infusion of carboxyfluorescein diacetete succinimidyl ester-labeled progenitors. In a syngeneic model lacking resistance, cytotoxically impaired donor T-cells supported increased numbers of progenitor cells in the marrow equivalent to the support provided by wild-type donor T-cells. Examination of peripheral chimerism indicated that during the first month after B6-->BALB/c BMT, donor chimerism was detected in BMT recipients receiving unfractionated T-cells or CD8(+) T-cells from B6-wt donors, and chimerism was maintained at least 80 days after BMT. In contrast, B6-cdd unfractionated or CD8(+) T-cells failed to maintain long-term B6 donor chimerism in the host. Experiments with highly enriched populations of positively selected CD8(+) T-cells from B6-pko, B6-gld, or B6-cdd donors demonstrated that although each of these T-cell populations could promote the initial presence of donor CFU-GM early post-BAIT, B6-pko and B6-cdd CD8(+) T-cell populations were not able to support long-term peripheral chimerism. These results demonstrate that donor T-cells lacking major cytotoxic effector pathways have functions that support initial donor progenitor cell presence in the host hematopoietic compartment after BMT. They also demonstrate that support of long-term donor BM engraftment requires CD8(+) T-cells with intact cytotoxic, that is, perforin, function. Finally, syngeneic B6-->B6 BMT suggests activation of CD8(+) T-cells posttransplantation apparently is required to support enhanced progenitor cell activity. This study provides new findings concerning the role of cytotoxic function in the process of facilitating allogeneic donor BM engraftment. C1 Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA. RP Levy, RB (reprint author), Univ Miami, Sch Med, Dept Microbiol & Immunol, POB 016960 R-138, Miami, FL 33101 USA. FU NCRR NIH HHS [R01 RR11576]; NHLBI NIH HHS [R01 HL52461]; NIAID NIH HHS [R01 AI46689] NR 42 TC 24 Z9 24 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. PY 2002 VL 8 IS 11 BP 588 EP 596 DI 10.1053/bbmt.2002.v8.abbmt080588 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 618EH UT WOS:000179405100002 PM 12463477 ER PT J AU Alyea, EP Weller, E Fisher, DC Freedman, AS Gribben, YG Lee, S Schlossman, RL Stone, RM Friedberg, Y DeAngelo, D Liney, D Windawi, S Ng, A Mauch, P Antin, JH Soiffer, RJ AF Alyea, EP Weller, E Fisher, DC Freedman, AS Gribben, YG Lee, S Schlossman, RL Stone, RM Friedberg, Y DeAngelo, D Liney, D Windawi, S Ng, A Mauch, P Antin, JH Soiffer, RJ TI Comparable outcome with T-cell-depleted unrelated-donor versus related-donor allogeneic bone marrow transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE CD6(+); graft-versus-host disease; donor source ID CHRONIC MYELOGENOUS LEUKEMIA; VERSUS-HOST DISEASE; HLA-IDENTICAL SIBLINGS; PROPHYLAXIS; ANTIBODIES; RECIPIENTS; RELAPSE; PROGRAM; THERAPY AB To assess the effect of related versus unrelated donors on outcomes in patients following T-cell-depleted (TCD) allogeneic BMT, we compared engraftment, GVHD, relapse rates, and survival in BMT patients who received CD6(+) TCD marrow from HLA-matched related donors (MRD) with those in patients who received CD6(+) TCD marrow from unrelated donors (URD). A total of 170 consecutive patients (120 with related donors, 50 with unrelated donors) were analyzed. The 2 groups were similar in age, sex, prior cytomegalovirus exposure, and stage of disease at the time of transplantation. GVHD prophylaxis was identical in the 2 groups, with TCD as the only method of GVHD prophylaxis. The total number of nucleated, CD34(+), CD3(+), and CD6(+) cells infused did not significantly differ between the 2 groups. The median day to reach 500 x 106 neutrophils/L was 12 days for both related (range, 8-22 days) and unrelated (range, 9-23 days) graft recipients (P = .92). Incidence of grades 2 through 4 acute GVHD was higher in URD than in MRD recipients (42% versus 20%, P = .004). According to multivariable analysis results, donor source was the single most important factor influencing GVHD (P = .01). The 2-year estimated risk of relapse was 45.9% in MRD recipients compared to 25.7% in URD recipients (P = .06). Multivariable Analysis revealed that the 2 most pertinent factors adversely affecting overall survival were advanced disease stage (P = .0002) and age greater than 50 years (P = .0003) at transplantation. There was no difference in relapse-free survival in URD and MRD recipients. We conclude that for patients undergoing TCD-BMT, use of unrelated marrow is associated with a higher risk of GVHD and other transplantation-related complications. However, these adverse events do not lead to inferior probability of relapse-free survival because they are accompanied by a reduction in relapse rates. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 29530] NR 31 TC 17 Z9 17 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. PY 2002 VL 8 IS 11 BP 601 EP 607 DI 10.1053/bbmt.2002.v8.abbmt080601 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 618EH UT WOS:000179405100004 PM 12463479 ER PT J AU Soiffer, RJ Alyea, ER Hochberg, E Wu, C Canning, C Parikh, B Zahrieh, D Webb, I Antin, J Ritz, J AF Soiffer, RJ Alyea, ER Hochberg, E Wu, C Canning, C Parikh, B Zahrieh, D Webb, I Antin, J Ritz, J TI Randomized trial of CD8(+) T-cell depletion in the prevention of graft-versus-host disease associated with donor lymphocyte infusion SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE CD8(+) T-cell depletion; graft-versus-host disease; donor lymphocyte infusion ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; RECENT THYMIC EMIGRANTS; BLOOD STEM-CELL; SELECTIVE DEPLETION; LEUKOCYTE INFUSIONS; MULTIPLE-MYELOMA; ADD-BACK; RELAPSE AB The application of DLI is limited by the potential development of GVHD. Results of single-arm trials suggest that CD8(+) depletion of DLI may reduce the incidence of GVHD while still inducing pathologic and cytogenetic remissions. To test the impact of CD8 depletion on GVHD, we initiated a randomized trial comparing outcome among patients receiving unselected donor lymphocytes or CD8(+)-depleted cells. DLI was administered to patients with disease in remission to prevent relapse 6 months after T-cell-depleted allogeneic BMT. CD8 depletion was performed with monoclonal antibody and rabbit complement. Donor lymphocytes obtained from the original donor were infused fresh without cryopreservation. Infusions were adjusted so that all patients received 1.0 x 10(7) CD4(+) cells/kg. Patients randomized to CD8 depletion received a median of 0.7 x 10(5) versus 32.0 x 10(5) CD8(+) cells/kg in the unmanipulated cohort. Six (67%) of 9 patients receiving unselected DLI developed acute GVHD compared with 0 (0%) of 9 recipients of CD8-depleted DLI (P =.009). In the unselected group, 2 patients died while the disease was in remission, and 3 patients had relapses. In the CD8-depleted cohort, there were no toxic deaths and only 1 relapse. Measures of immunologic reconstitution by T-cell receptor excision circle analysis and T-cell receptor spectratyping demonstrated similar patterns of T-cell recovery in both the CD8-depleted and the unselected cohorts. Both groups converted from mixed to full donor hematopoietic chimerism after DLI. Our results indicate that CD8 depletion reduces the incidence of GVHD associated with DLI without adversely affecting conversion to donor hematopoiesis or immunologic recovery. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU PHS HHS [29530] NR 45 TC 72 Z9 79 U1 1 U2 1 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. PY 2002 VL 8 IS 11 BP 625 EP 632 DI 10.1053/bbmt.2002.v8.abbmt080625 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 618EH UT WOS:000179405100007 PM 12463482 ER PT J AU White, MF AF White, MF TI Insulin receptor substrate 2 branch of the insulln/lnsulin-like growth factor signaling system coordinates nutrient homeostasis and female fertility. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 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 2002 VL 66 SU 1 MA M32 BP 88 EP 89 PG 2 WC Reproductive Biology SC Reproductive Biology GA 568UD UT WOS:000176561900046 ER PT J AU Sidis, Y Schneyer, AL Sluss, PM Keutmann, HT AF Sidis, Y Schneyer, AL Sluss, PM Keutmann, HT TI Regulation of activin action by follistatin: Role of the heparin-binding region. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 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 2002 VL 66 SU 1 MA 58 BP 121 EP 121 PG 1 WC Reproductive Biology SC Reproductive Biology GA 568UD UT WOS:000176561900118 ER PT J AU Schneyer, A Sidis, Y Sluss, P AF Schneyer, A Sidis, Y Sluss, P TI Distinct forms of follistatin in human serum and follicular fluid. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 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 2002 VL 66 SU 1 MA 91 BP 135 EP 135 PG 1 WC Reproductive Biology SC Reproductive Biology GA 568UD UT WOS:000176561900151 ER PT J AU Zhang, B Ambrosi, DJ Pru, JK Davis, JS Rueda, BR Tsang, PCW AF Zhang, B Ambrosi, DJ Pru, JK Davis, JS Rueda, BR Tsang, PCW TI Collagenase 3 (MMP-13): Expression in the bovine corpus luteum and its regulation by cytokines in luteal-derived endothelial cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Vet Adm Med Ctr, Omaha, NE 68105 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Olson Ctr Womens Hlth, Omaha, NE USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Univ New Hampshire, Dept Anim & Nutrit Sci, Durham, NH 03824 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 2002 VL 66 SU 1 MA 214 BP 184 EP 184 PG 1 WC Reproductive Biology SC Reproductive Biology GA 568UD UT WOS:000176561900273 ER PT J AU O'Donnell, JM Alpert, NM White, LT Lewandowski, ED AF O'Donnell, JM Alpert, NM White, LT Lewandowski, ED TI Coupling of mitochondrial fatty acid uptake to oxidative flux in the intact heart SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; PERFUSED RAT HEARTS; CARNITINE PALMITOYLTRANSFERASE; ISCHEMIC HEART; RABBIT HEARTS; METABOLISM; CYCLE; COA; MYOCARDIUM; PALMITATE AB The coordination of long chain fatty acid (LCFA) transport: across the mitochondrial membrane (V-PAL) with subsequent oxidation rate through beta-oxidation and the tricarboxylic acid (TCA) cycle (V-toa) has been difficult to characterize in the intact heart. Kinetic analysis of dynamic C-13-NMR distinguished these flux rates in isolated rabbit hearts. Hearts were perfused in a 9.4 T magnet with either 0.5 mM [2,4,6,8,10,12,14,16-C-13(8)] palmitate (n = 4), or 0.5 mM C-13-labeled palmitate plus 0.08 mM unlabeled butyrate (n = 4). Butyrate is a short chain fatty acid (SCFA) that bypasses the LCFA transporters of mitochondria. In hearts oxidizing palmitate alone, the ratio of V-TCA to V-PAL was 8:1. This is consistent with one molecule of palmitate yielding eight molecules of acetyl-CoA for the subsequent oxidation through the TCA cycle. Addition of butyrate elevated this ratio; V-TCA/V-PAL = 12:1 due to an SCFA-induced increase in V-TCA of 43% (p < 0.05). However, SCFA oxidation did not significantly reduce palmitate transport into the mitochondria: V-PAL = 1.0 +/- 0.2 μmol/min/g dw with palmitate alone versus 0.9 +/- 0.1 with palmitate plus butyrate. Thus, the products of β-oxidation are preferentially channeled to the TCA cycle, away from mitochondrial efflux via carnitine acetyltransferase. C1 Univ Illinois, Coll Med, Dept Physiol & Biophys MC 901, Program Integrat Cardiac Metab, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Lewandowski, ED (reprint author), Univ Illinois, Coll Med, Dept Physiol & Biophys MC 901, Program Integrat Cardiac Metab, 835 S Wolcott Ave,E-202 MSB, Chicago, IL 60612 USA. FU NCI NIH HHS [5T32CA09362]; NHLBI NIH HHS [R01HL49244, R01HL62702] NR 35 TC 29 Z9 31 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 BP 11 EP 18 PG 8 WC Biophysics SC Biophysics GA 511DZ UT WOS:000173250500002 PM 11751291 ER PT J AU Mannella, CA Buttle, KF Scorrano, L Korsmeyer, SJ McDonald, KL van der Bliek, AM AF Mannella, CA Buttle, KF Scorrano, L Korsmeyer, SJ McDonald, KL van der Bliek, AM TI Unusual mitochondrial inner-membrane morphologies associated with apoptosis and MGM-1 mutation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 MA 108 BP 23A EP 23A PN 2 PG 1 WC Biophysics SC Biophysics GA 511EY UT WOS:000173252700110 ER PT J AU Struyk, AF Cannon, SC AF Struyk, AF Cannon, SC TI Substituted cysteines in the outer pore of the Na channel are equally accessible in fast- and slow-inactivated states SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 MA 434 BP 89A EP 89A PN 2 PG 1 WC Biophysics SC Biophysics GA 511EY UT WOS:000173252700438 ER PT J AU Perrett, SG Timpanaro, G Montalbetti, N Essafi, M Arnaout, AM Cantiello, HF AF Perrett, SG Timpanaro, G Montalbetti, N Essafi, M Arnaout, AM Cantiello, HF TI Actin cytoskeleton dynamics regulates the human polycystin-2 cation channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Buenos Aires, Fac Farm & Bioquim, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Univ Buenos Aires, Fac Med, Dept Fisiol, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 MA 1023 BP 210A EP 210A PN 2 PG 1 WC Biophysics SC Biophysics GA 511EY UT WOS:000173252701033 ER PT J AU Walton, SP Stephanopoulos, GN Yarmush, ML Roth, CM AF Walton, SP Stephanopoulos, GN Yarmush, ML Roth, CM TI Thermodynamic and kinetic characterization of antisense oligodeoxynucleotide binding to a structured mRNA SO BIOPHYSICAL JOURNAL LA English DT Article ID RNA SECONDARY STRUCTURE; IMMUNODEFICIENCY-VIRUS TYPE-1; STRUCTURE PREDICTION; HYBRIDIZATION KINETICS; OLIGONUCLEOTIDE ARRAYS; THEORETICAL APPROACH; DNA PROBES; PARAMETERS; SEQUENCES; PSEUDOKNOTS AB Antisense oligonucleotides act as exogenous inhibitors of gene expression by binding to a complementary sequence on the target mRNA, preventing translation into protein. Antisense technology is being applied successfully as a research tool and as a molecular therapeutic. However, a quantitative understanding of binding energetics between short oligonucleotides and longer mRNA targets is lacking, and selecting a high-affinity antisense oligonucleotide sequence from the many possibilities complementary to a particular RNA is a critical step in designing an effective antisense inhibitor. Here, we report measurements of the thermodynamics and kinetics of hybridization for a number of oligodeoxynucleotides (ODNs) complementary to the rabbit beta-globin (RBG) mRNA using a binding assay that facilitates rapid separation of bound from free species in solution. A wide range of equilibrium dissociation constants were observed, and association rate constants within the measurable range correlated strongly with binding affinity. In addition, a significant correlation was observed of measured binding affinities with binding affinity values predicted using a thermodynamic model involving DNA and RNA unfolding, ODN hybridization, and RNA restructuring to a final free energy minimum. In contrast to the behavior observed for hybridization of short strands, the association rate constant increased with temperature, suggesting that the kinetics of association are related to disrupting the native structure of the target RNA. The rate of cleavage of the RBG mRNA in the presence of ribonuclease H and ODNs of varying association kinetics displayed apparent first-order kinetics, with the rate constant exhibiting binding-limited behavior at low association rates and reaction-limited behavior at higher rates. Implications for the rational design of effective antisense reagents are discussed. C1 Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Biochem Engn, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Roth, CM (reprint author), Rutgers State Univ, Dept Chem, 98 Brett Rd, Piscataway, NJ 08854 USA. RI Walton, S. Patrick/A-7007-2008; OI Walton, S. Patrick/0000-0003-1708-8603; Roth, Charles/0000-0002-4924-0721 FU NIGMS NIH HHS [GM08334] NR 40 TC 37 Z9 40 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 BP 366 EP 377 PG 12 WC Biophysics SC Biophysics GA 511DZ UT WOS:000173250500034 PM 11751323 ER PT J AU Oh, KJ Weiler, S Korsmeyer, SJ AF Oh, KJ Weiler, S Korsmeyer, SJ TI Interaction and conformation of N-myristoylated BID, a pro-apoptotic BCL-2 family member, with phospholipid vesicles. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 MA 2342 BP 480A EP 480A PN 2 PG 1 WC Biophysics SC Biophysics GA 511EY UT WOS:000173252702359 ER PT J AU Burton, K Wang, XY AF Burton, K Wang, XY TI An aperture-shifting light microscope method for quantifying the positions of cells in 3D SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Rad Oncol, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2002 VL 82 IS 1 MA 2435 BP 498A EP 498A PN 2 PG 1 WC Biophysics SC Biophysics GA 511EY UT WOS:000173252702452 ER PT J AU Cariani, PA AF Cariani, PA TI Extradimensional bypass SO BIOSYSTEMS LA English DT Article DE Michael conrad; theoretical biology; biological cybernetics; molecular computing; adaptability; self-organization; evolution; emergence; dimensionality AB We discuss the concept of extradimensional bypass as it was developed by the late theoretical biologist Michael Conrad. An evolving system that optimizes its performance by gradient ascent (hill climbing) can avoid being trapped in local maxima by increasing the effective dimensionality of its search space. Many local maxima may become saddle points in the higher dimensional space, such that gradient ascent can continue unimpeded. Extradimensional bypass as a concept has parallels in theories of open-ended learning and functional emergence, where new structural, functional, and informational primitives can increase the effective dimensionality of material systems. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otol & Laryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otol & Laryngol, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM cariani@mae.com NR 30 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0303-2647 EI 1872-8324 J9 BIOSYSTEMS JI Biosystems PD JAN PY 2002 VL 64 IS 1-3 SI SI BP 47 EP 53 AR PII S0303-2647(01)00174-5 DI 10.1016/S0303-2647(01)00174-5 PG 7 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 586LW UT WOS:000177586300007 PM 11755488 ER PT J AU Husson, H Carideo, EG Neuberg, D Schultze, J Munoz, O Marks, PW Donovan, JW Chillemi, AC O'Connell, P Freedman, AS AF Husson, H Carideo, EG Neuberg, D Schultze, J Munoz, O Marks, PW Donovan, JW Chillemi, AC O'Connell, P Freedman, AS TI Gene expression profiling of follicular lymphoma and normal germinal center B cells using cDNA arrays SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; RECEPTOR GAMMA-CHAIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMOSOMAL-ABNORMALITIES; CLINICAL CORRELATIONS; FUNCTIONAL COMPONENT; CYTOGENETIC ANALYSIS; RESIDUAL DISEASE; MESSENGER-RNA; UP-REGULATION AB Follicular lymphomas (FLs) are neoplastic counterparts of normal germinal center (GC) B cells. FLs are characterized by t(14;18) with deregulation of the Bcl-2 (BCL2) gene. The presence of t(14;18) and overexpression of Bcl-2 is necessary, but not sufficient, to cause this disease. An array containing 588 complementary DNAs (cDNAs) was used to compare the gene expression between GC B cells and FL cells. To specifically monitor genes expressed in normal GC B and FIL cells and not the entire tissue compartment, normal and malignant B cells were purified from tissues. Using the array, 37 genes were up-regulated and 28 were down-regulated In FL cells as compared to normal GC B cells. The expression level of each differentially expressed gene was verified by quantitative polymerase chain reaction. Following these studies 24 genes were up-regulated and 8 genes down-regulated with a P value less than .1. Included among the genes that were up-regulated in FLs were cell cycle regulator proteins CDK10, p120, p21CIP1, and p16INK4A; transcription factors/regulators Pax-5 and Id-2, which are involved in normal B-cell development; and genes involved in cell-cell interactions, tumor necrosis factor, interleukin-2R gamma (IL-2R gamma), and IL-4r alpha. Among the genes that were down-regulated In FLs were MRP8 and MRP14, which are Involved In adhesion. Interestingly, several of these genes are localized within chromosomal regions already described to be altered In FLs. These findings provide a basis for future studies Into the pathogenesis and pathophysiology of FL and may lead to the identification of potential therapeutic targets as well as antigens for Immunotherapeutic strategies. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA55207, CA66996] NR 72 TC 101 Z9 103 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 2002 VL 99 IS 1 BP 282 EP 289 DI 10.1182/blood.V99.1.282 PG 8 WC Hematology SC Hematology GA 506PK UT WOS:000172980800043 PM 11756183 ER PT J AU Mukerjee, P Ostrow, JD Tiribelli, C AF Mukerjee, Pasupati Ostrow, J. Donald Tiribelli, Claudio TI Low solubility of unconjugated bilirubin in dimethylsulfoxide - water systems: implications for pK(a) determinations SO BMC BIOCHEMISTRY LA English DT Article AB Background: Aqueous pK(a) values of unconjugated bilirubin are important determinants of its solubility and transport. Published pK(a) data on an analog, mesobilirubin-XIII alpha, studied by C-13-NMR in buffered solutions containing 27 and 64 vol% ((CH3)-H-2)(2)SO because of low aqueous solubility of mesobilirubin, were extrapolated to obtain pK(a) values in water of 4.2 and 4.9. Previous chloroform-water partition data on bilirubin diacid led to higher estimates of its pK(a), 8.12 and 8.44, and its aqueous solubility. A thermodynamic analysis, using this solubility and a published solubility in DMSO, suggested that the systems used to measure C-13-NMR shifts were highly supersaturated. This expectation was assessed by measuring the residual concentrations of bilirubin in the supernatants of comparable DMSO-buffer systems, after mild centrifugation to remove microprecipitates. Results: Extensive sedimentation was observed from numerous systems, many of which appeared optically clear. The very low supernatant concentrations at the lowest pH values (4.1-5.9) were compatible with the above thermodynamic analysis. Extensive sedimentation and low supernatant concentrations occurred also at pH as high as 7.2. Conclusions: The present study strongly supports the validity of the aqueous solubility of bilirubin diacid derived from partition data, and, therefore, the corresponding high pK(a) values. Many of the mesobilirubin systems in the C-13-NMR studies were probably supersaturated, contained microsuspensions, and were not true solutions. This, and previously documented errors in pH determinations that caused serious errors in pK(a) values of the many soluble reference acids and mesobilirubin, raise doubts regarding the low pK(a) estimates for mesobilirubin from the C-13-NMR studies. C1 [Mukerjee, Pasupati] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. [Ostrow, J. Donald] Acad Med Ctr, Gastroenterol Hepatol Dept, NL-1100 DE Amsterdam, Netherlands. [Ostrow, J. Donald] VA Puget Sound Healthcare Syst, Seattle Div, GI Hepatol Lab, Res Serv 151L, Seattle, WA 98108 USA. [Tiribelli, Claudio] Univ Trieste, Dept BBCM, Liver Study Ctr, I-34127 Trieste, Italy. RP Ostrow, JD (reprint author), Acad Med Ctr, Gastroenterol Hepatol Dept, NL-1100 DE Amsterdam, Netherlands. EM pmukerjee@aol.com; jdostrow@medicine.washington.edu; liver@fmc.units.it NR 31 TC 15 Z9 16 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2091 J9 BMC BIOCHEM JI BMC Boichem. PY 2002 VL 3 AR 17 DI 10.1186/1472-2091-3-17 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34NH UT WOS:000209092600017 PM 12079498 ER PT J AU Falardeau, JL Kennedy, JC Acierno, JS Sun, M Stahl, S Goldin, E Slaugenhaupt, SA AF Falardeau, JL Kennedy, JC Acierno, JS Sun, M Stahl, S Goldin, E Slaugenhaupt, SA TI Cloning and characterization of the mouse McolnI gene reveals an alternatively spliced transcript not seen in humans SO BMC GENOMICS LA English DT Article ID MUCOLIPIDOSIS TYPE-IV; ABNORMAL TRANSPORT; MUTATIONS; IDENTIFICATION; DISEASE; MAP AB Background: Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. Recently the MLIV gene, NICOLN1, has been identified as a new member of the transient receptor potential (TRP) cation channel superfamily. Here we report the cloning and characterization of the mouse homologue, Mcoln 1, and report a novel splice variant that is not seen in humans. Results: The human and mouse genes display a high degree of synteny. Mcoln I shows 91% amino acid and 86% nucleotide identity to NICOLN1. Also, Mcoln I maps to chromosome 8 and contains an open reading frame of 580 amino acids, with a transcript length of approximately 2 kb encoded by 14 exons, similar to its human counterpart. The transcript that results from murine specific alternative splicing encodes a 611 amino acid protein that differs at the c-terminus. Conclusions: Mcoln I is highly similar to NICOLN1, especially in the transmembrane domains and ion pore region. Also, the late endosomal/lysosomal targeting signal is conserved, supporting the hypothesis that the protein is localized to these vesicle membranes. To date, there are very few reports describing species-specific splice variants. While identification of Mcoln I is crucial to the development of mouse models for MLIV, the fact that there are two transcripts in mice suggests an additional or alternate function of the gene that may complicate phenotypic assessment. C1 Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Sch Med, Inst Human Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [R01 NS039995] NR 18 TC 8 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2002 VL 3 AR 3 DI 10.1186/1471-2164-3-3 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 654CW UT WOS:000181477100003 PM 11897010 ER PT J AU Gruber, HE Yamaguchi, D Ingram, J Leslie, K Huang, WB Miller, TA Hanley, EN AF Gruber, HE Yamaguchi, D Ingram, J Leslie, K Huang, WB Miller, TA Hanley, EN TI Expression and localization of estrogen receptor-beta in annulus cells of the human intervertebral disc and the mitogenic effect of 17-beta-estradiol in vitro SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article ID MOLECULAR MECHANISMS; STEROID-HORMONES; HUMAN BONE; IN-VITRO; ER-BETA; RAT; GROWTH; PROLIFERATION; CHONDROCYTES; SUPERFAMILY AB Background: Recent evidence suggests that estrogens exert effects in different tissues throughout the body, and that the estrogen receptor beta (ERbeta) may be important for the action of estrogen (17-beta-estradiol) on the skeleton. The cellular localization of ERbeta in the human intervertebral disc, however, has not yet been explored. Methods: Human disc tissue and cultured human disc cells were used for immunocytochemical localization of ERbeta. mRNA was isolated from cultured human disc cells, and RT-PCR amplification of ERbeta was employed to document molecular expression of this receptor. Cultured human disc cells were tested to determine if 17-beta-estradiol stimulated cell proliferation. Results: In this report data are presented which provide evidence for ERbeta gene expression in human intervertebral disc cells in vivo and in vitro. Culture of annulus cells in the presence of 10-7 M 17-beta-estradiol significantly increased cell proliferation. Conclusions: These data provide new insight into the biology of cells in the annulus of the intervertebral disc. C1 Carolinas Med Ctr, Charlotte, NC 28203 USA. Vet Adm Greater Los Angeles Healthcare Syst, Educ & Clin Ctr, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Plast Surg Res Lab, Los Angeles, CA USA. RP Gruber, HE (reprint author), Carolinas Med Ctr, Charlotte, NC 28203 USA. NR 21 TC 18 Z9 19 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKELET DI JI BMC Musculoskelet. Disord. PY 2002 VL 3 AR 4 DI 10.1186/1471-2474-3-4 PG 5 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 654CQ UT WOS:000181476500004 PM 11846890 ER PT S AU Hoge, R Atkinson, J Gill, B Crelier, G Marrett, S Pike, B AF Hoge, R Atkinson, J Gill, B Crelier, G Marrett, S Pike, B BE Tomita, M Kanno, I Hamel, E TI Flow-metabolism regulation during brain activation and respiratory manipulations SO BRAIN ACTIVATION AND CBF CONTROL, PROCEEDINGS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Symposium on Brain Activation and Cerebral Blood Flow Control CY JUN 05-08, 2001 CL TOKYO, JAPAN DE metabolism; perfusion; brain; MRI; hypercapnia ID CEREBRAL BLOOD-FLOW; OXIDATIVE-METABOLISM; OXYGEN-CONSUMPTION; STIMULATION; CORTEX; MRI AB Flow-metabolism coupling was examined in awake human volunteers during graded focal brain activation and during graded exposure to CO2, a systemic vasodilator. Data acquired during activation with arterial CO2 levels stabilized to normal values suggest an invariant flow-metabolism coupling relationship, but CO2-related variations in cerebral blood flow combined additively with activation-related flow responses, with negligible interaction between focal and systemic effects. These findings are inconsistent with the existence of a strictly homeostatic feedback scheme for the regulation of cerebral blood flow, and support the existence of multiple independent pathways of cerebrovascular control. (C) 2002 Elsevier Science B.V All rights reserved. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Montreal Neurol Inst, Montreal, PQ, Canada. US Natl Inst Hlth, Bethesda, MD USA. RP Hoge, R (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Pike, Bruce/K-5562-2014 OI Pike, Bruce/0000-0001-8924-683X NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50874-0 J9 INT CONGR SER PY 2002 VL 1235 BP 33 EP 38 AR PII S0531-5131(02)00170-X DI 10.1016/S0531-5131(02)00170-X PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BV28G UT WOS:000178455900004 ER PT S AU Barnes, GR Schmid, AM Jarrett, CB AF Barnes, GR Schmid, AM Jarrett, CB BE Hyona, J Munoz, DP Heide, W Radach, R TI The role of expectancy and volition in smooth pursuit eye movements SO BRAIN'S EYE: NEUROBIOLOGICAL AND CLINICAL ASPECTS OF OCULOMOTOR RESEARCH SE Progress in Brain Research LA English DT Review CT 11th European Conference on Eye Movements CY AUG 22-25, 2001 CL TURKU, FINLAND ID SUPPLEMENTARY MOTOR AREA; SLOW OCULOMOTOR CONTROL; VELOCITY STORE; TARGET; HUMANS; EXPECTATIONS; SACCADES; SEQUENCE; MOTION; FIELD AB The most important factor allowing the generation of pursuit eye movements prior to target onset is confidence in the likelihood of imminent target appearance. We show how these anticipatory pursuit responses are essentially ballistic motor primitives and how the signal that drives them is normally defined by stored information concerning target speed, duration and direction. But we also show how static cues may be used to grade the level of these motor primitives 'on-line'. We further demonstrate that, when concatenated, these graded motor primitives can be rapidly combined to form predictive smooth movement trajectories in response to complex multi-ramp sequences. C1 Univ Manchester, Dept Optometry & Neurosci, Manchester M60 1QD, Lancs, England. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Univ Manchester, Dept Optometry & Neurosci, POB 88, Manchester M60 1QD, Lancs, England. EM g.r.barnes@umist.ac.uk NR 43 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51097-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2002 VL 140 BP 239 EP 254 PG 16 WC Neurosciences SC Neurosciences & Neurology GA BV82W UT WOS:000180135500016 PM 12508594 ER PT J AU Geng, LP Rudd, CE AF Geng, LP Rudd, CE TI Signalling scaffolds and adaptors in T-cell immunity SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE immunology; T cells; receptors; kinases; adaptors ID PROTEIN-TYROSINE KINASE; HUMAN LYMPHOCYTES-T; TANDEM SH2 DOMAINS; TCR ZETA-CHAIN; ANTIGEN-RECEPTOR; MOLECULAR-CLONING; INTERLEUKIN-2 PRODUCTION; EXCHANGE FACTOR; DEFICIENT MICE; CYTOSKELETAL REORGANIZATION C1 Hammersmith Hosp, Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc immunol & AIDS, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Hammersmith Hosp, Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Du Cane Rd, London, England. NR 105 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2002 VL 116 IS 1 BP 19 EP 27 DI 10.1046/j.1365-2141.2002.03243.x PG 9 WC Hematology SC Hematology GA 521DQ UT WOS:000173824000005 PM 11841396 ER PT J AU Gitelson, E Spaner, D Buckstein, R Franssen, E Hewitt, K Lim, MS Pennell, N Schultze, JL Berinstein, NL AF Gitelson, E Spaner, D Buckstein, R Franssen, E Hewitt, K Lim, MS Pennell, N Schultze, JL Berinstein, NL TI T-cell analysis in identical twins reveals an impaired anti-follicular lymphoma immune response in the patient but not in the healthy twin SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE follicular lymphoma; T-cell insuciency; immune response; twins ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; COSTIMULATORY MOLECULES; IN-VITRO; B-CELLS; IMMUNOTHERAPY; EXPRESSION; INDUCTION; TOLERANCE; CD40 AB In lymphomas an innate defect in the T-cell repertoire could account for the impaired tumour-specific immune response: alternatively, the tumour itself could exert an inhibitory effect on the immune system. To address this issue we analysed the T-cell responses against follicular lymphoma (FL) in identical twins as it can be postulated that their overall T-cell repertoire is identical. While differences between the T-cell response of the patient and the healthy twin would point to a tumour-induced T-cell unresponsiveness, impaired responses in both would point to a defective T-cell repertoire. We demonstrated an impaired tumour-specific proliferation (P = 0.035 and P = 0.013) and cytokine release (P = 0.004 and P = 0.0008) of both peripheral blood and tumour-derived T-cells, respectively, in the FL patient compared with the T-cell response of the healthy twin. Moreover, only syngeneic primed T cells were able to directly lyse unmodified FL cells of the patient. These data support previous findings in murine lymphomas and suggest that inhibitory mechanisms during tumour growth, rather than a defective T-cell repertoire, are responsible for the insufficient T-cell response in lymphoma. C1 Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto Sunnybrook Reg Canc Ctr, Adv Therapeut Program, Toronto, ON M4N 3M5, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Dis Ctr Hematol Oncol, Boston, MA 02115 USA. RP Berinstein, NL (reprint author), Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto Sunnybrook Reg Canc Ctr, Adv Therapeut Program, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 27 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2002 VL 116 IS 1 BP 122 EP 127 DI 10.1046/j.1365-2141.2002.03240.x PG 6 WC Hematology SC Hematology GA 521DQ UT WOS:000173824000013 PM 11841404 ER PT J AU Lipinski, B AF Lipinski, B TI Evidence in support of a concept of reductive stress SO BRITISH JOURNAL OF NUTRITION LA English DT Editorial Material ID RADICALS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. RP Lipinski, B (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. NR 7 TC 31 Z9 32 U1 0 U2 4 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD JAN PY 2002 VL 87 IS 1 BP 93 EP 94 DI 10.1079/BJN2001435 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 521WY UT WOS:000173865400012 PM 11895317 ER PT J AU Arroyo, JG AF Arroyo, JG TI Atherosclerotic cardiovascular disease and diabetic retinopathy SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material C1 Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Arroyo, JG (reprint author), Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 12th Floor, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2002 VL 86 IS 1 BP 3 EP 4 DI 10.1136/bjo.86.1.3 PG 2 WC Ophthalmology SC Ophthalmology GA 509ZM UT WOS:000173184300003 PM 11801492 ER PT J AU Yang, Y Liao, H Ke, QG Cai, JB Xiao, YF Morgan, JP AF Yang, Y Liao, H Ke, QG Cai, JB Xiao, YF Morgan, JP TI Enhancement of nitric oxide production by methylecgonidine in cultured neonatal rat cardiomyocytes SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE methylecgonidine; carbachol; muscarinic receptor; nitric oxide; cardiomyocyte ID COCAINE ABUSE; MITOCHONDRIAL RESPIRATION; CARDIAC MYOCYTES; SIGNALING SYSTEM; MAMMALIAN-CELLS; METHYL-ESTER; HEART; ACETYLCHOLINE; SUPEROXIDE; RECEPTORS AB 1 In the present experiments, we investigated the effects of methylecgonidine (MEG) on nitric oxide (NO) production in cultured neonatal rat cardiomyocytes. Incubation of cultured cardiomyocytes with carbachol or MEG for 48 h significantly enhanced NO production. No release was increased from 1.48+/-0.13 muM (mg protein)(-1) for control to 5.73+/-0.19 muM (mg protein)(-1) for 1 Aim carbachol treated cells (P<0.001). In addition, incubation with 1 Aim MEG enhanced NO production to 5.55+/-0.28 muM (mg protein)(-1). The effects of MEG on NO production were concentration-dependent. The muscarinic antagonist atropine prevented the enhancement of NO production induced by carbachol or MEG. Compared to MEG-induced NO production, cocaine was much less potent. 2 The enhancement of NO production by carbachol or MEG was even greater in cultured cardiomyocytes transfected with the M-2 cDNA. After 48-h incubation with 1 muM carbachol or 1 muM MEG, NO production was increased by 6.5 and 6.7 fold, respectively, in cardiomyocytes overexpressing M, receptors. Coincubation with atropine or N-G-vitro-L-arginine methyl ester abolished the enhancement of NO production. In contrast, NO production enhanced by carbachol or MEG in M-1- or M-2-transfected cardiomyocytes was similar to the level in non-transfected cells. 3 Western blot analysis showed that the protein levels of M-1, M-2, and M-3 were significantly increased in cardiomyocytes transfected with the receptor cDNAs, but MEG had no effect on the expressions. It is interesting that both carbachol and MEG caused a significant increase in constitutive endothelial NO synthase (eNOS) only in M-2-transfected cardiomyocytes, not in nontransfected, M-1- or M-2-transfected cells. Again, atropine blocked the MEG-produced induction of eNOS. 4 Our data demonstrate that MEG significantly enhanced NO production in cultured cardiomyocytes and that the enhancement of NO production may result from MEG stimulation of muscarinic M-2 receptors. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc,Charles A Dana Res Inst,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc,Dept Med,Harvard Thornkike Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02215 USA. RP Morgan, JP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc,Charles A Dana Res Inst,Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. FU NIDA NIH HHS [DA11762, DA12774] NR 46 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2002 VL 135 IS 1 BP 188 EP 196 DI 10.1038/sj.bjp.0704414 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 514TL UT WOS:000173457100022 PM 11786494 ER PT J AU Domchek, SM Hecht, JL Fleming, MD Pinkus, GS Canellos, GP AF Domchek, SM Hecht, JL Fleming, MD Pinkus, GS Canellos, GP TI Lymphomas of the breast - Primary and secondary involvement SO CANCER LA English DT Article DE breast; lymphoma; mammography; autoimmune ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; PRIMARY MALIGNANT-LYMPHOMA; LYMPHOCYTIC MASTOPATHY; TISSUE; THYROIDITIS; DISEASE AB BACKGROUND. The involvement of the breast by lymphoma is a rare form of extralymph node lymphoma and represents either primary disease or systemic involvement. The authors hypothesized that screening mammography may influence the detection of lymphomatous involvement of the breast. METHODS. All patients (n = 81 patients) who were diagnosed with lymphomatous involvement of the breast at the Study institution between 1988 and 1999 were evaluated retrospectively. RESULTS. Clinical information was available for 73 patients who could be classified into three major groups according to their diagnosis: primary breast lymphoma (PBL) (44%), breast involvement from disseminated disease at the time of initial diagnosis (29%), and recurrence of preexisting lymplioma to the breast (27%). The majority of PBL were of intermediate or high grade, and the majority of disseminated lymphomas involving the breast were of low grade. Lymphomatous recurrence to the breast was slightly more likely to be of intermediate grade rather than low grade. In 91% of patients, the diagnosis of lymphoma was made after the evaluation of a palpable mass. All patients who were identified after the evaluation of an abnormal screening mammogram (9%) had low-grade lymphomas. Of the 32 patients with PBL, screening mammography discovered only 1. Nineteen percent of patients with PBL also had a history of an autuimmune disorder. CONCLUSIONS. These Findings suggest that screening mammography has not altered substantially the detection of breast lymphoma. The clinical outcome of patients with breast lymphoma is dependent on histology and appears to parallel that of patients with lymphoma of similar histology involving other sites. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Domchek, SM (reprint author), Univ Penn, Rena Rowan Breast Ctr, 3400 Spruce St,14th Floor Penn Tower, Philadelphia, PA 19104 USA. NR 45 TC 96 Z9 103 U1 0 U2 4 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 2002 VL 94 IS 1 BP 6 EP 13 DI 10.1002/cncr.10163 PG 8 WC Oncology SC Oncology GA 509FC UT WOS:000173134800002 PM 11815954 ER PT J AU Harris, L Batist, G Belt, R Rovira, D Navari, R Azarnia, N Welles, K Winer, E AF Harris, L Batist, G Belt, R Rovira, D Navari, R Azarnia, N Welles, K Winer, E CA TLC D-99 Study Grp TI Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma SO CANCER LA English DT Article DE doxorubicin; anthracyclines; TLC D-99; breast carcinoma; liposomal chemotherapy ID CONGESTIVE HEART-FAILURE; TOPOISOMERASE-II; CANCER; CHEMOTHERAPY; MITOXANTRONE; CARDIOPROTECTION; CARDIOTOXICITY; DEXRAZOXANE; PACLITAXEL; DOCETAXEL AB BACKGROUND. The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin, TLC D-99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first-line treatment of metastatic breast carcinoma (MBC). METHODS, Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 (75 mg/m(2)) or doxorubicin (75 mg/m(2)) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF). RESULTS. Median age was 54 years in both treatment groups. All relevant prognostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group. Protocol-defined cardiotoxicity was observed in 13% of TLC D-99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m(2) for TLC D-99 versus 570 mg/m(2) for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months With a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D-99, although the difference was not statistically significant, There was only one report of palmar-plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin. CONCLUSIONS. Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity. (C) 2002 American Cancer Society. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. St Lukes Hosp, Kansas City, MO 64111 USA. Univ Colorado, Denver, CO 80202 USA. Simon Williamson Clin, Birmingham, AL USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Elan Pharmaceut, Princeton, NJ USA. RP Harris, L (reprint author), Dana Farber Canc Inst, Room D1210,44 Binney St, Boston, MA 02115 USA. NR 31 TC 268 Z9 274 U1 3 U2 43 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 2002 VL 94 IS 1 BP 25 EP 36 DI 10.1002/cncr.10201 PG 12 WC Oncology SC Oncology GA 509FC UT WOS:000173134800005 PM 11815957 ER PT J AU Michaelson, J Satija, S Moore, R Weber, G Halpern, E Garland, A Puri, D Kopans, DB AF Michaelson, J Satija, S Moore, R Weber, G Halpern, E Garland, A Puri, D Kopans, DB TI The pattern of breast cancer screening utilization and its consequences SO CANCER LA English DT Article DE mammogram; screen detected; nonmammographic criteria; invasive tumors ID GROWTH-RATE; REPEAT MAMMOGRAPHY; WOMEN; PROGRAM; AGE; INTERVAL; DENSITY AB BACKGROUND. The objective of this study was to describe the pattern of screening utilization and its consequences in terms of tumor size and time of tumor appearance of invasive breast carcinoma among a population of women who were examined at a large service screening/diagnostic program over the last decade. METHODS. Utilization of mammography was assessed from a population of 59,899 women who received 196,891 mammograms at the Massachusetts General Hospital Breast Imaging Division from January 1, 1990 to March 1, 1999, among which 604 invasive breast tumors were found. Two hundred six invasive, clinically detected tumors also were seen during this period among women who had no record of a previous mammogram. Additional information was available on screening of women from March 1, 1999 to June 1, 2001. RESULTS. Fifty percent of the women who used screening did not begin until the age of 50 years, although 25% of the invasive breast tumors were found in women age < 50 years, Relatively few of the women who used screening returned promptly for their annual examinations; by 1.5 years, only 50% had returned. Approximately 25% of the invasive breast tumors were found in women for whom there was no record of a previous screening mammogram, and these tumors were larger (median, 15 mm) than the screen-detected tumors (median, 10 mm). Approximately 30% of the 604 invasive breast tumors in the screening population were found on nonmammographic grounds, and they also were larger (median, 15 mm) than the screen-detected tumors (median, 10 mm). However, only 3% of these 604 tumors were found by nomnammographic criteria within 6 months of the previous negative examination, and only 12% were found within 1 year. By back calculating the likely size of each of these tumors at the time of the negative mammogram, it could be seen that most tumors probably emerged as larger, palpable masses not because they were missed at the previous negative mammogram, because most were too small then to have been detected, but because too much time had been allowed to pass. CONCLUSIONS. Far too many women did not comply with the American Cancer Society recommendation of prompt annual screening from the age of 40 years. Consequently, almost 50% of the invasive tumors emerged as larger and, thus, potentially more lethal, palpable masses. (C) 2002 American Cancer Society. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Michaelson, J (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. OI Weber, Griffin/0000-0002-2597-881X NR 26 TC 47 Z9 49 U1 1 U2 1 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 2002 VL 94 IS 1 BP 37 EP 43 DI 10.1002/cncr.10154 PG 7 WC Oncology SC Oncology GA 509FC UT WOS:000173134800006 PM 11815958 ER PT J AU Ryan, DP Kulke, MH Fuchs, CS Grossbard, ML Grossman, SR Morgan, JA Earle, CC Shivdasani, R Kim, H Mayer, RJ Clark, JW AF Ryan, DP Kulke, MH Fuchs, CS Grossbard, ML Grossman, SR Morgan, JA Earle, CC Shivdasani, R Kim, H Mayer, RJ Clark, JW TI A phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma SO CANCER LA English DT Article DE pancreatic neoplasms; gemcitabine; docetaxel; chemotherapy ID COLONY-STIMULATING FACTOR; TRACT CANCER GISCAD; ONCOLOGY-GROUP; ITALIAN GROUP; TRIAL; ADENOCARCINOMA; 5-FLUOROURACIL; COMBINATION AB BACKGROUND. Patients with metastatic pancreatic carcinoma have a poor survival. Chemotherapy with gemcitabine is the standard first-line treatment. In a Phase 11 trial at one academic cancer center, the clinical safety and activity of combining gemcitabine and docetaxel were assessed. METHODS. Patients with previously untreated, advanced pancreatic carcinoma were eligible. Bidimensionally measurable disease or evaluable disease with an elevated tumor marker, good performance status, and adequate organ function were required. Patients received docetaxel 60 mg/m(2) on Day I and gemcitabine 600 mg/m(2) on Days 1, 8, and 15 every 28 days. Ciprofloxacin was administered on Days 8-18. Dose attenuations were made as indicated for toxicity. Patients were restaged radiographically after every two cycles. RESULTS. Thirty-four patients were enrolled, and 33 patients were evaluable for response. There were 23 men and 10 women among the evaluable patients. The median age was 63 years, and all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. Three patients had received prior chemoradiation for postresection adjuvant therapy. One hundred forty-six cycles of chemotherapy were administered, and 5 cycles (3%) in 4 patients (12%) were complicated by febrile neutropenia. Twenty percent and 11% of patients on Day 8 and Day 15 doses of gemcitabine, respectively, were omitted for toxicity. The objective response rate was 18%, and the median survival was 8.9 months (95% confidence interval, 5.2-11.2 months). The 1-year survival rate was 29%. CONCLUSIONS. The combination of gemcitabine and docetaxel in patients with advanced pancreatic carcinoma is well tolerated and is associated with moderate activity despite aggressive dose reduction. Whether combination regimens are more effective than single agents in the treatment of patients with pancreatic carcinoma awaits evaluation in randomized studies. (C) 2002 American Cancer Society. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. St Lukes Roosevelt Hosp, Ctr Canc, New York, NY 10025 USA. Dana Farber Partners Canc Ctr, Gastrointestinal Canc Ctr, Boston, MA USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 28 TC 69 Z9 71 U1 0 U2 1 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 2002 VL 94 IS 1 BP 97 EP 103 DI 10.1002/cncr.10202 PG 7 WC Oncology SC Oncology GA 509FC UT WOS:000173134800012 PM 11815964 ER PT J AU Smith, MR AF Smith, MR TI Osteoporosis and other adverse body composition changes during androgen deprivation therapy for prostate cancer SO CANCER AND METASTASIS REVIEWS LA English DT Review DE androgen deprivation therapy; bicalutamide; bone; estrogen; fat; fracture; gonadotropin-releasing hormone agonist; muscle; osteoporosis; prostate cancer ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; HIV-INFECTED MEN; QUALITY-OF-LIFE; OLDER MEN; TESTOSTERONE REPLACEMENT; HORMONE AGONISTS; AROMATASE DEFICIENCY; RANCHO BERNARDO; HYPOGONADAL MEN AB Osteoporosis and other body composition changes are important complications of androgen deprivation therapy (ADT) for prostate cancer. Bilateral orchiectomy and gonadotropin-releasing hormone agonist treatment decrease bone mineral density and increase fracture risk. Other factors including diet and lifestyle may contribute to bone loss in men with prostate cancer. Estrogens play an important role in male bone metabolism. Androgen deprivation therapy with estrogens probably causes less bone loss than bilateral orchiectomy or gonadotropin-releasing hormone agonist treatment. Bicalutamide monotherapy increases serum estrogen levels and may also spare bone. Lifestyle modification including smoking cessation, moderation of alcohol use, and regular weight bearing exercise are recommended to decrease treatment-related bone loss. Supplemental calcium and vitamin D are also recommended. Pamidronate (Aredia(R)), an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective but have not been studied in hypogonadal men. Androgen deprivation therapy increases fat mass and decreases muscle mass. These body composition changes may contribute to treatment-related decreases in physical capacity and quality of life. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 64 TC 34 Z9 34 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PY 2002 VL 21 IS 2 BP 159 EP 166 DI 10.1023/A:1020840311573 PG 8 WC Oncology SC Oncology GA 609WT UT WOS:000178929900007 PM 12465755 ER PT J AU Polyak, K AF Polyak, K TI Is p53 a breast cancer gene? SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material ID SUSCEPTIBILITY GENE; BRCA2 MUTATIONS; PROGNOSIS; CARCINOMA C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN-FEB PY 2002 VL 1 IS 1 BP 37 EP 38 PG 2 WC Oncology SC Oncology GA 635DQ UT WOS:000180383100010 PM 12197482 ER PT J AU Li, FP AF Li, FP TI 9/11: War on terrorism and war on cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2002 VL 11 IS 1 BP 1 EP 1 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 517WE UT WOS:000173632800001 ER PT J AU Zhou, W Liu, G Thurston, SW Xu, LL Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC AF Zhou, W Liu, G Thurston, SW Xu, LL Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC TI Genetic polymorphisms in N-acetyltransferase-2 and microsomal epoxide hydrolase, cumulative cigarette smoking, and lung cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ACETYLTRANSFERASE NAT2 GENOTYPE; GLUTATHIONE-S-TRANSFERASE; SQUAMOUS-CELL CARCINOMA; N-ACETYLTRANSFERASES; METABOLIC-ACTIVATION; ACETYLATOR GENOTYPE; RISK; ASSOCIATION; SUSCEPTIBILITY; POPULATION AB N-acetyltrasferase-2 (NAT2) and microsomal epoxide hydrolase (mEH) are polymorphic genes that metabolize different tobacco carcinogens. Smaller studies found inconsistent relationships between NAT2 or mEH polymorphisms and lung cancer risk. To determine whether there is gene-environment interaction between NAT2 polymorphisms, alone or in combination with mEH polymorphisms, and cumulative smoking exposure in the development of lung cancer, we conducted a case control study of 1115 Caucasian lung cancer patients and 1250 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between NAT2 genotype and lung cancer risk; the adjusted odds ratio (OR) of the rapid versus slow acetylator genotypes was 0.96 [95% confidence interval (CI), 0.79-1.16]. However, gene-environment interaction analyses revealed that the adjusted ORs increased significantly as pack-years increased. For nonsmokers, the fitted OR was 0.66 (95% CI, 0.44-0.99), whereas for heavy smokers (80 pack-years), the OR increased to 1.22 (95% CI, 0.89-1.67). When comparing the extreme genotype combinations of the NAT2 rapid acetylator, higher mEH activity genotype to the NAT2 slow acetylator, and very low mEH activity genotype, the corresponding ORs at 0 and 80 pack-years were 0.30 (95% CI, 0.14-0.62) and 2.19 (95% CI, 1.26-3.81), respectively. Results were similar with ORs derived from stratified models. In conclusion, NAT2 rapid acetylator genotypes are protective against lung cancer in nonsmokers but are risk factors in heavy smokers. The joint effects of NAT2 and mEH polymorphisms are consistent with an independent, additive effect of these two genes, modified by smoking history. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [T32 ES 07069, ES/CA 06409, ES 00002] NR 44 TC 64 Z9 64 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2002 VL 11 IS 1 BP 15 EP 21 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 517WE UT WOS:000173632800004 PM 11815396 ER PT J AU Lipton, A Small, E Saad, F Gleason, D Gordon, D Smith, M Rosen, L Kowalski, MO Reitsma, D Seaman, J AF Lipton, A Small, E Saad, F Gleason, D Gordon, D Smith, M Rosen, L Kowalski, MO Reitsma, D Seaman, J TI The new bisphosphonate, Zometa((R)) (Zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: A comparison to pamidronate SO CANCER INVESTIGATION LA English DT Article; Proceedings Paper CT 19th Chemotherapy Foundation Symposium CY NOV, 2001 CL NEW YORK, NEW YORK ID METASTATIC PROSTATE-CANCER; FIBROBLAST-GROWTH-FACTOR; ANDROGEN-DEPRIVATION THERAPY; PAINFUL BONE METASTASES; BREAST-CANCER; ORAL CLODRONATE; DOUBLE-BLIND; IN-VITRO; CARCINOMA; RESORPTION AB Bisphosphonates are the treatment of choice for lytic bone lesions associated with breast cancer. In contrast, bone lesions associated with prostate cancer are predominately osteoblastic. Zoledonic acid (Zol) is a new-generation bisphosphonate that is approximately 2-3 orders of magnitude more potent than pamidronate (Pam) in preclinical models and has demonstrated clinical efficacy in patients with both lytic and blastic lesions. Zoledonic acid (4 mg via 15 min infusion) every 3-4 weeks was directly compared to Pam (90 mg via 2 hr infusion) in 767 patients with breast cancer and bone metastases. The primary endpoint was the proportion of patients experiencing a skeletal-related event (SRE) over 13 months. Zoledonic acid was as effective as Pam, and the proportion of Zol-treated patients with an SRE (42% in the hormonal therapy strata and 44% in the chemotherapy strata) was comparable to the original studies comparing Pam to placebo. Among 371 breast cancer patients receiving hormonal therapy, the proportion of patients with an SRE was 47% for Pam vs. 57%,for placebo (P = 0.057), and among 380 patients treated with chemotherapy, the proportions with an SRE were 43% for Pain vs. 56% for placebo (P = 0.008) at 12 months. Zoledronic acid (4 mg) has been compared to placebo in a randomized Phase Ill trial involving 422 men with hormone-refractory prostate cancer metastatic to bone. Zoledonic acid demonstrated a significant advantage over placebo for median time to first SRE (median not reached for Zol vs. 321 days, for placebo; P = 0.011), the proportion of patients with an SRE over 15 months (33 vs. 44% for placebo; P = 0.021), and mean skeletal morbidity rate (number of SREs/time, 0.08 vs. 1.49 for placebo; P = 0.006). In addition, the effects of Zol were apparent early. At 3 months, only 12% of Zol-treated patients had an SRE vs. 23% for placebo (P = 0.003), and at 6 months, the proportions were 21 vs. 31% for placebo (P = 0.025). In contrast, a previous study of Pam in 236 prostate cancer patients found that Pam. was no more effective than placebo in reducing bone pain or SREs over 6 months. In these studies, Zol was well tolerated with a safety profile similar to other IV bisphosphonates. In conclusion, Zol is the first bisphosphonate to demonstrate efficacy in both lytic and blastic disease. The unique properties of this novel agent should be further explored in future clinical trials. C1 Milton S Hershey Med Ctr, Hershey, PA 17003 USA. Univ Calif San Francisco, Mt Zion Canc Ctr, San Francisco, CA 94143 USA. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. Adv Clin Therapeut, Tucson, AZ USA. US Oncol, San Antonio, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Lipton, A (reprint author), Milton S Hershey Med Ctr, POB 850 H-46, Hershey, PA 17003 USA. NR 55 TC 72 Z9 72 U1 0 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2002 VL 20 SU 2 BP 45 EP 54 DI 10.1081/CNV-120014886 PG 10 WC Oncology SC Oncology GA 612GB UT WOS:000179065200007 PM 12442349 ER PT J AU Oh, WK Manola, J George, DJ Fierman, A Fontaine-Rothe, P Morrissey, S Prisby, J Kaufman, DS Shapiro, CL Kantoff, PW Smith, MR AF Oh, WK Manola, J George, DJ Fierman, A Fontaine-Rothe, P Morrissey, S Prisby, J Kaufman, DS Shapiro, CL Kantoff, PW Smith, MR TI A phase II trial of interferon-alpha and toremifene in advanced renal cell cancer patients SO CANCER INVESTIGATION LA English DT Article ID METASTATIC BREAST-CANCER; TAMOXIFEN; CARCINOMA; BETA; LINES AB Treatment options for patients with metastatic renal cell carcinoma are limited. Interferon-alpha has an overall response rate of 10-15% in phase II and III clinical trials and is considered a standard option for patients. Though the anti-estrogen toremifene has shown only modest single agent activity in renal cell carcinoma, evidence for synergy of anti-estrogens with interferon-alpha exists in renal cell and other cancers. Therefore, a phase 11 trial was undertaken to test the combination of interferon -alpha and toremifene in advanced renal cell carcinoma. Thirteen patients with measurable metastatic or unresectable local disease were treated with interferon -alpha at a dose of 5 million units/m(2) 2 three times a week and daily oral toremifene at 300 mg daily in divided doses. Patients were treated for 12 weeks and then restaged. Clinical response was the primary endpoint of the trial. Four patients (31%) had evidence of stable disease at 12 weeks, while the remaining nine patients (69%) progressed on treatment. Toxicity was moderate, with grade 2 or 3 fatigue, nausea and anorexia each noted in 31%, of patients. We conclude that the combination of interferon-alpha plus toremifene demonstrates no significant activity in advanced renal cell carcinoma. Copyright (C) 2002 by Marcel Dekker, Inc. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. Ohio State Univ, Arthur James Canc Ctr, Columbus, OH USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 26 TC 3 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2002 VL 20 IS 2 BP 186 EP 191 DI 10.1081/CNV-120001145 PG 6 WC Oncology SC Oncology GA 528VM UT WOS:000174265000005 PM 11901538 ER PT J AU Saito, RM van den Heuvel, S AF Saito, RM van den Heuvel, S TI Malignant worms: What cancer research can learn from C. elegans SO CANCER INVESTIGATION LA English DT Article ID CELL-CYCLE PROGRESSION; CLEAVAGE PLANE SPECIFICATION; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR; VULVAR DEVELOPMENT; GENE; KINASE; HOMOLOG; APOPTOSIS; PATHWAY C1 Massachuetts Gen Hosp, Canc Ctr, Charlestown, MA 02129 USA. RP Massachuetts Gen Hosp, Canc Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011 FU NIGMS NIH HHS [R01 GM57990-02] NR 49 TC 10 Z9 66 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0735-7907 EI 1532-4192 J9 CANCER INVEST JI Cancer Invest. PY 2002 VL 20 IS 2 BP 264 EP 275 DI 10.1081/CNV-120001153 PG 12 WC Oncology SC Oncology GA 528VM UT WOS:000174265000013 PM 11901546 ER PT J AU Johnson, EA Klimstra, DS Herndon, JE Catalano, E Canellos, GP Graziano, SL Kern, JA Green, MR AF Johnson, EA Klimstra, DS Herndon, JE Catalano, E Canellos, GP Graziano, SL Kern, JA Green, MR TI Aberrant p53 staining does not predict cisplatin resistance in locally advanced non-small cell lung cancer SO CANCER INVESTIGATION LA English DT Article ID RANDOMIZED TRIAL; CHEMOTHERAPY; APOPTOSIS; EXPRESSION; RADIATION; ONCOPROTEIN; INDUCTION; SURGERY; GENE AB Cisplatin based chemotherapies have increased the survival in nonsmall cell lung cancer. A mechanism for identifying tumors resistant to cisplatin would be useful in avoiding unnecessary toxicity of platinum regimens. Mutation of p53 has been shown to induce chemotherapy resistance in vitro. We hypothesized that tumors staining for p53 would be resistant to cisplatin. In Cancer and Leukemia Group B protocol 8935, patients with stage IIIA (N2 node positive) nonsmall cell lung cancer received chemotherapy followed by surgery, then post-operative chemotherapy and/or radiation. All patients underwent pre-treatment staging mediastinoscopy. Twenty-five out of forty-nine pre-treatment mediastinal lymph node specimens stained positively for p53. Positive staining did not correlate with response to chemotherapy or survival. It did predict a slightly higher complete or partial resection rate compared to negative staining (76 vs. 45%) (p = 0.042). A trend toward longer median survivals was seen inpatients with positive p53 staining. This study does not support the ability of p53 staining to predict chemotherapy resistance. C1 Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. CALGB Stat Ctr, Durham, NC USA. Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. Dana Farber Partners Canc Care, Boston, MA USA. SUNY Upstate Med Univ, Syracuse, NY USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Johnson, EA (reprint author), Mayo Clin Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. FU NCI NIH HHS [CA32291, CA03927, CA21060, CA33601] NR 15 TC 8 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2002 VL 20 IS 5-6 BP 686 EP 692 DI 10.1081/CNV-120003537 PG 7 WC Oncology SC Oncology GA 584HM UT WOS:000177461200011 PM 12197224 ER PT J AU Demetri, GD AF Demetri, GD TI GIST 1, chemotherapy 0, with a brand new hitter up next SO CANCER INVESTIGATION LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; MUTATIONS; KIT C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2002 VL 20 IS 5-6 BP 853 EP 854 DI 10.1081/CNV-120002501 PG 2 WC Oncology SC Oncology GA 584HM UT WOS:000177461200034 PM 12197245 ER PT J AU Kunschner, LJ Fine, H Hess, K Jaeckle, K Kyritsis, AP Yung, WKA AF Kunschner, LJ Fine, H Hess, K Jaeckle, K Kyritsis, AP Yung, WKA TI CI-980 for the treatment of recurrent or progressive malignant gliomas: National Central Nervous System Consortium Phase I-II Evaluation of CI-980 SO CANCER INVESTIGATION LA English DT Article DE CI-980; chemotherapy; malignant gliomas ID NEUROTOXICITY; PROCARBAZINE; VINCRISTINE; NSC-370147; CARCINOMA; TRIAL AB Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m(2), given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m(2) per cycle. Treatment response was based on serial MRI imaging characteristics. Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI = 0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma. C1 Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Allegheny Neurol Associates, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Univ Ioannina, GR-45110 Ioannina, Greece. RP Yung, WKA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, 1515 Holcombe Blvd,Box 431, Houston, TX 77030 USA. NR 16 TC 4 Z9 5 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2002 VL 20 IS 7-8 BP 948 EP 954 DI 10.1081/CNV-120005910 PG 7 WC Oncology SC Oncology GA 614HW UT WOS:000179183300013 PM 12449727 ER PT J AU Anderson, KC Boise, LH Louie, R Waxman, S AF Anderson, KC Boise, LH Louie, R Waxman, S TI Arsenic trioxide in multiple myeloma: Rationale and future directions SO CANCER JOURNAL LA English DT Review DE multiple myeloma; arsenic trioxide; Trisenox; apoptosis; cellular redox; clinical trials ID ACUTE PROMYELOCYTIC LEUKEMIA; HIGH-DOSE THERAPY; NF-KAPPA-B; IN-VITRO METHYLATION; CELL-CYCLE ARREST; GROWTH-INHIBITION; ANTITUMOR-ACTIVITY; FOLLOW-UP; APOPTOSIS; ACTIVATION AB Multiple myeloma remains an incurable malignancy with a median survival that does not exceed 3 years. At least one third of patients with multiple myeloma fail to respond to induction chemotherapy, and those who initially achieve remission eventually relapse and require additional therapy. Recent reports demonstrating the efficacy of arsenic trioxide in acute promyelocytic leukemia have prompted a revival in the clinical use of this compound. The achievement of clinical responses marked by molecular conversion of the malignant phenotype and remissions in patients who had failed to respond to multiple courses of conventional chemotherapy provided the impetus to explore its use in multiple myeloma. Properties that favor the use of arsenic trioxide are its ability to target selectively malignant cells for apoptosis through enhancement of reactive oxygen species, to induce differentiation, and to inhibit angiogenesis. Multiple events involved in the pathogenesis of multiple myeloma coincide with pathways targeted by arsenic trioxide, and early results have suggested that clinical responses and safety in patients are promising with advanced disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Mt Sinai Sch Med, New York, NY USA. Cell Therapeut Inc, Seattle, WA USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 90 TC 44 Z9 46 U1 0 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 2002 VL 8 IS 1 BP 12 EP 25 DI 10.1097/00130404-200201000-00003 PG 14 WC Oncology SC Oncology GA 525DD UT WOS:000174052700003 PM 11895198 ER PT J AU Wood, BJ AF Wood, BJ TI Feasibility of thermal ablation of lytic vertebral metastases with radiofrequency current SO CANCER JOURNAL LA English DT Editorial Material C1 NIH, Hlth Clin Ctr, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wood, BJ (reprint author), NIH, Hlth Clin Ctr, Bldg 10,Room 1C-660, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 5 TC 4 Z9 4 U1 0 U2 0 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 2002 VL 8 IS 1 BP 26 EP 28 DI 10.1097/00130404-200201000-00004 PG 3 WC Oncology SC Oncology GA 525DD UT WOS:000174052700004 PM 11895200 ER PT J AU Gupta, VK Jaskowiak, NT Beckett, MA Mauceri, HJ Grunstein, J Johnson, RS Calvin, DA Nodzenski, E Pejovic, M Kufe, DW Posner, MC Weichselbaum, RR AF Gupta, VK Jaskowiak, NT Beckett, MA Mauceri, HJ Grunstein, J Johnson, RS Calvin, DA Nodzenski, E Pejovic, M Kufe, DW Posner, MC Weichselbaum, RR TI Vascular endothelial growth factor enhances endothelial cell survival and tumor radioresistance SO CANCER JOURNAL LA English DT Article DE ionizing radiation; vascular endothelial growth factor; cell survival; mitogen activated protein kinase; tumor endothelium ID FACTOR-NEUTRALIZING ANTIBODY; IONIZING-RADIATION; GASTRIC-CARCINOMA; LIVER METASTASIS; HUMAN COLON; EXPRESSION; MITOGEN; PROTEIN; CANCER; VEGF C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Harvard Univ, Dana Farber Canc Inst, Div Pharmacol, Boston, MA 02115 USA. Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, CAM 1332,MC 9006,5758 S Maryland Ave, Chicago, IL 60637 USA. OI Johnson, Randall/0000-0002-4084-6639 NR 50 TC 115 Z9 123 U1 0 U2 2 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 2002 VL 8 IS 1 BP 47 EP 54 DI 10.1097/00130404-200201000-00009 PG 8 WC Oncology SC Oncology GA 525DD UT WOS:000174052700009 PM 11895203 ER PT J AU Enerback, C Porter, DA Seth, P Sgroi, D Gaudet, J Weremowicz, S Morton, CC Schnitt, S Pitts, RI Stampl, J Barnhart, K Polyak, K AF Enerback, C Porter, DA Seth, P Sgroi, D Gaudet, J Weremowicz, S Morton, CC Schnitt, S Pitts, RI Stampl, J Barnhart, K Polyak, K TI Psoriasin expression in mammary epithelial cells in vitro and in vivo SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; NORMAL SKIN; S100A7; KERATINOCYTES; GENES; DIFFERENTIATION; IDENTIFICATION; CARCINOMA; TISSUES; CLONING AB We determined, by serial analysis of gene expression (SAGE) analysis of normal and DCIS (ductal carcinoma in situ) mammary epithelial cells, that psoriasin and several other genes implicated in psoriasis are aberrantly expressed in high-grade, comedo DCIS. Real-time PCR, mRNA in situ hybridization, and immunohistochemical analysis of breast carcinomas confirmed that psoriasin is frequently overexpressed in estrogen receptor-negative tumors. To gain insight into regulatory pathways that control psoriasin expression, we developed polyclonal and monoclonal antibodies and investigated mechanisms that may account for elevated levels of psoriasin in DCIS. Here, we report that loss of attachment to extracellular matrix, growth factor deprivation, and confluent conditions dramatically up-regulate psoriasin expression in MCF10A mammary epithelial cells. All of these conditions are characteristic of high,grade DCIS and psoriatic skin lesions; therefore, the same mechanisms, may be responsible for increased expression of psoriasin in vitro and in vivo. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Gynecol & Reprod Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Imgenex Corp, San Diego, CA 92121 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, D740C,44 Binney St, Boston, MA 02115 USA. NR 23 TC 66 Z9 68 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2002 VL 62 IS 1 BP 43 EP 47 PG 5 WC Oncology SC Oncology GA 513MP UT WOS:000173382600010 PM 11782356 ER PT J AU DiRenzo, J Signoretti, S Nakamura, N Rivera-Gonzalez, R Sellers, W Loda, M Brown, M AF DiRenzo, J Signoretti, S Nakamura, N Rivera-Gonzalez, R Sellers, W Loda, M Brown, M TI Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line SO CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; REPLICATIVE SENESCENCE; TELOMERASE ACTIVITY; MAMMALIAN-CELLS; P53 HOMOLOG; STEM-CELLS; P63; PTEN; GLAND; PROLIFERATION AB Carcinogenesis involves a multistep process whereby a normal healthy cell undergoes both immortalization and oncogenesis to become fully transformed. Immortalization results from the subversion of critical cell cycle regulatory checkpoints, thereby allowing a cell to extend its finite life span and to maintain telomeric length. Oncogenesis is the manifestation of additional genetic events that are capable of conferring upon the cell an actual growth advantage. Such an advantage may relieve a cell of its normal requirements for a particular growth factor or may enhance the ability of a cell to proliferate outside of its normal microenvironment. To further investigate this multistep process, we developed an immortalized mammary epithelial cell line by overexpressing the catalytic subunit of telomerase (human telomerase reverse transcriptase) in primary human mammary epithelial cell lines. We present evidence that the over expression of human telomerase reverse transcriptase was sufficient to extend the life span of the cells and allow for additional events that lead to immortalization. The result was the establishment of an IMEC line. Biochemical analysis of these cells indicates a basal epithelial phenotype with expression of high molecular weight cytokeratins. We show that continued growth of the IMECs is rigorously dependent upon both insulin and epidermal growth factor, and that the mitogenic effects of these factors on the IMECs are mediated in part by AKT. In addition, IMECs express the p53 family member DeltaN-p63-alpha, which is found in basal epithelial cells of many tissues and has been implicated as playing an essential role in normal epithelial development. Our studies suggest that the immortalization of basal epithelial cells of the mammary gland, may be an early step in the initiation of a subset of breast cancers with a basal epithelial phenotype. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D730, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [1P50CA089393-01] NR 54 TC 99 Z9 103 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2002 VL 62 IS 1 BP 89 EP 98 PG 10 WC Oncology SC Oncology GA 513MP UT WOS:000173382600018 PM 11782364 ER PT J AU Chakravarti, A Loeffler, JS Dyson, NJ AF Chakravarti, A Loeffler, JS Dyson, NJ TI Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling SO CANCER RESEARCH LA English DT Article ID HUMAN CANCER-CELLS; EGF RECEPTOR; IONIZING-RADIATION; ANTITUMOR-ACTIVITY; EPITHELIAL-CELLS; PROTEIN; KINASE; INHIBITION; C225; TRANSDUCTION AB Overexpression of the epidermal growth factor receptor (EGFR) has been shown previously to correlate with enhanced malignant potential of many human tumor types, including glioblastoma multiforme (GBM). Anti-EGFR targeting has been demonstrated to enhance apoptosis and reduce both cellular invasion and angiogenic potential. It remains unclear whether absolute EGFR expression levels are sufficient to predict which tumors will respond best to anti-EGFR therapy. We have identified two primary GBM cell lines with equivalent EGFR expression levels with very different sensitivities to the EGFR receptor tyrosine kinase inhibitor, AG1478. This was apparent despite similar reductions in EGFR signaling in both cell lines, as measured by phospho-EGFR levels. AG1478 enhanced both spontaneous and radiation-induced apoptosis and reduced invasive potential in the GBM(S), but not in the GBM(R), cell line. The resistant GBMR cell line demonstrated an up-regulation of insulin-like growth factor receptor I (IGFR-I) levels on AG1478 administration. This resulted in sustained signaling through the phosphoinositide 3-kinase pathway, resulting in potent antiapoptotic and proinvasion effects. Cotargeting IGFR-I with EGFR greatly enhanced both spontaneous and radiation-induced apoptosis of the GBMR Cells and reduced their invasive potential. Akt1 and p70(s6k) appeared to be important downstream targets of IGFR-I-mediated resistance to anti-EGFR targeting. These findings suggest that IGFR-I signaling through phosphoinositide 3-kinase may represent a novel and potentially important mechanism of resistance to anti-EGFR therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol Oncol,Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Oncol, Charlestown, MA 02129 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol Oncol,Dept Radiat Oncol, 13th St,Bldg 149,Room 7330, Charlestown, MA 02129 USA. FU NCI NIH HHS [K08CA82163, R01CA64402] NR 51 TC 383 Z9 402 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2002 VL 62 IS 1 BP 200 EP 207 PG 8 WC Oncology SC Oncology GA 513MP UT WOS:000173382600032 PM 11782378 ER PT J AU Simon, HB AF Simon, HB TI Atherosclerosis or atheroscleritis: What's in a name? SO CARDIOLOGY LA English DT Editorial Material ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; STATIN THERAPY; INFLAMMATION; MARKERS; RISK C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Simon, HB (reprint author), Massachusetts Gen Hosp, Dept Internal Med, 55 Fruit St, Boston, MA 02114 USA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2002 VL 98 IS 3 BP 111 EP 112 DI 10.1159/000066323 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 615LQ UT WOS:000179247200001 PM 12417807 ER PT J AU Rich, MM McGarvey, ML Teener, JW Frame, LH AF Rich, MM McGarvey, ML Teener, JW Frame, LH TI ECG changes during septic shock SO CARDIOLOGY LA English DT Article DE cardiac excitability; sepsis; systemic inflammatory response syndrome; low QRS voltage ID ACUTE QUADRIPLEGIC MYOPATHY; ANIMAL-MODEL; DYSFUNCTION; SEPSIS; MUSCLE AB We have previously found that skeletal muscle becomes electrically inexcitable in septic patients. Work in an animal model suggests that a decrease in the available sodium current underlies the loss of electrical excitability. We examined ECGs from patients during periods of septic shock to determine whether there were any ECG abnormalities that might suggest a similar loss of excitability in cardiac tissue during sepsis. Fourteen out of 17 patients had low or significantly decreased QRS amplitudes during septic shock; 8 of 17 had long or increased QRS duration with or without bundle branch block. The mean decrease in QRS amplitude in septic patients was 41%, significantly higher than in controls where no consistent decrease in QRS amplitude was found (p < 0.01). In patients who recovered from septic shock, the QRS amplitude and the increased QRS duration both returned to normal. We conclude that there is a loss of QRS amplitude during septic shock that may be due to altered cardiac excitability. Copyright (C) 2002 S. Karger AG, Basel. C1 Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. St Marys Duluth Clin, Hlth Syst, Philadelphia, PA USA. Vet Affairs Med Ctr, Cardiol Sect, Philadelphia, PA USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Rich, MM (reprint author), Emory Univ, Dept Neurol, Suite 6000 WMB,1639 Pierce Dr, Atlanta, GA 30322 USA. NR 13 TC 21 Z9 21 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2002 VL 97 IS 4 BP 187 EP 196 DI 10.1159/000063120 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 581EP UT WOS:000177278400004 PM 12145473 ER PT J AU Goldmann, WH AF Goldmann, WH TI The coupling of vinculin to the cytoskeleton is not essential for mechano-chemical signaling in F9 cells SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE mechano-chemical signaling; vinculin; integrin; cytoskeleton ID ATOMIC-FORCE MICROSCOPY; INTEGRINS; ADHESION; FIBRONECTIN; SHAPE; TRANSDUCTION; LOCOMOTION; ELASTICITY; PATHWAYS; GROWTH AB It is well established that mechanical forces can regulate cell growth and guide tissue remodeling, yet little is known about how mechanical signals act at the cell surface membrane to produce biochemical changes in the cell. To explore this question, I used a mouse embryonic F9 vinculin-deficient cell line (gamma229), which, unlike wild-type cells, shows no fibronectin-dependent cell spreading. The wild-type cell line exhibited a twofold increase in area over four hours. I observed (i) an earlier rise in intracellular free calcium from similar to 0.2 to similar to 3 muM in wild-type compared with gamma229 cells, thus similar calcium levels after 4 h; (ii) an initial higher ratio of p-MAP/MAP-Kinase for gamma229, but similar FA-Kinase activation; and (iii) a marginal change in intracellular pH [pH]i in both F9 cell lines. When I applied controlled local stresses directly to integrin receptors using RGD-coated magnetic beads, they displaced to a lesser extent in wild-type than in gamma229 cells. Both F9 cell lines showed a small stress-dependent rise in [Ca2+](i) levels and similar PKA-c activity. In summary, the mechanical linkage of integrin-vinculin-cytoskeleton seemed not to be essential for chemical signal transduction. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 28 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2002 VL 26 IS 3 BP 279 EP 286 DI 10.1006/cbir.2001.0854 PG 8 WC Cell Biology SC Cell Biology GA 556AQ UT WOS:000175825600008 PM 11991656 ER PT J AU Goldmann, WH AF Goldmann, WH TI Mechanical aspects of cell shape regulation and signaling SO CELL BIOLOGY INTERNATIONAL LA English DT Review DE integrin; vinculin; actin; mechano-transduction; extracellular matrix ID CYTOSKELETAL MECHANICS; EXTRACELLULAR-MATRIX; MIGRATION; INTEGRINS; ADHESION; BINDING; TENSION; FORCE; F9 AB Physical forces play a critical role in cell integrity and development, but little is known how cells convert mechanical signals into biochemical responses. This mini-review examines potential molecular mediators like integrins, focal adhesion proteins, and the cytoskeleton in the context of a complex cell structure. These molecules when activated by cell binding to the extracellular matrix-associate with the skeletal scaffold via the focal adhesion complex. Vinculin is presented as a mechanical coupling protein that contributes to the integrity of the cytoskeleton and cell shape control, and examples are given of how mechanical signals converge into biochemical responses through force-dependent changes in cell geometry and molecular mechanics. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Bldg 149,13th St,Room 8200, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 23 TC 51 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2002 VL 26 IS 4 BP 313 EP 317 DI 10.1006/cbir.2002.0857 PG 5 WC Cell Biology SC Cell Biology GA 559TU UT WOS:000176042100002 PM 11991660 ER PT J AU Goldmann, WH AF Goldmann, WH TI Examination of actin polymerization and viscosity induced by cations and ionic strength when cross-linked by alpha-actinin SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE alpha-actinin; actin polymerization; viscosity; cations; ionic strength ID TEMPERATURE; PROTEIN; BINDING; FRAGMENTS; NETWORKS; GELATION; FILAMIN; COMPLEX; TALIN; PH AB Increasing potassium chloride concentration from 0 to 100 mM and magnesium chloride from 0 to 2 mM show a parallel rate increase in polymerizing actin, whereas increasing calcium chloride concentration from 0 to 0.2 mM decreases the rate of polymerizing actin. The presence of alpha-actinin has little influence on the polymerization kinetics of actin under these conditions. Viscometric measurements indicate that the presence of various mono- and divalent cations, ionic strength, and alpha-actinin in combination are responsible for changes in the mechanical properties of solutions containing actin. The actin filament dynamic behavior is drastically reduced under these conditions as confirmed by quasi-elastic light scattering. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Room 8200,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 33 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2002 VL 26 IS 6 BP 541 EP 546 DI 10.1006/cbir.2002.0898 PG 6 WC Cell Biology SC Cell Biology GA 578BF UT WOS:000177097000006 PM 12119180 ER PT J AU Goldmann, WH AF Goldmann, WH TI p56(lck) controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK)) SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE tyrosine phosphorylation; p56(lck); pp125(FAK); PKC; filamin (ABP-280) ID PROTEIN-TYROSINE KINASE; GTPASE-ACTIVATING PROTEIN; THYMOCYTE DEVELOPMENT; ACTIN CYTOSKELETON; BINDING-PROTEIN; 3T3 FIBROBLASTS; CROSS-LINKING; ZETA-CHAIN; T-CELLS; RECEPTOR AB Transformation of cells by src-like kinases leads to altered cell morphology associated with the disassembly of focal contacts and concomitant increase in tyrosine phosphorylation of pp125(FAK).p56(lck) is a lymphocyte-specific member of the src family of protein tyrosine kinases that associates with cell surface glycoproteins such as CD4 and CD8. It phosphorylates and activates pp125(FAK) and increases its autokinase activity, thus pretreatment of pp125(FAK) with protein kinase C (PKC) markedly attenuates its phosphorylation and activation, suggesting a potential regulatory pathway of pp125(FAK) activation in focal contacts. p56(lck) further phosphorylates and activates actin binding protein (ABP-280; filamin) and controls its association with cell surface receptors such as beta-2 integrins, actin filament cross-linking, and possibly lipid membrane insertion. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Bldg 149,13th St,Rm 8200, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 40 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2002 VL 26 IS 6 BP 567 EP 571 DI 10.1006/cbir.2002.0900 PG 5 WC Cell Biology SC Cell Biology GA 578BF UT WOS:000177097000010 PM 12171035 ER PT J AU Goldmann, WH Isenberg, G AF Goldmann, WH Isenberg, G TI Actin-related protein (Arp2) inserts into artificial lipid membranes SO CELL BIOLOGY INTERNATIONAL LA English DT Article; Proceedings Paper CT ASBC 2001 Meeting CY 2001 CL WASHINGTON, D.C. DE Arp2; actin; lipid membrane ID VINCULIN; COMPLEX; TALIN; FILAMIN AB Arp2 is localized in the cytoplasm of eukaryotic cells where it controls actin dynamics. Computer analyses have suggested one possible lipid binding site, residues 185-202 of the primary amino acid sequence on Arp2, that could allow for membrane attachment/insertion. We expressed this region as a fusion protein with schistosomal glutathione S-transferase (GST) and investigated the interaction of this fragment with mixtures of dioleoylphosphatidylserine (DOPS) and dioleoylphosphatidylglycerol (DOPG) phospholipids in reconstituted lipid bilayers using differential scanning calorimetry (DSC). Calorimetric measurements showed that as the fusion protein increased, the main chain transition enthalpy decreased and the chain-melting temperature shifted, which is indicative of partial protein insertion into the hydrophobic region of the lipid membrane. This was confirmed using the Langmuir Blodgett technique (film balance) on lipid monolayers. The dissociation constant (K-d) determined by the temperature jump method was approximately 1.1 muM. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Charlestown, MA 02129 USA. Tech Univ Munich, Dept Biophys E22, D-85747 Garching, Germany. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bldg 149,13th St,Room 8200, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 20 TC 3 Z9 3 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2002 VL 26 IS 12 BP 1073 EP 1078 DI 10.1006/cbir.2002.0954 PG 6 WC Cell Biology SC Cell Biology GA 626NE UT WOS:000179878400008 PM 12468383 ER PT J AU Pardee, AB AF Pardee, Arthur B. TI Introducing Cell Cycle SO CELL CYCLE LA English DT Editorial Material C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Pardee@mbcrr.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JAN PY 2002 VL 1 IS 1 BP 2 EP 2 DI 10.4161/cc.1.1.91 PG 1 WC Cell Biology SC Cell Biology GA V40OM UT WOS:000209487900001 ER PT J AU Matarazzo, M Giardina, MG Guardasole, V Davalli, AM Horton, ES Weir, GC Sacca, L Napoli, R AF Matarazzo, M Giardina, MG Guardasole, V Davalli, AM Horton, ES Weir, GC Sacca, L Napoli, R TI Islet transplantation under the kidney capsule corrects the defects in glycogen metabolism in both liver and muscle of streptozocin-diabetic rats SO CELL TRANSPLANTATION LA English DT Article DE islet transplantation; glycogen; glucose-6-phosphate; glycogen synthase; liver; muscle ID SYNTHASE PHOSPHATASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; INSULIN-RESISTANCE; TYROSINE PHOSPHORYLATION; TRANSGENIC MICE; CONSCIOUS RATS; ANIMAL-MODELS; INVIVO AB Insulin-deficient rats are characterized by multiple defects in the pathway of glycogen synthesis and breakdown in both liver and skeletal muscle. The aim of this study was to clarify whether islet transplantation under the kidney capsule, which is associated with delivery of insulin into the peripheral circulation, is able to normalize glycogen metabolism in liver and muscle of streptozotocin-diabetic rats. Three groups of male Lewis rats were studied under fasting condition: controls, untreated diabetics, and islet transplanted diabetics. Glycogen content. glucose-6-phosphate concentration, and glycogen synthase activity were measured in both liver and skeletal muscle. Untreated diabetic rats were characterized by an increase in glycogen content of 178% and a reduction of glucose-6-phosphate level of 50%. Both glycogen and glucose-6-phosphate contents were restored to normal in transplanted diabetic rats. Active glycogen synthase (0.35 +/- 0.1 nmol/min/mg) and activity ratio (0.22 +/- 0.04) were significantly impaired compared with controls (0.99 +/- 0.2 nmol/min/mg and 0.43 +/- 0.06, respectively) and were normalized by islet transplantation. In the skeletal muscle, glycogen content was similar in the three groups of animals, whereas muscle glucose-6-phosphate level was reduced by 28% and glycogen synthase was in a less active state in the untreated diabetic rats. Both the glucose -6-phosphate concentration and the kinetic profile of glycogen synthase were normalized by islet transplantation. In conclusion. islet transplantation under the kidney capsule corrects the diabetes-induced abnormalities in glycogen and glucose-6-phosphate content and glycogen synthase activity in both liver and skeletal muscle. C1 Univ Naples Federico II, Sch Med, Dept Internal Med & Cardiovasc Sci, Naples, Italy. San Raffaele Sci Inst, I-20132 Milan, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Sacca, L (reprint author), Via Pansini 5, I-80131 Naples, Italy. OI NAPOLI, Raffaele/0000-0002-3366-2321 FU Telethon [A.118] NR 66 TC 6 Z9 6 U1 0 U2 2 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 2002 VL 11 IS 2 BP 103 EP 112 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 553VK UT WOS:000175696500003 PM 12099634 ER PT J AU Hamoen, KE Morgan, JR AF Hamoen, KE Morgan, JR TI Transient hyperproliferation of a transgenic human epidermis expressing hepatocyte growth factor SO CELL TRANSPLANTATION LA English DT Article DE skin graft; growth factor; wound healing; tissue engineering ID SCATTER FACTOR; HUMAN KERATINOCYTES; PLASMINOGEN-ACTIVATOR; SKIN EQUIVALENT; BARRIER LIPIDS; MESSENGER-RNA; RAT PLATELETS; PURIFICATION; GENE; DIFFERENTIATION AB Hepatocyte growth factor (HGF) is a fibroblast-derived protein that affects the growth, motility, and differentiation of epithelial cells including epidermal keratinocytes. To investigate the role of HGF in cutaneous biology and to explore the possibility of using it in a tissue engineering approach, we used retroviral-mediated gene transfer to introduce the gene encoding human HGF into diploid human keratinocytes. Modified cells synthesized and secreted significant levels of HGF in vitro and the proliferation of keratinocytes expressing HGF was enhanced compared with control unmodified cells. To investigate the effects of HGF in vivo, we grafted modified keratinocytes expressing HGF onto athymic mice using acellular dermis as a substrate. When compared with controls, HGF-expressing keratinocytes formed a hyperproliferative epidermis. The epidermis was thicker, had more cells per length of basement membrane, and had increased numbers of Ki-67-positive proliferating cells, many of which were suprabasal in location. Hyperproliferation subsided and the epidermis was equivalent to controls by 2 weeks, a time frame that coincides with healing of the graft. Transient hyperproliferation may be linked to the loss of factors present in the wound that activate HGF. These data suggest that genetically modified skin substitutes secreting HGF may have applications in wound closure and the promotion of wound healing. C1 Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Harvard Univ, Sch Med, Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 35 TC 21 Z9 23 U1 0 U2 2 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 2002 VL 11 IS 4 BP 385 EP 395 PG 11 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 575UL UT WOS:000176966800009 PM 12162379 ER PT J AU Ikushima, H Munakata, Y Iwata, S Ohnuma, K Kobayashi, S Dang, NH Morimoto, C AF Ikushima, H Munakata, Y Iwata, S Ohnuma, K Kobayashi, S Dang, NH Morimoto, C TI Soluble CD26/dipeptidyl peptidase IV enhances transendothelial migration via its interaction with mannose 6-phosphate/insulin-like growth factor II receptor SO CELLULAR IMMUNOLOGY LA English DT Article DE CD26; dipeptidyl peptidase IV; mannose 6-phosphate/insulin-like growth factor II receptor; cell migration ID T-CELL ACTIVATION; IMMUNE-RESPONSE; CD26 ANTIGEN; RANTES; PROLIFERATION; 6-PHOSPHATE; CHEMOTAXIS; FLUID; 1F7 AB CD26 is a T cell surface molecule with dipeptidyl peptidase IV (DPPIV) enzyme activity in its extracellular region. In addition to its membrane form, CD26 exists in plasma as a soluble form (sCD26), which is the extracellular domain of the molecule thought to be cleaved from the cell surface. In this paper, we demonstrate that sCD26 mediates enhanced transendothelial T cell migration, an effect that requires its intrinsic DPPIV enzyme activity. We also show that sCD26 directly targets endothelial cells and that mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIR) on the endothelial cell surface acts as a receptor for sCD26. Our findings therefore suggest that sCD26 influences T cell migration through its interaction with M6P/IGFIIR. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Clin Immunol,Minato Ku, Tokyo 1088639, Japan. MD Anderson Canc Ctr, Dept Lymphomal Myeloma, Houston, TX 77030 USA. RP Morimoto, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, 44 Binney St, Boston, MA 02115 USA. RI Iwata, Satoshi/A-8819-2011 NR 17 TC 41 Z9 43 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN PY 2002 VL 215 IS 1 BP 106 EP 110 AR PII S0008-8749(02)00010-2 DI 10.1016/S0008-8749(02)00010-2 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 585JM UT WOS:000177521700012 PM 12142042 ER PT S AU Hunter, G Hamberg, L Lev, MH Gonzalez, RG AF Hunter, G Hamberg, L Lev, MH Gonzalez, RG BE Pinsky, MR TI Computed tomography angiography and perfusion imaging of acute stroke SO CEREBRAL BLOOD FLOW: MECHANISMS OF ISCHEMIA, DIAGNOSIS AND THERAPY SE UPDATE IN INTENSIVE CARE AND EMERGENCY MEDICINE LA English DT Proceedings Paper CT 5th Symposium on Applied Physiology of the Peripheral Circulation CY 2000 CL PITTSBURGH, PA ID ACUTE ISCHEMIC STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; 3-DIMENSIONAL FUNCTIONAL CT; ACUTE HEMISPHERIC STROKE; THROMBOLYTIC THERAPY; PROUROKINASE; INFARCTION; AGREEMENT; PROACT; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. RP Hunter, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0933-6788 BN 3-540-42037-1 J9 UPD INT CAR PY 2002 VL 37 BP 165 EP 178 PG 14 WC Critical Care Medicine; Emergency Medicine; Neurosciences SC General & Internal Medicine; Emergency Medicine; Neurosciences & Neurology GA BT80E UT WOS:000174088900012 ER PT J AU Ay, H Oliveira-Filho, J Buonanno, FS Schaefer, PW Furie, KL Chang, YC Rordorf, G Schwamm, LH Gonzalez, RG Koroshetz, WJ AF Ay, H Oliveira-Filho, J Buonanno, FS Schaefer, PW Furie, KL Chang, YC Rordorf, G Schwamm, LH Gonzalez, RG Koroshetz, WJ TI 'Footprints' of transient ischemic attacks: A diffusion-weighted MRI study SO CEREBROVASCULAR DISEASES LA English DT Article DE diffusion-weighted imaging; transient ischemic attack; infarction; ischemic stroke ID WHITE-MATTER HYPERINTENSITIES; LIFE MIGRAINE ACCOMPANIMENTS; FOCAL CEREBRAL-ISCHEMIA; COMPUTED-TOMOGRAPHY; STATUS EPILEPTICUS; COEFFICIENT ADC; WATER DIFFUSION; RISK-FACTORS; TIME-COURSE; STROKE AB Objective: Diffusion-weighted imaging (DWI) conveys temporal as well as anatomic information about brain infarction, and is therefore well suited to identify ischemic injury that has occurred simultaneously, or closely linked in time, with a transient ischemic attack (TIA). We aimed to determine the proportion and clinical characteristics of patients with TIA who harbor infarction(s) on DWI. Methods: Using T-2-weighted imaging (T-2-WI), fast fluid attenuated inversion recovery (FLAIR), and DWI, we studied 57 consecutive patients presenting with acute focal neurologic symptoms lasting less than 24 h. Results:A hyperintense DWI lesion was identified in a vascular territory appropriate to the symptoms in 27 patients (47%). Lesions judged to be clinically appropriate on T-2-WI and FLAIR overlapped with a DWI lesion in 41 and 48% of patients, respectively. Independent predictors of infarction on DWI were previous nonstereotypic TIAs, presentation with motor symptoms, and identified stroke mechanism. Conclusion: DWI establishes that recent infarction occurs in almost half of patients with the clinical syndrome of TIA and this subgroup is more likely to harbor an underlying cardiac or cerebrovascular abnormality. Copyright (C) 2002 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ay, H (reprint author), Hacettepe Hastanesi, Norol Anabilm Dalu, TR-06100 Ankara, Turkey. OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [NS33765, 5 RO1 NS35284, NS32324, NS34447, P50 NS108288-22, R01-NS28371] NR 51 TC 74 Z9 83 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 2002 VL 14 IS 3-4 BP 177 EP 186 DI 10.1159/000065682 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 613QW UT WOS:000179143800006 PM 12403950 ER PT J AU Rosand, J Eskey, C Chang, Y Gonzalez, RG Greenberg, SM Koroshetz, WJ AF Rosand, J Eskey, C Chang, Y Gonzalez, RG Greenberg, SM Koroshetz, WJ TI Dynamic single-section CT demonstrates reduced cerebral blood flow in acute intracerebral hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Article DE intracerebral hemorrhage; cerebral blood flow; X-ray computed tomography ID COMPUTED-TOMOGRAPHY; ISCHEMIC STROKE; PERFUSION CT; XENON CT; VALIDATION; MANAGEMENT; VOLUME AB Optimum blood pressure (BP) management in acute intracerebral hemorrhage (ICH) remains controversial. BP reduction may limit hematoma expansion, but may also exacerbate ischemia. Reduced regional cerebral blood flow (rCBF) has been reported in ICH. Its extent and precise pattern, however, remain uncertain. Dynamic single-section CT perfusion (CTP) is rapid, easily performed and offers superior spatial resolution to PET, SPECT and MRI. It may be the most applicable method for assessing the effects of BP management on rCBF in ICH. We sought to assess whether CTP can identify rCBF abnormalities in acute ICH in 5 patients with ICH who underwent CTP within 24 h of symptom onset. rCBF was measured in serially expanded 2-mm rings around the hematoma and compared with rCBF in the uninvolved hemisphere. Mean time to CTP was 9 h (range 3-23). Mean ICH volume was 25 ml (range 9-64). Perihematoma perfusion was reduced in all patients compared with contralateral hemisphere rCBF. rCBF reduction was most pronounced immediately adjacent to the hematoma (p < 0.05 at 2 mm, p = 0.084 at 4 mm, p > 0.2 at 6 and 8 mm). Perihematoma rCBF increased as a function of the distance from hematoma perimeter. Rate of rCBF increase over distance correlated With time from onset (p = 0.006). We conclude that CTP identifies a rim of reduced rCBF in ICH. A gradient of hypoperfusion appears to extend at least 4 mm beyond the hematoma edge and may be time dependent. Whether reduced CBF is associated with perihematoma ischemia requires additional study. Copyright (C) 2002 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03766 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Neurocrit Care Trial Unit, ACC-836,15 Parkman St, Boston, MA 02114 USA. NR 24 TC 47 Z9 59 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 2002 VL 14 IS 3-4 BP 214 EP 220 DI 10.1159/000065681 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 613QW UT WOS:000179143800010 PM 12403954 ER PT J AU Greenberg, SM AF Greenberg, SM TI Cerebral amyloid angiopathy and vessel dysfunction SO CEREBROVASCULAR DISEASES LA English DT Article DE amyloid; congophilic material; angiopathy; hereditary; beta-amyloid precursor protein; vascular dementia; stroke; transgenic mouse ID APOLIPOPROTEIN-E EPSILON-2; PRECURSOR PROTEIN GENE; WHITE-MATTER LESIONS; DUTCH-TYPE MUTANT; ALZHEIMERS-DISEASE; BETA-PROTEIN; A-BETA; ENDOTHELIAL-CELLS; E GENOTYPE; HCHWA-D AB Cerebral amyloid angiopathy (CAA), defined by deposition of the beta-amyloid peptide in medium and small cortical and meningeal vessels, is a well-recognized cause of hemorrhagic stroke. This paper reviews the accumulating evidence supporting an additional role for CAA in producing vessel dysfunction, reduced cerebral blood flow and ischemia. Ischemic lesions are characteristic of several hereditary CAA syndromes, including a recently described mutation of the amyloid precursor protein associated with dementia (but not hemorrhagic stroke) in an Iowa family. Ischemic lesions are seen in some sporadic CAA patients as well, and recent data from transgenic mice suggest potential mechanisms by which beta-amyloid may alter vessel physiology. Future studies will seek to define the clinical importance of vascular beta-amyloid as a potential target for drug therapy in dementia. Copyright (C) 2002 S. KargerAG, Basel. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang AC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 58 TC 58 Z9 60 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2002 VL 13 SU 2 BP 42 EP 47 DI 10.1159/000049149 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 538BM UT WOS:000174794200008 PM 11901242 ER PT J AU Balasubramanian, SV Campbell, RB Straubinger, RM AF Balasubramanian, SV Campbell, RB Straubinger, RM TI Propofol, a general anesthetic, promotes the formation of fluid phase domains in model membranes SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article DE propofol; general anesthetic; anesthetic-membrane interaction; Laurdan fluorescence; generalized polarization; small-scale domains; lipid mixing and lateral reorganization; phase inter conversion ID PHOSPHOLIPASE A(2) ACTIVITY; PROTEIN-KINASE-C; LAURDAN FLUORESCENCE; LOCAL-ANESTHETICS; LIPID BILAYER; VESICLES; CHOLESTEROL; POLARIZATION; MODULATION; ACTIVATION AB The molecular site of anesthetic action remains an area of intense research interest. It is not clear whether general anesthetics act through direct binding to proteins or by perturbing the membrane properties of excitable tissues. Several studies indicate that anesthetics affect the properties of either membrane lipids or proteins. However, gaps remain in our understanding of the molecular mechanism of anesthetic action. Recent developments in membrane biology have led to the concept of small-scale domain structures in lipid and lipid-protein coupled systems. The role of such domain structures in anesthetic action has not been studied in detail, In the present study, we investigated the effect of anesthetics on lipid domain structures in model membranes using the fluorescent spectral properties of Laurdan (6-dodecancyl-2-diracthylamino naphthalene). Propofol, a general anesthetic, promoted the formation of fluid domains in model membranes of dipalmitoyl phosphatidyl choline (DPPC) or mixtures of lipids of varying acyl chains (DPPC:DMPC dimyristoyl phosphatidyl choline 1: 1). The estimated size of these domains is 20-50 Angstrom. Based on these studies, we speculate that the mechanism of anesthetic action may involve effects on protein-lipid coupled systems through alterations in small-scale lipid domain structures. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 SUNY Buffalo, Dept Pharmaceut Sci, Amherst, NY 14260 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Balasubramanian, SV (reprint author), SUNY Buffalo, Dept Pharmaceut Sci, 539 Cooke Hall, Amherst, NY 14260 USA. FU NCRR NIH HHS [S10 RR015877, S10 RR015877-01A1, S10 RR027232, S10 RR027232-01] NR 29 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD JAN PY 2002 VL 114 IS 1 BP 35 EP 44 AR PII S0009-3084(01)00199-2 DI 10.1016/S0009-3084(01)00199-2 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 525GW UT WOS:000174061400004 PM 11841824 ER PT J AU Witucki, LA Huang, X Shah, K Liu, Y Kyin, S Eck, MJ Shokat, KM AF Witucki, LA Huang, X Shah, K Liu, Y Kyin, S Eck, MJ Shokat, KM TI Mutant tyrosine kinases with unnatural nucleotide specificity retain the structure and phospho-acceptor specificity of the wild-type enzyme SO CHEMISTRY & BIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; PHASE PEPTIDE-SYNTHESIS; PHAGE DISPLAY; C-SRC; CATALYTIC SPECIFICITY; SUBSTRATE-SPECIFICITY; CELLULOSE PAPER; ATP ANALOG; V-SRC; PHOSPHORYLATION AB The direct substrates of one protein kinase in a cell can be identified by mutation of the ATP binding pocket to allow an unnatural ATP analog to be accepted exclusively by the engineered kinase. Here, we present structural and functional assessment of peptide specificity of mutant protein kinases with unnatural ATP analogs. The crystal structure (2.8 Angstrom resolution) of c-Src (T338G) with N-6-(benzyl) ADP bound shows that the creation of a unique nucleotide binding pocket does not alter the phospho-acceptor binding site of the kinase.,A panel of optimal peptide substrates of defined sequence, as well as a degenerate peptide library, was utilized to assess the phospho-acceptor specificity of the engineered "traceable" kinases. The specificity profiles for the mutant kinases were found to be identical to those of their wild-type counterparts. C1 Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Princeton Univ, Dept Mol Biol Synth & Sequencing Facil, Princeton, NJ 08544 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. RP Shokat, KM (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Box 0450, San Francisco, CA 94143 USA. FU NCI NIH HHS [1R011CA70331-01] NR 49 TC 40 Z9 41 U1 1 U2 6 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 2002 VL 9 IS 1 BP 25 EP 33 DI 10.1016/S1074-5521(02)00091-1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 518YN UT WOS:000173696100004 PM 11841936 ER PT J AU Abrahm, JL Hansen-Flaschen, J AF Abrahm, JL Hansen-Flaschen, J TI Hospice care for patients with advanced lung disease SO CHEST LA English DT Review DE cystic fibrosis; hospices; interstitial lung diseases; lung diseases; obstructive lung diseases; palliative care; pulmonary hypertension; respiraton track diseases; terminal care ID TERMINALLY ILL PATIENTS; SURVIVAL; LIFE; END AB Hospices are organized programs of support services for patients in the advanced stages of a terminal illness and their families. Although hospices serve dying patients regardless of diagnosis, limited available evidence suggests that these programs are relatively underutilized by patients dying of nonmalignant lung diseases. one explanation may, be a lower awareness of hospice eligibility criteria and services among pulmonologists than oncologists. The unpredictability, of death from advanced lung disease is another likely reason. Certain limitations on federal and private insurance coverage for patients with advanced lung disease probably, contribute as well. For those patients who do enroll, hospice offers expert palliation of physical, psychological, social, and spiritual distress, as well as practical support for home care needs, hospitalization for short-term control of symptoms, and inpatient respite care for relief of home caregivers. Hospice workers view dying as an active phase of life filled with the pursuit of goals that patients and family members wish to complete before or shortly, after the end of life. This article reviews hospice care in the United States with particular attention to eligibility criteria and services available for patients who are dying of an advanced lung disease. Specific recommendations are offered for referring respiratory disease patients to hospice programs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Sch Med, Pulm & Allergy & Crit Care Div, Philadelphia, PA 19104 USA. RP Hansen-Flaschen, J (reprint author), Hosp Univ Penn, 873 Maloney Bldg,3400 Spruce St, Philadelphia, PA 19096 USA. OI Hansen-Flaschen, John/0000-0003-1989-7244 NR 33 TC 24 Z9 25 U1 2 U2 3 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 2002 VL 121 IS 1 BP 220 EP 229 DI 10.1378/chest.121.1.220 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 514GU UT WOS:000173431400037 PM 11796455 ER PT J AU Beresin, EV AF Beresin, EV TI The administration of residency training programs SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CHILD-PSYCHIATRY; ADOLESCENT AB The position of training director is perhaps the most difficult job in a department of psychiatry. The training director must implement the values, culture, and philosophy of the department; nurture residents, faculty, and support staff; maintain collaborative ties with the hospital and medical school-allied specialties and administration; and monitor the integrity and quality of clinical and academic training. All this must be accomplished in a role that has considerable authority but no real power. The director needs to understand the context in which training occurs and take into account the limited resources of the health care delivery system and the constraints imposed by the current era of managed care. This article provides an overview of the requirements for successfully achieving these complex goals and objectives. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bulfinch 449,Fruit St, Boston, MA 02114 USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2002 VL 11 IS 1 BP 67 EP + DI 10.1016/S1056-4993(03)00061-0 PG 24 WC Psychiatry SC Psychiatry GA 510MW UT WOS:000173212700006 PM 11793573 ER PT J AU DeJong, S Alexakos, M Jellinek, M AF DeJong, S Alexakos, M Jellinek, M TI Child and adolescent psychiatry - Exploring the option to be a manager in an academic medical center SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ISSUES AB Traditionally, few child psychiatrists have opted for careers as senior managers in academic medical centers, preferring to emphasize their clinical role and hoping their clinical work will be valued and reimbursed despite economic pressures. Yet the career of a hospital-wide manager in an academic medical center provides opportunities to promote an individual's career, the mission of the whole organization, and child psychiatry itself. Drawing on some of the issues discussed in the general literature on the clinician-executive, this article outlines the basic qualities and skills required to be a successful child psychiatrist executive and delineates the essential steps and potential pitfalls in building such a career. This delineation looks at the developmental stage of both the psychiatrist and the organization involved. The authors emphasize the importance of child psychiatrists assuming active roles within academic medical centers to protect and enhance the field of child psychiatry. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. McLean Hosp, Boston, MA USA. Newton Wellesley Hosp, Newton, MA USA. RP Jellinek, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2002 VL 11 IS 1 BP 113 EP + DI 10.1016/S1056-4993(03)00064-6 PG 18 WC Psychiatry SC Psychiatry GA 510MW UT WOS:000173212700009 PM 11793568 ER PT J AU Liu, XM Chapman, GB Wang, H Durante, W AF Liu, XM Chapman, GB Wang, H Durante, W TI Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in vascular smooth muscle cells SO CIRCULATION LA English DT Article DE oxygenase; apoptosis; muscle; smooth; biliverdin; bilirubin ID CARBON-MONOXIDE; GUANYLATE-CYCLASE; METALLOPORPHYRINS; ANTIOXIDANT; INHIBITION; INDUCTION; ALPHA; DEATH; ROLES; RATS AB Background-Heme oxygenase-1 (HO-1) catalyzes the degradation of heme into biliverdin, iron, and carbon monoxide (CO). Although HO-1 is induced in vascular smooth muscle cells (SMCs), the biological role of HO-1 in these cells has not been completely characterized. Methods and Results-In the present study, we overexpressed HO-1 in rat aortic SMCs by generating a recombinant defective adenovirus containing the rat HO-1 1 gene (AdHO-1) and examined the effect on SMC proliferation. Infection of SMCs with AdHO-1 resulted in a dose-dependent increase in the expression of HO-1 mRNA, protein, and activity. Infection of SMCs with AdHO-1 inhibited serum-stimulated SMC proliferation in a dose-dependent manner. In contrast, the control adenovirus expressing, the green fluorescent protein failed to induce HO-1 expression and had minimal effects on SMC growth. Infection with AdHO-1 stimulated SMC apoptosis in a dose-dependent fashion, as demonstrated by DNA fragmentation, positive annexin V labeling, and caspase-3 activation. HO-1-mediated apoptosis was associated with a marked increase in the expression of the proapoptotic protein p53. Finally, the exogenous administration of biliverdin and bilirubin stimulated SMC apoptosis. In contrast, the administration of CO or iron failed to induce cell death. Conclusions-These results demonstrate that overexpression of HO-1 or the exogenous administration of biliverdin or bilirubin stimulates SMC apoptosis. Adenovirus-mediated transfer of the HO-1 gene may provide a novel therapeutic approach in treating occlusive vascular disease. C1 Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX USA. Baylor Coll Med, Dept Pharmacol, Houston, TX USA. RP Durante, W (reprint author), Houston VA Med Ctr, Bldg 109,Rm 130,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL-59976] NR 33 TC 111 Z9 125 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 2002 VL 105 IS 1 BP 79 EP 84 DI 10.1161/hc0102.101369 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509GF UT WOS:000173137400016 PM 11772880 ER PT J AU Refaai, MA Nguyen, PN Steffensen, TS Evans, RJ Cluette-Brown, JE Laposata, M AF Refaai, MA Nguyen, PN Steffensen, TS Evans, RJ Cluette-Brown, JE Laposata, M TI Liver and adipose tissue fatty acid ethyl esters obtained at autopsy are postmortem markers for premortem ethanol intake SO CLINICAL CHEMISTRY LA English DT Article ID RECENT ALCOHOL-CONSUMPTION; METABOLISM; BLOOD; ABUSE AB Background: Fatty acid ethyl esters (FAEEs) are nonoxidative ethanol metabolites that have been implicated as mediators of alcohol-induced organ damage. FAEEs are detectable in the blood after ethanol ingestion, and on that basis have been proposed as markers of ethanol intake. Because blood is not always available at autopsy, in this study we quantified FAEEs in human liver and adipose tissue as potential postmortem markers of premortem ethanol intake. Methods: Twenty-four sets of samples were collected at the Massachusetts State Medical Examiner's Office, and 7 sets of samples were obtained from the Pathology Department of Massachusetts General Hospital. Samples of liver and adipose tissue were collected at autopsy, and FAEEs were isolated and quantified from these organs as mass per gram of wet weight. Postmortem analysis of blood involved assessment for ethanol and other drugs. Results: The study shows a substantial difference in FAEE concentrations in liver and adipose tissue of patients with detectable blood ethanol at the time of autopsy vs those with no detectable blood ethanol, who were either chronic alcoholics or social drinkers. In addition, a specific FAEE, ethyl arachidonate, was found at concentrations >200 pmol/g almost exclusively in the liver and adipose tissue of individuals with detectable blood ethanol at the time of death, providing an additional FAEE-related marker for prior ethanol intake. Conclusions: The mass of FAEEs in liver and adipose tissue and the presence of ethyl arachidonate can serve as postmortem markers of premortem ethanol intake when no blood sample can be obtained. (C) 2002 American Association for Clinical Chemistry. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 22 TC 40 Z9 42 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2002 VL 48 IS 1 BP 77 EP 83 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 505VU UT WOS:000172936900010 PM 11751541 ER PT J AU Metlay, JP Singer, DE AF Metlay, JP Singer, DE TI Outcomes in lower respiratory tract infections and the impact of antimicrobial drug resistance SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE antimicrobial; mortality; morbidity; outcome; pneumonia; resistance; patient outcomes; cohort studies ID COMMUNITY-ACQUIRED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; STREPTOCOCCUS-PNEUMONIAE; PNEUMOCOCCAL PNEUMONIA; ACUTE EXACERBATIONS; PATIENT-OUTCOMES; MEDICAL OUTCOMES; ELDERLY PATIENTS; PENICILLIN; THERAPY AB Numerous published studies have documented the rapid rise in antimicrobial drug resistance among common respiratory pathogens, particularly Streptococcus pneumoniae. Yet, surprisingly few studies have evaluated the impact of these in vitro findings on clinical outcomes. Outcomes research is the measurement of the impact of illness and the effect of treatment on clinically relevant end-points. Studies of patients with community-acquired pneumonia have established certain expected rates of outcomes, including mortality, clinical complications, and time to resolution of symptoms. Recent studies have identified specific processes of care and treatment choices that have an impact upon these outcomes. However, there are no well-controlled studies that provide definitive estimates of the magnitude of the impact of antimicrobial therapy on these outcomes for patients with community-acquired pneumonia or other respiratory tract infections, such as acute exacerbations of chronic bronchitis. Most studies of the impact of drug resistance on outcomes for patients with respiratory tract infections have focused on the impact of beta-lactam drug resistance on outcomes for patients with community-acquired pneumococcal pneumonia. In general, these studies have demonstrated that outcomes are not affected by current levels of drug resistance, but most studies are hampered by small sample size, inability to control adequately for severity of illness and concordance of therapy, and inclusion of few subjects with high-level drug resistance. Additional studies are urgently needed to assess better whether the current empiric treatment guidelines are adequate or will need to be adjusted as patterns of resistance continue to evolve. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Metlay, JP (reprint author), Univ Penn, Sch Med, Vet Affairs Med Ctr, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 35 TC 41 Z9 41 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PY 2002 VL 8 SU 2 BP 1 EP 11 DI 10.1046/j.1469-0691.8.s.2.4.x PG 11 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 609BY UT WOS:000178883800004 PM 12427205 ER PT J AU Robbins, JH Kraemer, KH Merchant, SN Brumback, RA AF Robbins, JH Kraemer, KH Merchant, SN Brumback, RA TI Adult-onset xeroderma pigmentosum neurological disease - observations in an autopsy case SO CLINICAL NEUROPATHOLOGY LA English DT Article DE xeroderma pigmentosum; DNA repair; primary neuronal degeneration; sensorineural hearing loss; cochlea ID DEFECTIVE-DNA REPAIR; CACCHIONE SYNDROME; GROUP-C; NEURODEGENERATION; ABNORMALITIES; PATHWAY; CELLS AB Xeroderma pigmentosum (XP) is an inherited disease with defective DNA repair. Patients develop skin cancer because of unrepaired DNA damage produced by the ultraviolet radiation (UV) in sunlight. Many XP children also develop XP neurological disease (ND), consisting of sensorineural hearing loss (SNHL) and a primary neuronal degeneration of the central and peripheral nervous systems. Since the harmful UV in sunlight cannot reach the nervous system, the cause of the death of XP neurons has been hypothesized to result from the inability to repair their DNA that has been damaged by endogenous metabolites. Progressive XP ND originating in an adult has been identified in only a single case. Although clinically asymptomatic at the age of 47 years, the patient had audiometric evidence of a developing mild SNHL together with elicited signs and electrophysiologic evidence of a peripheral neuropathy. She died of metastatic endocervical adenocarcinoma at 49 years of age. We describe here the neuropathological findings in this patient, including examination of the inner ear. Despite clinical evidence of SNHL, there were no anatomic abnormalities of the inner ear. However, the dorsal root ganglia (DRG) showed ongoing neuronal loss. Our findings indicate that XP ND originating in this adult is, like XP ND in children, a primary neuronal degeneration that manifests first in the peripheral nervous system. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Creighton Univ, St Joseph Hosp, Sch Med, Dept Pathol, Omaha, NE USA. RP Robbins, JH (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Brumback, Roger/A-2404-2008 FU Intramural NIH HHS [Z01 BC004517-31] NR 37 TC 19 Z9 19 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0722-5091 J9 CLIN NEUROPATHOL JI Clin. Neuropathol. PD JAN-FEB PY 2002 VL 21 IS 1 BP 18 EP 23 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 518FY UT WOS:000173657000005 PM 11846040 ER PT J AU Gerard, SK Cavalieri, RR AF Gerard, SK Cavalieri, RR TI I-123 diagnostic thyroid tumor whole-body scanning with imaging at 6, 24, and 48 hours SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE diagnostic imaging; I-123; I-131; thyroid cancer ID CANCER PATIENTS; RADIOIODINE UPTAKE; I-131 THERAPY; DOSE I-131; CARCINOMA; ABLATION; REMNANTS AB Purpose: The use of I-123 in lieu of I-131 for diagnostic whole-body thyroid tumor scanning (DxRal) in patients with differentiated thyroid cancer obviates the risk for stunning and affords significantly improved image quality. Because of the shorter half-life (13 hours) of I-123, images have been acquired primarily 6 or 24 hours after injection, potentially decreasing the sensitivity for detecting weakly avid thyroid tumor or remnant. Materials and Methods: The authors evaluated the use of 111 1to 185 MBq (3 to 5 mCi) I-123 for DxRal under withdrawal conditions, imaging at 6, 24, and, in most cases, 48 hours. DxRal with I-123 was compared in 13 evaluations performed in 10 patients, with post-I-131 treatment scans acquired early (2 to 3 days) and late (7 to 10 days) in all cases but one. Results: Of 37 sites of tumor or remnant identified in post-treatment scans, 26 were found in the DxRal I-123 scan (sensitivity, 70%). Of the 11 sites missed by I-123, 7 were seen only in the late post-treatment scans. Therefore, the sensitivity of I-123 imaging compared with the early post-I-131 treatment scans was 26 of 30, or 86.7%. In 10 cases, 48-hour I-123 imaging was attempted, yielding images of acceptable quality in eight of them. Lesion identification was improved on the 48-hour images; in one case, this allowed the identification of a site of tumor recurrence that was confirmed positive on the I-131 post-treatment scan. Conclusions: I-123 doses of 111 to 185 MBq for DxRal provide acceptable levels of sensitivity overall and may permit 48-hour imaging for improved detection of weakly avid tumor or remnant without any risk for "stunning." C1 San Francisco VA Med Ctr, Nucl Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Gerard, SK (reprint author), San Francisco VA Med Ctr, Nucl Med Sect, Nucl Med 115,4150 Clement St, San Francisco, CA 94121 USA. NR 29 TC 34 Z9 34 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JAN PY 2002 VL 27 IS 1 BP 1 EP 8 DI 10.1097/00003072-200201000-00001 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 519GN UT WOS:000173717400001 PM 11805475 ER PT J AU Fischman, AJ Alpert, NM Rubin, RH AF Fischman, AJ Alpert, NM Rubin, RH TI Pharmacokinetic imaging - A noninvasive method for determining drug distribution and action SO CLINICAL PHARMACOKINETICS LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE SPECTROSCOPY; F-18 LABELED FLUCONAZOLE; LIVING HUMAN-BRAIN; DOPAMINE TRANSPORTER AVAILABILITY; MUSCARINIC CHOLINERGIC RECEPTOR; HEALTHY-HUMAN SUBJECTS; HUMAN COCAINE ADDICTS; IN-VIVO; BENZODIAZEPINE RECEPTORS AB Advances in positron emission tomography (PET), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS), and the ability to label a wide variety of compounds for in vivo use in humans, have created a new technology for making precise physiological and pharmacological measurements. Due to the noninvasive nature of these approaches, repetitive and/or continuous measurements have become possible, Thus far, these techniques have been primarily used for one-time assessments of individuals. However, experience suggests that a major use of this technology will be in the evaluation of new drug therapies. Already, these techniques have been used to measure precisely and noninvasively the pharmacokinetics of a variety of antimicrobial, antineoplastic and CNS agents. In the case of CNS drugs, imaging techniques (particularly PET) have been used to define the classes of neuroreceptors with \N hich the drug interacts. The physiololgical, pharmacological and biochemical measurements that can be performed noninvasively using modern imaging techniques can greatly facilitate the evaluation of new therapies. These measurements are most likely to be useful during drug development in preclinical studies and in phase I/II human Studies. Preclinically, new drug,,, can be precisely compared with standard therapies. or a series of analogues can he screened for further development on the basis of performance in animal models. In Phase I/II, imaging measurements can he combined with classical pharmacokinetic data to establish optimal administration, schedules, evaluate the utility of interventions in specific clinical situations. and aid in the design of Phase III trials. C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard MIT, Ctr Expt Pharmacol & Therapeut, Div Hlth Sci & Technol, Cambridge, MA USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. NR 97 TC 53 Z9 55 U1 1 U2 9 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2002 VL 41 IS 8 BP 581 EP 602 DI 10.2165/00003088-200241080-00003 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 581MX UT WOS:000177297100003 PM 12102642 ER PT J AU Bauer, KA AF Bauer, KA TI Fondaparinux sodium - The first selective factor Xa inhibitor: Mechanism of action and pharmacokinetics in humans - Foreword SO CLINICAL PHARMACOKINETICS LA English DT Editorial Material C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Bauer, KA (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2002 VL 41 SU 2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 603ZF UT WOS:000178590600001 ER PT J AU Vielhaber, A Homel, P Gold, E Malamud, S Blum, RH Portenoy, RK Kornblith, AB AF Vielhaber, A Homel, P Gold, E Malamud, S Blum, RH Portenoy, RK Kornblith, AB TI What is measured by the schedule for the evaluation of individual quality of life-direct weighting? SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract C1 Beth Israel Med Ctr, New York, NY 10003 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2002 VL 24 SU B MA 33 BP 44 EP 45 DI 10.1016/S0149-2918(02)85120-7 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550CF UT WOS:000175485500035 ER PT J AU Torosian, M O'Shaughnessy, J Parker, LM Vogel, C AF Torosian, M O'Shaughnessy, J Parker, LM Vogel, C TI Fulvestrant: Clinical application of an estrogen receptor downregulator SO CLINICAL THERAPEUTICS LA English DT Editorial Material ID ADVANCED BREAST-CANCER; FIRST-LINE THERAPY; POSTMENOPAUSAL WOMEN; TAMOXIFEN; ANASTROZOLE C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. US ONcol, Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP O'Shaughnessy, J (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2002 VL 24 SU A BP A31 EP A40 DI 10.1016/S0149-2918(02)85033-0 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 529VN UT WOS:000174321700004 PM 11911508 ER PT J AU Parker, LM AF Parker, LM TI Sequencing of hormonal therapy in postmenopausal women with metastatic breast cancer SO CLINICAL THERAPEUTICS LA English DT Article DE sequencing hormonal therapies; metastatic breast cancer; aromatase inhibitors; tamoxifen; estrogen receptor antagonists ID MEGESTROL-ACETATE; PHASE-III; RANDOMIZED TRIAL; MEDROXYPROGESTERONE ACETATE; ENDOCRINE THERAPIES; CROSS-OVER; FIRST-LINE; TAMOXIFEN; AMINOGLUTETHIMIDE; CARCINOMA AB Background: Hormonal therapy (HT) is an important consideration in the management of postmenopausal women with metastatic breast cancer. Despite the fact that the advanced-stage disease is virtually incurable, HTs can offer patients disease control equivalent to that of chemotherapy, but with improved quality of life (QOL). Knowledge of the estrogen and progesterone receptor status, as well as other clinical factors, allows for selection of patients who are most likely to benefit from HT. Disease that becomes refractory to an initial HT may respond to another agent or class of HTs. Thus, HTs are generally administered sequentially, delaying the need for cytotoxic chemotherapy, which often reduces QOL. Optimal sequencing is thus one of the more important facets of HT. Prior to the release of a number of newer agents, tamoxifen had been considered as initial HT. At present, more agents exist, including the aromatase inhibitors, progestins, and the estrogen receptor antagonist fulvestrant. Objective: This article reviews key trials evaluating the use of sequential HTs. Methods: Articles were identified for inclusion in this manuscript through the following searches, limited to English-language publications: MEDLINE (mid 1960s to January 2002), American Society of Oncology abstracts (1997-2001), and San Antonio Breast Cancer Symposium abstracts (2001 and 2002). The following search terms were used: breast cancer hormonal therapies, tamoxifen, toremifene, letrozole, anastrozole, exemestane, megestrol acetate, fulvestrant, and ICI 182,780. Results: Results of Phase III studies have shown many of these agents to be equivalent or superior to tamoxifen and can be used initially to treat patients who either have failed tamoxifen therapy or may be unable to tolerate some of the toxicities associated with tamoxifen. For example, the aromatase inhibitors have been shown to be highly active and tolerable in postmenopausal women with breast cancer who have failed tamoxifen therapy or who are naive to HT. Other clinical trials have demonstrated the efficacy of fulvestrant in patients with metastatic breast cancer who are tamoxifen-resistant, and have shown fulvestrant to be at least as effective as anastrozole in tamoxifen-resistant patients. Conclusions: Although the optimum sequence of HTs remains controversial, using the newer agents as initial or subsequent therapy should improve QOL and may improve overall survival. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Parker, LM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St,D1210, Boston, MA 02115 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2002 VL 24 SU C BP C43 EP C57 DI 10.1016/S0149-2918(02)85160-8 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 571DW UT WOS:000176700400004 PM 12117075 ER PT J AU Fishman, C Mihm, MC Sober, AJ AF Fishman, C Mihm, MC Sober, AJ TI Diagnosis and management of Nevi and cutaneous melanoma in infants and children SO CLINICS IN DERMATOLOGY LA English DT Article ID ACQUIRED MELANOCYTIC NEVI; MALIGNANT-MELANOMA; DYSPLASTIC NEVI; PRONE FAMILIES; CHILDHOOD MELANOMA; XERODERMA-PIGMENTOSUM; PREPUBERTAL CHILDREN; VANCOUVER MOLE; SKIN-CANCER; HIGH-RISK C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Fishman, C (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St Bartlett Hall 622, Boston, MA 02114 USA. NR 55 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JAN-FEB PY 2002 VL 20 IS 1 BP 44 EP 50 AR PII S0738-081X(01)00227-9 DI 10.1016/S0738-081X(01)00227-9 PG 7 WC Dermatology SC Dermatology GA 527ZM UT WOS:000174218300008 PM 11849894 ER PT J AU Tarsy, D Baldessarini, RJ Tarazi, FI AF Tarsy, D Baldessarini, RJ Tarazi, FI TI Effects of newer Antipsychotics on extrapyramidal function SO CNS DRUGS LA English DT Review ID NEUROLEPTIC MALIGNANT SYNDROME; ADVANCED PARKINSONS-DISEASE; INDUCED TARDIVE-DYSKINESIA; DRUG-INDUCED PSYCHOSIS; TREATMENT-RESISTANT SCHIZOPHRENIA; D-2 RECEPTOR OCCUPANCY; LEWY BODY DEMENTIA; DOUBLE-BLIND; ATYPICAL ANTIPSYCHOTICS; CLOZAPINE TREATMENT AB Following acceptance of clozapine as a superior antipsychotic agent with low risk of adverse extrapyramidal syndromes (EPS), such as dystonia, parkinsonism, akathisia or tardive dyskinesia, several novel antipsychotic drugs have been developed with properties modelled on those of clozapine. Though generally considered 'atypical' in their relatively low risk of inducing EPS, these agents vary considerably in their pharmacology and impact on neurological functioning. Although few comparative data are available, the atypical antipsychotics can be tentatively ranked by EPS risk (excluding akathisia and neuroleptic malignant syndrome) in the following order: clozapine < quetiapine < olanzapine = ziprasidone. At higher doses, risperidone is ranked with a higher EPS risk than olanzapine and ziprasidone, but its risk of EPS is lower with lower doses. In general, this ranking is inversely related to antidopaininergic (D-2 receptor) potency. The high antiserotonergic (5-HT2A receptor) potency of risperidone, clozapine, ziprasidone and olanzapine, but not quetiapine, as well as the antimuscarinic activity of olanzapine and clozapine may also limit EPS. For the treatment of psychotic reactions to dopamine agonist therapy in Parkinson's disease, clozapine is both effective and relatively well tolerated; quetiapine may be tolerated, olanzapine is not well tolerated, risperidone is poorly tolerated, and amisulpride and ziprasidone have not been well evaluated. Clozapine, perhaps because of its anticholinergic activity, can reduce parkinsonian tremor. It is useful for ongoing psychosis with tardive dyskinesia, especially for dystonic features. No atypical antipsychotic is clearly effective for motor abnormalities in Huntington's disease or Tourette's syndrome, and the effect of these drugs on other neurological disorders have been well evaluated in only small numbers of patients. In summary, with the exception of clozapine, and perhaps quetiapine, atypical antipsychotics have brought only relative avoidance of EPS, strongly encouraging continued searches for novel antipsychotic agents. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Boston, MA 02114 USA. RP Tarsy, D (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. FU NIMH NIH HHS [MH-47370] NR 238 TC 177 Z9 181 U1 7 U2 13 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2002 VL 16 IS 1 BP 23 EP 46 DI 10.2165/00023210-200216010-00003 PG 24 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 522KL UT WOS:000173895100003 PM 11772117 ER PT J AU Henderson, DC AF Henderson, DC TI Atypical antipsychotic-induced diabetes mellitus - How strong is the evidence? SO CNS DRUGS LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; SERUM TRIGLYCERIDE LEVELS; INDUCED WEIGHT-GAIN; SCHIZOPHRENIC-PATIENTS; RISPERIDONE TREATMENT; CLOZAPINE TREATMENT; OLANZAPINE TREATMENT; INSULIN-SECRETION; PC12 CELLS; KETOACIDOSIS AB Atypical antipsychotics offer significant improvements over older, conventional antipsychotic agents. However, recently the newer agents have been linked to medical morbidity including hyperglycaemia, diabetes mellitus, bodyweight gain and abnormal lipid levels. Even more concerning, because of a significant risk of death, there have been numerous case reports of patients treated with clozapine or olanzapine developing diabetic ketoacidosis shortly after initiation of the drug. Much of the information concerning the medical morbidity of diabetes mellitus is based on case reports, retrospective chart reviews, naturalistic studies and cross-sectional studies. While definitive studies have yet to be reported, mounting evidence suggests that the atypical antipsychotic agents, particularly clozapine and olanzapine, may significantly impair glucose metabolism and increase the risk of diabetes in patients with schizophrenia. Diabetic ketoacidosis, although it appears to be uncommon, is of great concern secondary to the risk of death. Patients treated with atypical antipsychotic agents should be routinely screened for diabetes and other metabolic abnormalities including raised lipid levels. Patients with risk factors for diabetes should be monitored more closely. Reports and clinical experience suggest that in a case of atypical antipsychotic-associated diabetes or diabetic ketoacidosis, discontinuation of the antipsychotic agent may result in complete resolution of the hyperglycaemia and diabetes. C1 Massachusetts Gen Hosp, Freedom Trail Clin, Psychot Disorders & Schizophrenia Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Massachusetts Gen Hosp, Freedom Trail Clin, Psychot Disorders & Schizophrenia Res Program, 25 Staniford St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066] NR 107 TC 111 Z9 116 U1 2 U2 5 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2002 VL 16 IS 2 BP 77 EP 89 DI 10.2165/00023210-200216020-00001 PG 13 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 523FY UT WOS:000173944400001 PM 11825099 ER PT J AU Kelleher, JP Centorrino, F Albert, MJ Baldessarini, RJ AF Kelleher, JP Centorrino, F Albert, MJ Baldessarini, RJ TI Advances in atypical antipsychotics for the treatment of schizophrenia - New formulations and new agents SO CNS DRUGS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SCHIZOAFFECTIVE DISORDER; ACUTE EXACERBATION; DOUBLE-BLIND; ZIPRASIDONE; HALOPERIDOL; RISPERIDONE; CLOZAPINE; OPC-14597; DOPAMINE AB Innovation in atypical antipsychotic agents continues with new preparations of available drugs as well as novel agents. In this article, we provide an update on these novel products by reviewing information from a computerised literature search, recent abstracts and discussions with industry representatives. A generic formulation of clozapine is now available. It may be less well absorbed and/or less effective than Clozaril(R)(1), although evidence is conflicting. A fatty acid amide derivative of clozapine is in early development. A liquid formulation of risperidone is currently available, which may be a useful treatment for psychotic agitation as well as a preferable alternative to tablets for some patients. A depot formulation is in development for the long-term management of psychosis. An orally disintegrating tablet formulation of olanzepine is a useful alternative to standard tablets, A short-acting injectable formulation of the drug is in development for psychotic agitation. Sachets and slow-release formulations of quetiapine are in development. Ziprasidone, a recently launched agent, is available in tablet form for schizophrenia/schizoaffective disorder, psychotic depression and mania. A short-acting injectable formulation is in development for psychotic agitation. Aripiprazole (tablets) and iloperidone (tablets and depot injection) are two antipsychotics in development for schizophrenia/schizoaffective disorder (available information regarding iloperidone is very limited). These new formulations and agents should broaden options for the treatment of psychosis. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. RP Kelleher, JP (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-43732] NR 55 TC 45 Z9 48 U1 0 U2 6 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2002 VL 16 IS 4 BP 249 EP 261 DI 10.2165/00023210-200216040-00004 PG 13 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 549LC UT WOS:000175444500004 PM 11945108 ER PT J AU Baldessarini, RJ AF Baldessarini, RJ TI Treatment research in bipolar disorder - Issues and recommendations SO CNS DRUGS LA English DT Article ID DOUBLE-BLIND; MAINTENANCE TREATMENT; LITHIUM-CARBONATE; SUICIDE RISK; I DISORDER; PLACEBO; MANIA; DIVALPROEX; EFFICACY; TRIALS AB Bipolar (manic-depressive) disorder is one of the most common of the severe mental illnesses. Officially recognised forms comprise type I (with mania), type II (with hypomania), cyclothymia and a rapid-cycling subtype. International lifetime prevalence estimates are 1 to 5% of the general population, and bipolar disorder accounts disproportionately for idiopathic psychoses. Psychiatric and substance-abuse comorbidities are common complications, and mortality rates are increased as a result of high suicidal risks, accidents, complications of substance abuse and increased fatality of stress-sensitive medical illnesses. Complex and labile symptomatic presentations, a tendency for patients to deny illness and reject treatment, and diagnostic heterogeneity severely complicate the design, conduct and interpretation of experimental treatment trials in bipolar disorder. Progress in the short-term treatment of mania with certain antiepileptic drugs and atypical antipsychotic agents has advanced greatly in recent years; however, long-term treatment trials other than with lithium remain rare, as are studies of type II disorder, bipolar depression and mixed states, and there is limited information on treatment effectiveness against comorbidity, dysfunction and mortality. There is a growing realisation that bipolar disorder represents a major, largely unmet, international public health challenged and that innovative methods for carrying out reliable and generalisable long-term pharmacological treatment trials, alone and in combination with cost-effective psychosocial and rehabilitative interventions, are urgently required. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02478 USA. NR 51 TC 40 Z9 42 U1 5 U2 5 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2002 VL 16 IS 11 BP 721 EP 729 DI 10.2165/00023210-200216110-00001 PG 9 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 610NF UT WOS:000178966000001 PM 12383028 ER PT S AU Pierce, MC Park, BH Cense, B Shishkov, MS de Boer, JF AF Pierce, MC Park, BH Cense, B Shishkov, MS de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Simultaneous intensity, birefringence and how measurements using high-speed fiber-based optical coherence tomography SO COHERENCE DOMAIN OPTICAL METHODS IN BIOMEDICAL SCIENCE AND CLINICAL APPLICATIONS VI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods in Biomedical Science and Clinical Applications VI CY JAN 21-23, 2002 CL SAN JOSE, CA SP SPIE ID VIVO HUMAN SKIN; BLOOD-FLOW; DOPPLER TOMOGRAPHY; BIOLOGICAL TISSUE AB Recent extensions to conventional OCT imaging include polarization-sensitive optical coherence tomography (PS-OCT) and optical Doppler tomography (ODT), enabling further information to be acquired in addition to tissue structure. We demonstrate here that structure, birefringence and blood flow measurements may be carried out simultaneously, using both techniques of polarization-sensitive OCT and phase-resolved ODT. Images of in vivo human skin acquired with a high-speed fiber-based system are presented. The concurrent processing of data is performed with no penalty to signal-to-noise ratio, and without degradation of either the individual structure, birefringence or flow images. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 18 TC 1 Z9 1 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 0-8194-4358-1 J9 P SOC PHOTO-OPT INS PY 2002 VL 4619 BP 171 EP 179 DI 10.1117/12.470480 PG 9 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BU92Q UT WOS:000177418300027 ER PT J AU Jain, RK AF Jain, RK TI Angiogenesis and lymphangiogenesis in tumors: Insights from intravital microscopy SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitiative Biology CY 2002 CL COLD SPRING HARBOR, NEW YORK SP Aventis Pharma AG, Bristol Mayers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Abbott Lab, Amersham Biosci Inc, Amgen Inc, Appl Biosyst, Bio Ventures Inc, Chugai Pharmaceut Co Ltd, Cogene Bio Tech Ventures Ltd, Diagnost Products Corp, Forest Lab, Genentech Inc, Hoffmann Rache Inc, Johnson & Johnson Pharmaceut, Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Merck Res Lab, New England BioLab Inc, OSI Pharmaceut Inc, Pall Corp, Pharmacia Corp, ResGen Inc, Schering Plough Res Inst, Wyeth Genet Inst ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; IN-VIVO MEASUREMENT; LYMPHATIC METASTASIS; SOLID TUMORS; HOST MICROENVIRONMENT; NEOPLASTIC TISSUES; GENE-EXPRESSION; FACTOR VEGF; VESSELS C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L steele Lab, Boston, MA 02114 USA. NR 59 TC 20 Z9 22 U1 0 U2 0 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 2002 VL 67 BP 239 EP 248 DI 10.1101/sqb.2002.67.239 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 694NM UT WOS:000183780700031 PM 12858546 ER PT J AU MacRae, CA Fishman, MC AF MacRae, CA Fishman, MC TI Zebrafish: The complete cardiovascular compendium SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitiative Biology CY 2002 CL COLD SPRING HARBOR, NEW YORK SP Aventis Pharma AG, Bristol Mayers Squibb Co, Eli Lilly & Co, GlaxoSmithKline, Novartis Pharma AG, Pfizer Inc, Abbott Lab, Amersham Biosci Inc, Amgen Inc, Appl Biosyst, Bio Ventures Inc, Chugai Pharmaceut Co Ltd, Cogene Bio Tech Ventures Ltd, Diagnost Products Corp, Forest Lab, Genentech Inc, Hoffmann Rache Inc, Johnson & Johnson Pharmaceut, Res & Dev L L C, Kyowa Hakko Kogyo Co Ltd, Merck Res Lab, New England BioLab Inc, OSI Pharmaceut Inc, Pall Corp, Pharmacia Corp, ResGen Inc, Schering Plough Res Inst, Wyeth Genet Inst ID HOLT-ORAM-SYNDROME; NEUREGULIN RECEPTOR; CARDIAC DEVELOPMENT; PACEMAKER CURRENT; HEART-RATE; MUTATIONS; VERTEBRATE; CARDIOMYOPATHY; GRIDLOCK; SCREENS C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 35 TC 7 Z9 7 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 2002 VL 67 BP 301 EP 307 DI 10.1101/sqb.2002.67.301 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 694NM UT WOS:000183780700038 PM 12858553 ER PT J AU Murphy, JM Nierenberg, AA Monson, RR Laird, NM Sobol, AM Leighton, AH AF Murphy, JM Nierenberg, AA Monson, RR Laird, NM Sobol, AM Leighton, AH TI Self-disparagement as feature and forerunner of depression: Findings from the Stirling County Study SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PSYCHIATRIC-DISORDERS; PRODROMAL SYMPTOMS; GENERAL-POPULATION; SLEEP DISTURBANCE; MAJOR DEPRESSION; ANXIETY; DIAGNOSIS; PERSPECTIVE; PRECURSORS; PREVALENCE AB Sleep disturbance has attracted considerable attention as an early indicator of depression. However, three epidemiologic investigations have shown psychological symptoms, such as self-disparagement, to be stronger predictors. This report examines the depressive symptoms commonly assessed in modern epidemiologic surveys and estimates the generalizability of this information using data from the Stirling County Study, a long-term epidemiologic investigation of psychiatric disorders. The Diagnostic Interview Schedule (DIS) was used to gather information about depression, defined as major depressive episode (MDE) and/or dysthymic disorder (DysD). A sample of 1,396 adults representing Stirling County in 1992 served to assess the prevalence of the different types of depressive symptoms and to investigate the associations between symptoms and lifetime diagnoses of MDE/DysD. A cohort of 489 follow-up subjects who were interviewed twice in the early part of the 1990s was used to examine the associations between baseline symptoms and subsequent incidence of MDE/ DysD. Both "symptom groups" (such as appetite or psychomotor disturbances) and "Individual symptoms" (such as weight gain or restlessness) were investigated. About one third of the representative sample had experienced the diagnostically required symptoms of "sadness" or "loss of pleasure," but many lacked sufficient other symptomatology to be diagnosed as depressed. Several of the symptom groups bore a different relationship to diagnosis than did the individual symptoms. Among the latter, "feeling worthless" and "having trouble concentrating" exhibited the strongest associations to diagnosis in the representative sample. The symptoms of "wanting to die" and "feeling worthless" were the most predictive of future depression in the twice-interviewed cohort. Thus, this study supports evidence from other epidemiologic studies that psychological symptoms are important in the prodromal phase of depression. Sleep disturbance, especially insomnia, cannot be ignored since it is a prominent manifestation of depression but it appears not to have as high specificity as some of the other symptoms. An exclusive focus on the symptom groups, as used to count symptoms according to diagnostic criteria, may obscure useful information about associations between individual symptoms and diagnosis. Feelings of personal inadequacy deserve particular attention in the population at large because they are strongly associated with lifetime diagnoses and forecast the incidence of depression when people are followed over time. Copyright (C) 2002 by WB. Saunders Company. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 4J3, Canada. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 9155, Charlestown, MA USA. FU NIMH NIH HHS [MH 39576] NR 44 TC 10 Z9 10 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2002 VL 43 IS 1 BP 13 EP 21 DI 10.1053/comp.2002.29842 PG 9 WC Psychiatry SC Psychiatry GA 511RF UT WOS:000173278800003 PM 11788914 ER PT S AU Zietman, AL Smith, CT AF Zietman, AL Smith, CT BE Wiegel, T Heicappell, R Miller, K Hinkelbein, W TI Neoadjuvant androgen suppression and external beam radiation therapy SO CONTROVERSIES IN URO-ONCOLOGY SE FRONTIERS OF RADIATION THERAPY AND ONCOLOGY LA English DT Article; Proceedings Paper CT 5th International Symposium on Special Aspects of Radiotherapy CY MAY 11-13, 2000 CL BERLIN, GERMANY SP Freie Univ Berlin, Dept Radiotherapy, Freie Univ Berlin, Dept Urol, Univ Hosp Benjamin Franklin ID PROSTATE-CANCER; HORMONE-THERAPY; IN-VIVO; DEPRIVATION; CARCINOMA; TUMOR; WITHDRAWAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0071-9676 BN 3-8055-7217-4 J9 FRONT RADIAT THER ON JI Front.Radiat.Ther.Oncol. PY 2002 VL 36 BP 87 EP 98 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BT94V UT WOS:000174537800011 PM 11842759 ER PT S AU Zietman, AL AF Zietman, AL BE Wiegel, T Heicappell, R Miller, K Hinkelbein, W TI Radiation, chemotherapy and transurethral surgery: An organ-sparing alternative to the radical cystectomy SO CONTROVERSIES IN URO-ONCOLOGY SE FRONTIERS OF RADIATION THERAPY AND ONCOLOGY LA English DT Article; Proceedings Paper CT 5th International Symposium on Special Aspects of Radiotherapy CY MAY 11-13, 2000 CL BERLIN, GERMANY SP Freie Univ Berlin, Dept Radiotherapy, Freie Univ Berlin, Dept Urol, Univ Hosp Benjamin Franklin ID INVASIVE BLADDER-CANCER; TRANSITIONAL-CELL-CARCINOMA; 5-YEAR FOLLOW-UP; CISPLATIN-BASED CHEMOTHERAPY; COMBINED-MODALITY THERAPY; QUALITY-OF-LIFE; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; PROSPECTIVE TRIAL; PLUS CISPLATIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 58 TC 0 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0071-9676 BN 3-8055-7217-4 J9 FRONT RADIAT THER ON JI Front.Radiat.Ther.Oncol. PY 2002 VL 36 BP 131 EP 146 PG 16 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BT94V UT WOS:000174537800015 PM 11842743 ER PT J AU Wiedemann, HP Arroliga, AC Komara, J Welsh, C Fulkerson, WJ MacIntyre, N Mallatratt, L Sebastian, M Sladen, R Wilcox, C Brower, RG Thompson, D Morris, AH Clemmer, T Davis, R Orme, J Lawton, CB d'Hulst, J Smith, C Gottlieb, J Girod, A Matthay, MA Daniel, B Kallet, R Luce, JM Gryzner, MA Abraham, E Piedalue, F Kalous, D Walberg, C Lockrem, J McIntyre, R Parsons, P Stevens, C Silverman, HJ Corral, W Toews, GB Arnoldi, D Bartlett, RH Dechert, R Watts, C Lanken, PN Anderson, H Finkel, B Hanson, CW Hudson, LD Lee, C Maier, RV Steinberg, KP Wheeler, AP Bernard, G Stone, L Schoenfeld, DA Thompson, BT Ancukiewicz, M Hayden, D Molay, F Ringwood, N Wenzlow, G Bernard, GR Gail, DB Bosken, CH Harabin, A Randall, P Waclawiw, M Paradise, C Dahlberg, S Spragg, RG Boyett, JM Kelley, J Leeper, K Secundy, MG Slutsky, AS Hyers, TM Emerson, SS Garcia, JGN Pingleton, SK Shasby, MD Sibbaid, WJ Abraham, E Parsons, P Matthay, M Steinberg, KP AF Wiedemann, HP Arroliga, AC Komara, J Welsh, C Fulkerson, WJ MacIntyre, N Mallatratt, L Sebastian, M Sladen, R Wilcox, C Brower, RG Thompson, D Morris, AH Clemmer, T Davis, R Orme, J Lawton, CB d'Hulst, J Smith, C Gottlieb, J Girod, A Matthay, MA Daniel, B Kallet, R Luce, JM Gryzner, MA Abraham, E Piedalue, F Kalous, D Walberg, C Lockrem, J McIntyre, R Parsons, P Stevens, C Silverman, HJ Corral, W Toews, GB Arnoldi, D Bartlett, RH Dechert, R Watts, C Lanken, PN Anderson, H Finkel, B Hanson, CW Hudson, LD Lee, C Maier, RV Steinberg, KP Wheeler, AP Bernard, G Stone, L Schoenfeld, DA Thompson, BT Ancukiewicz, M Hayden, D Molay, F Ringwood, N Wenzlow, G Bernard, GR Gail, DB Bosken, CH Harabin, A Randall, P Waclawiw, M Paradise, C Dahlberg, S Spragg, RG Boyett, JM Kelley, J Leeper, K Secundy, MG Slutsky, AS Hyers, TM Emerson, SS Garcia, JGN Pingleton, SK Shasby, MD Sibbaid, WJ Abraham, E Parsons, P Matthay, M Steinberg, KP CA ARDS Clinical Trials Network Natl Heart Lung Blood I Natl I Hlth TI Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; lisofylline; oxidant ID FREE FATTY-ACIDS; PHOSPHATIDIC-ACID; ARDS; MACROPHAGES; VENTILATION; THERAPY; MICE AB Objective; To determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Design: A prospective, randomized, double-blind, placebo-controlled, multicenter study. Setting. Intensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network. Patients. A total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group). Interventions., Patients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing. Measurements and Main Results. The trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure-free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo. Conclusions. In this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS. C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Denver VA Med Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. McKay Dee Hosp, Ogden, UT USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Vanderbilt Univ, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Abraham, E (reprint author), Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Box C272,4200 E 9th Ave, Denver, CO 80262 USA. EM edward.abraham@uchsc.edu RI Slutsky, Arthur/A-6013-2008; Garcia, Joe/E-8862-2010; OI Slutsky, Arthur/0000-0002-6063-3876; Wiedemann, Herbert/0000-0002-4587-4401 NR 30 TC 84 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2002 VL 30 IS 1 BP 1 EP 6 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 513YU UT WOS:000173409400001 ER PT J AU Alston, TA AF Alston, TA TI Stomach gas laboratory in critical care SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE CO2 electrode; CO2 Partial pressure; Lavoisier; phlogiston; regional capnometry; splanchnic perfusion; stomach ID METABOLISM C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2002 VL 30 IS 1 BP 251 EP 252 DI 10.1097/00003246-200201000-00040 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 513YU UT WOS:000173409400040 PM 11902275 ER PT J AU Sheridan, R AF Sheridan, R TI Modulation of types I and II acute phase reactants with insulin-like growth factor-1/binding protein-3 complex in severely burned children SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE muscle catabolism; hypermetabolic response; burns; sepsis; growth factors ID POSTBURN HYPERMETABOLISM; INJURY C1 Massachusetts Gen Hosp, Shriners Burns Hosp, Boston, MA 02114 USA. RP Sheridan, R (reprint author), Massachusetts Gen Hosp, Shriners Burns Hosp, Boston, MA 02114 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2002 VL 30 IS 1 BP 255 EP 256 DI 10.1097/00003246-200201000-00043 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 513YU UT WOS:000173409400043 PM 11902278 ER PT J AU Benjamin, LC Allan, JS Madsen, JC AF Benjamin, LC Allan, JS Madsen, JC TI Cytokines in immunity and allograft rejection SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE cytokines; transplantation; acute rejection; chronic rejection ID RENAL-TRANSPLANT RECIPIENTS; INDIRECT RECOGNITION; INTERFERON-GAMMA; GENE-EXPRESSION; CLASS-I; INDIRECT ALLORECOGNITION; DEFICIENT MICE; CELLS; ALLOPEPTIDES; RECEPTOR AB Cytokines are highly potent regulatory molecules that are secreted by a variety of cells into the local microenvironment. These chemical messengers participate in the activation and regulation of immune function by a variety of mechanisms, including the stimulation and inhibition of cellular proliferation and differentiation. Cytokines also may have chemotactic activity. Six cytokine receptor families have been described, on the basis of their conserved structural features. Many cytokines are classified as proinflammatory cytokines, which promote both innate and adaptive immune responses. Solid-organ transplantation presents several unique challenges to the immune system, and cytokines play an important role in both antigen-dependent and antigen-independent immune recognition. The selective blockade of cytokine-mediated immune responses is a cornerstone of modern immunosuppressive therapy. C1 Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Div Cardiac Surg, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, EDR 105, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL18642, HL54211-04]; NIAID NIH HHS [AI 50157] NR 52 TC 5 Z9 6 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 145 MADISON AVE, NEW YORK, NY 10016 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2002 VL 22 IS 4 BP 269 EP 279 PG 11 WC Immunology SC Immunology GA 660QW UT WOS:000181844700002 PM 12678428 ER PT J AU Todd, R Hinds, PW Munger, K Rustgi, AK Opitz, OG Suliman, Y Wong, DT AF Todd, R Hinds, PW Munger, K Rustgi, AK Opitz, OG Suliman, Y Wong, DT TI Cell cycle dysregulation in oral cancer SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE oral cancer; cell cycle; proliferation; apoptosis; senescence ID TUMOR-SUPPRESSOR GENE; HUMAN PAPILLOMAVIRUS DNA; WILD-TYPE P53; NECK-CANCER; TRANSGENIC MICE; DEPENDENT KINASES; D1 OVEREXPRESSION; RECURRENT HEAD; IN-VIVO; PREMALIGNANT LESIONS AB The dysregulation of the molecular events governing cell cycle control is emerging as a central theme of oral carcinogenesis. Regulatory pathways responding to extracellular signaling or intracellular stress and DNA damage converge on the cell cycle apparatus. Abrogation of mitogenic and anti-mitogenic response regulatory proteins, such as the retinoblastoma tumor suppressor protein (pRB), cyclin D1, cyclin-dependent kinase (CDK) 6, and CDK inhibitors (p21(WAF1/CIP1), P27(KIP1), and p16(INK4a)), occur frequently in human oral cancers. Cellular responses to metabolic stress or genomic damage through p53 and related pathways that block cell cycle progression are also altered during oral carcinogenesis. In addition, new pathways and cell cycle regulatory proteins, such as p12(DOC-1), are being discovered. The multistep process of oral carcinogenesis likely involves functional alteration of cell cycle regulatory members combined with escape from cellular senescence and apoptotic signaling pathways. Detailing the molecular alterations and understanding the functional consequences of the dysregulation of the cell cycle apparatus in the malignant oral keratinocyte will uncover novel diagnostic and therapeutic approaches. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Harvard Univ, Sch Dent Med, Dept Oral Diagnost Sci, Div Oral Pathol, Boston, MA 02115 USA. RP Todd, R (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. OI Munger, Karl/0000-0003-3288-9935 FU NIDCR NIH HHS [P01 DE12467] NR 132 TC 64 Z9 67 U1 0 U2 3 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2002 VL 13 IS 1 BP 51 EP 61 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 556DJ UT WOS:000175833800006 PM 12097237 ER PT J AU Yelick, PC Schilling, TF AF Yelick, PC Schilling, TF TI Molecular dissection of craniofacial development using zebrafish SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE molecular genetics; craniofacial development; zebrafish; ENU mutagenesis ID SERINE/THREONINE KINASE RECEPTOR; DORSOVENTRAL PATTERN-FORMATION; PHARYNGEAL ARCH DEVELOPMENT; NEURAL CREST DEVELOPMENT; GERM-LINE TRANSMISSION; ENDOTHELIN-B RECEPTOR; DANIO-RERIO TELEOSTEI; HOMEOBOX GENES; INSERTIONAL MUTAGENESIS; TOOTH DEVELOPMENT AB The zebrafish, Danio rerio, is a small, freshwater teleost that only began to be used as a vertebrate genetic model by the late George Streisinger in the early 1980s. The strengths of the zebrafish complement genetic studies in mice and embryo-logical studies in avians. Its advantages include high fecundity, externally fertilized eggs and transparent embryos that can be easily manipulated, inexpensive maintenance, and the fact that large-scale mutagenesis screens can be performed. Here we review studies that have used the zebrafish as a model for craniofacial development. Lineage studies in zebrafish have defined the origins of the cranial skeleton at the single-cell level and followed the morphogenetic behaviors of these cells in skeletal condensations. Furthermore, genes identified by random mutational screening have now revealed genetic pathways controlling patterning of the jaw and other pharyngeal arches, as well as the midline of the skull, that are conserved between fish and humans. We discuss the potential impact of specialized mutagenesis screens and the future applications of this versatile, vertebrate developmental model system in the molecular dissection of craniofacial development. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. RP Yelick, PC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pyelick@forsyth.org FU NIDCR NIH HHS [R01 DE013828] NR 143 TC 84 Z9 87 U1 0 U2 11 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2002 VL 13 IS 4 BP 308 EP 322 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 657ZY UT WOS:000181698200001 PM 12191958 ER PT J AU Smith, DJ AF Smith, DJ TI Dental caries vaccines: Prospects and concerns SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE mutans streptococci; secretory IgA; antigen I/II; glucosyltransferase; glucan-binding protein ID SURFACE PROTEIN ANTIGEN; STREPTOCOCCUS-MUTANS GLUCOSYLTRANSFERASE; GLUCAN-BINDING-PROTEIN; TOXIN-B-SUBUNIT; MINOR SALIVARY-GLANDS; SECRETORY IMMUNOGLOBULIN-A; MONKEY MACACA-FASCICULARIS; INDUCIBLE NIRB PROMOTER; ACTIVE-SITE PEPTIDE; CHOLERA-TOXIN AB Dental caries remains one of the most common infectious diseases of mankind. Cariogenic micro-organisms enter the dental biofilm early in life and can subsequently emerge, under favorable environmental conditions, to cause disease. In oral fluids, adaptive host defenses aroused by these infections are expressed in the saliva and gingival crevicular fluid. This review will focus on methods by which mucosal host defenses can be induced by immunization to interfere with dental caries caused by mutans streptococci. The natural history of mutans streptococcal colonization is described in the context of the ontogeny of mucosal immunity to these and other indigenous oral streptococci. Molecular targets for dental caries vaccines are explored for their effectiveness in intact protein and subunit (synthetic peptide, recombinant and conjugate) vaccines in pre-clinical studies. Recent progress in the development of mucosal adjuvants and viable and non-viable delivery systems for dental caries vaccines is described. Finally, the results of clinical trials are reviewed, followed by a discussion of the prospects and concerns of human application of the principles presented. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM dsmith@forsyth.org FU NIDCR NIH HHS [DE/AI-12324, DE-01653, DE-04733] NR 155 TC 50 Z9 54 U1 1 U2 9 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2002 VL 13 IS 4 BP 335 EP 349 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 657ZY UT WOS:000181698200003 PM 12191960 ER PT J AU Sonis, SL AF Sonis, SL TI The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE nuclear factor-kappaB; mucosal injury; anti-neoplastic therapy ID TUMOR-NECROSIS-FACTOR; B TRANSCRIPTION FACTORS; UBIQUITIN-PROTEASOME PATHWAY; GLAND CANCER-CELLS; INDUCED APOPTOSIS; ORAL MUCOSITIS; IONIZING-RADIATION; GENE-EXPRESSION; FACTOR-ALPHA; INFLAMMATORY DISEASES AB Oral mucosal barrier injury (mucositis) is a frequent, painful, serious, dose-limiting toxicity associated with many anti-neoplastic drugs and radiation to the head and neck. Results of recent studies suggest that mucositis is the result of a complex series of interactive biological events that take place in the submucosa and epithelium. The nuclear transcription factor NF-kappaB has been implicated in the control of a broad range of biological responses, the activation of a large number of specific cellular genes, and the determination of the fate of cells exposed to ionizing radiation and anti-neoplastic drugs. Of particular importance to mucositis is the fact that NF-kappaB regulates key elements in the apparent sequence that leads to normal tissue toxicity. Not the least of these is the effect that NF-kappaB activation has on apoptosis. In particular, a paradox exists between the potential pro-apoptotic effect NF-kappaB exerts on normal cells, and the anti-apoptotic and cytoprotective effect it causes in tumor cells. This paper provides a review of the structure and function of NF-kappaB and speculates how its apparent enigmatic effect on normal and tumor cells may occur. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Oral Maxillofacial Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Dent, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sonis, SL (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, 75 Francis St, Boston, MA 02115 USA. NR 87 TC 97 Z9 101 U1 1 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2002 VL 13 IS 5 BP 380 EP 389 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677PB UT WOS:000182815800001 PM 12393757 ER PT J AU Stewart, SA Hahn, WC AF Stewart, Sheila A. Hahn, William C. TI Prospects for Anti-Neoplastic Therapies Based on Telomere Biology SO CURRENT CANCER DRUG TARGETS LA English DT Article AB The maintenance of specialized nucleoprotein structures at the ends of human chromosomes called telomeres is essential for chromosome stability, and plays a fundamental role in the regulation of cellular lifespan. Without new synthesis of telomeres, chromosome ends shorten with progressive cell division, eventually triggering either replicative senescence or apoptosis when telomere length becomes critically short. The regulation of telomerase activity in human cells plays a significant role in the development of cancer. Telomerase is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cell immortalization and in cancers. Recent work has demonstrated that inhibiting or targeting telomerase shows promise as a novel antineoplastic strategy; however, the biology of telomeres and telomerase predict that such approaches will differ in important ways from traditional cytotoxic drug therapies. Understanding telomerase biology may eventually lead to several types of clinically effective, telomerase-based therapies for neoplastic disease. C1 [Stewart, Sheila A.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Hahn, William C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med,Dept Adult Oncol, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu FU Doris Duke Charitable Foundation Clinical Scientist Development Award; NCI Howard Temin Award; Department of Defense New Investigator Award; CaPCURE; American Association for Cancer Research-Anna D. Barker Fellowship FX We thank Dr. Robert Weinberg for helpful discussions and support. WCH is supported in part by a Doris Duke Charitable Foundation Clinical Scientist Development Award, a NCI Howard Temin Award, a Department of Defense New Investigator Award, and a Research Award from CaPCURE. SAS is a Herman and Margaret Sokol Fellow and is supported by the American Association for Cancer Research-Anna D. Barker Fellowship. NR 185 TC 3 Z9 5 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2002 VL 2 IS 1 BP 1 EP 17 DI 10.2174/1568009023334015 PG 17 WC Oncology SC Oncology GA V33XU UT WOS:000209052300001 PM 12188917 ER PT J AU Pardee, AB Li, YZ Li, CJ AF Pardee, Arthur B. Li, You Zhi Li, Chiang J. TI Cancer Therapy with beta-Lapachone SO CURRENT CANCER DRUG TARGETS LA English DT Article AB beta-Lapachone is an ortho naphthoquinone, originally isolated from a tree whose extract has been used medicinally for centuries. Recent investigations suggest its potential application against numerous diseases. Its lethality at micromolar (mu m) concentrations against a variety of cancer cells in culture indicates its potential against tumor growth. A few experiments with positive results have been performed that apply the compound to tumors growing in animals. Particularly promising is the remarkably powerful synergistic lethality between beta-lapachone and taxol against several tumor cell lines implanted into mice; the mice did not appear to be adversely affected. Enhanced lethality of X-rays and alkylating agents to tumor cells in culture was reported when beta-lapachone was applied during the recovery period, because of inhibition of DNA lesion repair. Clinical trials are still to be initiated. The detailed mechanism of cell death induced by beta-lapachone remains for investigation. DNA topoisomerase I was the first biochemical target of beta-lapachone to be discovered, although its role in cell death is not clear. A proposed mechanism of cell death is via activation of a futile cycling of the drug by the cytoplasmic two-electron reductase NAD(P) H: quinone oxidoreductase, also known as NQO1, DT-diaphorase and Xip3. Death of NQO1 expressing cells is prevented by the NQO1 inhibitor dicoumarol, and cells with low NQO1 are resistant. At higher drug concentrations the production of reactive oxygen species (ROS) appears to be responsible. Furthermore, this process is p53- and caspase-independent. Either apoptotic or necrotic cell death can result, as reported in various studies performed under differing conditions. beta-Lapachone is one of a few novel anticancer drugs currently under active investigation, and it shows promise for chemotherapy alone and especially in combinations. C1 [Pardee, Arthur B.] Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binny St, Boston, MA 02115 USA. EM pardee@mbcrr.harvard.edu FU Bruce and Giovanna Ames Foundation; Dana-Farber Cancer Institute FX We thank David A. Boothman for his most valuable and insightful comments and advice regarding this review. This work was supported by the Bruce and Giovanna Ames Foundation and the Dana-Farber Cancer Institute. NR 144 TC 148 Z9 154 U1 0 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PY 2002 VL 2 IS 3 BP 227 EP 242 DI 10.2174/1568009023333854 PG 16 WC Oncology SC Oncology GA V33XW UT WOS:000209052500003 PM 12188909 ER PT J AU Kelly, L Clark, J Gilliland, DG AF Kelly, L Clark, J Gilliland, DG TI Comprehensive genotypic analysis of leukemia: clinical and therapeutic implications SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; IN-SITU HYBRIDIZATION; TEL-AML1 FUSION GENE; PML-RAR-ALPHA; TEL/AML1 FUSION; CRYPTIC T(12-21); LOW-FREQUENCY; AML1 GENE AB Over the past several years, the application of a spectrum of cytogenetic and molecular diagnostic techniques has dramatically improved our understanding of the pathophysiology of leukemia, These techniques include chromosomal translocations visualized by G-banding techniques, fluorescence in-situ hybridization, spectral karyotyping, comparative genomic hybridization, loss of heterozygosity analysis, and characterization of point mutations by DNA sequence analysis. We will review the application of these techniques, update novel findings utilizing these techniques over the past year as they apply to specific leukemias, and review the clinical and therapeutic implications of these findings. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Harvard Univ, Sch Med,Howard Hughes Med Inst, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. RP Gilliland, DG (reprint author), Harvard Univ, Inst Med, 4 Blackfan Circle,Room 418, Boston, MA 02115 USA. NR 120 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JAN PY 2002 VL 14 IS 1 BP 10 EP 18 DI 10.1097/00001622-200201000-00003 PG 9 WC Oncology SC Oncology GA 508EQ UT WOS:000173076100003 PM 11790974 ER PT J AU Sekeres, MA Stone, RM AF Sekeres, MA Stone, RM TI The challenge of acute myeloid leukemia in older patients SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; SOUTHWEST-ONCOLOGY-GROUP; ACUTE NONLYMPHOCYTIC LEUKEMIA; HIGH-DOSE CYTARABINE; REMISSION-INDUCTION CHEMOTHERAPY; ADULT PATIENTS GREATER-THAN-55; PLACEBO-CONTROLLED TRIAL; RANDOMIZED PHASE-III; TREATMENT-OF-CANCER AB Acute myeloid leukemia is a disease predominantly affecting older adults, with a median age at diagnosis of 65 years. Compared with younger adults or children with AML, older adults have a poor prognosis and represent a discrete population in terms of disease features, treatment-related complications, and overall outcome. Management of AML in this population often includes intensive, anthracycline-based chemotherapy, which can effect a 1.5- to 4-month survival advantage compared with nonintensive therapy but at a cost of early deaths, long length of hospital stay, and substantial transfusional support. Nonintensive therapy or palliative care remains an important option for many patients, Aggressive postremission therapy or the use of hematopoietic growth factor support does not appear to improve survival, Future directions include therapies targeted at immunomodulation, at angiogenesis, and in particular against intracellular signals that promote proliferation at the expense of differentiation. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sekeres, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,560 Shields Warren Bldg, Boston, MA 02115 USA. NR 78 TC 37 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JAN PY 2002 VL 14 IS 1 BP 24 EP 30 DI 10.1097/00001622-200201000-00005 PG 7 WC Oncology SC Oncology GA 508EQ UT WOS:000173076100005 PM 11790976 ER PT J AU Polyak, K AF Polyak, K TI Molecular alterations in ductal carcinoma in situ of the breast SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID OLIGONUCLEOTIDE-PRIMED PCR; NIPPLE ASPIRATE FLUID; IN-SITU; GENETIC ALTERATIONS; CANCER; EXPRESSION; DNA; AMPLIFICATION; HYPERMETHYLATION; MICRODISSECTION AB Despite recent improvements in the breast cancer mortality rate, breast cancer remains the most common cancer and the second leading cause of cancer-related deaths in US women, A decreasing trend in mortality rates is caused by advances in early detection and, to a lesser degree, in cancer therapies. With the increased utilization of mammography, one of the earliest detectable breast tumors, ductal carcinoma in situ, has become the most rapidly increasing subset of breast cancers. Contrary to the dramatic improvement in our ability to detect ductal carcinoma in situ, the pathophysiology of this disease is still poorly understood. Many molecular studies have been performed in ductal carcinoma in situ lesions with the aims of identifying genes involved in breast cancer initiation and progression, defining the relation between in situ and invasive carcinomas, and identifying clinically useful markers for breast cancer diagnosis, prognostication, prevention, and treatment. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, 44 Binney St,Room D740C, Boston, MA 02115 USA. NR 38 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JAN PY 2002 VL 14 IS 1 BP 92 EP 96 DI 10.1097/00001622-200201000-00016 PG 5 WC Oncology SC Oncology GA 508EQ UT WOS:000173076100016 PM 11790987 ER PT J AU Otto, MW Hong, JJ Safren, SA AF Otto, MW Hong, JJ Safren, SA TI Benzodiazepine discontinuation difficulties in panic disorder: Conceptual model and outcome for cognitive-behavior therapy SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID ALPRAZOLAM DISCONTINUATION; ANXIETY; AGORAPHOBIA; IMIPRAMINE; DEPENDENCE; ATTACKS; METAANALYSIS; COMBINATION; MAINTENANCE; CHALLENGE AB There is consistent support for the efficacy of cognitive-behavior therapy (CBT) to aid the successful discontinuation of benzodiazepine (BZ) medication in patients with panic disorder, and help these individuals maintain treatment gains while off medication. In this article, we provide a conceptual model for BZ discontinuation difficulties in patients with panic disorder. Outcome studies are reviewed, and are placed in the context of other evidence for the efficacy of CBT in patients with this disorder. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 54 TC 23 Z9 23 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2002 VL 8 IS 1 BP 75 EP 80 DI 10.2174/1381612023396726 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 518HW UT WOS:000173662700006 PM 11812251 ER PT J AU Dell'Italia, LJ Rocic, P Lucchesi, PA AF Dell'Italia, LJ Rocic, P Lucchesi, PA TI Use of angiotensin-converting enzyme inhibitors in patients with diabetes and coronary artery disease SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID PLASMINOGEN-ACTIVATOR INHIBITOR; ISCHEMIC-HEART-DISEASE; SMOOTH-MUSCLE-CELLS; INSERTION-DELETION POLYMORPHISM; LEFT-VENTRICULAR DYSFUNCTION; CARDIOVASCULAR RISK-FACTORS; ACUTE MYOCARDIAL-INFARCTION; FATTY STREAK FORMATION; GROWTH-FACTOR-BETA; TISSUE ANGIOTENSIN C1 Univ Alabama, Birmingham Vet Affairs Med Ctr, Dept Med, Div Cardiovasc Dis, Birmingham, AL USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Birmingham Vet Affairs Med Ctr, Dept Med, Div Cardiovasc Dis, Birmingham, AL USA. RI Lucchesi, Pamela/E-3558-2011 NR 121 TC 7 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0146-2806 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD JAN PY 2002 VL 27 IS 1 BP 6 EP 36 DI 10.1067/med.2002.121580 PG 31 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 520PF UT WOS:000173789700002 PM 11815752 ER PT J AU Ogawa, Y Lee, JT AF Ogawa, Y Lee, JT TI Antisense regulation in X inactivation and autosomal imprinting SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; EMBRYONIC STEM-CELLS; MOUSE XIST GENE; CHROMOSOME INACTIVATION; DOSAGE COMPENSATION; CONTROL ELEMENT; TSIX FUNCTION; PRADER-WILLI; CPG ISLAND; RNA AB The regulation of epigenetic phenomena by elements encoding antisense RNA's is one of the most rapidly emerging themes in mammalian gene expression. Such regulation is epitomized by X chromosome inactivation (XCI) and autosomal imprinting. In XCI, Tsix serves as an antisense regulator of Xist, the silencer element for XCI which itself makes a non-coding transcript. Numerous antisense transcripts have also been discovered in autosomally imprinted loci, including the Igf2r/Air locus, the Prader-Willi/Angelman Syndrome (PWS/AS) locus, and the Beckwith-Wiedemann Syndrome (BWS) locus. How these antisense elements regulate XCI and imprinting remains unsolved. However, various structural and functional similarities among them imply the possibility of shared mechanism. Among the most interesting are the antagonistic relationship between sense and antisense loci and the initiation of antisense transcripts within imprinting centers. This article reviews the latest developments in antisense regulation in XCI and autosomal imprinting and speculates on molecular means by which antisense genes can regulate silencing in mammals. Copyright (C) 2002 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. NR 74 TC 32 Z9 33 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 2002 VL 99 IS 1-4 BP 59 EP 65 DI 10.1159/000071575 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 713RV UT WOS:000184872900009 PM 12900546 ER PT J AU Frohlich, L Liu, Z Beier, DR Lanske, B AF Frohlich, L Liu, Z Beier, DR Lanske, B TI Genomic structure and refined chromosomal localization of the mouse Ptch2 gene SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID SMOOTHENED RECEPTOR COMPLEX; BASAL-CELL CARCINOMA; PATCHED GENE; SONIC HEDGEHOG; CPG ISLANDS; EXPRESSION; SEQUENCES; MEDULLOBLASTOMA; EMBRYOGENESIS; HOMOLOG AB The vertebrate Patched 2 (Ptch2) gene encodes a putative membrane-embedded protein which may have roles in Hedgehog signaling during development and in tumorigenesis. We determined the genomic structure of the mouse Ptch2 gene and show that Ptch2 is composed of 22 exons spanning approximately 18 kb of genomic DNA. The exon-intron boundaries were found to be conserved within the human and mouse Ptch2 genes. Analysis of the 5' flanking region revealed a CpG island, the putative promoter region and the transcriptional start site while a polyadenylation signal as well as a mRNA destabilizing motif were identified in the 3' flanking region. Single-strand conformation polymorphism analysis was used to map mouse Ptch2 to chromosome 4 between the microsatellite markers D4Mit20 and D4Mit334. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Genet, Endocrine Unit, Boston, MA 02114 USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. RP Frohlich, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Genet, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. EM frohlich@helix.mgh.harvard.edu FU NHGRI NIH HHS [HG00951, HG29028] NR 26 TC 2 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2002 VL 97 IS 1-2 BP 106 EP 110 DI 10.1159/000064064 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 607BW UT WOS:000178771400019 PM 12438747 ER PT J AU Preffer, FI Dombkowski, D Sykes, M Yang, YG AF Preffer, FI Dombkowski, D Sykes, M Yang, YG TI Side-population [SP] cells with hematopoietic differentiating capacity circulate in normal adult human blood SO CYTOMETRY LA English DT Meeting Abstract C1 Harvard Med Sch, Massachusetts Gen Hosp, Tranplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PY 2002 SU 11 BP 90 EP 90 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 544VM UT WOS:000175182400213 ER PT J AU Reilly-Smorawski, B Armstrong, AV AF Reilly-Smorawski, B Armstrong, AV TI Bereavement support for couples following death of a baby: Program development and 14-year exit analysis SO DEATH STUDIES LA English DT Article ID INTENSIVE-CARE UNIT; GENDER DIFFERENCES; PARENTAL GRIEF; INFANT-DEATH; CHILD AB Program development, implementation, and a 14-year exit analysis of a bereavement support program for couples whose baby died in the Neonatal Intensive Care Unit (NICU) is presented. A closed, hospital-based, time-limited (12 weeks) format was used. Team leadership was used and 54% of bereaved NICU parents participated. Each group was structured with a 2-week introductory period, open format grief-focused weekly discussions, evaluation in Week 11, and summary session with termination in Week 12. The exit analysis details program strengths, weaknesses, and recommendations. Bereavement support-groups are one part of what we contend should be a comprehensive bereavement program, organized to care for families prior to, during, and after a baby death. A sensitive, spiritually aware, supportive environment should be maintained throughout with relationship building as a cornerstone of the program. C1 Massachusetts Gen Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Reilly-Smorawski, B (reprint author), Massachusetts Gen Hosp, Founders House 440, Boston, MA 02114 USA. NR 16 TC 23 Z9 23 U1 1 U2 4 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PD JAN PY 2002 VL 26 IS 1 BP 21 EP 37 DI 10.1080/07481180210145 PG 17 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 507CC UT WOS:000173008400002 PM 11865881 ER PT J AU Mendez, MF Ghajarania, M Perryman, KM AF Mendez, MF Ghajarania, M Perryman, KM TI Posterior cortical atrophy: Clinical characteristics and differences compared to Alzheimer's disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE posterior cortical atrophy; Alzheimer's disease; visual agnosia; Balint's syndrome; Gerstmann's syndrome ID PROGRESSIVE VISUAL AGNOSIA; BALINTS-SYNDROME; DEMENTIA; ALEXIA; DISCONNECTION; DISTURBANCES; ASSOCIATION; PATHWAYS; PATIENT; VARIANT AB Background. Predominant and progressive complex visual disorders are often due to posterior cortical atrophy (PCA), a rare early-onset dementing syndrome presenting with visual complaints. In clinicopathological studies, PCA is most commonly considered a form of Alzheimer's disease (AD); no prior study has evaluated clinical differences between PCA and AD. Methods: This study identified 15 patients who presented with progressive complex visual disorders and predominant occipitoparietal hypoperfusion on SPECT. These patients were retrospectively compared on clinical variables with 30 patients with clinically probable AD matched for gender, age and duration of illness. Results: The PCA patients presented with alexia, elements of Balint's syndrome, apperceptive visual agnosia, dressing apraxia and environmental disorientation along with elements of Gerstmann's syndrome. Compared to the AD patients, the 15 PCA patients (mean age of onset 58 years, range 51-64) had significantly better verbal fluency, less memory difficulty, more depression and greater insight into their illness but similar familial and apolipoprotein E risk factors. In the PCA patients, MRI often showed occipitoparietal atrophy without detectable mesiotemporal atrophy. Conclusions: PCA is a distinct clinical syndrome and not just AD with prominent visual deficits. Compared to AD controls, PCA patients have better language and memory but more insight and depression and more posterior atrophy on MRI. These results indicate clinical criteria for the diagnosis of PCA and recommend specific interventions such as visual aids and antidepressant medications. Similar risk factors and course suggest that PCA is most commonly an early-onset posteriorly shifted AD variant. Copyright (C) 2002 S. Karger AG, Basel. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Greater Los Angeles Hlthcare Syst, Neurobehav Unit 116AF, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Hlthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 50 TC 153 Z9 162 U1 1 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 2002 VL 14 IS 1 BP 33 EP 40 DI 10.1159/000058331 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 566CM UT WOS:000176409300006 PM 12053130 ER PT B AU Sasaki, H Stashenko, P AF Sasaki, H Stashenko, P BE Ishikawa, T Takahashi, K Maeda, T Suda, H Shimono, M Inoue, T TI Analysis of cytokine-related gene expression in periapical lesions using gene arrays SO DENTIN/PULP COMPLEX LA English DT Proceedings Paper CT International Conference on Dentin/Pulp Complex CY 2001 CL CHIBA, JAPAN SP Tokyo Dent Coll, Chiba Int Convent Ctr, Int Assoc Dent Res AB Gene arrays allow the assessment of the expression of large numbers of genes simultaneously. The present study used arrays to assess cytokine-related gene expression in induced periapical lesions. The dental pulps of mandibular first and second molars were exposed in BALB/cJ mice. Pulps were inoculated with a mixture of four endodontic pathogens (Prevotella intermedia, Peptostreptococcus micros, Streptococcus intermedius, and Fusobacterium nucleatum) on day 0. Animals were killed on days 3, 14, and 42 (n = 4 per group). Nonexposed and noninfected animals were established as negative controls (day 0, n = 4). Bone blocks containing molars and surrounding tissues were isolated, and total RNA was extracted. After reverse transcription using specific primers, cDNA was hybridized to a commercially available mouse cytokine gene array system. The levels of gene expression were determined and normalized to housekeeping genes using GENe Array Scripts software. The results demonstrated that signal transduction genes related to immune cell activation and pro-inflammatory cytokine production were expressed on day 3. On day 14, inflammatory cytokine receptor genes, TGF-beta superfamily-related genes, and angiogenesis factor genes were upregulated. On day 42, apoptosis-related genes were expressed, whereas many TGF-beta superfamily genes were downregulated. We conclude that gene array analysis is useful in providing a global overview of the pattern of gene expression as periapical lesions progress from acute to chronic phases. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Sasaki, H (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA BN 4-87417-733-6 PY 2002 BP 183 EP 184 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BV10C UT WOS:000177817500041 ER PT J AU Monnier, J Elhai, JD Frueh, BC Sauvageot, JA Magruder, KM AF Monnier, J Elhai, JD Frueh, BC Sauvageot, JA Magruder, KM TI Replication and expansion of findings related to racial differences in veterans with combat-related PTSD SO DEPRESSION AND ANXIETY LA English DT Article DE PTSD; anxiety disorders; psychotic disorders; trauma; combat ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; AFRICAN-AMERICAN; SYMPTOMS; RELIABILITY; VALIDITY; SCALE AB Racial differences in those seeking treatment at a Veterans Affairs Medical Center (VAMC) outpatient posttraumatic stress disorder (PTSD) treatment program were examined. One hundred eleven (71 Caucasian and 40 African American) veterans were compared on both self-report measures and interview measures of PTSD, depression, dissociation, and general psychopathology. Participants completed the following self-report measures: the Beck Depression Inventory, the Dissociative Experiences Scale, the Mississippi Combat PTSD Scale, and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Participants also completed the Clinician Administered PTSD Scale (CAPS-1), which is a structured interview for PTSD, and completed a non-structured clinical interview. The two groups did not differ on measured demographic variables, nor were there significant differences on self-report or interview measures of anxiety, depression, or PTSD symptomatology. Contrary to expectation, groups did not differ on se T-report measures of dissociation, paranoia, or schizophrenia. African Americans were significantly more likely to endorse items of bizarre mentation from the MMPI-2. These results suggest that African American and Caucasian veterans with combat-related PTSD do not differ with regard to manifestation or severity of psychopathology. (C) 2002 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Monnier, J (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250681, Charleston, SC 29425 USA. FU NIMH NIH HHS [MH01660, MH61983] NR 30 TC 18 Z9 18 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2002 VL 16 IS 2 BP 64 EP 70 DI 10.1002/da.10060 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 598DT UT WOS:000178260700003 PM 12219337 ER PT J AU Dierickx, CC AF Dierickx, CC TI Hair removal by lasers and intense pulsed light sources SO DERMATOLOGIC CLINICS LA English DT Article ID SWITCHED ND-YAG; MODE RUBY-LASER; PHOTODYNAMIC THERAPY; ALEXANDRITE LASER; SELECTIVE PHOTOTHERMOLYSIS; ENDOGENOUS PROTOPORPHYRIN; REDUCTION; FOLLICLES; OPTICS; DAMAGE AB This article explains the mechanisms of using light to remove hair, examines the attributes of specific laser systems, and focuses on treatment protocols for the various systems to provide safe and effective treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photo Med, Boston, MA USA. Laser Clin, Boom, Belgium. Univ Hosp, Dept Dermatol, Ghent, Belgium. RP Dierickx, CC (reprint author), Beukenlaan 52, B-2850 Boom, Belgium. NR 61 TC 34 Z9 34 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD JAN PY 2002 VL 20 IS 1 BP 135 EP + DI 10.1016/S0733-8635(03)00052-4 PG 13 WC Dermatology SC Dermatology GA 517XC UT WOS:000173634900012 PM 11859588 ER PT J AU Abeni, D Picardi, A Pasquini, P Melchi, CF Chren, MM AF Abeni, D Picardi, A Pasquini, P Melchi, CF Chren, MM TI Further evidence of the validity and reliability of the Skindex-29: An Italian study on 2,242 dermatological outpatients SO DERMATOLOGY LA English DT Article DE quality of life; outcome research; validity; reliability; factor analysis; Skindex-29 ID QUALITY-OF-LIFE; GENERAL HEALTH QUESTIONNAIRE; SKIN-DISEASE; VERSION; INSTRUMENT; COMMUNITY; SCIENCE; SAMPLE AB Background: Quality of life is increasingly recognized as an important measure in dermatology. The Skindex-29 is a self-administered questionnaire recently developed to measure comprehensively the complex effects of skin diseases on patients' quality of life. Objective: We aimed to provide further evidence of the reliability and validity of the Skindex-29 in a large sample of patients affected by a wide variety of skin diseases. Methods: An Italian version of the Skindex-29 was produced following accepted guidelines for the cross-cultural adaptation of questionnaires. All adult outpatients attending a dermatological hospital on predetermined days were given the Skindex-29 and the 12-item General Health Questionnaire (GHQ-12). Results: A total of 2,242 complete questionnaires were analyzed. The internal consistency and test-retest reliability of each scale were high. The factor structure of the Skindex-29 was strikingly similar to the one originally observed in American patients. The pattern of correlation with the GHQ-12 provided evidence of convergent validity of the Skindex-29. Conclusion: The instrument seems to measure three fundamental dimensions of skin health-related quality of life. Copyright (C) 2002 S. Karger AG, Basel. C1 IRCCS, IDI, Inst Dermatol, Clin Epidemiol Unit, I-00167 Rome, Italy. IRCCS, IDI, Inst Dermatol, Dermatol Clin 2, I-00167 Rome, Italy. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Serv Dermatol, San Francisco, CA USA. RP Abeni, D (reprint author), IRCCS, IDI, Inst Dermatol, Clin Epidemiol Unit, Via Monti Creta 104, I-00167 Rome, Italy. RI Picardi, Angelo/B-2181-2013; OI Picardi, Angelo/0000-0003-2392-3011; Abeni, Damiano/0000-0002-0167-7617 NR 27 TC 83 Z9 84 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2002 VL 204 IS 1 BP 43 EP 49 DI 10.1159/000051809 PG 7 WC Dermatology SC Dermatology GA 522AN UT WOS:000173873700010 PM 11834849 ER PT J AU Tachihara, R Choi, C Langley, RGB Anderson, RR Gonzalez, S AF Tachihara, R Choi, C Langley, RGB Anderson, RR Gonzalez, S TI In vivo confocal imaging of pigmented eccrine poroma SO DERMATOLOGY LA English DT Article DE optical imaging; optical microscopy; noninvasive imaging; confocal microscope; eccrine poroma; lasers ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN; MELANOCYTE COLONIZATION; MALIGNANT-MELANOMA; CONTRAST AB Background. Near-infrared reflectance confocal microscopy (CM) imaging is a noninvasive technique that can be utilized to evaluate histologic features of cutaneous lesions in vivo. Objective: A case of pigmented eccrine poroma was examined with CM. Methods: Confocal images were taken to define the features of the lesion and correlated with transverse hematoxylin-eosin (HE)stained sections. Results: In CM imaging, a well-demarcated homogeneous nest consisting of small uniform cells was seen. The nest contained nonrefractile dark spaces that may represent cuticuli. Many dendritic melanocytes containing melanin were intermingled with the tumor cells, and numerous melanophages were present in the upper dermis. A marked prominence of surrounding vessels was also demonstrated. Conclusions: CM could well demonstrate the features of a pigmented eccrine poroma, as correlated with transverse HE-stained sections. However, high reflectance signals from melanin had to be carefully considered before a definitive diagnosis could be made. Copyright (C) 2002 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Boston, MA USA. RP Gonzalez, S (reprint author), Dept Dermatol, Wellman Labs Photomed, Bartlett Hall 814,50 Blossom St, Boston, MA 02114 USA. NR 18 TC 14 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2002 VL 204 IS 3 BP 185 EP 189 DI 10.1159/000057879 PG 5 WC Dermatology SC Dermatology GA 560DQ UT WOS:000176067500004 PM 12037445 ER PT J AU Mueller, NJ Schiller, P Shimizu, N Flury, R Aschwanden, M Widmer, U Enzler, T AF Mueller, NJ Schiller, P Shimizu, N Flury, R Aschwanden, M Widmer, U Enzler, T TI Factor VII deficiency and a copper metabolism disorder in a patient with Klippel-Trenaunay syndrome SO DERMATOLOGY LA English DT Article DE Klippel-Trenaunay syndrome; factor VII deficiency; copper metabolism disorder ID WILSON DISEASE GENE; VASCULAR MALFORMATIONS; INHERITANCE; ATPASE AB We report on a patient with Klippel-Trenaunay (KT) syndrome, a factor VII deficiency and a copper metabolism disorder. The KT syndrome involved the left leg and, histologically, the liver. Dermatological examination, duplex ultrasonography and a skin and liver biopsy verified the KT syndrome. A long prothrombin time prompted clotting studies revealing a factor VII deficiency while the other factors were in the normal range. Further laboratory examinations showed a copper metabolism disorder similar to Wilson's disease with a low serum ceruloplasmin level, elevated copper concentration in the urine and increased copper deposition in the liver. Neither liver cirrhosis nor a Kayser-Fleischer corneal ring was present. Sequencing analysis of the Wilson's disease gene ATB7B showed no mutations. The occurrence of these three uncommon pathologies in a single patient has not been described to date, which may suggest a mutation in a hypothetical common regulatory gene leading to this unusual phenotype. Copyright (C) 2002 S. Karger AG, Basel. C1 Univ Zurich Hosp, Dept Internal Med, Zurich, Switzerland. Univ Zurich Hosp, Dept Pathol, Zurich, Switzerland. Univ Basel Hosp, Dept Dermatol, CH-4031 Basel, Switzerland. Univ Basel Hosp, Dept Angiol, CH-4031 Basel, Switzerland. Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. Toho Univ, Sch Med, Dept Pediat 2, Tokyo, Japan. RP Enzler, T (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 NR 18 TC 1 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2002 VL 204 IS 3 BP 244 EP 247 DI 10.1159/000057890 PG 4 WC Dermatology SC Dermatology GA 560DQ UT WOS:000176067500015 PM 12037456 ER PT J AU West, CA Fischer, GA Young, AJ He, CF Su, M Mentzer, SJ AF West, CA Fischer, GA Young, AJ He, CF Su, M Mentzer, SJ TI Biochemical changes in the efferent lymph plasma after oxazolone stimulation SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article ID DEHYDROGENASE LDH ISOENZYMES; NODE CORTEX; CHOLESTEROL; SERUM; MACROPHAGES; LYMPHOCYTES; CULTURE; CELLS; INVOLVEMENT; ACTIVATION AB The lymph node is a specialized microenvironment for the regulation of immune responses. The reticular network of the lymph node provides a structure that facilitates not only intercellular interactions, but the intranodal flow of lymph fluid. To assess biochemical changes in the nodal lymph plasma after antigen stimulation, prescapular lymph nodes in sheep were stimulated with the epicutaneous antigen oxazolone. The efferent lymph from both antigen-stimulated and contralateral control prescapular lymph nodes was continuously monitored for more than 120 h. The oxazolone-stimulated lymph plasma was associated with a selective increase in cholesterol content during the 'recruitment' phase of lymph node enlargement. The peak in cholesterol was followed closely by a significant increase in lymph plasma LDH concentration. In contrast, there was no significant difference between oxazolone-stimulated and control lymph plasma in the concentration of triglycerides, albumin, alkaline phosphatase, and alanine transferase. These selective biochemical changes in the efferent lymph appeared to reflect the dynamics of lymphocyte activation within the lymph node as well as provide a practical measure of the lymph node response to antigen stimulation. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Lab Immunophysiol, Dana Farber Canc Inst,Surg Res Labs, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Lab Immunophysiol, Dana Farber Canc Inst,Surg Res Labs, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 48 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PD JAN PY 2002 VL 26 IS 1 BP 111 EP 119 DI 10.1016/S0145-305X(01)00043-X PG 9 WC Immunology; Zoology SC Immunology; Zoology GA 498ER UT WOS:000172497300012 PM 11687269 ER PT J AU Ramet, M Lanot, R Zachary, D Manfruelli, P AF Ramet, M Lanot, R Zachary, D Manfruelli, P TI JNK signaling pathway is required for efficient wound healing in Drosophila SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; puckered; dual specificity phosphatase; epithelial cell shape; Fos; wound healing; JNK signaling; epithelial morphogenetic process; dorsal closure; MAPK kinase pathway ID EMBRYONIC DORSAL CLOSURE; AMINO-TERMINAL KINASE; CELL SHEET MOVEMENT; PROTEIN-KINASES; TRANSDUCTION PATHWAY; MORPHOGENESIS; JUN; FOS; EXPRESSION; APOPTOSIS AB Efficient wound healing including clotting and subsequent reepithelization is essential for animals ranging from insects to mammals to recover from epithelial injury. It is likely that genes involved in wound healing are conserved through the phylogeny and therefore, Drosophila may be an useful in vivo model system to identify genes necessary during this process. Furthermore, epithelial movement during specific developmental processes, such as dorsal closure, ressembles of those seen in mammalian wound healing. As puckered (puc) gene is a target of the JUN N-terminal kinase signaling pathway during dorsal closure, we investigated puc gene expression during wound healing in Drosophila. We showed that puc gene expression is induced at the edge of the wound in epithelial cells and Jun kinase is phosphorylated in wounded epidermal tissues, suggesting that the JUN N-terminal kinase signaling pathway is activated by a signal produced by an epidermal wound. In the absence of the Drosophila c-Fos homologue, puc gene expression is no longer induced. Finally, impaired epithelial repair in JUN N-terminal kinase deficient flies demonstrates that the JUN N-terminal kinase signaling is required to initiate the cell shape change at the onset of the epithelial wound healing. We conclude that the embryonic JUN N-terminal kinase gene cassette is induced at the edge of the wound. In addition, Drosophila appears as a good in vivo model to study morphogenetic processes requiring epithelial regeneration such as wound healing in vertebrates. (C) 2001 Elsevier Science. C1 Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. CNRS, UPR 9022, F-67084 Strasbourg, France. RP Manfruelli, P (reprint author), Massachusetts Gen Hosp, Lab Dev Immunol, 55 Fruit St,GRJ 1402, Boston, MA 02114 USA. NR 44 TC 176 Z9 181 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2002 VL 241 IS 1 BP 145 EP 156 DI 10.1006/dbio.2001.0502 PG 12 WC Developmental Biology SC Developmental Biology GA 513YV UT WOS:000173409600011 PM 11784101 ER PT J AU Scorrano, L Ashiya, M Buttle, K Weiler, S Oakes, SA Mannella, CA Korsmeyer, SJ AF Scorrano, L Ashiya, M Buttle, K Weiler, S Oakes, SA Mannella, CA Korsmeyer, SJ TI A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis SO DEVELOPMENTAL CELL LA English DT Article ID PERMEABILITY TRANSITION PORE; CELL-DEATH; RELEASE; MEMBRANE; BAX; BCL-2; DYSFUNCTION; ACTIVATION; CHANNELS; PROTEINS AB The mechanism during apoptosis by which cytochrome c is rapidly and completely released in the absence of mitochondrial swelling is uncertain. Here, we show that two distinct pathways are involved. One mediates release of cytochrome c across the outer mitochondrial membrane, and another, characterized in this study, is responsible for the redistribution of cytochrome c stored in intramitochondrial cristae. We have found that the "BH3-only" molecule tBID induces a striking remodeling of mitochondrial structure with mobilization of the cytochrome c stores (similar to85%) in cristae. This reorganization does not require tBID's BH3 domain and is independent of BAK, but is inhibited by CsA. During this process, individual cristae become fused and the junctions between the cristae and the intermembrane space are opened. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med, Boston, MA 02115 USA. Wadsworth Ctr, Resource Visualizat Biol Complex, Albany, NY 12201 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med, 44 Binney St, Boston, MA 02115 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [CA50239-14]; NCRR NIH HHS [RR01219]; NHLBI NIH HHS [T32-HL07627-16] NR 43 TC 655 Z9 676 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2002 VL 2 IS 1 BP 55 EP 67 DI 10.1016/S1534-5807(01)00116-2 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 546XP UT WOS:000175301900008 PM 11782314 ER PT J AU Dohrmann, CE Noramly, S Raftery, LA Morgan, BA AF Dohrmann, CE Noramly, S Raftery, LA Morgan, BA TI Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather tract SO DEVELOPMENTAL DYNAMICS LA English DT Article DE TSC-22; chick; feather bud; appendage development; EGF; BMP; FGF; receptor tyrosine kinase; TGF-beta superfamily; pattern formation ID BETA-STIMULATED CLONE-22; ANTERIOR-POSTERIOR ASYMMETRY; EPIDERMAL GROWTH-FACTOR; GENE-EXPRESSION; HAIR FOLLICLE; MESENCHYMAL CONDENSATION; DROSOPHILA-MELANOGASTER; DYNAMIC EXPRESSION; PATTERN-FORMATION; MOUSE DEVELOPMENT AB TSC-22 (transforming growth factor-beta -stimulated clone 22) belongs to a family of leucine zipper transcription factors that includes sequences from invertebrates and vertebrates. The single Drosophila family member, encoded by the bunched gene, serves to integrate opposing bone morphogenic protein (BMP) and epidermal growth factor (EGF) signals during oogenesis. Similarly, mammalian TSC-22 expression is regulated by several families of secreted signaling molecules in cultured cells. Here, we show that chick TSC-22 is dynamically expressed in the condensing feather bud, as well as in many tissues of the chick embryo. BMP-2/4, previously shown to inhibit bud development, repress TSC-22 expression during feather bud formation in vivo. Noggin, a BMP antagonist, promotes TSC-22 expression. EGF, TGF-alpha, and fibroblast growth factor all promote both feather bud development and TSC-22 expression; each can promote ectopic feather buds that are regularly spaced between existing feather buds. Thus, TSC-22 is a candidate to integrate small imbalances in receptor tyrosine kinase and BMP signaling during feather tract development to generate stable and reproducible morphogenetic responses. (C) 2002 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Sch Med, Charlestown, MA 02129 USA. RP Raftery, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Sch Med, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NICHD NIH HHS [R01 HD38465] NR 45 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 2002 VL 223 IS 1 BP 85 EP 95 DI 10.1002/dvdy.1236 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 507PP UT WOS:000173037100021 PM 11803572 ER PT J AU Rais-Keeley, P AF Rais-Keeley, P TI Nutrition interventions in early diabetic renal disease SO DIABETES EDUCATOR LA English DT Editorial Material C1 Joslin Clin, Boston, MA 02215 USA. RP Rais-Keeley, P (reprint author), Joslin Clin, 1 Joslin Pl, Boston, MA 02215 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 2002 VL 28 IS 1 BP 62 EP + DI 10.1177/014572170202800107 PG 6 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 516HY UT WOS:000173548900006 PM 11852745 ER PT J AU Sweny, SE AF Sweny, SE TI Toward a better understanding of diabetic nephropathy SO DIABETES EDUCATOR LA English DT Editorial Material C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. RP Sweny, SE (reprint author), Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 2002 VL 28 IS 1 BP 72 EP + DI 10.1177/014572170202800108 PG 4 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 516HY UT WOS:000173548900007 PM 11852746 ER PT J AU Weijnen, CF Rich, SS Meigs, JB Krolewski, AS Warram, JH AF Weijnen, CF Rich, SS Meigs, JB Krolewski, AS Warram, JH TI Risk of diabetes in siblings of index cases with Type 2 diabetes: implications for genetic studies SO DIABETIC MEDICINE LA English DT Article DE Type 2 diabetes; sibling recurrence risk; vertical transmission; obesity; Caucasians ID GENOME-WIDE SEARCH; SUSCEPTIBILITY GENES; FAMILIAL AGGREGATION; SEGREGATION ANALYSIS; ASCERTAINMENT BIAS; LINKAGE STRATEGIES; COMPLEX DISEASES; PIMA-INDIANS; MELLITUS; NIDDM AB Aims The goal was to estimate the sibling recurrence-risk ratio for Type 2 diabetes in families with diabetes occurring in middle age. Because diabetes aetiology involves environmental exposures and genetic susceptibility, we sought to identify determinants of the recurrence risk. Methods We surveyed patients diagnosed at ages 35-59 years (n = 563) to obtain information on the occurrence of diabetes in their relatives, particularly siblings (n = 1675). Age-specific prevalences of diabetes in the US population were used for comparison. Results The overall sibling recurrence-risk ratio for diabetes was low, about 1.8 in the Joslin families and even lower in three other studies that were reanalysed for comparison. In all studies, the diabetes risk in siblings of index cases without a history of diabetes in a parent was similar to that in the general population, suggesting that genetic factors contributed to the occurrence of diabetes in only a minority of these siblings. The fact that recurrence-risk ratios were elevated only in families with one or two diabetic parents indicates that susceptibility to Type 2 diabetes is transmitted primarily through an affected parent. In addition, the sibling recurrence-risk ratios were elevated even further in families with diabetes in both a parent and grandparent of the index case, and in siblings of non-obese index cases (percent ideal body weight < 120%). Conclusions The selection of families with non-obese index cases and vertical transmission of diabetes through three generations may improve the success of efforts to map susceptibility genes for Type 2 diabetes. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Joslin Diabet Ctr, Div Res, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Warram, JH (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-47475, DK-36836] NR 49 TC 54 Z9 56 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JAN PY 2002 VL 19 IS 1 BP 41 EP 50 DI 10.1046/j.1464-5491.2002.00624.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 543QE UT WOS:000175112000006 PM 11869302 ER PT J AU Pape, TLB Kim, J Weiner, B AF Pape, TLB Kim, J Weiner, B TI The shaping of individual meanings assigned to assistive technology: a review of personal factors SO DISABILITY AND REHABILITATION LA English DT Review ID SPINAL-CORD INJURY; QUALITY-OF-LIFE; DEVICE USE; OLDER PERSONS; COPING STRATEGIES; DISABILITY; REHABILITATION; DISEASE; ADULTS; HOME AB Purpose: This review article examines the development of individualized meanings assigned to assistive technology and how these personal meanings influence the integration of assistive technology into daily activities. Methods: A review of the published literature regarding assistive technology use and abandonment was conducted by performing two independent searches using 26 search terms and three databases. Publications were reviewed for whether they addressed device use, device abandonment, coping, adjustment, adaptation, values, outcomes and/or cultural issues; 81 publications met these criteria. Results: The evidence suggests that psychosocial and cultural issues influence the shaping of individualized meanings assigned to assistive technology. Theoretical arguments suggest that the process of adapting to disability is another influential factor. Conclusions: The synthesis of evidence and theories suggests that successful integration of assistive technology into daily lives requires potential device users to explore: (1) the meanings they assign to devices; (2) their expectations of assistive technology; (3) the anticipated social costs; and (4) ways to understand that disability is one, but not the defining, feature of one's identity. C1 Rehabil Inst Chicago, Rehabil Serv Evaluat Unit, Chicago, IL 60611 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Northwestern Univ, Sch Med, Dept Phys Med & Rehabil, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Psychiat & Behav Sci, Div Psychol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Neuropsychol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Phys Med & Rehabil, Off Med Educ, Chicago, IL 60611 USA. RP Pape, TLB (reprint author), Rehabil Inst Chicago, Rehabil Serv Evaluat Unit, 345 E Super St,Suite 1374, Chicago, IL 60611 USA. OI Pape, Theresa/0000-0001-7738-5963 NR 72 TC 50 Z9 52 U1 1 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PD JAN PY 2002 VL 24 IS 1-3 BP 5 EP 20 DI 10.1080/09638280110066235 PG 16 WC Rehabilitation SC Rehabilitation GA 511BV UT WOS:000173245200002 ER PT S AU Cole, AJ Koh, S Zheng, Y AF Cole, AJ Koh, S Zheng, Y BE Sutula, T Pitkanen, A TI Are seizures harmful: what can we learn from animal models? SO DO SEIZURES DAMAGE THE BRAIN SE PERSPECTIVES IN ANALYTICAL PHILOSOPHY LA English DT Article; Proceedings Paper CT Workshop on Do Seizures Damage the Brain CY JUN 27-JUL 01, 2001 CL ROVANIEMI, FINLAND ID MESSENGER-RNA EXPRESSION; INDUCED BRAIN INJURY; P44/42 MAP KINASE; RAT-BRAIN; ELECTROCONVULSIVE SHOCK; HIPPOCAMPAL-NEURONS; STATUS EPILEPTICUS; SYNAPTIC REORGANIZATION; NEONATAL SEIZURES; NEUROPEPTIDE-Y AB Epilepsy is a brain disease that requires distributed neuronal networks for its expression. Several characteristics of epilepsy, including its natural history, the latency between an initial insult and the first manifestation of seizures, the complex interaction of seizures with development as a function of developmental stage, the modulating effect of systemic physiological responses, and the fact that seizures are ultimately defined by a combination of electrical and behavioral criteria all suggest that epilepsy should ideally be studied in an intact whole animal preparation. Such preparations offer the ability to study acute and chronic changes in brain structure and function after single or repeated seizures. Animal models have major limitations, however, including strain specificity, difficulty in isolating potentially confounding variables, a relative lack of accessible higher cortical functions, such as language and abstract processing, and shorter lifespans that may be insufficient to allow the complete expression of seizure-related injury. Information we have learned from animal studies includes a broad understanding of the chemical, molecular and anatomic consequences of seizures, including their temporal and spatial relationships to each other, and information on the consequences of seizures as a function of development. Recent studies have cast light on potential mechanisms of resistance to seizure-induced injury in the developing brain. In the future, we can anticipate that animal models will continue to be useful, especially when whole-animal preparations are used to generate material for detailed in vitro examination. C1 Massachusetts Gen Hosp, MGH Epilepsy Serv, Epilepsy Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epilepsy Serv, Epilepsy Res Lab, VBK 830,Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [K08 NS002068] NR 60 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50814-7 J9 PROG BRAIN RES PY 2002 VL 135 BP 13 EP 23 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BW09B UT WOS:000180831700002 PM 12143335 ER PT J AU Gariti, P Alterman, AI Ehrman, R Mulvaney, FD O'Brien, CP AF Gariti, P Alterman, AI Ehrman, R Mulvaney, FD O'Brien, CP TI Detecting smoking following smoking cessation treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE urinalysis; cotinine; self-report; carbon monoxide; treatment research ID SELF-REPORTED SMOKING; CIGARETTE-SMOKING; COTININE; NICOTINE; VALIDITY; SMOKERS AB Our study compared the results of self-report (SR) plus breath carbon monoxide (CO) monitoring to SR plus urine cotinine (COT) analysis of recent tobacco use for a recently completed smoking cessation study that compared the efficacy of different intensities of psychosocial treatments coupled with 8 weeks of patch treatment. Treatment outcomes were assessed 9, 26, and 52 weeks from treatment initiation in 200+ patients using both measurement types. COT was able to detect self-reported smoking in over 97% of the cases at all time points, while CO detected self-reported smoking 62, 84, and 89% of the time for the three follow-up assessments. Under 2% of those reporting nonsmoking were found to be smoking via CO, whereas COT found smoking to have occurred for 23, 15, and 7% of the 'nonsmoking' SRs at the three time points. Abstinence rates using SR plus CO were 49, 29, and 26%, contrasted with abstinence rates of 38, 26, and 25%, for SR plus COT. These findings suggest, that use of urine analysis for COT may lead to more accurate but lowered measured abstinence rates. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Sch Med, Dept Psychiat, Treatment Res Ctr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Gariti, P (reprint author), Univ Penn, Sch Med, Dept Psychiat, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA10070, P60 DA 05186] NR 20 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2002 VL 65 IS 2 BP 191 EP 196 DI 10.1016/S0376-8716(01)00162-4 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 515UK UT WOS:000173514900009 PM 11772480 ER PT B AU Rogers, JT AF Rogers, JT BE Fillit, HM OConnell, AW TI Targeting an RNA structure in the amyloid precursor protein gene as a new therapeutic strategy for Alzheimer's disease SO DRUG DISCOVERY AND DEVELOPMENT FOR ALZHEIMER'S DISEASE, 2000 LA English DT Proceedings Paper CT 1st Annual Investigators Meeting CY OCT 29-31, 2000 CL TARRYTOWN, NY ID NF-KAPPA-B; GAMMA-SECRETASE; MESSENGER-RNA; IN-VIVO; NUCLEAR TRANSLOCATION; RESPONSIVE ELEMENT; SERINE-PROTEASE; ACTIVE-SITE; TRANSLATION; INHIBITORS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rogers, JT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 0-8261-1542-X PY 2002 BP 74 EP 88 PG 15 WC Biochemistry & Molecular Biology; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BV93Q UT WOS:000180452600011 ER PT J AU Cholerton, B Gleason, CE Baker, LD Asthana, S AF Cholerton, B Gleason, CE Baker, LD Asthana, S TI Estrogen and Alzheimer's disease - The story so far SO DRUGS & AGING LA English DT Review ID AMYLOID PRECURSOR PROTEIN; HORMONE REPLACEMENT THERAPY; APOLIPOPROTEIN-E GENOTYPE; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; SPATIAL MEMORY TASK; CEREBRAL BLOOD-FLOW; DENDRITIC SPINE DENSITY; FEMALE RAT HIPPOCAMPUS; PITUITARY-ADRENAL AXIS AB The ovarian hormone estrogen has long been used to treat the physical symptoms of menopause and to aid in the prevention of osteoporosis in postmenopausal women. Cumulative evidence from basic science and clinical research suggests that estrogen also plays a significant neuromodulatory and neuroprotective role. The numerous estrogenic effects in the brain include the modulation of synaptogenesis, increased cerebral blood flow, mediation of important neurotransmitters and hormones, protection against apoptosis, anti-inflammatory actions, and antioxidant properties. These multiple actions in the central nervous system support estrogen as a potential treatment for the cognitive decline associated with Alzheimer's disease (AD), the most common form of dementia. Evidence from epidemiological studies supports enhanced cognitive function in women with AD taking estrogen replacement therapy (ERT) as well as a reduced risk for developing AD in healthy women receiving ERT. Additional clinical evidence suggests that estrogen may modulate specific cognitive functions such as working memory and verbal learning and memory. However, results from more recent controlled trials have not consistently shown a beneficial effect of estrogen on the cognitive function of women with AD. Future research should focus on examining the influence of multiple potential mediators of ERT including the route of estrogen administration, form of estrogen (conjugated estrogens vs estradiol), duration of treatment, opposed versus unopposed estrogen and the use of estrogen analogues. Further, sensitive neuropsychological measures may provide more detailed information concerning the specific effects of estrogen on cognitive function. These important issues must be addressed in order to establish the role of estrogen for the prevention and treatment of AD in women. C1 Univ Wisconsin, Sch Med, Sect Geriatr, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. RP Asthana, S (reprint author), Univ Wisconsin, Sch Med, Sect Geriatr, Dept Med, 2870 Univ Ave,Ste 100, Madison, WI 53705 USA. FU NIA NIH HHS [AG17196, AG05136] NR 230 TC 52 Z9 54 U1 6 U2 11 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2002 VL 19 IS 6 BP 405 EP 427 DI 10.2165/00002512-200219060-00002 PG 23 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 587WL UT WOS:000177666800002 PM 12149049 ER PT J AU Lenze, EJ Mulsant, BH Shear, MK Houck, P Reynolds, CF AF Lenze, EJ Mulsant, BH Shear, MK Houck, P Reynolds, CF TI Anxiety symptoms in elderly patients with depression what is the best approach to treatment? SO DRUGS & AGING LA English DT Article ID PRIMARY-CARE PATIENTS; LATE-LIFE; ANXIOUS DEPRESSION; MAJOR DEPRESSION; DISORDERS; NORTRIPTYLINE; COMORBIDITY; PREDICTORS; RECOVERY; ECT AB Depressed elderly persons frequently have concurrent symptoms of anxiety or comorbid anxiety disorders. Such comorbidity is associated with a more severe presentation of depressive illness, including greater suicidality. Additionally, most antidepressant treatment studies in the elderly have found poorer treatment outcomes in those with comorbid anxiety (including delayed or diminished response and increased likelihood of dropout from treatment). While antidepressants such as selective serotonin reuptake inhibitors and tricyclic agents are efficacious for late-life depression, there is no evidence that either class is superior, in terms of efficacy or tolerability, in the treatment of anxious depression. Rather, the amount and quality of clinical management, and not the particular medication chosen, appears to influence the likelihood of re, mission or treatment withdrawal in anxious depressed elderly patients. Co-prescription of benzodiazepines, typically lorazepam, is also warranted in some cases for severe anxiety or insomnia, but carries the risk of cognitive or motor impairment. It is our experience that close clinical monitoring, together with maximisation of antidepressant treatment (by maximising dosage, augmenting or switching agents in cases of partial or no response, and/or adding psychotherapy) will almost always result in remission of depressive symptoms, together with improvement of anxiety, in these individuals. Therefore, optimism should be maintained when treating the depressed elderly individual, even when comorbid anxiety is present. The term 'anxious depression' refers to individuals in a major depressive episode who concurrently have significant anxiety symptoms. This presentation is common, because anxiety and depressive symptoms are overlapping and share risk factors.([1]) Symptoms of anxiety are seen in as many as 65% of older patients with depression.([2]) Anxious depression can also be used to describe individuals with depression who have a comorbid anxiety disorder. While in adults these comorbid anxiety disorders are common,([3]) similar studies of older adults have shown mixed results, with some studies finding low rates of comorbid anxiety disorders ([4,5]) and others showing higher rates. ([1,6]) The most common comorbid anxiety disorders in elderly patients with depression are phobias and generalised anxiety disorder (GAD). This review of the literature on anxious depression in the elderly will show that the disorder is associated with increased suicidality and treatment resistance compared with nonanxious depression (the combination of suicidality and treatment resistance is of obvious concern). Possible reasons for treatment resistance are discussed, as are clinical management strategies for improving treatment outcomes in anxious depression. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat,Sch Med, Intervent Res Ctr Late Life Mood Disorders, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Syst, GRECC, Pittsburgh, PA USA. RP Lenze, EJ (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat,Sch Med, Intervent Res Ctr Late Life Mood Disorders, 3811 Ohara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [K23 MH64196, K05 MH00295, R01 MH37869, R37 MH43832, T32 MH19986, P30 MH 52247] NR 37 TC 15 Z9 17 U1 2 U2 6 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2002 VL 19 IS 10 BP 753 EP 760 DI 10.2165/00002512-200219100-00004 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 615ET UT WOS:000179233400004 PM 12390052 ER PT J AU Nanda, NC Wistran, DC Karlsberg, RP Hack, TC Smith, WB Foley, DA Picard, MH Cotter, B AF Nanda, NC Wistran, DC Karlsberg, RP Hack, TC Smith, WB Foley, DA Picard, MH Cotter, B TI Multicenter evaluation of SonoVue for improved endocardial border delineation SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE SonoVue; Albunex; endocardial border delineation; echocardiography ID DOBUTAMINE STRESS ECHOCARDIOGRAPHY; LEFT-VENTRICULAR OPACIFICATION; CONTRAST AGENT; WALL-MOTION; EJECTION FRACTION; ALBUNEX; TRIAL; MICROBUBBLES; ENHANCEMENT; ULTRASOUND AB Objectives: Two multicenter studies were conducted to evaluate the safety and efficacy of SonoVue as a contrast agent for enhanced left ventricular endocardial border delineation (LVEBD), and to compare the efficacy of SonoVue and Albunex in adult patients with a suboptimal, nonenhanced echocardiogram. Background: The use of contrast to enhance echocardiographic assessment of LVEBD is well-established. SonoVue is a new microbubble contrast agent that contains sulfur hexafluoride. Methods: Patients were randomized to receive four injections of SonoVue (0.5, 1, 2, and 4 ml), or two injections of Albunex and two injections of hand-agitated saline (0.08 and 0.22 ml/kg). Echocardiographic images were evaluated at the study centers and by four blinded, offsite reviewers for degree of left ventricle opacification (LVO), duration of contrast enhancement, and LVEBD. Results: LVO scores were significantly higher for all doses of SonoVue. Patients with complete LVO ranged from 34%-87% for SonoVue and from 0%-16% for Albunex. The mean duration of useful contrast effect ranged from 0.8-4.1 minutes for SonoVue and < 15 seconds for Albunex. Mean increases in LVEBD scores ranged from 3.8-18.2 for SonoVue and 0.1-4.3 for Albunex. SonoVue (cumulative 7.5 ml dose) was well-tolerated, with a safety profile similar to that observed in the control group. Conclusions: SonoVue is superior to Albunex for improving visualization of endocardial borders in patients with suboptimal noncontrast echocardiograms. Optimal increases in LVEBD, LVO, and duration of useful contrast effect were observed at the 2.0 ml dose of SonoVue. C1 Univ Alabama, Birmingham, AL 35249 USA. Cardiol Phys Inc, Salem, MA USA. Cardiovasc Res Inst So Calif, Beverly Hills, CA USA. Primary Care Cardiol Res, Ayre, MA USA. New Orleans Ctr Clin Res, New Orleans, LA USA. Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. RP Nanda, NC (reprint author), Univ Alabama, Heart Stn SW-S102,619 S 19th St, Birmingham, AL 35249 USA. OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 29 Z9 35 U1 0 U2 4 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2002 VL 19 IS 1 BP 27 EP 36 DI 10.1046/j.1540-8175.2002.00027.x PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 532HE UT WOS:000174467600004 PM 11884252 ER PT B AU Elahi, D Muller, DC Egan, JM Andres, R Veldhuis, J Meneilly, GS AF Elahi, D Muller, DC Egan, JM Andres, R Veldhuis, J Meneilly, GS BE Chadwick, D TI Glucose tolerance, glucose utilization and insulin secretion in ageing SO ENDOCRINE FACETS OF AGEING SE NOVARTIS FOUNDATION SYMPOSIUM LA English DT Article; Proceedings Paper CT Novartis Foundation Symposium on Endocrine Facets of Ageing CY JAN 30-FEB 01, 2001 CL NOVARTIS FDN, LONDON, ENGLAND HO NOVARTIS FDN ID GLUCAGON-LIKE PEPTIDE-1(7-37); DEPENDENT DIABETES-MELLITUS; BETA-CELL; CARBOHYDRATE-METABOLISM; HEALTHY CENTENARIANS; NONDIABETIC SUBJECTS; PERIPHERAL TISSUE; BODY-FAT; RESISTANCE; INDIVIDUALS AB Ageing is associated with an increased incidence of hypertension, macrovascular disease and type 2 diabetes (non-insulin-dependent diabetes). It has been suggested that a common mechanism may be responsible for all of these pathological states since all of these conditions often cluster in the same individual. Epidemiological and clinical data have consistently demonstrated an association between insulin resistance and/or hyperinsulinaemia and glucose intolerance, dyslipidaemia and elevated systolic blood pressures. Therefore, insulin resistance and hyperinsulinaemia have been proposed as the causal link among the elements of the clusters. The elderly are more glucose intolerant and insulin resistant, but it remains controversial whether this decrease in function is due to an inevitable consequence of 'biological ageing' or due to environmental or lifestyle variables, noticeably increased adiposity/altered fat distribution and physical inactivity. An increase of these modifiable factors has been shown to result in increases in insulin resistance and hyperinsulinaemia and vice versa. However, insulin secretion appears to decrease with age even after adjustments for differences in adiposity, fat distribution and physical activity. The glucose intolerance of ageing may be due, in part, to decreased insulin sensitivity of pancreatic beta cells to insulinotropic gut hormones (GLP1/GIP) and in part to alterations of hepatic glucose production. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. NIA, Gerontol Res Ctr, Lab Clin Physiol, NIH, Baltimore, MD 21224 USA. Univ Virginia, Div Endocrinol & Metab, Charlottesville, VA 22908 USA. Univ British Columbia, Dept Med, Vancouver, BC V6T 1Z3, Canada. RP Muller, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. FU NIA NIH HHS [AG-00599] NR 64 TC 32 Z9 33 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND BN 0-471-48636-1 J9 NOVART FDN SYMP PY 2002 VL 242 BP 222 EP 242 PG 21 WC Endocrinology & Metabolism; Geriatrics & Gerontology; Medicine, General & Internal SC Endocrinology & Metabolism; Geriatrics & Gerontology; General & Internal Medicine GA BU35C UT WOS:000175745900013 PM 11855690 ER PT J AU Divieti, P John, MR Juppner, H Bringhurst, FR AF Divieti, P John, MR Juppner, H Bringhurst, FR TI Human PTH-(7-84) inhibits bone resorption in vitro via actions independent of the type 1 PTH/PTHrP receptor SO ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE FRAGMENTS; GENE-EXPRESSION; CELL-FORMATION; IN-VITRO; PTH; CALCIUM; RAT; PEPTIDE; RELEASE; INVITRO AB The linear sequence of intact mammalian PTH consists of 84 amino acids, of which only the most amino(N)-terminal portion, i.e. PTH-(1-34), is required for the classical actions of the hormone on mineral ion homeostasis mediated by the type 1 PTH/PTHrP receptor (PTH1R). Like the N-terminus, the carboxyl (C)-terminal sequence of PTH is highly conserved,among species, and various circulating PTH C-fragments are generated by peripheral metabolism of intact PTH or are directly secreted, in a calcium-dependent manner, by the parathyroid glands. Certain synthetic PTH C-fragments exert actions on bone and cartilage cells that are not shared by PTH-(1-34), and specific binding of PTH C-peptides has been demonstrated in bone cells in which PTH1R expression was eliminated by gene targeting. The peptide human (h) PTH-(784) recently was shown to inhibit the calcemic actions of hPTH-(1-34) or hPTH-(1-84) in parathyroidectomized animals. To determine whether this anticalcemic effect of hPTH-(7-84) in vivo might result from direct actions on bone, we studied its effects on both resorption of intact bone in vitro and formation of osteoclasts in primary cultures of murine bone marrow. Human (h) PTH-(7-84) (300 nM) reduced basal 72-h release of preincorporated Ca-45 from neonatal mouse calvariae by 50% (9.6+/-1.9% vs. 17.8+/-5.7%; P<0.001) and similarly inhibited resorption induced by hPTH-(1-84), hPTH-(1-34), 1,25-dihydroxyvitamin D-3 (VitD), PGE(2), or IL-11. In 12-d murine marrow cultures, both hPTH-(7-84) (300 nM) and hPTH-(39-84) (3000 nM) lowered VitD-dependent formation of osteoclast-like cells by 70%. On the contrary, these actions of hPTH-(7-84) were not observed with the PTH1R antagonists hPTH-(3-34)NH2 and [L-11,D-W-12,W-23,Y-36] hPTHrP-(7-36)NH2, which, unlike hPTH-(7-84), did inhibit PTH1R-dependent cAMP accumulation in ROS 17/2.8 cells. We conclude that hPTH-(7-84), acting via receptors distinct from the PTH1R and presumably specific for PTH C-fragments, exerts a direct antiresorptive effect on bone that may be partly due to impaired osteoclast differentiation. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Divieti, P (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. NR 38 TC 128 Z9 132 U1 3 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2002 VL 143 IS 1 BP 171 EP 176 DI 10.1210/en.143.1.171 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 508EH UT WOS:000173075400021 PM 11751606 ER PT J AU Grill, HJ Schwartz, MW Kaplan, JM Foxhall, JS Breininger, J Baskin, DG AF Grill, HJ Schwartz, MW Kaplan, JM Foxhall, JS Breininger, J Baskin, DG TI Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR MESSENGER-RNA; GLUCAGON-LIKE PEPTIDE-1; BODY-WEIGHT; RAT HYPOTHALAMUS; LONG-FORM; IMMUNOHISTOCHEMICAL LOCALIZATION; ARCUATE NUCLEUS; SOLITARY TRACT; BINDING-SITES; BLOOD-GLUCOSE AB Three experiments were performed to investigate the hypothesis that leptin action within the caudal brain stem (CBS) contributes to its intake inhibitory effects. The first experiment evaluated the anatomical distribution of leptin receptor mRNA in rat CBS using a sensitive fluorescence in situ hybridization method with a riboprobe specific for the long form of the leptin receptor (Ob-Rb). An Ob-Rb mRNA hybridization signal was detected in neurons of several CBS nuclei involved in the control of food intake, including the dorsal vagal complex and parabrachial nucleus. A strong hybridization signal was also obtained from neuronal cell bodies of a number of other structures including the hypoglossal, trigeminal, lateral reticular, and cochlear nuclei; locus ceruleus; and inferior olive. The anatomical profile revealed by fluorescence in situ hybridization was in good agreement with immunocytochemical analysis with an antibody specific to Ob-Rb. In a second experiment, exploring the relevance of CBS Ob-Rb to feeding behavior, rats were given a fourth intracerebroventricular (i.c.v.) injection of leptin (0.1, 0.83, or 5.0 mug; n = 9-11/group) or vehicle 30 min before lights-out on three consecutive days The two higher doses reduced food intake significantly at 2,4, and 24 h after injection and caused significant reductions of body weight. The dose-response profiles for fourth i.c.v. administration were indistinguishable from those obtained from separate groups of rats that received leptin via a lateral i.c.v. cannula. In the last experiment, a ventricle-subthreshold dose of leptin (0.1 mug) microinjected unilaterally into the dorsal vagal complex suppressed food intake at 2,4, and 24 h. The results indicate that the CBS contains neurons that are potentially direct targets for the action of leptin in the control of energy homeostasis. C1 Univ Penn, Dept Psychol, Grad Grp Psychol, Philadelphia, PA 19104 USA. Univ Penn, Grad Grp Neurosci, Philadelphia, PA 19104 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. RP Grill, HJ (reprint author), Univ Penn, Dept Psychol, Grad Grp Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [DK-42284, DK-17047, DK-52989, DK-21397, DK-12829]; NINDS NIH HHS [NS-32272] NR 51 TC 251 Z9 256 U1 0 U2 8 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2002 VL 143 IS 1 BP 239 EP 246 DI 10.1210/en.143.1.239 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 508EH UT WOS:000173075400030 PM 11751615 ER PT J AU Wasterlain, CG Mazarati, AM Naylor, D Niquet, J Liu, HT Suchomelova, L Baldwin, R Katsumori, H Shirasaka, Y Shin, D Sankar, R AF Wasterlain, CG Mazarati, AM Naylor, D Niquet, J Liu, HT Suchomelova, L Baldwin, R Katsumori, H Shirasaka, Y Shin, D Sankar, R TI Short-term plasticity of hippocampal neuropeptides and neuronal circuitry in experimental status epilepticus SO EPILEPSIA LA English DT Article; Proceedings Paper CT 6th Workshop on the Neurology of Epilepsy (WONOEP VI) CY MAY 08-12, 2001 CL FOZ DO IGUACU, BRAZIL DE self-sustaining status epilepticus; galanin; dynorphin ID SUSTAINING STATUS EPILEPTICUS; BRIEF ELECTRICAL-STIMULATION; ACETYLCHOLINE-RELEASE; PERFORANT PATH; GRANULE CELLS; GALANIN; RAT; MODEL; MAINTENANCE; SEIZURES AB Purpose: We used a model of self-staining status epilepticus (SSSE), induced by brief intermittent stimulation of the perforant path in unanesthetized rats, to study the mechanism of initiation and of maintenance of SSSE and the role of neuropeptides in those processes. Methods: The perforant path was stimulated intermittently for 7 min (ineffective stimulation) or 30 min (generating SSSE). Peptides and their agonists and antagonists were delivered either intraperitoneally, or directly into the hippocampus through a implanted cannula. Behavior and electroencephalogram (EEG) were recorded through a videotape-telemetry system with automatic spike and seizures detection programs, which were supplemented by manual review of the records to confirm the diagnosis. Immunocytochemistry and enzyme-linked immunosorbent assay followed published methods. Results: Initiation of SSSE was blocked by many agonists of inhibitory neurotransmitters or neuromodulators, and by many antagonists of excitatory synapses, and was facilitated by agents with the opposite action, suggesting the activation of a complex circuit with multiple potential entry points. Once SSSE was established, however, only N-methyl-D-aspartate (NMDA)-receptor ligands and a few neuropeptides had major effects on its maintenance. Galanin and dynorphin had powerful anticonvulsant roles in the maintenance phase of SSSE, whereas somatostatin and neuropeptide Y suppressed seizures only transiently. SSSE seemed to induce maladaptive changes in neuropeptides: it depleted the hippocampus of the galanin- and dynorphin-immunoreactive (IR) fibers, which normally function as endogenous anticonvulsants; whereas it induced overexpression of the proconvulsant neuropeptides substance P and neurokinin B; however, late in the course of SSSE galanin-IR interneurons appeared in the dentate hilus. Conclusions: Initiation of SSSE seems to involve a circuit with many points of entry, and blockage of any point along this circuit inhibits the development of SSSE. Far fewer agents alter the maintenance phase of SSSE. Galanin, dynorphin, somatostatin, and neuropeptide Y have anticonvulsant roles, matching the previous described convulsant role of substance P and neurokinin B. Galanin and dynorphin seem to undergo maladaptive changes, which appear to play an important role of the maintenance phase of SSSE. Later, the de novo expression of inhibitory neuropeptides in novel cells in hippocampus coincides with the waning of seizures and may play a role in their termination. C1 VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. RP Wasterlain, CG (reprint author), VA Greater Los Angeles Healthcare Syst, Serv Neurol, 127,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 49 TC 33 Z9 34 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2002 VL 43 SU 5 BP 20 EP 29 DI 10.1046/j.1528-1157.43.s.5.1.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 584AW UT WOS:000177445900006 PM 12121290 ER PT J AU Sankar, R Shin, D Liu, HT Wasterlain, TC Mazarati, T AF Sankar, R Shin, D Liu, HT Wasterlain, TC Mazarati, T TI Epileptogenesis during development: Injury, circuit recruitment, and plasticity SO EPILEPSIA LA English DT Article; Proceedings Paper CT 6th Workshop on the Neurology of Epilepsy (WONOEP VI) CY MAY 08-12, 2001 CL FOZ DO IGUACU, BRAZIL DE seizures; status epilepticus; epilepsy; development; neuronal injury; synaptic plasticity ID GRANULE CELL NEUROGENESIS; NEURON-SPECIFIC ENOLASE; INDUCED STATUS EPILEPTICUS; DEVELOPING BRAIN; RECURRENT SEIZURES; FEBRILE SEIZURES; SYNAPTIC REORGANIZATION; NEONATAL SEIZURES; LIMBIC EPILEPSY; IMMATURE BRAIN AB Purpose: To use animal models of variable seizure induction in rats at different developmental stages to determine contributing factors for spontaneous seizures resulting from status epilepticus (SE) early in life. Methods: Two models of SE with distinct modes of seizure induction, lithium-pilocarpine (LiPC) and perforant path stimulation (PPS), were used at different ages. Multiple methods of determining neurodegeneration during an acute period and plastic changes in those monitored during the chronic phase were used. Results: Different modes of seizure induction lead to varying types and extents of damage, dependent on the age of the animals at the time of insult. LiPC resulted in injury to animals as young as 2 weeks and became widespread in animals 3 weeks old, whereas widespread damage after PPS was not seen until P35. Rats at an age with widespread damage in response to seizures also showed extensive immediate-early gene activation and often developed spontaneous seizures and features of hippocampal plasticity seen in the epileptic brain. Conclusions: SE early in life results in multiple consequences to the developing brain. These changes, coexisting in the nonepileptic brain, can overlap in a maladaptive combination to result in the diseased state of epilepsy. The consequence of early seizures in immature animals is a function of both the developmental stage and the method of seizure induction. C1 Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Serv Neurol, Los Angeles, CA USA. RP Sankar, R (reprint author), Univ Calif Los Angeles, Sch Med, Dept Pediat, 22-474 MDCC, Los Angeles, CA 90095 USA. NR 44 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2002 VL 43 SU 5 BP 47 EP 53 DI 10.1046/j.1528-1157.43.s.5.11.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 584AW UT WOS:000177445900011 PM 12121295 ER PT J AU Mazarati, A Bragin, A Baldwin, R Shin, D Wilson, C Sankar, T Naylor, D Engel, J Wasterlain, CG AF Mazarati, A Bragin, A Baldwin, R Shin, D Wilson, C Sankar, T Naylor, D Engel, J Wasterlain, CG TI Epileptogenesis after self-sustaining status epilepticus SO EPILEPSIA LA English DT Article; Proceedings Paper CT 6th Workshop on the Neurology of Epilepsy (WONOEP VI) CY MAY 08-12, 2001 CL FOZ DO IGUACU, BRAZIL DE status epilepticus; epilepsy; epileptogenesis; hippocampus; antiepileptic drugs ID TEMPORAL-LOBE EPILEPSY; SPONTANEOUS RECURRENT SEIZURES; BRIEF ELECTRICAL-STIMULATION; RAT MODEL; PERFORANT PATH; CELL LOSS; PILOCARPINE; KAINATE; SPIKES AB Purpose: To describe the natural history of chronic epilepsy after experimental self-sustaining status epilepticus (SSSE) and to correlate patterns of SSSE with ictal, interictal, and plastic changes that characterize chronic epilepsy. Methods: SSSE was induced in adult Wistar rats by 30-min intermittent electrical stimulation of the perforant path. In some animals, SSSE was treated by short-term administration of antiepileptic drugs (AEDs). After SSSE, EEG and animal behavior were monitored for less than or equal to1 year. Some animals were killed to study mossy fiber sprouting in the dentate gyrus. Results: Despite the high reproducibility of the electro-graphic and behavioral manifestations of SSSE, patterns of chronic epilepsy varied considerably among animals in terms of seizure frequency, initial seizure pattern at the onset of chronic epilepsy, and frequency of interictal spikes. Statistically significant correlations were found between spike frequency during SSSE and interictal spike frequency, as well as between the frequency of spontaneous seizures and degree of mossy fiber sprouting. Early treatment of SSSE prevented the occurrence of spontaneous seizures and significantly decreased frequency of interictal spikes. Late treatment of SSSE did not prevent spontaneous seizures, but significantly decreased their frequency, and eventually may lead to remission of epilepsy. Conclusions: SSSE leads after a "silent" period to chronic epilepsy, which is maintained for 1 year in the rat. The silence is only behavioral, because EEG paroxysmal activity is seen in every animal. In this model of SSSE, the timing of treatment is a major determinant of outcome. Early treatment reduces the incidence of chronic epilepsy, whereas late treatment only reduces its severity. The possibility that this reduction of the severity of epilepsy may led to spontaneous remissions merits further study. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. RP Mazarati, A (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS 02808, NS 11315, NS 33310] NR 21 TC 32 Z9 32 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2002 VL 43 SU 5 BP 74 EP 80 DI 10.1046/j.1528-1157.43.s.5.25.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 584AW UT WOS:000177445900015 PM 12121299 ER PT J AU Van Cott, AC AF Van Cott, AC TI Epilepsy and EEG in the elderly SO EPILEPSIA LA English DT Article DE epilepsy; elderly; seizures; EEG; CCTV-EEG ID SEIZURES; OLDER; AGE AB Seizures are now the third most frequently encountered neurologic problem in the elderly population. The incidence of recurrent unprovoked seizures peaks in older patients. Because of this a-e-related increase and the growing elderly population, evaluation and treatment of the elderly patient has received increasing attention. This article focuses on epilepsy, not acute seizures in the elderly. The causes and types of epilepsy older individuals experience are reviewed, along with the diagnostic role of EEG. Treatment options are briefly addressed. C1 Va Pittsburgh Hlth Care Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Van Cott, AC (reprint author), Va Pittsburgh Hlth Care Syst, Neurol MDP 111 N U,Univ Dr C, Pittsburgh, PA 15240 USA. NR 42 TC 33 Z9 35 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2002 VL 43 SU 3 BP 94 EP 102 DI 10.1046/j.1528-1157.43.s.3.10.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 574KA UT WOS:000176887100012 PM 12060011 ER PT J AU Naylor, D AF Naylor, D TI Changes in Nonlinear signal processing in rat hippocampus associated with loss of paired-pulse inhibition or epileptogenesis SO EPILEPSIA LA English DT Article; Proceedings Paper CT 6th Workshop on the Neurology of Epilepsy (WONOEP VI) CY MAY 08-12, 2001 CL FOZ DO IGUACU, BRAZIL DE epilepsy; hippocampus; paired-pulse inhibition; Wiener analysis; nonlinear ID SEIZURES; MODEL; BRAIN; OSCILLATIONS; REDUCTION; EPILEPSY; DAMAGE AB Purpose: To study acute and chronic physiological effects of perforant path stimulation using paired-pulse and nonlinear signal analysis techniques (Wiener kernel analysis). Methods: Two to 3-month-old Wistar rats were implanted with stimulating electrodes in the perforant path and recording electrodes in the granule cell layer. Loss of paired-pulse inhibition was produced with 2 Hz continuous and 20 Hz (10 s/min) intermittent stimulation for periods of 1-15 min (0.1 ms, 20 v pulses). Some animals received 30-60 min of stimulation, a model for status epilepticus/epileptogenesis. Responses to paired-pulse or white noise inputs were recorded sequentially. Results: Loss of inhibition with brief 1-3 min of stimulation, measured by increase paired-pulse ratio (P2/P1 ISI 40 ms) from 0.25 (+/-0.27) pre- to 1.02 (+/-0.18) poststimulation (p < 0.001), lasted 43 ( 15) min. For 30-60 min of stimulation, the paired-pulse ratios were 0.088 (+/-0.11), 1.59 (+/-0.036), 0.06 (+/-0.11), 0.82 (+/-0.22) for pre-, immediate post-, 1 week post-, and 1 month poststimulation, respectively (p < 0.025). Compared to prestimulation values, Wiener kernel amplitudes for immediate, I week, and I month poststimulation were 24% (+/-13%), 72% (+/-17%). and 31% (+/-21%), respectively (p < 0.05). Wiener kernels 1 month poststimulation showed response prolongation with increased opportunity for excitatory interactions of inputs (particularly those separated by 4 ms). Conclusions: Brief perforant path stimulation causes sustained loss of inhibition in the dentate, possibly an early event in the transition to status epilepticus. Stimulation for 30-60 min causes chronic changes in paired-pulse and white noise (Wiener kernel) responses. Transient recovery occurs by I week, but later new features appear (including delayed/late inhibition and potential excitatory cross-talk) that might favor epileptic seizures. C1 Univ Calif Los Angeles, Med Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90073 USA. RP Naylor, D (reprint author), Univ Calif Los Angeles, Med Ctr, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 500,Rm 3256, Los Angeles, CA 90073 USA. NR 16 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2002 VL 43 SU 5 BP 188 EP 193 DI 10.1046/j.1528-1157.43.s.5.37.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 584AW UT WOS:000177445900035 PM 12121319 ER PT J AU Husain, Z Pinto, C Sofia, RD Yunis, EJ AF Husain, Z Pinto, C Sofia, RD Yunis, EJ TI Felbamate-induced apoptosis of hematopoietic cells is mediated by redox-sensitive and redox-independent pathways SO EPILEPSY RESEARCH LA English DT Article DE felbamate; apoptosis; glutathione; redox changes ID CLOZAPINE-INDUCED AGRANULOCYTOSIS; DIFFERENT ETHNIC-GROUPS; APLASTIC-ANEMIA; IN-VITRO; GLUTATHIONE; EXPRESSION; NECROSIS; METABOLITE; INFECTION; PROTEIN AB Felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate) is an approved antiepileptic drug shown to be effective in a variety of seizure disorders refractory to other treatments. However, its use has been restricted because of association with occurrence of rare cases of aplastic anemia and hepatic failure. Since it was shown that FBM metabolism requires glutathione (GSH), we used two experimental protocols to determine if the effects of specific metabolites were sensitive to redox pathways. FBM and its metabolite W873 (2-phenyl-1,3-propanediol monocarbamate). at 0.1 mg/ml, induced increased apoptosis of bone marrow cells from B10.AKM mice as compared with B10.BR mice. Study of the effects of the drug on human promonocytic cell line U937 cells showed that FBM and the metabolite W2986 [2-(4-hydroxyphenyl)-1,3 propanediol dicarbamate], at higher concentrations (0.5 mg/ml), induced apoptosis in this cell line. We also observed that while FBM and its metabolites induced increased apoptosis of B cells with reduced intracellular GSH levels, addition of exogenous GSH decreased apoptosis induced by W873 but did not significantly affect apoptosis induced by FBM or W2986. Our results suggest that, at concentrations used during the present investigations, FBM metabolites induce apoptosis via redox-sensitive and redo x-independent pathways. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Wallace Labs, Preclin & Clin Res, Cranbury, NJ USA. RP Husain, Z (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583]; NIMH NIH HHS [MH-47029] NR 31 TC 3 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2002 VL 48 IS 1-2 BP 57 EP 69 AR PII S0920-1211(01)00320-5 DI 10.1016/S0920-1211(01)00320-5 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 522UY UT WOS:000173916400006 PM 11823110 ER PT J AU Tache, Y Martinez, V Million, M Maillot, C AF Tache, Y Martinez, V Million, M Maillot, C TI Role of corticotropin releasing factor receptor subtype 1 in stress-related functional colonic alterations: Implications in irritable bowel syndrome SO EUROPEAN JOURNAL OF SURGERY LA English DT Article DE stress; CRF; CRF receptor; CRF antagonist; visceral pain; colonic motility; anxiety; IBS ID WATER-AVOIDANCE STRESS; CHRONIC HEPATITIS-C; FACTOR CRF; MOTOR FUNCTION; HIGH-AFFINITY; VISCERAL HYPERSENSITIVITY; PARAVENTRICULAR NUCLEUS; GASTROINTESTINAL-TRACT; CONSENSUS INTERFERON; MAJOR DEPRESSION AB The identification of the various elements of the Corticotropin Releasing Factor (CRF) system including the characterisation of four mammalian CRF-related peptides, the cloning of two CRF receptor subtypes 1 and 2 (CRF1; CRF2) and the development of selective CRF1 receptor antagonists has allowed investigators to establish an important role for the CRF signalling pathways in coordinating the physiological and behavioural components of the stress response. In particular, compelling preclinical evidence showed that both central and peripheral injection of CRF mimicked stress-induced stimulation of colonic motility, transit, defaecation, and occurrence of diarrhoea along with degranulation of mast cells, and increased secretion of prostaglandin E-2, Mucus, and ionic permeability. Central CRF also increased abdominal pain from colorectal distention in rats and peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. Non-selective CRF antagonists for receptors 1 and 2 and selective CRF1 antagonists inhibit exogenous (central or peripheral) CRF, and acute stress-induced stimulation of colonic motor and secretory function and visceral hyperalgesia. CRF1 receptors mediate stress-related anxiogenic and depression-like behaviours in rodents and CRF1 antagonist reduced depression in a phase II clinical trial. These findings lend support to the hypothesis that hyperactivation of CRF, receptors may contribute to the co-morbidity of anxiety and depression and irritable bowel syndrome. Targeting these pathways with selective CRF1 antagonists may be a novel therapeutic venue for diarrhoea-predominant IBS patients. C1 VA Greater Los Angeles Healthcare Syst, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [R01 DK-33061] NR 70 TC 19 Z9 20 U1 1 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1102-4151 J9 EUR J SURG JI Eur. J. Surg. PY 2002 VL 168 SU 587 BP 16 EP 22 PG 7 WC Surgery SC Surgery GA 670DE UT WOS:000182391500004 PM 16144197 ER PT J AU Plesnila, N Zinkel, S Amin-Hanjani, S Qiu, JH Korsmeyer, SJ Moskowitz, MA AF Plesnila, N Zinkel, S Amin-Hanjani, S Qiu, JH Korsmeyer, SJ Moskowitz, MA TI Function of BID - a molecule of the bcl-2 family - in ischemic cell death in the brain SO EUROPEAN SURGICAL RESEARCH LA English DT Article DE cerebral ischemia; apoptotic cell death; cytochrome c release; BID; knock-out mice ID FOCAL CEREBRAL-ISCHEMIA; CYTOCHROME-C; APOPTOSIS; MITOCHONDRIA; CASPASE-3; RELEASE; DAMAGE; ACTIVATION; INHIBITION; RECEPTOR AB Mitochondrial mechanisms, particularly the release of cytochrome c, play a role in the death of nerve and glial cells in cerebral ischemia. We have currently investigated whether BID, a proapoptotic molecule of the bcl-2 family and promoter of the release of cytochrome c is expressed in the brain, activated by cerebral ischemia in vivo, and contributes to ischemic cell death. We found BID in the cytosol of mouse brain and of primary cultured mouse neurons and showed that neuronal BID is a substrate for caspase 8. BID was cleaved in vivo 4 h after transitory occlusion of the middle cerebral artery. Further, BID-/- mice had a significant attenuation of infarction (-67%) and significantly lower release of cytochrome c (-41 %). The findings indicate that the proapoptotic molecule BID may contribute to the demise of nerve cells from cerebral ischemia by release of cytochrome c and activation of caspase. Copyright (C) 2002 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. RP Plesnila, N (reprint author), Univ Munich, Inst Surg Res, Marchioninistr 27, D-81377 Munich, Germany. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828, NS374141-02] NR 32 TC 24 Z9 26 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-312X J9 EUR SURG RES JI Eur. Surg. Res. PD JAN-APR PY 2002 VL 34 IS 1-2 BP 37 EP 41 DI 10.1159/000048885 PG 5 WC Surgery SC Surgery GA 535QQ UT WOS:000174655900007 PM 11867899 ER PT J AU Ogawa, M AF Ogawa, M TI Changing phenotypes of hematopoietic stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the International-Society-for-Experimental-Hematology CY AUG 25, 2001 CL TOKYO, JAPAN SP Int Soc Exptl Hematol ID COLONY-STIMULATING FACTOR; CD34(+) BLOOD-CELLS; PERIPHERAL-BLOOD; BONE-MARROW; IN-VIVO; EXPRESSION; TRANSPLANTATION; PROGENITOR C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Ogawa, M (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 29 TC 56 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 2002 VL 30 IS 1 BP 3 EP 6 DI 10.1016/S0301-472X(01)00770-6 PG 4 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 518XP UT WOS:000173693700002 PM 11823030 ER PT J AU Joussen, AM Poulaki, V Mitsiades, N Kirchhof, B Koizumi, K Dohmen, S Adamis, AP AF Joussen, AM Poulaki, V Mitsiades, N Kirchhof, B Koizumi, K Dohmen, S Adamis, AP TI Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression SO FASEB JOURNAL LA English DT Article DE cyclooxygenase; nitric oxide; NF-kappa B; Erk kinase ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; CELL-ADHESION MOLECULE-1; SMOOTH-MUSCLE CELLS; NITRIC-OXIDE SYNTHASE; RHEUMATOID-ARTHRITIS; IN-VIVO; SUPEROXIDE PRODUCTION; NEUTROPHIL ADHESION; PROSTAGLANDIN E-2 AB Leukocyte adhesion to the diabetic retinal vasculature results in blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Intercellular adhesion molecule-1 (ICAM-1) and the leukocyte integrin CD18 are required for these processes. Diabetes was induced in Long Evans rats, resulting in a two- to threefold increase in retinal leukocyte adhesion. Following one week of diabetes, neutrophil CD11a, CD11b, and CD18 expression was increased significantly, as were retinal ICAM-1 levels. Animals were treated with aspirin, a cyclooxygenase 2 (COX-2) inhibitor (meloxicam), or a soluble tumor necrosis factor alpha (TNF-alpha) receptor/Fc construct (TNFR-Fc, etanercept). High-dose aspirin, etanercept, and high-dose meloxicam each reduced leukocyte adhesion and suppressed blood-retinal barrier breakdown. High-dose aspirin also reduced the expression of CD11a, CD11b, and CD18, whereas meloxicam and etanercept did not. High-dose aspirin, etanercept, and high-dose meloxicam each reduced retinal ICAM-1 expression. Aspirin and meloxicam both lowered retinal TNF-alpha levels. Notably, aspirin, meloxicam, and etanercept did not change retinal vascular endothelial growth factor levels. High-dose aspirin, etanercept and high-dose meloxicam, each suppressed the retinal expression of eNOS and the DNA-binding capacity of retinal nuclear factor-kappaB. High-dose aspirin also suppressed Erk kinase activity, which is involved in CD18 up-regulation. Taken together, these data identify COX-2 and TNF-alpha as operative in the early signature pathologies of diabetic retinopathy, a newly recognized inflammatory disease. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Lab, Boston, MA 02114 USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Med ZMMK, D-50931 Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Lab, 324 Cambridge St, Boston, MA 02114 USA. EM tony_adamis@meei.harvard.edu NR 72 TC 322 Z9 356 U1 2 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2002 VL 16 IS 1 BP 438 EP + DI 10.1096/fj.01-0707fje PG 29 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 518FU UT WOS:000173656600014 PM 11821258 ER PT J AU Eroglu, A Toner, M Toth, TL AF Eroglu, A Toner, M Toth, TL TI Beneficial effect of microinjected trehalose on the cryosurvival of human oocytes SO FERTILITY AND STERILITY LA English DT Article DE cryopreservation; human oocyte; microinjection; trehalose ID UNFERTILIZED MOUSE OVA; WATER PERMEABILITY; ACTIVATION-ENERGY; CRYOPRESERVATION; EMBRYOS; VITRIFICATION; FERTILIZATION; PREGNANCY; BIRTH; SURVIVAL AB Objective: To determine the effectiveness of trehalose as an intracellular cryoprotectant for the cryopreservation of human oocytes. Design: In vitro comparative study. Setting: Clinical and academic research environment at a medical school teaching hospital. Patient(s): Women undergoing in vitro fertilization (IVF). Intervention(s): Discarded human oocytes, obtained from IVF patients, were randomly distributed into three groups: control group (no trehalose), extracellular trehalose group (0.5 M extracellular trehalose), and intracellular trehalose group (0.15 M intra- and 0.5 M extracellular trehalose). Trehalose was introduced into oocytes by microinjection. The oocytes in each group were cooled to different temperatures (i.e., -15degreesC, -30degreesC. and -60degreesC) at rate of 1degreesC/minute and thawed at ambient air temperature. Survival was examined after overnight culture. Main Outcome Measure(s): Survival of human oocytes cryopreserved in the presence and absence of trehalose. Result(s): The majority of oocytes in the intracellular trehalose group survived cooling to -15degreesC (63%), -30degreesC (53%), and -60degreesC (66%). In contrast, only a small number of oocytes in both the control (13%) and extracellular trehalose group (22%) survived cooling to -15degreesC, while all oocytes degenerated when cooled to -30degreesC and -60degreesC. Conclusion(s): Small amounts of intracellular trehalose in the absence of any other cryoprotectant provide a significant protection against freeze-associated stresses. Our results suggest that sugars such as trehalose should be considered as intracellular cryoprotectants for cryopreservation of human oocytes. (Fertil Sterile(R) 2002:77:152-8. (C) 2002 by American Society for Reproductive Medicine). C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Toth, TL (reprint author), Massachusetts Gen Hosp, OB GYN Serv, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 119 Z9 132 U1 2 U2 14 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 2002 VL 77 IS 1 BP 152 EP 158 DI 10.1016/S0015-0282(01)02959-4 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 513PQ UT WOS:000173387400023 PM 11779606 ER PT J AU Huisman, TAGM Wisser, J Stallmach, T Krestin, GP Huch, R Kubik-Huch, RA AF Huisman, TAGM Wisser, J Stallmach, T Krestin, GP Huch, R Kubik-Huch, RA TI MR autopsy in fetuses SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE magnetic resonance autopsy; fetus; obstetric management; risk counseling; necropsy ID POSTMORTEM EXAMINATION; PERINATAL NECROPSY AB Objective: The purpose of this study was to determine whether postmortem magnetic resonance imaging (MR autopsy) could serve as an alternative to necropsy of fetuses. The value of MR autopsy in the validation of the obstetric management and in risk counseling concerning future pregnancies is discussed. Methods: 10 consecutive, malformed fetuses were examined by postmortem MRI within 24 h of delivery. Prenatal ultrasound (US) was performed in all fetuses. Complete necropsy served as gold standard, Results. MR autopsy confirmed every US diagnosis responsible for termination. All MRI findings were confirmed by necropsy. In two fetuses, necropsy gave additional information relevant for risk counseling. Histologic examination corrected the diagnosis in one case. Conclusions: MR autopsy provides valuable information previously only available from necropsy. In parents who refuse perinatal necropsy, the information obtained by MR autopsy can be used to validate obstetric management and to evaluate the risk for future pregnancies. Necropsy however remains the gold standard. Copyright (C) 2002 S. Karger AG, Basel. C1 Univ Zurich Hosp, Dept Diagnost Radiol, CH-8091 Zurich, Switzerland. Univ Zurich Hosp, Dept Obstet, CH-8091 Zurich, Switzerland. Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, MGH NMT Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Kubik-Huch, Rahel A./0000-0002-3636-8697 NR 14 TC 41 Z9 41 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PD JAN-FEB PY 2002 VL 17 IS 1 BP 58 EP 64 DI 10.1159/000048008 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 517EZ UT WOS:000173599300014 PM 11803219 ER PT J AU Henderson, JA Smith, JJ AF Henderson, JA Smith, JJ TI Financial conflict of interest in medical research: Overview and analysis of federal and state controls SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Ctr Integrat Med & Innovat Technol, Regulatory Affairs Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Henderson, JA (reprint author), Ctr Integrat Med & Innovat Technol, Regulatory Affairs Program, Boston, MA USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2002 VL 57 IS 3 BP 445 EP 456 PG 12 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 653AR UT WOS:000181413500003 PM 12710405 ER PT J AU Ayasolla, K Giri, S Khan, M Singh, A Singh, I AF Ayasolla, K Giri, S Khan, M Singh, A Singh, I TI Amyloid induced upregulation of inducible nitric oxide synthase by amyloid peptide in glial cells: Implications to Alzheimer's disease. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Med Univ S Carolina, Dept Pediat & Pathol & Lab Med, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 1 MA 489 BP S186 EP S187 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 578AY UT WOS:000177096300488 ER PT J AU Booth, L Redemond, R AF Booth, L Redemond, R TI Can lipid peroxidation of plasma membranes induce DNA strand breaks SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 9th Annual Meeting of the Oxygen-Society CY NOV 20-24, 2002 CL SAN ANTONIO, TEXAS SP Oxygen Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 2 MA 272 BP S390 EP S390 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 614PY UT WOS:000179199600290 ER PT J AU Green, PS Mendez, AJ Jacob, JS Crowley, J Tansey, M Growdon, W Hyman, BT Heinecke, JW AF Green, PS Mendez, AJ Jacob, JS Crowley, J Tansey, M Growdon, W Hyman, BT Heinecke, JW TI Neuronal expression of myeloperoxidase is increased in Alzheimer's disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. St Louis Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Univ Miami, Sch Med, Diabet Res Inst, Dept Med, Miami, FL 33136 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 1 MA 318 BP S123 EP S123 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 578AY UT WOS:000177096300318 ER PT J AU Ouedraogo, GD Redmond, RW AF Ouedraogo, GD Redmond, RW TI Photosensitized membrane oxidation leads to remote DNA damage by secondary reactive oxygen species SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 9th Annual Meeting of the Oxygen-Society CY NOV 20-24, 2002 CL SAN ANTONIO, TEXAS SP Oxygen Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 2 MA 360 BP S421 EP S421 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 614PY UT WOS:000179199600379 ER PT J AU Richardson, A AF Richardson, A TI Utilization of transgenic mice to study the role of free radicals in aging SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 9th Annual Meeting of the Oxygen-Society CY NOV 20-24, 2002 CL SAN ANTONIO, TEXAS SP Oxygen Soc C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, GRECC, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 2 MA P5 BP S300 EP S300 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 614PY UT WOS:000179199600006 ER PT J AU Mitsumoto, A Takeuchi, A Okawa, K Nakagawa, Y AF Mitsumoto, A Takeuchi, A Okawa, K Nakagawa, Y TI A subset of newly synthesized polypeptides in mitochondria from human endothelial cells exposed to hydroperoxide stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE H2O2; mitochondria; endothelial cells; translocation; 2D-PAGE; free radicals ID RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; PROTEIN IMPORT; OXIDATIVE STRESS; INNER MEMBRANE; SACCHAROMYCES-CEREVISIAE; HEAT-SHOCK; THIOREDOXIN PEROXIDASE; SUPEROXIDE-DISMUTASE; TRANSCRIPTION FACTOR; PRECURSOR PROTEINS AB The synthesis of 40 polypeptides in mitochondria was found to be stimulated after transient exposure of human endothelial cells to sublethal levels of hydroperoxides, such as H2O2, using comparative two-dimensional polyacrylamide gel electrophoresis. Eleven proteins were identified; these include 60 kDa heat shock protein (HSP60), a mitochondrial type of 70 kDa HSP (mtHSP70), manganese-dependent superoxide dismutase (MnSOD), three metabolic enzymes in citric acid cycle, two components for respiratory chain complexes, a ribosomal protein for translation in mitochondria (RM12), and an unnamed protein. These proteins are involved in reduction-oxidation and protein biogenesis, suggesting that their synthesis, which is triggered under oxidative stress conditions, is aimed at playing a defensive role in mitochondria. Moreover, mtHSP70, HSP60, MnSOD, and RM12 were revealed as their respective precursor proteins with mitochondrial targeting sequences. The preproteins of HSP60 and mtHSP70 were transiently accumulated in mitochondria after the removal of H2O2 in a processing competent state, while the accumulated preprotein of MnSOD localized inside mitochondria and remained unchanged. Membrane potential of mitochondria and cellular ATP levels were unchanged under these conditions. Taken together, these results suggest that hydroperoxide stress leads to preprotein accumulation, possibly due to the impairment of the protein-processing system in mitochondria, independent of membrane potential dissipation and ATP depletion. (C) 2001 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Kitasato Univ, Sch Pharmaceut Sci, Tokyo 108, Japan. Kirin Brewery Co Ltd, Pharmaceut Res Lab, Gunma, Japan. RP Mitsumoto, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, 70 Blossom St,WEL224, Boston, MA 02114 USA. NR 59 TC 38 Z9 40 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 1 PY 2002 VL 32 IS 1 BP 22 EP 37 DI 10.1016/S0891-5849(01)00755-9 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 507QK UT WOS:000173039000005 PM 11755314 ER PT J AU Van Remmen, H Hamilton, M Ikeno, Y Chang, J Shibatani, T Richardson, A AF Van Remmen, H Hamilton, M Ikeno, Y Chang, J Shibatani, T Richardson, A TI Using knockout and transgenic mouse models to study oxidative stress and mitochondria in aging. SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT Conference on European Research on Functional Effects of Dietary Antioxidants - Benefits and Risks CY SEP 25-28, 2002 CL CHURCHILL COLL, CAMBRIDGE, ENGLAND HO CHURCHILL COLL ID MICE C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. NR 4 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 2002 VL 36 SU S BP 23 EP 24 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 611VQ UT WOS:000179038800014 ER PT J AU Dulai, GS Guha, S Kahn, KL Gornbein, J Weinstein, WM AF Dulai, GS Guha, S Kahn, KL Gornbein, J Weinstein, WM TI Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: A systematic review SO GASTROENTEROLOGY LA English DT Article ID ESOPHAGOGASTRIC JUNCTION; SURGICAL-TREATMENT; GASTRIC CARDIA; CARCINOMA; CANCER; SURVEILLANCE; RISK; EPIDEMIOLOGY; METAPLASIA; DYSPLASIA AB Background & Aims: The public health impact of past screening and surveillance practices on the outcomes of Barrett's related cancers has not previously been quantified. Our purpose was to determine the prior prevalence of Barrett's esophagus in reported cases of incident adenocarcinoma undergoing resection, as an indirect measure of impact. Methods: We performed a systematic review of the literature from 1966 to 2000. Studies were included if they reported: (1) the number of consecutive adenocarcinomas resected, and (2) the number of those resected who had a previously known diagnosis of Barrett's. We generated summary estimates using a random effects model. Results: We identified and reviewed 752 studies. Twelve studies representing a total of :1503 unique cases of resected adenocarcinomas met inclusion criteria. Using a random effects model, the overall percentage of patients undergoing resection who had a prior diagnosis of Barrett's was 4.7% +/- 2.9%. Conclusions: The low prior prevalence (similar to5%) of Barrett's esophagus in this study population provides indirect evidence to suggest that recent efforts to identify patients with Barrett's-whether through endoscopic screening or evaluation of symptomatic patients-have had minimal public health impact on esophageal adenocarcinoma outcomes. The potential benefits of endoscopic surveillance seem to have been limited to only a fraction of those individuals at risk. These data thus provide a clear and compelling rationale for the development of effective screening strategies to identify patients with Barrett's esophagus. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Sch Med, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Sch Med, Div Biomath,Dept Med, Los Angeles, CA 90073 USA. RP Dulai, GS (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Greater Los Angeles Vet Adm Healthcare Syst, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 53 TC 175 Z9 176 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2002 VL 122 IS 1 BP 26 EP 33 DI 10.1053/gast.2002.30297 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 508AQ UT WOS:000173065100007 PM 11781277 ER PT J AU Gukovskaya, AS Mouria, M Gukovsky, I Reyes, CN Kasho, VN Faller, LD Pandol, SJ AF Gukovskaya, AS Mouria, M Gukovsky, I Reyes, CN Kasho, VN Faller, LD Pandol, SJ TI Ethanol metabolism and transcription factor activation in pancreatic acinar cells in rats SO GASTROENTEROLOGY LA English DT Article ID KAPPA-B ACTIVATION; ACID ETHYL-ESTER; FATTY-ACID; GAS-CHROMATOGRAPHY; ALCOHOL; ACETALDEHYDE; LIVER; INJURY; BLOOD; INFLAMMATION AB Background & Aims: Ethanol metabolism by pancreatic acinar cells and the role of its metabolites in ethanol toxicity to the pancreas remain largely unknown. Here, we characterize ethanol metabolism in pancreatic acinar cells and determine the effects of ethanol metabolites on nuclear factor kappaB (NF-kappaB) and activator protein (AP)-1, transcription factors that are activated in pancreatitis and mediate expression of inflammatory molecules critical for this disease. Methods: We measured activities of fatty acid ethyl ester (FAEE) synthase and alcohol dehydrogenase (ADH), as well as accumulation of ethanol metabolites. We measured the effects of ethanol and its metabolites on NF-kappaB and AP-1 activation by using a gel shift assay, Results: Pancreas metabolizes ethanol via both oxidative and nonoxidative pathways. Acinar cells are the main source of ethanol metabolism in the pancreas. Compared with the liver, FAEE synthase activity in the pancreas Is greater, whereas that of ADH is much less. FAEEs activated NF-kappaB and AP-1, whereas acetaldehyde inhibited NF-kappaB activation. Ethanol decreased NF-kappaB binding activity in acinar cells, which was potentiated by cyanamide. Conclusion: Oxidative and nonoxidative ethanol metabolites regulate transcription factors differently in pancreatic acinar cells. Ethanol may regulate NF-kappaB and AP-1 positively or negatively, depending on which metabolic pathway's effect predominates. These regulatory mechanisms may play a role in ethanol toxicity to the pancreas. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU PHS HHS [P50-A11999] NR 55 TC 108 Z9 109 U1 1 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2002 VL 122 IS 1 BP 106 EP 118 DI 10.1053/gast.2002.30302 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 508AQ UT WOS:000173065100017 PM 11781286 ER PT J AU Mizoguchi, E Mizoguchi, A Takedatsu, H Cario, E De Jong, YP Ooi, CJ Xavier, RJ Terhorst, C Podolsky, DK Bhan, AK AF Mizoguchi, E Mizoguchi, A Takedatsu, H Cario, E De Jong, YP Ooi, CJ Xavier, RJ Terhorst, C Podolsky, DK Bhan, AK TI Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice SO GASTROENTEROLOGY LA English DT Article ID ALPHA-MUTANT MICE; T-CELLS; BOWEL-DISEASE; INTERFERON-GAMMA; CROHNS-DISEASE; COLITIS; EXPRESSION; ACTIVATION; CYTOKINES; LINES AB Background & Aims: Tumor necrosis factor (TNF) induces multiple effects including cell proliferation and death by ligation with TNF receptor type II (TNFR2). We studied the role of TNFR2 in chronic inflammation-induced colonic epithelial alteration. Methods: TNFR2 expression in colonic epithelial cells (CECs) was assessed by ribonuclease protection assay (RPA) and immunohistochemistry (IHC) in patients with inflammatory bowel disease (IBD) and murine colitis models, TNFR2 expression was also analyzed using COLO205 cells. The role of TNFR2 in colonic epithelial homeostasis was examined by generating interleukin 6-deficient TCRalphaKO (alphaIL-6DKO) or TNFR2-deficient TCRalpha (alphaTNFR2DKO) mice. Results: TNFR2 expression was up-regulated in CEC in both human ulcerative colitis and Crohn's disease. In vitro studies showed that TNFR2 expression was up-regulated by a cooperative effect of key proinflammatory cytokines. By RPA, the increased expression of TNFR2 was detectable in TCRalphaKO mice with colitis compared with TCRalphaKO mice without colitis or wild-type mice. In alphaIL-6DKO mice, TNFR2 expression, proliferation, and nuclear factor kappa B activation of CECs were markedly reduced compared with TCRalphaKO mice. alphaTNFR2 mice also showed significantly less colonic epithelial proliferation compared with TCRalphaKO mice. Conclusions: Expression of TNFR2 is consistently increased on CECs in both murine colitis models as well as patients with IBD. TNFR2 may play an important role in colonic inflammation-associated alteration in the intestinal epithelium. C1 Massachusetts Gen Hosp, Immunopathol Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, Ctr Study Inflammatory Bowel Dis, Warren 501C,875 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK47677] NR 46 TC 104 Z9 106 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2002 VL 122 IS 1 BP 134 EP 144 DI 10.1053/gast.2002.30347 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 508AQ UT WOS:000173065100019 PM 11781288 ER PT J AU Brand, S Sakaguchi, T Gu, XB Colgan, SP Reinecker, HC AF Brand, S Sakaguchi, T Gu, XB Colgan, SP Reinecker, HC TI Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells SO GASTROENTEROLOGY LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE PATHWAY; CHEMOKINE RECEPTORS; NEUTROPHIL MIGRATION; ENDOTHELIAL-CELLS; CX3C CHEMOKINE; TNF-ALPHA; EXPRESSION; P53; ACTIVATION AB Background & Aims: In this study, we determined the signal transduction and functional consequences after ligand-specific activation of the fractalkine receptor CX3CR1 in human intestinal epithelial cells. Methods: CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction. The regulation of mitogen-activated protein kinase (MAPK) activation was assessed by immunoblotting. Regulation of chemokine messenger RNA (mRNA) expression was determined by Northern blotting. NF-kappaB and p53 activation was assessed by electromobility shift assays. Results: Fractalkine mediated the MEK-1 and Galphai-dependent but phosphatidylinositol-3-kinase-independent activation of extracellular signal-regulated kinase-MAPK. Fractalkine activated NF-kappaB and p53 resulting in interleukin 8 and fractalkine mRNA expression. CX3CR1-mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithellal cell monolayer. Conclusions: CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell-survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium. C1 Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Gastrointestinal Unit, Jackson Bldg R711,32 Fruit St, Boston, MA 02114 USA. RI Colgan, Sean/B-4573-2009 FU NIDDK NIH HHS [DK 51003, DK 54427, P01 DK 33506] NR 47 TC 74 Z9 75 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2002 VL 122 IS 1 BP 166 EP 177 DI 10.1053/gast.2002.30329 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 508AQ UT WOS:000173065100022 PM 11781291 ER PT J AU Keck, T Balcom, JH IV Fernandez-Del Castillo, C Antoniu, BA Warshaw, AL AF Keck, T Balcom, JH IV Fernandez-Del Castillo, C Antoniu, BA Warshaw, AL TI Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat SO GASTROENTEROLOGY LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; BASEMENT-MEMBRANE; IN-VITRO; INCREASED EXPRESSION; GELATINASE-B; LEUKOCYTES; INHIBITOR; MODEL; MECHANISMS; OXYGEN AB Background & Aims: In pancreatitis-associated lung injury, neutrophils (PMN) access the lung by migration through endothelial basement membranes. We hypothesize that degeneration of the basement membrane by specific PMN-produced matrix metalloproteinases (MMPs) may facilitate this process. Methods: Mild or severe pancreatitis was induced in rats and the consequent pulmonary injury characterized. MMP-2 and MMP-9 activity in supernatant of PMN cultures and homogenates of lungs were assessed by zymography and Western blot. Congruence of PMN and MMP expression In lung tissue was evaluated by neutrophil depletion and fluorescent immunohistochemistry (IHC). The contribution of MMPs to PMN transmigration and lung injury was tested with the MMP inhibitor batimastat (BB-94) in vitro (PMN transmigration across matrigel chambers) and in vivo (myeloperoxidase activity and Evans blue in broncho-alveolar lavage fluid). Results: MMP-9 was highly expressed in lungs and supernatant of neutrophil cultures In severe pancreatitis, and, to a lesser degree, in mild pancreatitis. Lung IHC showed colocalization of MMP-9 and PMN. PMN depletion simultaneously reduced neutrophil infiltration and MMP-9 levels in lung tissue. Trypsin, interleukin 1beta, and tumor necrosis factor (TNF)-alpha all potently stimulated MMP-9 release from PMN. BB-94 significantly reduced TNF-alpha-induced PMN transmigration across matrigel and ameliorated transendothelial PMN migration and protein leak in severe pancreatitis. Conclusions: MMP-9 secretion by PMN can be stimulated by trypsin and proinflammatory cytokines and increases in pancreatitis in proportion to its severity. MMP inhibition reduces PMN transmigration and reduces resultant alveolar-capillary leakage. These findings suggest an important role for MMP-9 from PMN in the pathogenesis of pancreatitis-associated lung injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St WHT 506, Boston, MA 02114 USA. NR 67 TC 106 Z9 116 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2002 VL 122 IS 1 BP 188 EP 201 DI 10.1053/gast.2002.30348 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 508AQ UT WOS:000173065100024 PM 11781293 ER PT J AU Poneros, JM Tearney, GJ Shiskov, M Kelsey, PB Lauwers, GY Nishioka, NS Bouma, BE AF Poneros, JM Tearney, GJ Shiskov, M Kelsey, PB Lauwers, GY Nishioka, NS Bouma, BE TI Optical coherence tomography of the biliary tree during ERCP SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week/102nd Annual Meeting of the American-Gastroenterological-Association CY MAY 20-23, 2001 CL ATLANTA, GEORGIA SP Amer Gastroenterol Assoc ID IN-VIVO; HILAR CHOLANGIOCARCINOMA; SURGICAL RESECTION; BIOPSY AB Background: Optical coherence tomography (OCT) is a high-resolution imaging technique that produces cross-sectional images in vivo. This is a report of the first use of OCT to acquire images of the biliary tree during ERCR. Methods: A 2.6-mm diameter OCT catheter delivered through the accessory channel of a duodenoscope was used to acquire images of the intrahepatic and extrahepatic bile ducts in 5 patients. Histology-correlated OCT images of 5 cadaveric livers, each imaged at 3 sites, were used to guide interpretation of the in vivo images. Results: Biliary ductal epithelium and subepithelial structures, including peribiliary glands, vasculature, and hepatic parenchyma, were visualized in vivo. The papillary architecture of cholangiocarcinoma was identified by OCT. There were no OCT-related complications. Conclusions: High-resolution OCT imaging of the biliary tree is feasible and may provide useful diagnostic information during ERCR. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Wellman Labs Photomed, BAR 703,50 Blossom St, Boston, MA 02114 USA. NR 15 TC 43 Z9 47 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 2002 VL 55 IS 1 BP 84 EP 88 DI 10.1067/mge.2002.120098 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 509TN UT WOS:000173165900021 PM 11756925 ER PT J AU Wang, S Fraefel, C Breakefield, X AF Wang, S Fraefel, C Breakefield, X TI HSV-1 amplicon vectors SO GENE THERAPY METHODS SE METHODS IN ENZYMOLOGY LA English DT Review ID SIMPLEX-VIRUS TYPE-1; ESCHERICHIA-COLI; GENE-TRANSFER; SYSTEM; CELLS; EXPRESSION; NEURONS C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. RP Wang, S (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. FU NCI NIH HHS [CA99004, CA69246] NR 25 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 346 BP 593 EP 603 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT92H UT WOS:000174462100034 PM 11883093 ER PT J AU Katon, W Russo, J Frank, E Barrett, J Williams, JW Oxman, T Sullivan, M Cornell, J AF Katon, W Russo, J Frank, E Barrett, J Williams, JW Oxman, T Sullivan, M Cornell, J TI Predictors of nonresponse to treatment in primary care patients with dysthymia SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE dysthymia; depression; paroxetine ID PERSONALITY-DISORDERS; MEDICAL OUTCOMES; RISK-FACTORS; LIFE EVENTS; DEPRESSION; HEALTH; NEUROTICISM; COMORBIDITY; MODEL; TRIAL AB Dysthymia is one of the most prevalent problems in primary care, especially in the elderly. In this study, we evaluated the demographic and clinical predictors of nonresponse to treatment in primary care patients with dysthymia. The study sample consisted of 338 primary care patients meeting DSMIII-R criteria for dysthymia from 4 diverse geographic sites in a randomized controlled 11-week trial of paroxetine, problem-solving therapy or placebo. Patients who attended at least 4 treatment sessions were used in the analysis. A score of less than 7 on the Hamilton was defined as a positive response to treatment. By Week 11, 52.2% of patients had a positive response to treatment. Patients with lower levels of education (odds ratio 0.44, 95% CI 0.23, 0.86), higher scores on the personality dimension of neuroticism (odds ratio 0.58, 95% CI 0.36, 0.92) and those with more severe medical illness (odds ratio 0.97, 95% CI 0.95, 0.99) were less likely to recover with either active or placebo treatments. Elderly women (>60 years of age, odds ratio 0.19, 95% CI 0.05, 0.66) were also less likely to respond to all treatments; however, females had a significantly higher response to placebo treatment compared to males. The factors associated with lack of response to treatment included lower-levels of education. high neuroticism, more severe medical illness and being an older female. This analysis is based on patients agreeing to participate in a randomized controlled trial, limiting representativeness of the sample, however, the demographic and clinical characteristics are common in elderly depressed primary care patients, and may signal the need for increased mental health specialty consultation. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Univ Texas, Hlth Sci Ctr, Div Gen Internal Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Dartmouth Coll Sch Med, Dept Psychiat, Hanover, NH USA. Univ Texas, Hlth Sci Ctr, Div Geriatr, San Antonio, TX USA. RP Katon, W (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 45 TC 31 Z9 33 U1 1 U2 2 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 2002 VL 24 IS 1 BP 20 EP 27 DI 10.1016/S0163-8343(01)00171-2 PG 8 WC Psychiatry SC Psychiatry GA 518YG UT WOS:000173695400004 PM 11814530 ER PT J AU Rosen, ED Hsu, CH Wang, XZ Sakai, S Freeman, MW Gonzalez, FJ Spiegelman, BM AF Rosen, ED Hsu, CH Wang, XZ Sakai, S Freeman, MW Gonzalez, FJ Spiegelman, BM TI C/EBP alpha induces adipogenesis through PPAR gamma: a unified pathway SO GENES & DEVELOPMENT LA English DT Article DE adipogenesis; PPAR gamma; C/EBP alpha; PPAR gamma null fibroblasts ID EMBRYONIC STEM-CELLS; ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; PROMOTER ACTIVITY; IN-VITRO; EXPRESSION; PROTEINS AB PPARgamma and C/EBPalpha are critical transcription factors in adipogenesis, but the precise role of these proteins has been difficult to ascertain because they positively regulate each other's expression. Questions remain about whether these factors operate independently in separate, parallel pathways of differentiation, or whether a single pathway exists. PPARgamma can promote adipogenesis in C/EBPalpha-deficient cells, but the converse has not been tested. We have created an immortalized line of fibroblasts lacking PPARgamma, which we use to show that C/EBPalpha has no ability to promote adipogenesis in the absence of PPARgamma. These results indicate that C/EBPalpha and PPARgamma participate in a single pathway of fat cell development with PPARgamma being the proximal effector of adipogenesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lipid Unit, Boston, MA 02114 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK02535, R37 DK031405, R37DK31405] NR 20 TC 629 Z9 663 U1 4 U2 34 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2002 VL 16 IS 1 BP 22 EP 26 DI 10.1101/gad.948702 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 510BD UT WOS:000173188100003 PM 11782441 ER PT J AU Antipova, AA Tamayo, P Golub, TR AF Antipova, Alena A. Tamayo, Pablo Golub, Todd R. TI A strategy for oligonucleotide microarray probe reduction SO GENOME BIOLOGY LA English DT Article AB Background: One of the factors limiting the number of genes that can be analyzed on high-density oligonucleotide arrays is that each transcript is probed by multiple oligonucleotide probes of distinct sequence in order to magnify the sensitivity and specificity of detection. Over the years, the number of probes per gene has decreased, but still no single array for the entire human genome has been reported. To reduce the number of probes required for each gene, a robust systematic approach to choosing the most representative probes is needed. Here, we introduce a generalizable empiric method for reducing the number of probes per gene while maximizing the fidelity to the original array design. Results: The methodology has been tested on a dataset comprising 317 Affymetrix HuGeneFL GeneChips. The performance of the original and reduced probe sets was compared in four cancer-classification problems. The results of these comparisons show that reduction of the probe set by 95% does not dramatically affect performance, and thus illustrate the feasibility of substantially reducing probe numbers without significantly compromising sensitivity and specificity of detection. Conclusions: The strategy described here is potentially useful for designing small, limited-probe genome-wide arrays for screening applications. C1 [Antipova, Alena A.; Tamayo, Pablo; Golub, Todd R.] MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. [Antipova, Alena A.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Golub, TR (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM golub@genome.wi.mit.edu NR 10 TC 1 Z9 1 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 2002 VL 3 IS 12 AR 0073.1 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EL UT WOS:000207582400013 ER PT J AU Xu, GM Arnaout, MA AF Xu, GM Arnaout, MA TI WAC, a novel WW domain-containing adapter with a coiled-coil region, is colocalized with splicing factor SC35 SO GENOMICS LA English DT Article DE WW domain; splicing; SNRP70; RD domain; domain fusion analysis; Rosetta stone protein ID NUCLEAR RIBONUCLEOPROTEIN PARTICLE; PROTEIN-PROTEIN INTERACTIONS; RNA-RECOGNITION MOTIF; SACCHAROMYCES-CEREVISIAE; INDUCED DEGRADATION; GENE-EXPRESSION; POLYMERASE-II; 70K PROTEIN; U1 RNA; PROLINE AB WW domains mediate protein-protein interactions in many intracellular processes. In pre-mRNA splicing, WW domains participate in cross-intron bridging. These WW domains are characterized by a central aromatic block of three tyrosine residues. We identified a novel protein containing the same type of WW domain. The gene encoding the protein, named WAC, is located in human chromosome 10p11.2-10p12.1. A Drosophila melanogaster WAC homolog (CG8949) was identified as a Rosetta stone protein. Domain fusion analysis of the Rosetta stone protein linked WAC to splicing factor SNRP70. WAC existed mainly in a tyrosine-phosphorylated form. Immunofluorescence analysis colocalized WAC with SC35, the marker for pre-mRNA splicing machinery. Our analysis suggests that WAC represents a novel member of WW-domain-containing proteins for RNA processing. C1 Massachusetts Gen Hosp, Renal Unit, Polycyst Kidney Dis Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Xu, GM (reprint author), Massachusetts Gen Hosp, Renal Unit, Polycyst Kidney Dis Program, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK07540-16, P01 DK54711] NR 44 TC 12 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2002 VL 79 IS 1 BP 87 EP 94 DI 10.1006/geno.2001.6683 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 511ZL UT WOS:000173296600012 PM 11827461 ER PT J AU Jacobson, AM Samson, JA Weinger, K Ryan, CM AF Jacobson, AM Samson, JA Weinger, K Ryan, CM TI Diabetes, the brain, and behavior: Is there a biological mechanism underlying the association between diabetes and depression? SO GLUCOSE METABOLISM IN THE BRAIN SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID RECURRENT SEVERE HYPOGLYCEMIA; MAGNETIC-RESONANCE SPECTROSCOPY; 10-YEAR FOLLOW-UP; CHRONIC MEDICAL CONDITIONS; WHITE-MATTER LESIONS; COGNITIVE FUNCTION; MAJOR DEPRESSION; YOUNG-ADULTS; NEUROPSYCHOLOGICAL IMPAIRMENT; PSYCHIATRIC-DISORDERS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Jacobson, AM (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 124 TC 36 Z9 36 U1 14 U2 16 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2002 VL 51 BP 455 EP 479 PG 25 WC Neurosciences SC Neurosciences & Neurology GA BV51T UT WOS:000179204300011 PM 12420367 ER PT J AU Henderson, DC Ettinger, ER AF Henderson, DC Ettinger, ER TI Schizophrenia and diabetes SO GLUCOSE METABOLISM IN THE BRAIN SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; TARDIVE-DYSKINESIA; OLANZAPINE TREATMENT; CLOZAPINE TREATMENT; COGNITIVE FUNCTION; PREFRONTAL CORTEX; PC12 CELLS; MELLITUS; KETOACIDOSIS; INSULIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schizophrenia Program, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schizophrenia Program, Boston, MA 02114 USA. NR 106 TC 15 Z9 16 U1 4 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2002 VL 51 BP 481 EP 501 PG 21 WC Neurosciences SC Neurosciences & Neurology GA BV51T UT WOS:000179204300012 PM 12420368 ER PT J AU Endoh, H Vincent, S Jacob, Y Real, E Walhout, AJM Vidal, M AF Endoh, H Vincent, S Jacob, Y Real, E Walhout, AJM Vidal, M TI Integrated version of reverse two-hybrid system for the postproteomic era SO GUIDE TO YEAST GENETICS AND MOLECULAR AND CELL BIOLOGY, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID PROTEIN-PROTEIN INTERACTIONS; GREEN FLUORESCENT PROTEIN; YEAST ACTIN MUTATIONS; 2-HYBRID SYSTEM; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; LARGE NUMBERS; COMPLEX; MUTANTS; SELECTION C1 Yamanouchi Pharmaceut Co Ltd, Tsukuba, Ibaraki, Japan. Enanta Pharmaceut Inc, Cambridge, MA 02139 USA. Inst Pasteur, Lyssavirus Lab, F-75015 Paris, France. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Endoh, H (reprint author), Yamanouchi Pharmaceut Co Ltd, Tsukuba, Ibaraki, Japan. OI Walhout, Marian/0000-0001-5587-3608 FU NCI NIH HHS [P01CA80111-02, 7 R33 CA81658-02]; NHGRI NIH HHS [5R01HG01715-02] NR 40 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 350 BP 525 EP 545 PN B PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU60A UT WOS:000176466300030 PM 12073334 ER PT J AU Schuyler, SC Pellman, D AF Schuyler, SC Pellman, D TI Analysis of the size and shape of protein complexes from yeast SO GUIDE TO YEAST GENETICS AND MOLECULAR AND CELL BIOLOGY, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; MODULES; GENES; EFFICIENT; VERSATILE; DELETION; VOLUMES C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schuyler, SC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 31 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 351 BP 150 EP 168 PN C PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU60B UT WOS:000176466400008 PM 12073341 ER PT J AU Lea, JS Sheets, EE Wenham, RM Duska, LR Coleman, RL Miller, DS Schorge, JO AF Lea, JS Sheets, EE Wenham, RM Duska, LR Coleman, RL Miller, DS Schorge, JO TI Stage IIB-IVB cervical adenocarcinoma: Prognostic factors and survival SO GYNECOLOGIC ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX; CISPLATIN; CHEMOTHERAPY; HYSTERECTOMY; RADIATION; PATTERNS; CANCER AB Objective. The incidence of cervical adenocarcinoma is increasing relative to squamous cell carcinoma and all cervical cancers. Few reports have described the outcome of patients with advanced cervical adenocarcinoma. The purpose of this study was to determine the prognostic factors and survival for patients with stage IIB-IVB disease. Methods. Institutional Review Board approval was obtained to perform a computerized search of all women diagnosed with cervical adenocarcinoma at our three institutions between 1982 and 2000. Medical records were retrospectively reviewed. Clinical follow-up was obtained from the SGO database and tumor registry and via correspondence with health care providers. Statistical analysis was performed using logistic regression for clinical variables and the log-rank test to compare Kaplan-Meier survival estimates. Results. Eighty-three women with FIGO stage IIB-IVB cervical adenocarcinoma were identified. The median patient age was 53 years (range, 22-88). The median follow-up of 17 (20%) surviving patients was 33 months (range, 6-147); 66 (80%) died during the study interval. Stage IIB disease, young patient age, and grade I histology were independent variables having a favorable impact on survival (each P<0.02). Stage IIB patients (n=41) were more likely to be alive at 2 (64% vs 8%) and 5 years (30% vs 0%) than women with stage IIIA-IVB disease (n=42; P <0.01). Conclusions. Women diagnosed with advanced stage cervical adenocarcinoma have a poor prognosis. Prospective, multicenter trials of platinum-based chemoradiation or other novel therapies are urgently needed in the treatment of this highly lethal disease. (C) 2002 Elsevier Science. C1 Univ Texas, SW Med Ctr, Div Gynecol Oncol, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Schorge, JO (reprint author), Univ Texas, SW Med Ctr, Div Gynecol Oncol, 5323 Harry Hines Blvd,J7-124, Dallas, TX 75390 USA. RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 NR 26 TC 33 Z9 36 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 2002 VL 84 IS 1 BP 115 EP 119 DI 10.1006/gyno.2001.6473 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 510UL UT WOS:000173225600020 PM 11748986 ER PT J AU Dickey, CC McCarley, RW Shenton, ME AF Dickey, CC McCarley, RW Shenton, ME TI The brain in Schizotypal personality disorder: A review of structural MRI and CT findings SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID SCHIZOPHRENIA-RELATED DISORDERS; FIRST-EPISODE SCHIZOPHRENIA; SUPERIOR TEMPORAL GYRUS; LATERAL VENTRICULAR ENLARGEMENT; CAUDATE NUCLEI VOLUMES; ROSCOMMON FAMILY; THOUGHT-DISORDER; GRAY-MATTER; PSYCHOTIC-PATIENTS; HOMOVANILLIC-ACID AB Studies of schizotypal personality disorder (SPD) are important because the condition is genetically related to schizophrenia and because data accumulating to confirm its biological underpinnings are challenging some traditional views about the nature of personality disorders. This review of 17 structural imaging studies in SPD indicates that individuals with this disorder show brain abnormalities in the superior temporal gyrus, parahippocampus, temporal horn region of the lateral ventricles, corpus callosum, thalamus, and septum pellucidum, as well as in total cerebrospinal fluid volume, similar to those seen in persons with schizophrenia. Differences between SPD and schizophrenia include lack of abnormalities in the medial temporal lobes and lateral ventricles in SPD. Whether the normal volume, and possibly normal functioning, of the medial temporal lobes in individuals with SPD may help to suppress psychosis in this disorder remains an intriguing but still unresolved question. Such speculation must be tempered due to a paucity of studies, and additional work is needed to confirm these preliminary findings. The imaging findings do suggest, however, that SPD probably represents a milder form of disease along the schizophrenia continuum. With further clarification of the neuroanatomy of SPD, researchers may be able to identify which neuroanatomical abnormalities are associated with the frank psychosis seen in schizophrenia. C1 VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. Brigham & Womens Hosp, Div Behav Neurol, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Behav Neurol, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Surg Planning Lab, MRI Div, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Shenton, ME (reprint author), VA Boston Healthcare Syst, Psychiat 116A, 940 Belmont St, Brockton, MA 02401 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [K02 MH001110, K02 MH001110-10, R01 MH040799, R01 MH040799-13, R01 MH050740, R01 MH050740-10, R01 MH052807, R01 MH052807-06] NR 84 TC 69 Z9 69 U1 3 U2 10 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2002 VL 10 IS 1 BP 1 EP 15 PG 15 WC Psychiatry SC Psychiatry GA 510WQ UT WOS:000173230600001 PM 11751641 ER PT J AU Young, A Flower, L AF Young, A Flower, L TI Patients as partners, patients as problem-solvers SO HEALTH COMMUNICATION LA English DT Article ID BIOPSYCHOSOCIAL MODEL; PHYSICIAN; COMMUNICATION; DISCOURSE; OUTCOMES; CARE AB This article reports our ongoing work in developing a model of health care communication called collaborative interpretation, which we define as a rhetorical practice that generates building blocks for a more complete and coherent diagnostic story and for a collaborative treatment plan. It does this by situating patients as problem-solvers. Our study begins with an analysis of provider-patient interactions in a specific setting-the emergency department (ED) of an urban trauma-level hospital-where we observed patients and providers miscommunicating in at least 3 distinct areas: over the meaning of key terms, in the framing of the immediate problem, and over the perceived role of the ED in serving the individual and the community. From our observations, we argue that all of these miscommunications and missed opportunities are rooted in mismatched expectations on the part of both provider and patient and the lack of explicit comparison and negotiation of expectations-in other words, a failure to see the patient-provider interaction as a rhetorical, knowledge-building event. In the process of observing interactions, conversing with patients and providers, and working with a team of providers and patients, we have developed an operational model of communication that could narrow the gap between the lay public and the medical profession-a gap that is especially critical in intercultural settings like the one we have studied This model of collaborative interpretation (CI) provides strategies to help patients to represent their medical problems in the context of their life experiences and to share the logic behind their health care decisions. In addition, CI helps both patient and provider identify their goals and expectations in treatment, the obstacles that each party perceives, and the available options. It is adaptable to various settings, including short, structured conversations in the emergency room, extended dialogue between a health educator and a patient in a clinical setting, and group discussions in support groups, community groups, or health education classrooms. C1 VA Pittsburgh Healthcare Syst, OOGR U, GREEC, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Carnegie Mellon Univ, Ctr Univ Outres, Pittsburgh, PA 15213 USA. RP Young, A (reprint author), VA Pittsburgh Healthcare Syst, OOGR U, GREEC, Univ Dr C, Pittsburgh, PA 15240 USA. NR 81 TC 11 Z9 11 U1 0 U2 8 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 2002 VL 14 IS 1 BP 69 EP 97 DI 10.1207/S15327027HC1401_4 PG 29 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 516UE UT WOS:000173574500004 PM 11853210 ER PT J AU Rosen, HR Miner, C Sasaki, AW Lewinsohn, DM Conrad, AJ Bakke, A Bouwer, HGA Hinrichs, DJ AF Rosen, HR Miner, C Sasaki, AW Lewinsohn, DM Conrad, AJ Bakke, A Bouwer, HGA Hinrichs, DJ TI Frequencies of HCV-specific effector CD4+T cells by flow cytometry: Correlation with clinical disease stages SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; CD4(+) T-CELLS; IMMUNE-RESPONSES; FOLLOW-UP; INFECTION; LIVER; LYMPHOCYTES; VIREMIA; MECHANISM; SUBTYPES AB Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, affecting approximately 2% of the world's population. The immune mechanisms responsible for the highly variable natural history in a given individual are unknown. We used a multiparameter flow cytometric technique to functionally and phenotypically characterize HCV-specific effector T cells in the peripheral blood of 32 individuals with different stages of hepatitis C disease (resolved, mild chronic, advanced chronic) and normal controls. We found the highest frequencies of virus-specific effector cells with an activated memory phenotype (CD45RO+CD69+) in subjects who had resolved HCV infection, either spontaneously or with antiviral therapy. Effector cells from patients with resolved infection produced Th I type cytokines following stimulation with nonstructural antigens (NS3 and NS4), whereas effector cells from chronically infected patients produced Th1 type cytokines predominantly following stimulation with the HCV core antigen. Stimulation with superantigen staphylococcal enterotoxin (SEB) induced the same levels of cytokine production in the different patient groups. Among the HCV-seropositive patients, viral load inversely correlated with the Th1 effector cell response to NS3. Interleukin (IL)-4 was produced only in response to the control antigens, but not in response to the HCV recombinant proteins. Taken together, these findings suggest that a vigorous HCV-specific CD4+ Th1 response, particularly against the nonstructural proteins of the virus, may be associated with viral clearance and protection from disease progression. Prospective studies using this new flow cytometric assay will be required to determine whether antiviral therapy modifies the frequency, specificity, and function of these virus-specific effector cells. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Gastroenterol Hepatol & Liver Transplantat, Portland, OR 97201 USA. Natl Inst Genet, Los Angeles, CA USA. Providence Med Ctr, Earle A Chiles Res Inst, Portland, OR USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, 3710 SW US Vet Hosp Rd,P3-GI Portland, Portland, OR 97207 USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 38 TC 139 Z9 148 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2002 VL 35 IS 1 BP 190 EP 198 DI 10.1053/jhep.2002.30293 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 506QM UT WOS:000172983300025 PM 11786976 ER PT J AU Lee, JT AF Lee, JT TI Is X-chromosome inactivation a homology effect? SO HOMOLOGY EFFECTS SE ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE LA English DT Review ID EMBRYONIC STEM-CELLS; DOUBLE-STRANDED-RNA; MOUSE XIST GENE; HISTONE MACROH2A1; DOSAGE COMPENSATION; MEDIATES INITIATION; REPEAT HYPOTHESIS; TRANSGENIC MICE; DNA METHYLATION; MALE DROSOPHILA C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02114 USA. NR 95 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 J9 ADV GENET PY 2002 VL 46 BP 25 EP 48 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA BX64G UT WOS:000185944200002 PM 11931227 ER PT J AU Caplan, D Vijayan, S Kuperberg, G West, C Waters, G Greve, D Dale, AM AF Caplan, D Vijayan, S Kuperberg, G West, C Waters, G Greve, D Dale, AM TI Vascular responses to syntactic processing: Event-related fMRI study of relative clauses SO HUMAN BRAIN MAPPING LA English DT Article DE localization of syntactic processing ID SENTENCE COMPREHENSION; FUNCTIONAL MRI; WORKING-MEMORY; BROCA APHASIA; TIME-COURSE; LANGUAGE; ACTIVATION; BRAIN; DETERMINANTS; COMPONENTS AB Event-related functional magnetic resonance imaging was used to investigate the localization of syntactic processing in sentence comprehension. Matched pairs of sentences containing identical lexical items were compared. One member of the pair consisted of a syntactically simpler sentence, containing a subject relativized clause. The second member of the pair consisted of a syntactically more complex sentence, containing an object relativized clause. Ten subjects made plausibility judgments about the sentences, which were presented one word at a time on a computer screen. There was an increase in BOLD hemodynamic signal in response to the presentation of all sentences compared to fixation in both right and left occipital cortex, the left perisylvian cortex, and the left premotor and motor areas. BOLD signal increased in the left angular gyrus when subjects processed the complex portion of syntactically more complex sentences. This study shows that a hemodynamic response associated with processing the syntactically complex portions of a sentence can be localized to one part of the dominant perisylvian association cortex. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Magnet Resonance Imaging, Dept Radiol, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Dept Neurol, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. RI Dale, Anders/A-5180-2010 FU NIDCD NIH HHS [DC 02146] NR 51 TC 50 Z9 50 U1 3 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2002 VL 15 IS 1 BP 26 EP 38 DI 10.1002/hbm.1059 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 505AA UT WOS:000172887500002 PM 11747098 ER PT J AU Wang, YM Mukherjee, S Fraefel, C Breakefield, XO Allen, PD AF Wang, YM Mukherjee, S Fraefel, C Breakefield, XO Allen, PD TI Herpes simplex virus type 1 amplicon vector-mediated gene transfer to muscle SO HUMAN GENE THERAPY LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; DEFECTIVE HSV-1 VECTORS; EPSTEIN-BARR VIRUS; SKELETAL-MUSCLE; HELPER VIRUS; MYOBLAST TRANSPLANTATION; IN-VIVO; ADENOASSOCIATED VIRUS; ADENOVIRAL VECTOR; RAT-BRAIN AB Herpes simplex virus type 1 (HSV-1) amplicon vectors were evaluated for feasibility in gene therapy of Duchenne's muscular dystrophy (DMD). An amplicon vector expressing enhanced green fluorescent protein (eGFP) was examined for transduction efficiency and cytotoxicity in cultured muscle cells, and for transduction efficiency, duration of transgene expression, and immunogenicity in tibialis anterior (TA) muscles of neonatal mice. Transduction efficiencies in murine and human myoblasts were 60-90 and 50-60%, respectively, when myoblasts were transduced at multiplicities of infection (MOIs) of 1-5. Similar transduction efficiencies were observed in myotubes of both species. No cytotoxic effects were noticed at an MOI of 10, the highest MOI tested. An amplicon vector, HyMD, containing the full-length mouse dystrophin cDNA and its muscle creatine kinase (MCK) promoter-enhancer, with a total size of 26 kb, was constructed and used to transduce mdx mouse myotubes. The expression of dystrophin in these cells was demonstrated by immunocytochemistry. After injecting 4-6 x 10(5) transduction units (TU) of HSVGN amplicon vectors, 10-50% of myofibers in the injected TA muscles expressed GFP. Although transgene expression was attenuated over time, significant improvement in long-term transgene expression and persistence of vector DNA was achieved, when compared with the first generation of recombinant HSV-1 vectors. Immunohistochemistry showed a modest CD4(+) lymphocyte infiltration in the vicinity of the injection. A gradually developed CD8(+) lymphocyte infiltration was also seen, most likely related to the antigenicity of the transgene product, GFP. We conclude that the HSV-1 amplicon vector is a promising vehicle for gene delivery in DMD. However, new strategies need to be evaluated to increase the stability of transgene expression. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wang, YM (reprint author), Brigham & Womens Hosp, Dept Anesthesia Res, B Mid SR 158, 20 Shattuck St, Boston, MA 02115 USA. FU NIAMS NIH HHS [K01AR02148] NR 77 TC 25 Z9 26 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2002 VL 13 IS 2 BP 261 EP 273 DI 10.1089/10430340252769789 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515ML UT WOS:000173499600008 PM 11812282 ER PT J AU Penfornis, A Tuomilehto-Wolf, E Faustman, DL Hitman, GA AF Penfornis, A Tuomilehto-Wolf, E Faustman, DL Hitman, GA CA DiMe Study Grp TI Analysis of TAP2 polymorphisms in Finnish individuals with type I diabetes SO HUMAN IMMUNOLOGY LA English DT Article DE type I diabetes mellitus; TAP2 gene; polymorphisms; HLA class II; linkage disequilibrium ID HLA CLASS-II; COMPLEX CLASS-I; MULTIPLE-SCLEROSIS; LINKAGE DISEQUILIBRIUM; PRIMARY ASSOCIATION; TRANSPORTERS TAP1; GENE POLYMORPHISM; POINT MUTATION; LMP GENES; MELLITUS AB Type I diabetes mellitus is an immune-mediated disease that is known to be associated and linked with genes in the human leukocyte antigen (HLA) region on chromome 6. Functionally, HLA class I antigen presentation may be deranged in type I diabetes. The TAP1 and TAP2 transporters, which mediate the translocation of antigenic peptides into the endoplasmic reticulum and whose genes are located in the HLA class II region, are potential candidates for conferring predisposition to type I diabetes. Five known coding region variants (codons 379, 565, 651, 665, and 687) as well as three new polymorphisms of TAP2, one silent (codon 604) and two intronic (nucleotide positions 49,270 and 49,471), were typed in a cohort of 146 welt-characterized Finnish individuals with type I diabetes and 90 control subjects, Absolute linkage disequilibrium was apparent for the polymorphisms at codons 604, 665, and 687 as well as the two downstream intronic polymorphisms in a 613-bp region of the 3' portion of TAP2; the polymorphism at codon 651, which is also present within this region, was excluded from this linkage. The codon 651 polymorphism defines the allele TAP2F, the frequency of which in HLA-DR4(+) diabetic subjects was 5.4 times that in DR4(+) controls (27 vs. 5%, p = 0.002, p(c) = 0.01). These data are consistent with the existence of susceptibility haplotypes for type I diabetes in the Finnish population consisting of DRB1*04 (*0401 and *0404), DQ8, and TAP2F. (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc. C1 Massachusetts Gen Hosp East, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Hop Jean Minjoz, F-25030 Besancon, France. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ London, Bart & London Queen Marys Sch Med & Dent, Dept Diabet & Metab Med, London, England. RP Faustman, DL (reprint author), Massachusetts Gen Hosp East, Immunobiol Lab, Room 3602,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 53 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JAN PY 2002 VL 63 IS 1 BP 61 EP 70 DI 10.1016/S0198-8859(01)00365-2 PG 10 WC Immunology SC Immunology GA 513NY UT WOS:000173385700008 PM 11916171 ER PT J AU Andrulis, IL Anton-Culver, H Beck, J Bove, B Boyd, J Buys, S Godwin, AK Hopper, JL Li, F Neuhausen, SL Ozcelik, H Peel, D Santella, RM Southey, MC van Orsouw, NJ Venter, DJ Vijg, J Whittemore, AS AF Andrulis, IL Anton-Culver, H Beck, J Bove, B Boyd, J Buys, S Godwin, AK Hopper, JL Li, F Neuhausen, SL Ozcelik, H Peel, D Santella, RM Southey, MC van Orsouw, NJ Venter, DJ Vijg, J Whittemore, AS CA Cooperative Family Registry Breast TI Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations SO HUMAN MUTATION LA English DT Article DE BRCA1; molecular testing; two-dimensional gene scanning; TDGS; DHPLC; enzymatic mutation detection; EMD; single strand conformation polymorphism analysis; SSCP; protein truncation test; PTT ID T4 ENDONUCLEASE-VII; 2-DIMENSIONAL ELECTROPHORESIS; SIGNAL PEPTIDASE; OVARIAN-CANCER; SCANNING TESTS; CODING REGION; BREAST-CANCER; GENE; SEQUENCE; COST AB A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP It will continue to be important to use complementary methods for mutational analysis. C1 Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Univ Calif Irvine, Div Epidemiol, Irvine, CA USA. Coriell Inst Med Res, Camden, NJ USA. Fox Chase Canc Ctr, New York, NY USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Melbourne, Ctr Genet Epidemiol, Parkville, Vic 3052, Australia. Harvard Univ, Ctr Canc, Boston, MA 02114 USA. Univ Utah, Dept Med Informat, Salt Lake City, UT 84112 USA. Columbia Univ, New York, NY 10032 USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Andrulis, IL (reprint author), Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. RI Andrulis, Irene/E-7267-2013 FU NCI NIH HHS [R01CA78564, CA74415, R35 CA47448, U01 CA69398, U01 CA69417, U01 CA69446, U01 CA69467, U01 CA69631, U01 CA69638, U01 CA78296] NR 40 TC 63 Z9 63 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2002 VL 20 IS 1 BP 65 EP 73 DI 10.1002/humu.10097 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 571XM UT WOS:000176744500008 PM 12112659 ER PT J AU Zhang, YZ Kaur, M Price, BD Tetradis, S Makrigiorgos, GM AF Zhang, YZ Kaur, M Price, BD Tetradis, S Makrigiorgos, GM TI An amplification and ligation-based method to scan for unknown mutations in DNA SO HUMAN MUTATION LA English DT Article DE mutation scanning; glycosylases; ligation-mediated PCR; PCR; SNP; TP53; XRCC5; Ku; ATM, mutation detection ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ENZYME MISMATCH CLEAVAGE; POINT MUTATIONS; MEDIATED PCR; LINKAGE DISEQUILIBRIUM; ESCHERICHIA-COLI; HUMAN GENOME; CANCER; ELECTROPHORESIS; IDENTIFICATION AB A new approach is presented for the sensitive and selective scanning for unknown DNA mutations, based on ligation-mediated PCR and the use of the glycosylases TDG and Muff These two highly selective enzymes together can detect about 70% of commonly observed polymorphisms and mutations in human tumors. DNA is cross-hybridized to form mismatches at the positions of point mutations, dephosphorylated to eliminate any pre-existing phosphorylated DNA ends, and then exposed to enzymatic treatment to remove mismatched thymidine (TDG) or adenine (MutY). The resulting apurinic/apyrimidinic sites at the position of the mismatches are heat-converted to 5'-phosphate-containing strand breaks, the DNA is denatured, and an oligonucleotide is ligated at the position of the newly created 5'-phosphate containing DNA ends. The ligated oligonucleotide then participates in a PCR reaction that amplifies exponentially only the mutation. containing fragments. Using this method, A G mutations in a p53 (TP53)-containing system, T-->G, G-->A, and C-->A, mutations in the Ku gene (XRCC5), and ATM, gene for a number of patient-derived genomic DNA samples have been successfully screened. This PCR,based assay is capable of detecting one mutated allele in 100 normal alleles and requires 5 to 100 ng of genomic DNA as starting material. The assay allows final visualization of the mutated fragments on a common ethidium gel or biotinylation and use in a capture format, potentially allowing the isolation of diverse mutated DNA fragments simultaneously. This versatile new approach should allow high throughput detection of DNA alterations and application in diverse areas of human mutation research. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Longwood Radiat Oncol Ctr, Level L2,Radiat Therapy,75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 83234] NR 42 TC 17 Z9 18 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2002 VL 20 IS 2 BP 139 EP 147 DI 10.1002/humu.10106 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 577WN UT WOS:000177085700008 PM 12124995 ER PT J AU Ishizaka, N Aizawa, T Ohno, M Usui, S Mori, I Tang, SS Ingelfinger, JR Kimura, S Nagai, R AF Ishizaka, N Aizawa, T Ohno, M Usui, S Mori, I Tang, SS Ingelfinger, JR Kimura, S Nagai, R TI Regulation and localization of HSP70 and HSP25 in the kidney of rats undergoing long-term administration of angiotensin II SO HYPERTENSION LA English DT Article DE angiotensin; AT(1) receptor; hypertension; heat shock protein; kidney ID HEAT-SHOCK-PROTEIN; VASCULAR SMOOTH-MUSCLE; RENAL TUBULAR CELLS; HEME OXYGENASE-1; HYPERTENSIVE RATS; OXIDATIVE INJURY; IN-VIVO; STRESS; EXPRESSION; KINASE AB Various renal insults result in induction of heat shock protein (HSP) expression within the kidney. Some of the HSPs induced in that manner are postulated to have renoprotective effects via either chaperoning actions or antioxidative properties. We have previously reported that long-term angiotensin (Ang) II administration induces the expression of renal HSP32, also known as heme oxygenase-1 (HO-1). Here, we investigated the regulation of expression and localization of other HSPs, including HSP70, HSP25, and alphabeta-crystallin, in the kidney of rats undergoing long-term administration of Ana II (0.7 mg . kg(-1) . d(-1)). Immunoblot analysis demonstrated that Ang II increased renal expression of HSP70 and HSP25, as well as HO-1, but that expression of alphabeta-crystallin was unaffected by this treatment. The Ang II-induced increase in renal HSP70 and HSP25 was dependent on the angiotensin type 1 receptor activation but not on hypertension per se. Immunohistochemistry revealed that HSP70 and HSP25 were expressed in the medullar regions and in the renal arterial wall in the kidney of control rats. After Ang II infusion, signals for HSP70, HSP25, and HO-1 proteins increased in intensity in the endothelium and medial smooth muscle of the renal artery. In addition, all of these HSPs were induced in proximal renal tubular epithelial cells from the same segments, suggesting that similar mechanisms are responsible for upregulating these HSPs. Our data show that Ang II infusion induces renal HSP70 and HSP25, as well as HO-1, and that Ang II can induce expression of these HSPs in renal cells in a pressor-independent manner. C1 Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Tokyo, Japan. Wakayama Med Coll, Dept Pathol, Wakayama, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Tokyo, Grad Sch Med, Dept Infect Control & Prevent, Tokyo, Japan. RP Ishizaka, N (reprint author), Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Hongo 7-3-1, Tokyo, Japan. NR 32 TC 47 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2002 VL 39 IS 1 BP 122 EP 128 DI 10.1161/hy1201.096818 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 517ZM UT WOS:000173640900022 PM 11799090 ER PT J AU Cooper, RA Corfman, TA Fitzgerald, SG Boninger, ML Spaeth, DM Ammer, W Arva, J AF Cooper, RA Corfman, TA Fitzgerald, SG Boninger, ML Spaeth, DM Ammer, W Arva, J TI Performance assessment of a pushrim-activated power-assisted wheelchair control system SO IEEE TRANSACTIONS ON CONTROL SYSTEMS TECHNOLOGY LA English DT Article DE gain scheduling; human machine interface; power-assist; user interface; wheelchair ID BODY-WEIGHT; PROPULSION; BIOMECHANICS; RESPONSES; KINETICS; FORCES AB Wheelchairs are an important form of mobility ibr people with disabilities. For many years, there have only been three wheelchair varieties: electric powered wheelchairs, scooters, and manual wheelchairs. Recently there has been development of wheelchairs that use a combination of human power and electric power. The human power is delivered by the arms through the pushrims while the electric power is delivered by a battery through two electric motors. The shared control system for a pushrim-activated power-assisted wheelchair (PAPAW) must account for the human behavior and the interaction with the device. The PAPAW uses a form of gain scheduling based. upon events recorded from the pushrim torque. The control system significantly altered (p < 0.05) selected variables from pushrim torque curves for manual wheelchair propulsion and PAPAW operation as desired. The peak torque was reduced by over 50%, and the time on the rim was nearly doubled with the PAPAW. The PAPAW provided intuitive control and was capable of significantly reducing the strain on the upper extremities commonly associated with secondary disabling conditions among manual wheelchair users. C1 VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 23 TC 66 Z9 66 U1 2 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1063-6536 J9 IEEE T CONTR SYST T JI IEEE Trans. Control Syst. Technol. PD JAN PY 2002 VL 10 IS 1 BP 121 EP 126 DI 10.1109/87.974345 PG 6 WC Automation & Control Systems; Engineering, Electrical & Electronic SC Automation & Control Systems; Engineering GA 506WY UT WOS:000172995800014 ER PT J AU Reilly, CM Gilkeson, GS AF Reilly, CM Gilkeson, GS TI Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice SO IMMUNOLOGIC RESEARCH LA English DT Article DE lupus; mouse; knock out; autoimmune ID NITRIC-OXIDE SYNTHASE; TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; AUTOREACTIVE T-CELLS; MRL-LPR/LPR MICE; AUTOIMMUNE KIDNEY-DISEASE; B-CELLS; SYSTEMIC AUTOIMMUNITY; RHEUMATOID-ARTHRITIS; MRL-FAS(LPR) MICE; LPR MICE AB MRL-MPJ Fas(1pr) (MRL/1pr) mice are a prototypic murine model for lupus characterized by an accelerated autoimmune syndrome. Disease begins as early as 8-wk-of-age in these animals with polyclonal B cell activation and elevated levels of serum IgM. By 12 to 16-wk-of-age MRL/1pr mice begin to produce a variety of autoantibodies including anti-dsDNA and anti-ss-DNA antibodies. From 16 to 24 wk, MRL/1pr mice develop proliferative immune complex mediated glomerulonephritis, vasculitis, arthritis, and massive lymphadenopathy that results in renal failure and death in 50% of the mice by 24-wk-of-age. This review will discuss several different genetic knockout experimental approaches used to study disease expression in MRL/1pr mice including various approaches in our laboratory aimed at autoantibody (Ab) production and inflammatory mediators. C1 Med Univ S Carolina, Med Res Serv, Div Rheumatol & Immunol, Ralph H Johnson VAMC, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Reilly, CM (reprint author), Med Univ S Carolina, Med Res Serv, Div Rheumatol & Immunol, Ralph H Johnson VAMC, 96 Jonathon Lucas St,Suite 912,POB 25063, Charleston, SC 29425 USA. FU NIAMS NIH HHS [R01AR45499] NR 94 TC 24 Z9 24 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2002 VL 25 IS 2 BP 143 EP 153 DI 10.1385/IR:25:2:143 PG 11 WC Immunology SC Immunology GA 535CZ UT WOS:000174628800004 PM 11999168 ER PT S AU Jaeckel, E Manns, M von Herrath, M AF Jaeckel, E Manns, M von Herrath, M BE Sanjeevi, CB TI Viruses and diabetes SO IMMUNOLOGY OF DIABETES: AUTOIMMUNE MECHANISMS AND THE PREVENTION AND CURE OF TYPE 1 DIABETES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th Meeting of the Immunology-of-Diabetes-Society CY FEB 14-16, 2001 CL CHENNAI, INDIA SP Immunol Diabetes Soc DE IDDM; viral infection; enterovirus; Coxsackie virus; retrovirus; rubella virus; cytomegalovirus; Epstein-Barr virus; LCMV; regulatory T-cells; oral tolerance; DNA vaccines ID GLUTAMIC-ACID DECARBOXYLASE; T-CELL-ACTIVATION; BETA-CELLS; MOLECULAR MIMICRY; COXSACKIE-B; ENCEPHALOMYOCARDITIS VIRUS; AUTOIMMUNE-DISEASE; TRANSGENIC MODEL; IMMUNE-RESPONSE; VIRAL-INFECTION AB Insulin-dependent diabetes mellitus (IDDM) is a multifactorial disease. Besides a genetic predisposition environmental factors have been implicated in the pathogenesis of beta cell destruction. Among these environmental factors viruses have been the focus of many studies. Some viruses are diabetogenic in animals, and others have been implicated as triggers in human IDDM by temporal and geographical association between IDDM and viral infections, serological evidence of infection in recently diagnosed diabetic patients, and the isolation of viruses from the pancreas of affected individuals. We discuss possible pathomechanisms of viral infections in beta cell destruction and review the studies on involvement of enteroviruses, retroviruses, rubella viruses, cytomegaloviruses, and Epstein-Barr viruses in human IDDM. We also report on studies of diabetogenic viruses in animal models as well as on viral infections protecting from IDDM. Some of the difficulties in linking viral infections to IDDM will be illustrated with data from a transgenic mouse model in which IDDM can be precipitated by infections with certain strains of lymphocytic choriomeningitis virus (LCMV). Emerging treatment concepts that do not rely on defining the initiating autoantigens but involve self-reactive regulatory lymphocytes such as oral antigen administration, as well as DNA vaccines, will be discussed briefly. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Hannover Med Sch, Dept Hepatol Gastroenterol & Endocrinol, D-30625 Hannover, Germany. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Jaeckel, E (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM jaeckel_elmar@yahoo.com NR 101 TC 57 Z9 65 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-362-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 958 BP 7 EP 25 PG 19 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU76Q UT WOS:000176952100004 PM 12021080 ER PT S AU Palmer, JP AF Palmer, JP BE Sanjeevi, CB TI Beta cell rest and recovery - Does it bring patients with latent autoimmune diabetes in adults to euglycemia? SO IMMUNOLOGY OF DIABETES: AUTOIMMUNE MECHANISMS AND THE PREVENTION AND CURE OF TYPE 1 DIABETES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th Meeting of the Immunology-of-Diabetes-Society CY FEB 14-16, 2001 CL CHENNAI, INDIA SP Immunol Diabetes Soc DE LADA; type 1.5 diabetes; type 2 diabetes; beta cell rest ID GLUTAMIC-ACID DECARBOXYLASE; ENDOGENOUS INSULIN-SECRETION; RETROVIRAL ANTIGEN P73; FUNCTIONAL-STATE; HIGH-RISK; LYMPHOCYTIC THYROIDITIS; SUBCUTANEOUS INSULIN; ANTITHYROID DRUGS; ADOPTIVE TRANSFER; RANDOMIZED-TRIAL AB Diabetes mellitus in humans is a heterogeneous disorder classified clinically into two main types. The diagnosis of type 1 versus type 2 diabetes is made phenotypically using criteria such as age at onset, abruptness of hyperglycemic symptoms, presence of ketosis, degree of obesity and the perceived need for insulin replacement. The pathogeneses of type 1 and type 2 diabetes are believed to be different. Type I diabetes is an autoimmune disease mediated by cellular effector mechanisms; whereas classic type 2 diabetes is not autoimmune but results from insulin resistance and a nonautoimmune insulin secretory defect. Most type 1 diabetes patients are diagnosed in childhood or young adulthood before the age of 35 years. However, there is clearly a subgroup of patients clinically diagnosed with type 2 diabetes who are greater than 35 years of age and have evidence of autoimmunity. The disease of these autoantibody-positive type 2 diabetics is often termed latent autoimmune diabetes in adults (LADA), slowly progressive type I diabetes, latent type 1 diabetes, and type 1.5 diabetes. This group of patients comprises approximately 10-15% of Caucasian type 2 diabetes patients. Type 1.5 diabetes patients tend to present with islet cell autoantibodies, islet-reactive T cells, higher HbA(1c) levels, lower C peptide, and a propensity toward insulin dependency compared to autoantibody-negative classic type 2 diabetes subjects. C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98198 USA. RP Palmer, JP (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way, Seattle, WA 98198 USA. EM jpp@u.washington.edu NR 79 TC 12 Z9 13 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-362-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 958 BP 89 EP 98 PG 10 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BU76Q UT WOS:000176952100011 PM 12021087 ER PT J AU Chang, MP Wang, Q Norman, DC AF Chang, MP Wang, Q Norman, DC TI Diminished proliferation of B blast cell in response to cytokines in ethanol-consuming mice SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article ID RETROVIRUS INFECTION; MURINE AIDS; OLD MICE; T-CELLS; ALCOHOL; EXPRESSION; MECHANISM; IL-4; CONSUMPTION; IMMUNE AB We and others have demonstrated that ethanol suppresses the antibody response in humans and animals. The purpose of this study was to determine whether ethanol affects cytokine-induced proliferative responses of splenic B blast cells, and whether the decreased response was due to an imbalance of the cytokine activity. Thus, the ability of spleen cells from individual ethanol-diet-fed C57BL/6 mice to proliferate and produce cytokines was determined. The ability of anti-IgM monoclonal antibodies (mAb)-activated splenic B blast cells in response to mouse recombinant IL-2 (rIL-2) or rIL-4 was also assessed. A thymidine incorporation assay was used to determine cell proliferation, and the conventional bioassays for cytokine-dependent cell proliferation were used for determining the bioactivity of cytokines. Data were analyzed with general linear model procedure. Our results showed that ethanol weakened the proliferative response of B cells in response to mitogen as well as to mouse rIL-2 and rIL-4. The decreased B cell responses may result from an increase in the production of IL-4 by helper T cells. Finally, in the presence of excessive dose of rIL-4, the proliferative responses of B blast cells from all three groups of mice were diminished (p < 0.01). Thus, our data clearly indicated that the diminished B cell proliferation in ethanol-consuming mice was due in part to an excessive amount of IL-4 produced and an inability of the B cell to interact properly with IL-4 that was secreted by helper T cells. The results should extend our basic understanding of the mechanism by which chronic alcoholism impairs the interactions and interdependence of T- and B-cell immune functions. C1 W Los Angeles Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90025 USA. RP Chang, MP (reprint author), W Los Angeles Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 40 TC 5 Z9 6 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 2002 VL 24 IS 1 BP 69 EP 82 DI 10.1081/IPH-120003404 PG 14 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 553DJ UT WOS:000175660100006 PM 12022446 ER PT J AU Augood, SJ McGowan, EM Finsen, BR Heppelmann, B Emson, PC AF Augood, SJ McGowan, EM Finsen, BR Heppelmann, B Emson, PC TI Non-radioactive in situ hybridization using alkaline phosphatase-labelled oligonucleotides SO IN SITU HYBRIDIZATION PROTOCOLS FOR THE BRAIN, 2ND EDITION SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID ORGANOTYPIC SLICE CULTURES; NONRADIOACTIVE INSITU HYBRIDIZATION; HYDROXYLASE MESSENGER-RNA; MYELIN BASIC-PROTEIN; CENTRAL-NERVOUS-SYSTEM; RAT STRIATUM; CELLULAR COEXPRESSION; GENE-EXPRESSION; NEUROPEPTIDE-Y; SOMATOSTATIN C1 Massachusetts Gen Hosp, Neurol Res, Charlestown, MA 02129 USA. Mayo Clin, Jacksonville, FL USA. Univ So Denmark, Odense Univ, DK-5000 Odense, Denmark. Univ Wurzburg, Inst Physiol, D-97070 Wurzburg, Germany. Babraham Inst, Lab Mol Neurosci, Cambridge CB2 4AT, England. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Neurol Res, Charlestown, MA 02129 USA. NR 47 TC 1 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2002 VL 47 BP 173 EP 201 PG 29 WC Neurosciences SC Neurosciences & Neurology GA BU97E UT WOS:000177531900011 PM 12198799 ER PT J AU Yunis, EJ AF Yunis, EJ TI The entelechial genes: A new hierarchy of biological variability SO IN VIVO LA English DT Article DE entelechial genes; biological variability AB Earlier results on the existence of genes affecting variability are revisited in the context of effects of phase-shifts on lifespan. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Yunis, EJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JAN-FEB PY 2002 VL 16 IS 1 BP 29 EP 30 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 541QX UT WOS:000174996200003 ER PT J AU Panigada, M Sturniolo, T Besozzi, G Boccieri, MG Sinigaglia, F Grassi, GG Grassi, F AF Panigada, M Sturniolo, T Besozzi, G Boccieri, MG Sinigaglia, F Grassi, GG Grassi, F TI Identification of a promiscuous T-cell epitope in Mycobacterium tuberculosis Mce proteins SO INFECTION AND IMMUNITY LA English DT Article ID INTERFERON-GAMMA; ANTIMICROBIAL ACTIVITY; INFECTION; PEPTIDE; GENE; SPECIFICITY; ASSOCIATION; EXPRESSION; RESISTANCE; DEPLETION AB The characterization of Mycobacterium tuberculosis antigens inducing CD4(+) T-cell responses could critically contribute to the development of subunit vaccines for M. tuberculosis. Here we performed computational analysis by using T-cell epitope prediction software (known as TEPITOPE) to predict promiscuous HLA-DR ligands in the products of the mce genes of M. tuberculosis. The analysis of the proliferative responses of CD4(+) T cells from patients with pulmonary tuberculosis to selected peptides displaying promiscuous binding to HLA-DR in vitro led us to the identification of a peptide that induced proliferation of CD4(+) cells from 50% of the tested subjects. This study demonstrates that a systematic computational approach can be used to identify T-cell epitopes in proteins expressed by an intracellular pathogen. C1 Univ Milan, Dipartimento Biol & Genet Sci Med, I-20133 Milan, Italy. Roche Milano Ric, I-20132 Milan, Italy. Consorzio Antitubercolare Ist Villa Marelli, I-20100 Milan, Italy. Univ Pavia, Cattedra Chemioterapia, I-27100 Pavia, Italy. Azienda Osped S Maria Angeli, I-33170 Pordenone, Italy. RP Grassi, F (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith Bldg,Room 736,1 Jimmy Fund Way, Boston, MA 02115 USA. EM fabio_grassi@dfci.harvard.edu FU NIAID NIH HHS [N01 AI-75320] NR 33 TC 53 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2002 VL 70 IS 1 BP 79 EP 85 DI 10.1128/IAI.70.1.79-85.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 504FX UT WOS:000172847600011 PM 11748166 ER PT J AU Kesavalu, L Falk, CW Davis, KJ Steffen, MJ Xu, XP Holt, SC Ebersole, JL AF Kesavalu, L Falk, CW Davis, KJ Steffen, MJ Xu, XP Holt, SC Ebersole, JL TI Biological characterization of lipopolysaccharide from Treponema pectinovorum SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN GINGIVAL FIBROBLASTS; BORRELIA-BURGDORFERI LIPOPROTEINS; TOLL-LIKE RECEPTOR-2; OUTER-MEMBRANE; INFLAMMATORY MEDIATORS; MURINE MODEL; LIPID-A; DENTICOLA; BACTEROIDES; ENDOTOXIN AB This study investigated the endotoxic and biological properties of purified lipopolysaccharide (LPS) isolated from an oral spirochete, Treponema pectinovorum. Endotoxicity, measured by Limulus amoebocyte lysate kinetic assay, showed that the LPS contained 1.28 endotoxin units per mug of purified LPS, which was approximately 4,000 times less than Escherichia coli 055:B5 LPS. To determine in vivo endotoxicity, LPS responder mice were administered LPS following galactosamine (GalN) sensitization. The LPS induced neither endotoxic symptoms nor lethality for 96 h, suggesting negligible or very low endotoxicity. In contrast, infection with live T. pectinovorum induced 100% lethality within 12 h in GalN-sensitized LPS responder mice, indicating an endotoxin-like property of this treponeme. Heat-killed microorganisms exhibited no lethality in GalN-sensitized mice, suggesting that the endotoxicity was associated with heat-labile components. To determine cytokine and chemokine induction by LPS, human gingival fibroblasts were stimulated and secretion of interleukin 1 beta (IL-1 beta), granulocyte-macrophage colony-stimulating factor, gamma interferon, IL-6, IL-8, and monocyte chemoattractant protein 1 (MCP-1) was assessed. The purified LPS induced significant amounts of only IL-6, IL-8, and MCP-1, although they were substantially lower than levels after challenge with live T. pectinovorum. After injection of LPS or live or heat-killed T. pectinovorum, serum was collected from mice and analyzed for proinflammatory cytokines IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. LPS induced only IL-6 consistently. Both live and heat-killed T. pectinovorum induced serum IL-6, which was higher than the level detected following LPS administration. Importantly, live bacteria elicited systemic TNF-alpha and IL-1 beta levels similar to those induced by a lethal dose of live E. coli O111. The results indicated that T. pectinovorum LPS has very low or no endotoxicity, although it can elicit low levels of cytokines from host cells. In contrast to the LPS, live T. pectinovorum demonstrated in vivo toxicity, which was associated with serum IL-1 beta, TNF-alpha, and IL-6, suggesting an endotoxin-like property of a heat-labile molecule(s) of the spirochete. C1 Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY 40536 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. Forsyth Inst, Boston, MA 02115 USA. RP Kesavalu, L (reprint author), Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, 159 Hlth Sci Res Bldg, Lexington, KY 40536 USA. FU NIDCR NIH HHS [DE-11368, R01 DE011368] NR 42 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2002 VL 70 IS 1 BP 211 EP 217 DI 10.1128/IAI.70.1.211-217.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 504FX UT WOS:000172847600030 PM 11748185 ER PT J AU Matsunaga, J Young, TA Barnett, JK Barnett, D Bolin, CA Haake, DA AF Matsunaga, J Young, TA Barnett, JK Barnett, D Bolin, CA Haake, DA TI Novel 45-kilodalton leptospiral protein that is processed to a 31-kilodalton growth-phase-regulated peripheral membrane protein SO INFECTION AND IMMUNITY LA English DT Article ID INTERROGANS SEROVAR HARDJO; OUTER-MEMBRANE; BORRELIA-BURGDORFERI; TREPONEMA-PALLIDUM; PATHOGENIC LEPTOSPIRA; MOLECULAR-CLONING; IMMUNOLOGICAL CHARACTERIZATION; MAMMALIAN INFECTION; SEQUENCE-ANALYSIS; IN-VIVO AB Leptospiral protein antigens are of interest as potential virulence factors and as candidate serodiagnostic and immunoprotective reagents. We identified leptospiral protein antigens by screening a genomic expression library with serum from a rabbit hyperimmunized with formal in-killed, virulent Leptospira kirschneri serovar grippotyphosa. Genes expressing known outer membrane lipoproteins LipL32 and LipL41, the heat shock protein GroEL, and the alpha, beta, and beta' subunits of RNA polymerase were isolated from the library. In addition, a new leptospiral gene that in Escherichia coli expressed a 45-kDa antigen with an amino-terminal signal peptide followed by the spirochetal lipobox Val(-4)-Phe(-3)-Asn(-2)-Ala(-1) down arrow Cys(+1) was isolated. We designated this putative lipoprotein LipL45. Immunoblot analysis of a panel of Leptospira strains probed with LipL45 antiserum demonstrated that many low-passage strains expressed LipL45. In contrast, LipL45 was not detected in high-passage, culture-attenuated strains, suggesting that LipL45 is a virulence-associated protein. In addition, all leptospiral strains tested, irrespective of culture passage, expressed a 31-kDa antigen that was recognized by LipL45 antiserum. Southern blot and peptide mapping studies indicated that this 31-kDa antigen was derived from the carboxy terminus of LipL45; therefore, it was designated P31(LipL35). Membrane fractionation studies demonstrated that P31(LipL45) is a peripheral membrane protein. Finally, we found that P31(LipL45) levels increased as Leptospira entered the stationary phase, indicating that P31(LipL45) levels were regulated. Hamsters infected with L. kirschneri formed an antibody response to LipL45, indicating that LipL45 was expressed during infection. Furthermore, the immunohistochemistry of kidneys from infected hamsters indicated that LipL45 was expressed by L. kirschneri that colonized the renal tubule. These observations suggest that expression of LipL45 responds to environmental cues, including those encountered during infection of a mammalian host. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ So Indiana, Dept Biol, Evansville, IN 47712 USA. Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. RP Matsunaga, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 113,Room 306, Los Angeles, CA 90073 USA. FU NIAID NIH HHS [R21 AI034431-06, AI-34431, R01 AI034431, R21 AI034431, R29 AI034431] NR 56 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2002 VL 70 IS 1 BP 323 EP 334 DI 10.1128/IAI.70.1.323-334.2002 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 504FX UT WOS:000172847600043 PM 11748198 ER PT B AU Podolsky, DK AF Podolsky, DK BE Campieri, M Fiocchi, C Hanauer, SB Jewell, DP Rachmilewitz, D Scholmerich, J TI Inflammatory bowel disease: how does basic science help clinical management? SO INFLAMMATORY BOWEL DISEASE: A CLINICAL CASE APPROACH TO PATHOPHYSIOLOGY, DIAGNOSIS, AND TREATMENT SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 122 on Inflammatory Bowel Disease CY JUN 22-23, 2001 CL BOLOGNA, ITALY C1 Harvard Univ, Massachusetts Gen Hosp, Sch,Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch,Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, 55 Fruit St,GRJ 719, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8772-4 J9 FALK SYMP PY 2002 VL 122 BP 335 EP 342 PG 8 WC Gastroenterology & Hepatology; Genetics & Heredity; Immunology; Pediatrics SC Gastroenterology & Hepatology; Genetics & Heredity; Immunology; Pediatrics GA BU67Y UT WOS:000176702700042 ER PT J AU Weinberg, RA Hahn, WC Watnick, R Stewart, S Mani, SA Yang, J AF Weinberg, RA Hahn, WC Watnick, R Stewart, S Mani, SA Yang, J TI Rules governing the creation of human tumor cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 1 EP 1 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900002 ER PT J AU Korkmaz, KS Korkmaz, CG Pretlow, TG Loda, M Saatcioglu, F AF Korkmaz, KS Korkmaz, CG Pretlow, TG Loda, M Saatcioglu, F TI Differential gene structure and expression pattern of KLK4 compared with other serine proteases and overexpression in prostate cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Oslo, N-0316 Oslo, Norway. Case Western Reserve Univ, Cleveland, OH 44106 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 115 EP 115 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900364 ER PT J AU Yock, TI Sharis, C Tarbell, NJ Schneider, RJ Adams, J AF Yock, TI Sharis, C Tarbell, NJ Schneider, RJ Adams, J TI Proton radiation compared to photon radiation for orbital rhabdomyosarcoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 120 EP 120 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900380 ER PT J AU Hoffman, TJ Gali, H Sieckman, GL Owen, NK Mazuru, DG Forte, LR Volkert, WA AF Hoffman, TJ Gali, H Sieckman, GL Owen, NK Mazuru, DG Forte, LR Volkert, WA TI Development of a new indium-111 labeled Escherichia coli st(h) analog for specific-targeting of human colorectal cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Missouri, Columbia, MO USA. US Dept Vet Affairs, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 225 EP 225 PG 1 WC Oncology SC Oncology GA 565PP UT WOS:000176378900717 ER PT J AU Huang, YH Wu, YY Zhang, Y Wu, MX AF Huang, YH Wu, YY Zhang, Y Wu, MX TI Synergistic and opposing regulation of the anti-apoptotic gene IEX-1 by p53, c-Myc, and multiple NF-kappaB/rel complexes SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 325 EP 326 PG 2 WC Oncology SC Oncology GA 565PP UT WOS:000176378901044 ER PT J AU Hoffman, TJ Smith, CJ Gali, H Owen, NK Sieckman, GL Foster, BN Mazuru, DG Shelton, TD Volkert, WA AF Hoffman, TJ Smith, CJ Gali, H Owen, NK Sieckman, GL Foster, BN Mazuru, DG Shelton, TD Volkert, WA TI Preclinical evaluation of Y-90 and Lu-177 radiolabeled peptides for in vivo targeted radiotherapy of prostate cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Meeting Abstract C1 US Dept Vet Affairs, Columbia, MO USA. Univ Missouri, Columbia, MO 65211 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 2002 SU 13 BP 462 EP 463 PG 2 WC Oncology SC Oncology GA 565PP UT WOS:000176378901490 ER PT J AU Riess, H AF Riess, H TI Integrative time-limited group therapy for bulimia nervosa SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; EATING DISORDERS; RESPONSE PREVENTION; INTERPERSONAL PSYCHOTHERAPY; PHARMACOLOGICAL TREATMENT; PSYCHOLOGICAL TREATMENTS; ADJUSTMENT; EXPOSURE; EFFICACY AB This article presents an integrative group therapy model for the treatment of bulimia nervosa (BN) and describes the 12-session format, incorporating components of cognitive-behavioral therapy (CBT), psychoeducation, interpersonal therapy (IPT), and relational therapy (RT), in detail. Previous reports have found CBT, IPT, and RT to be effective approaches for BN when used separately. The integrative approach may have the advantage of achieving symptom reduction by two different)mediating mechanisms, those that directly affect eating behaviors and those that address the interpersonal and relational context in which the disordered eating has developed. The group approach makes use of the peer group in providing new opportunities for self-exploration and self-correction. One advantage of an integrative model is Patients' exposure to several different treatment modalities from which they can identify specific approaches that are most helpful to their recovery. This identification is valuable in directing future treatment, if needed. Pilot data for this approach are presented. C1 Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Riess, H (reprint author), Massachusetts Gen Hosp, Eating Disorders Unit, 15 Parkman St,Wang ACC Suite 708, Boston, MA 02114 USA. NR 52 TC 7 Z9 7 U1 1 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JAN PY 2002 VL 52 IS 1 BP 1 EP 26 DI 10.1521/ijgp.52.1.1.45469 PG 26 WC Psychology, Clinical SC Psychology GA 506PR UT WOS:000172981400001 PM 11797240 ER PT J AU Motherwell, L AF Motherwell, L TI Women, money, and psychodynamic group psychotherapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID SOCIALIZATION; GENDER AB Developmental concerns and sociocultural expectations may keep female patients and therapists from addressing financial issues openly in group psychotherapy. Interpersonal theory provides a different view of nurturing that may help women leaders deal better with financial discussions in group. This paper includes a review of the literature on group psychotherapy and fees; feminist literature relevant to leadership; money management in group therapy; countertransference; and case examples. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Motherwell, L (reprint author), 1180 Beacon St,Suite 4B, Brookline, MA 02446 USA. NR 30 TC 2 Z9 2 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JAN PY 2002 VL 52 IS 1 BP 49 EP 66 DI 10.1521/ijgp.52.1.49.45465 PG 18 WC Psychology, Clinical SC Psychology GA 506PR UT WOS:000172981400003 PM 11797245 ER PT J AU Baker, PM Rosai, J Young, RH AF Baker, PM Rosai, J Young, RH TI Ovarian teratomas with florid benign vascular proliferation: A distinctive finding associated with the neural component of teratomas that may be confused with a vascular neoplasm SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovarian teratoma; neural tissue; vascular proliferation ID CYSTIC TERATOMA; CARCINOMAS; TUMOR AB Prominent benign vascular proliferations associated with neural tissue in five cases of ovarian teratoma are described. The ages of the patients ranged from 15 to 35 years. Three of the five had tumors confined to the ovary. one had peritoneal implants. and one had widespread metastatic immature teratoma. Two of the patients are alive and well, 8 and 9 years postoperatively, Follow-up is unavailable in two cases and the final case was recent. The tumor in three of the cases had features of mature cystic teratoma including abundant mature neural tissue and, in one instance, microscopic foci of primitive neuroepithelium. The tumor in the fourth case, as an immature teratoma with abundant primitive neuroepithelium, and in the fifth case was a mixed germ cell tumor, composed mostly of immature teratoma with a minor component of yolk sac tumor. In all the tumors there was a prominent vascular proliferation composed of long thin-wailed. curved vessels or a solid glomeruloid arrangement, Immunohistochemistry done in two cases confirmed the vascular nature of the proliferation . Angiogenesis , likely as an expression of vascular endothelial growth factors, is a well-known phenomenon in a variety of neural and neuroendocrine neoplasms, in particular high-grade gliomas. However. very few Cases of this phenomenon have been described in association with neural tissue in the ovary, Recognition of this proliferation as a benign secondary one is important to avoid misdiagnosis of a vascular neoplasm or an immature teratoma, as happened in one of our cases. C1 Univ Manitoba, Hlth Sci Ctr, Dept Pathol, Winnipeg, MB R3A 1R9, Canada. Inst Nazl Tumori, Dipartimento Patol, Milan, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Baker, PM (reprint author), Univ Manitoba, Hlth Sci Ctr, Dept Pathol, 820 Sherbrook Ave,MS 459, Winnipeg, MB R3A 1R9, Canada. NR 9 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2002 VL 21 IS 1 BP 16 EP 21 DI 10.1097/00004347-200201000-00004 PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 506HB UT WOS:000172963000004 PM 11781518 ER PT J AU Oliva, E Clement, PB Young, RH AF Oliva, E Clement, PB Young, RH TI Epithelioid endometrial and endometrioid stromal tumors: A report of four cases emphasizing their distinction from epithelioid smooth muscle tumors and other oxyphilic uterine and extrauterine tumors SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE uterus; endometrial-endometrioid stromal tumor epithelioid cells; oxyphilic cells; immunohistochemistry ID MALIGNANT RHABDOID TUMOR; CORD-LIKE AREAS; MESENCHYMAL TUMORS; UTERUS; SARCOMA; DIFFERENTIATION; NEOPLASMS; PHENOTYPE AB Three endometrial and one extrauterine endometrioid stromal tumors (three sarcomas and one stromal nodule) with a prominent component of epithelioid cells with abundant eosinophilic cytoplasm are described. The patients were 39, 48, 56 and 86 years of age. The endometrial sarcomas were described grossly as an ill-defined tan nodule and "ragged and papillary," respectively, and had the typical infiltrative pattern of low-grade endometrial stromal sarcoma. The stromal nodule was a 13-cm, well circumscribed. yellow, fleshy mass. The extrauterine tumor was probably primary in the sigmoid colon. Oval to polygonal epithelioid cells with abundant eosinophilic cytoplasm accounted for 50% to 90% of the tumor cells. The cytoplasm was granular in one case. None of the tumors contained cells with a rhabdoid appearance. Nuclear and other features did not differ from those of usual endometrial-endometrioid stromal tumors except in one case in which there was greater nuclear pleomorphism. There was strong diffuse cytoplasmic immunoreactivity of all four tumors for vimentin and for CD10 in three of three tumors tested. as well as extensive and moderate reactivity for NK1/C3 and focal weak, reactivity for CD68 in two of three tumors tested. Muscle actin positivity was very focal to extensive and weak to strong in all three tumors tested. mainly in the epithelioid areas a-smooth muscle actin was focally to extensively positive in the epithelioid areas of two of three tumors tested and focal strong desmin positivity (interpreted as indicating smooth muscle metaplasia) was found in the epithelioid areas of one of four tumors, A vaginal recurrence in one case had similar cytologic features to the primary, tumor but when examined initially in the absence of adequate history posed diagnostic difficulty, as did evaluation of the uterine tumor in two other cases and the extrauterine tumor in the Final case, The differential in these cases is primarily with an epithelioid smooth muscle tumor when they are uterine primaries. The typical infiltration facilitates this distinction in the cases of endometrial stromal sarcomas. but this feature is usually only evident in hysterectomy specimens, In limited samples such as biopsy or curettage specimens, and in some cases of recurrent tumor. awareness that endometrial-endometrioid stromal tumors can have epithelioid cells is crucial in the formulation Of the differential diagnosis. Diverse oxyphilic tumors, including deciduoid malignant mesothelioma, can potentially be in the differential diagnosis with extrauterine (endometrioid) stromal sarcomas with epithelioid cells. Immunohistochemical evaluation may potentially provide major aid in diagnosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,James Homer Wright Pathol Labs, Dept Pathol, Fruit St, Boston, MA 02114 USA. NR 33 TC 39 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2002 VL 21 IS 1 BP 48 EP 55 DI 10.1097/00004347-200201000-00009 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 506HB UT WOS:000172963000009 PM 11781523 ER PT J AU Anderson, AE Yang, X Young, RH AF Anderson, AE Yang, X Young, RH TI Epithelioid angiomyolipoma of the ovary: A case report and literature review SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE angiomyolipoma; ovary; oxyphilic tumor ID RENAL ANGIOMYOLIPOMA; TUBEROUS SCLEROSIS; SARCOMATOUS TRANSFORMATION; HEPATIC ANGIOMYOLIPOMA; HMB-45; METASTASES; HAMARTOMAS; VARIANTS; LESIONS; GENE AB Angiomyolipoma (AML) is a benign mesenchymal neoplasm that mainly occurs in the kidney either sporadically or in patients with tuberous sclerosis complex (TSC). Extra-renal AML is uncommon. We describe a 39-year-old female with a history of TSC and bilateral multicentric renal AML who presented with a persistent cystic ovarian mass that fluctuated in size during 2 years of ultrasonographic observation before its removal by salpingo-oophorectomy. The 4.5-cm mass was solid and cystic and tan-yellow. Microscopic examination showed an admixture of epithelioid cells, smooth muscle bundles, large thick-walled blood vessels, and mature adipose tissue. The epithelioid cells had abundant eosinophilic cytoplasm and many had bizarre atypical nuclei including multinucleated forms. Mitoses were rare, Typical smooth muscle cells and the epithelioid cells were strongly immunoreactive for HMB-45. To our knowledge, this represents the first report of an AML arising in the ovary. The differential with other oxyphilic tumors of the ovary is discussed. C1 Long Isl Jewish Med Ctr, Dept Pathol, New Hyde Pk, NY 11040 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Anderson, AE (reprint author), Long Isl Jewish Med Ctr, Dept Pathol, New Hyde Pk, NY 11040 USA. NR 38 TC 36 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2002 VL 21 IS 1 BP 69 EP 73 DI 10.1097/00004347-200201000-00013 PG 5 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 506HB UT WOS:000172963000013 PM 11781527 ER PT J AU Yorioka, CW Coletta, RD Alves, F Nisitimoto, IN Kowalski, LP Graner, E AF Yorioka, CW Coletta, RD Alves, F Nisitimoto, IN Kowalski, LP Graner, E TI Matrix metalloproteinase-2 and-9 activities correlate with the disease-free survival of oral squamous cell carcinoma patients SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE oral squamous cell carcinoma; matrix metalloproteinase; zymography ID LYMPH-NODE METASTASIS; TUMOR INVASION; CLINICOPATHOLOGICAL FEATURES; EXPRESSION; CANCER; INHIBITOR; CAVITY; MODEL AB The aim of the present study was to determine whether matrix metalloproteinase (MMP) activities are associated with the clinicopathological features of oral squamous cell carcinomas (OSCCs). Forty-four samples of primary OSCCs were microdissected, incubated in serum-free cell culture medium for 16 h, and the activity of secreted MMPs analyzed by gelatin zymography and densitometry. Two major enzymes with gelatinolytic activity were produced by all tumor samples and characterized as MMP-2 and -9 by their molecular weight, immunoprecipitation using monoclonal antibodies, and specific inhibition by 1,10-phenanthroline or EDTA. Patients with tumors showing elevated activity of MMP-2 and -9 had shorter disease-free survival after treatment than patients with tumors exhibiting low MMP activities. These results suggest that the zymographic measurement of the MMP-2 and -9 activities in OSCC specimens may be useful to predict the disease-free survival period of patients affected by these tumors. C1 UNICAMP, Sch Dent Piracicaba, Dept Oral Pathol, BR-13414018 Piracicaba, Brazil. Hosp Canc AC Camargo, Fundacao Antonio Prudente, Dept Otorhinolaryngol Head & Neck Surg, BR-01509010 Sao Paulo, SP, Brazil. RP Graner, E (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Room D-742,44 Binney St, Boston, MA 02115 USA. RI Graner, Edgard/K-4411-2012; Francisco, Suely/D-9065-2014; Coletta, Ricardo/B-4909-2015; Alves, Fabio/B-7892-2011; Kowalski, Luiz/D-1701-2012; OI Coletta, Ricardo/0000-0001-5285-3046; Alves, Fabio/0000-0003-3372-1536; Kowalski, Luiz/0000-0001-5865-9308; Kowalski, Luiz Paulo/0000-0002-0481-156X NR 29 TC 54 Z9 60 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 2002 VL 20 IS 1 BP 189 EP 194 PG 6 WC Oncology SC Oncology GA 505ML UT WOS:000172916500028 PM 11743663 ER PT J AU Wu, QW Mohan, R Niemierko, A Schmidt-Ullrich, R AF Wu, QW Mohan, R Niemierko, A Schmidt-Ullrich, R TI Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE intensity-modulated radiotherapy; IMRT; optimization; biologic models; equivalent uniform dose ID NORMAL TISSUE; VOLUME CONSTRAINTS; COMPLICATION PROBABILITIES; RADIATION-THERAPY; IRRADIATION; TOLERANCE; CANCER AB Purpose: The equivalent uniform dose (EUD) for tumors is defined as the biologically equivalent dose that, if given uniformly, will lead to the same cell kill in the tumor volume as the actual nonuniform dose distribution. Recently, a new formulation of EUD was introduced that applies to normal tissues as well. EUD can be a useful end point in evaluating treatment plans with nonuniform dose distributions for three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. In this study, we introduce an objective function based on the EUD and investigate the feasibility and usefulness of using it for intensity-modulated radiotherapy optimization. Methods and Materials: We applied the EUD-based optimization to obtain intensity-modulated radiotherapy plans for prostate and head-and-neck cancer patients and compared them with the corresponding plans optimized with dose-volume-based criteria. Results: We found that, for the same or better target coverage, EUD-based optimization is capable of improving the sparing of critical structures beyond the specified requirements. We also found that, in the absence of constraints on the maximal target dose, the target dose distributions are more inhomogeneous, with significant hot spots within the target volume. This is an obvious consequence of unrestricted maximization target cell kill and, although this may be considered beneficial for some cases, it is generally not desirable. To minimize the magnitude of hot spots, we applied dose inhomogeneity constraints to the target by treating it as a "virtual" normal structure as well. This led to much-improved target dose homogeneity, with a small, but expected, degradation in normal structure sparing. We also found that, in principle, the dose-volume objective function may be able to arrive at similar optimum dose distributions by using multiple dose-volume constraints for each anatomic structure and with considerably greater trial-and-error to adjust a large number of objective function parameters. Conclusion: The general inference drawn from our investigation is that the EUD-based objective function has the advantages that it needs only a small number of parameters and allows exploration of a much larger universe of solutions, making it easier for the optimization system to balance competing requirements in search of a better solution. (C) 2002 Elsevier Science Inc. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. McGuire Vet Affairs Hosp, Richmond, VA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Wu, QW (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, 401 Coll St, Richmond, VA 23298 USA. FU NCI NIH HHS [CA 74043, CA 84430] NR 22 TC 230 Z9 243 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2002 VL 52 IS 1 BP 224 EP 235 DI 10.1016/S0360-3016(01)02585-8 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 508TF UT WOS:000173105100028 PM 11777642 ER PT J AU Scully, RE AF Scully, RE TI One pathologist's reminiscences of the 20th century and random thoughts about the 21st: Reflections at the millenium SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article ID CLINICIAN INTERPRETATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Scully, RE (reprint author), Massachusetts Gen Hosp, Warren Bldg 242,Fruit St, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JAN PY 2002 VL 10 IS 1 BP 8 EP 13 DI 10.1177/106689690201000103 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 534GP UT WOS:000174577000003 PM 11927964 ER PT J AU Kampman, KM Pettinati, H Volpicelli, J Kaempf, G Turk, E Insua, A Lipkin, C Sparkman, T O'Brien, CP AF Kampman, KM Pettinati, H Volpicelli, J Kaempf, G Turk, E Insua, A Lipkin, C Sparkman, T O'Brien, CP TI Concurrent cocaine withdrawal alters alcohol withdrawal symptoms SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE cocaine; alcohol; withdrawal; detoxification ID HUMANS; COCAETHYLENE; SEVERITY; DEPENDENCE; DISORDERS; ADDICTION; ABUSERS; MODEL AB This study compares alcohol withdrawal severity during outpatient detoxification in alcohol dependent subjects (ALC) and in subjects dependent on both alcohol and cocaine (ALC/COC). Subjects included 123 ALC and 66 ALC/COC subjects. Baseline demographic and drug use variables, alcohol withdrawal symptoms, and the total amount of oxazepam taken during alcohol detoxification were compared between the two groups. Compared to ALC subjects, ALC/COC subjects were younger, more likely to be African-American, and had less severe histories of alcohol dependence. However, alcohol withdrawal symptom severity did not differ significantly between the two groups. Nevertheless, controlling for differences in alcohol use history, ALC/COC subjects still received less oxazepam than did ALC subjects to treat alcohol withdrawal symptoms. Despite similar intensity of alcohol withdrawal symptoms, ALC/COC subjects received less oxazepam to treat alcohol withdrawal symptoms compared to ALC subjects. Both subject and clinician factors may explain the difference in oxazepam use. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [P60 DA051186] NR 25 TC 2 Z9 2 U1 3 U2 3 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2002 VL 21 IS 4 BP 13 EP 26 DI 10.1300/J069v21n04_02 PG 14 WC Substance Abuse SC Substance Abuse GA 606BC UT WOS:000178711900002 PM 12296498 ER PT J AU Alenius, H Laouini, D Woodward, A Mizoguchi, E Bhan, AK Castigli, E Oettgen, HC Geha, RS AF Alenius, H Laouini, D Woodward, A Mizoguchi, E Bhan, AK Castigli, E Oettgen, HC Geha, RS TI Mast cells regulate IFN-gamma expression in the skin and circulating IgE levels in allergen-induced skin inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE atopic dermatitis; mast cells; inflammation; antibodies; cytokines; in vivo animal models ID DEFICIENT W/WV MICE; ATOPIC-DERMATITIS; IN-VIVO; INTERFERON-GAMMA; T-CELLS; AIRWAY HYPERRESPONSIVENESS; HUMAN KERATINOCYTES; DENDRITIC CELLS; ADHESION MOLECULE-1; CONTROLLED TRIAL AB Background: Mast cells are important effector cells in IgE-mediated allergic reactions. They are present in normal skin and increased in skin lesions of patients with atopic dermatitis (AD). Objective: We used mice deficient in mast cells (W/W-v) to assess, the role of these cells in a marine model of allergen-induced skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA); the model exhibits many of the characteristics of AD. Methods: Mice deficient in mast cells were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 and IFN-gamma mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined. Results. Infiltration in W/W-v mice by mononuclear cells, T cells, and eosinophils in OVA-sensitized skin was comparable to that in wild-type (WT) controls. Expression of IL-4 mRNA in sensitized skin sites was similarly increased in WT and W/W-v mice. However. IFN-gamma mRNA expression was significantly increased in sensitized skin of W/W-v mice but not in that of WT controls. IL-4 mRNA was readily detectable in unsensitized skin of WT controls but not in that of W/W-v mice, whereas expression of IL-12 p40 mRNA was significantly increased in unsensitized skin of W/W-v mice in comparison with WT controls. Total serum IgE levels were. significantly increased after epicutancous sensitization in W/W-v mice in comparison with WT controls. Conclusion: These results suggest that mast cells regulate IFN-gamma expression in the skin and IgE levels in the circulation in a model of allergen-induced skin inflammation with similarities to AD. This is important, given the role of IFN-gamma in keratinocyte injury in AD and the role of IgE-mediated reactions in exacerbating AD. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. RP Geha, RS (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Enders 8,300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-31541]; NIAMS NIH HHS [AR-47417]; NIDDK NIH HHS [DK43351, DK47677] NR 68 TC 47 Z9 48 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 BP 106 EP 113 DI 10.1067/mai.2002.120553 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 519RM UT WOS:000173739300017 PM 11799374 ER PT J AU Camargo, CA Clark, S AF Camargo, CA Clark, S TI Emergency department management of acute asthma between 1996-2001: Potential impact of the 1997 NAEPP guidelines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 457 BP S156 EP S156 DI 10.1016/S0091-6749(02)81593-7 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800456 ER PT J AU Clark, S Kamarthi, GS Okafo, T Gaeta, TJ Camargo, CA AF Clark, S Kamarthi, GS Okafo, T Gaeta, TJ Camargo, CA TI Multicenter study of emergency department visits for bee sting allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York Methodist Hosp, Brooklyn, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 822 BP S269 EP S269 DI 10.1016/S0091-6749(02)81957-1 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800819 ER PT J AU Hong, SJ Bloch, KJ Wong, JT AF Hong, SJ Bloch, KJ Wong, JT TI Rapid IV challenge/desensitization using iso-osmolor radio-contrast medium (RCM) in two patients at high risk for anaphylactoid reactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 441 BP S150 EP S150 DI 10.1016/S0091-6749(02)81577-9 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800440 ER PT J AU Krishna, VM Bloch, KJ Carey, RW AF Krishna, VM Bloch, KJ Carey, RW TI A new parameter of the tumor lysis syndrome: Marked increase in serum IgM M-component in two patients with Waldenstrom's macroglobulinemia (WM) treated with 2-chlorodeoxyadenosine (cladribine) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 701 BP S232 EP S232 DI 10.1016/S0091-6749(02)81836-X PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800698 ER PT J AU Nguyen, R Yu, FC Klaustermeyer, WB AF Nguyen, R Yu, FC Klaustermeyer, WB TI Response to cyclosporin in tacrolimus resistant patient with atopic dermatitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 1089 BP S349 EP S349 DI 10.1016/S0091-6749(02)82223-0 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744801085 ER PT J AU Shearer, WT Rosenblatt, HM Spector, S Stiehm, ER Wara, D Douglas, S Luzuriaga, K McFarland, E Yogev, R Rathore, M Levy, W Graham, BI Oyomopito, R Gelman, R AF Shearer, WT Rosenblatt, HM Spector, S Stiehm, ER Wara, D Douglas, S Luzuriaga, K McFarland, E Yogev, R Rathore, M Levy, W Graham, BI Oyomopito, R Gelman, R TI Age-related expression of naive (CD45RA/62L) and activation (HLA DR/CD38) surface markers on CD4(+) and CD8(+) T-cell in normal children (birth to 18 years) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp, Philadelphia, PA 19104 USA. Univ Massachusetts, Worcester, MA 01605 USA. Univ Colorado, Denver, CO 80202 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Florida, Jacksonville, FL USA. SSS, Rockville MD FSTRF, Amherst, MA USA. HSPH, Boston, MA USA. DFCI, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 596 BP S199 EP S199 DI 10.1016/S0091-6749(02)81732-8 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800595 ER PT J AU Wong, JT Hsu, YL Chen, HJL Bloch, KJ AF Wong, JT Hsu, YL Chen, HJL Bloch, KJ TI Severe angioedema: Interaction among ACEI, ASA/NSAID, narcotics, and other contributing factors SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 369 BP S128 EP S128 DI 10.1016/S0091-6749(02)81505-6 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800368 ER PT J AU Yu, FC Klaustermeyer, WB AF Yu, FC Klaustermeyer, WB TI Cholinergic urticaria associated with acquired hypohidrosis in an HIV-positive patient SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2002 VL 109 IS 1 SU S MA 366 BP S127 EP S127 DI 10.1016/S0091-6749(02)81502-0 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 519UX UT WOS:000173744800365 ER PT J AU Amory, JK Anawalt, BD Blaskovich, PD Gilchriest, J Nuwayser, ES Matsumoto, AM AF Amory, JK Anawalt, BD Blaskovich, PD Gilchriest, J Nuwayser, ES Matsumoto, AM TI Testosterone release from a subcutaneous, biodegradable microcapsule formulation (Viatrel) in hypogonadal men SO JOURNAL OF ANDROLOGY LA English DT Article DE hypogonadism; poly-lactide-co-glycolide; pharmacokinetics; androgen; dihydrotestosterone; estradiol ID ANDROGEN REPLACEMENT; THERAPY; PHARMACOKINETICS; UNDECANOATE; DENSITY; MOOD AB Men with hypogonadism require testosterone replacement for optimal health. In the United States, testosterone is currently administered by daily transdermal patches, topical gels or intramuscular injections every 1-3 weeks. Biodegradable polylactide-co-glycolide microcapsules are currently used for long-term drug delivery in humans. Such microcapsules that contain testosterone could provide a better means of long-term testosterone therapy. We therefore studied the pharmacokinetics and pharmacodynamics of testosterone release from testosterone microcapsules in men with hypogonadism. Fourteen men who had been treated previously with testosterone were enrolled in an open-label, prospective study of testosterone microcapsule administration, Subjects were enrolled if 2 consecutive serum total testosterone levels were lower than 8.7 nmol/L after a 4-week washout from testosterone therapy. Subjects were injected with a single dose of either 267 mg (n = 7) or 534 mg (n = 7) of (Viatrel) testosterone microcapsule, and serum total testosterone, dihydrotestosterone, estradiol, sex-hormone binding globulin, luteinizing hormone, and follicle-stimulating hormone levels were determined at days -14, -7, and 0 before the injection; at days 1, 2, and 7 after the injection; and then weekly thereafter for 8-12 weeks. Mean serum total testosterone levels peaked immediately following injection on day 1 at 25.2 +/- 2.6 nmol/L in the 267 mg group and 34.7 +/- 2.4 nmol/L in the 534 mg group. Total serum testosterone levels declined gradually and fell below 8.7 nmol/L at 42 days after injection in the 267 mg group, and 70 days after injection in the 534 mg group. Estradiol and dihydrotestosterone levels followed a similar pattern. Mean serum free testosterone also peaked immediately following injection on day 1 at 0.51 +/- 0.05 nmol/L in the 267 mg group and 0.97 +/- 0.08 nmol/L in the 534 mg group. No significant adverse reactions were seen, although 2 subjects complained of transient tenderness and fullness at their injection sites. We conclude that a single injection of 534 mg of testosterone microcapsules to men with hypogonadism normalizes serum hormone levels for up to 10-11 weeks, albeit with a pronounced early peak and a relatively long period of low-normal serum total testosterone. Subcutaneously administered testosterone microcapsules may provide a safe and convenient method for the long-term treatment of male hypogonadism or testosterone replacement in male contraceptive regimens. C1 Univ Washington, Dept Med, Sch Med, Seattle, WA 98185 USA. Vet Affairs Puget Sound Hlth Care Syst, Populat Ctr Res Reprod, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Biotek Inc, Woburn, MA USA. RP Amory, JK (reprint author), Univ Washington, Dept Med, Sch Med, 1959 NE Pacific St, Seattle, WA 98185 USA. FU NCRR NIH HHS [2RR4 HD20347-02A1] NR 18 TC 14 Z9 17 U1 0 U2 3 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2002 VL 23 IS 1 BP 84 EP 91 PG 8 WC Andrology SC Endocrinology & Metabolism GA 504EA UT WOS:000172843300015 PM 11780927 ER PT J AU Burnett, AL Chang, AG Crone, JK Huang, PL Sezen, SF AF Burnett, AL Chang, AG Crone, JK Huang, PL Sezen, SF TI Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase SO JOURNAL OF ANDROLOGY LA English DT Article DE transgenic mice; carbachol; cholinergic; endothelium; penis ID CAVERNOSUM SMOOTH-MUSCLE; CORPUS CAVERNOSUM; RELAXATION; ACETYLCHOLINE; DYSFUNCTION; RAT; RESPONSES; MEDIATOR; THERAPY AB With the current understanding that nitric oxide (NO) mediates penile erection, the endothelial isoform of NO synthase (eNOS) has been implicated in this function. We undertook this study applying transgenic mice with targeted deletion of the eNOS gene (eNOS-/- mice) as an experimental approach to evaluate the importance of eNOS in cholinergically stimulated erectile function in vivo. Combined pharmacostimulation with intracavernosal carbachol (3 ng) administration and submaximal cavernous nerve (CN) electrical stimulation (16 Hz, 5 millisecond, 1 V) simultaneous with intracavernosal pressure (ICP) monitoring, and both biochemical assay of NO synthase activity and Western blot analysis of eNOS protein content in penile tissue, were performed on eNOS-/- mice and wild-type controls. Combined intracavernosal carbachol administration and submaximal CN electrical stimulation raised the recorded ICP, elicited by CN electrical stimulation alone in wild-type mice (from 35.7 +/- 2.7 to 48.1 +/- 5.5 mm Hg, P < .05) but not in eNOS-/- mice (from 54.9 +/- 6.3 to 51.0 +/- 9.5 mm Hg, not significant [NS]). Pretreatment with the nonselective nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 100 mg intracavernosally) blocked electrically stimulated ICP responses in eNOS-/- mice to baseline levels (37.8 +/- 4.4 vs 12.7 +/- 4.0 mm Hg, P < .05). In penes of eNOS-/- mice, approximately 60% NO synthase activity of wildtype penis levels was retained (NS), and eNOS protein was absent. We concluded that eNOS-/- mice preserve erectile function on the basis of a noncholinergic but NO-dependent mechanism and that eNOS physiologically mediates penile erection under cholinergic stimulation. C1 Johns Hopkins Univ Hosp, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Burnett, AL (reprint author), Johns Hopkins Univ Hosp, Dept Urol, James Buchanan Brady Urol Inst, Marburg 407,600 N Wolfe St, Baltimore, MD 21287 USA. FU NHLBI NIH HHS [HL57818]; NIDDK NIH HHS [DK02568]; NINDS NIH HHS [NS33335] NR 30 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2002 VL 23 IS 1 BP 92 EP 97 PG 6 WC Andrology SC Endocrinology & Metabolism GA 504EA UT WOS:000172843300016 PM 11780929 ER PT J AU Buhlmann, U McNally, RJ Wilhelm, S Florin, I AF Buhlmann, U McNally, RJ Wilhelm, S Florin, I TI Selective processing of emotional information in body dysmorphic disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE body dysmorphic disorder; stroop; cognitive bias; selective attention ID POSTTRAUMATIC-STRESS-DISORDER; STROOP TASK; ANXIETY; CUES AB Body dysmorphic disorder (BDD) is a syndrome characterized by distress about imagined defects in one's appearance. Though categorized as a somatoform disorder, BDD is marked by many characteristics associated with social phobia (e.g., fear of negative evaluation) and obsessive-compulsive disorder (e.g., intrusive thoughts about one's ugliness, checking). In the present experiment, we tested whether BDD patients exhibit selective processing of threat in the emotional Stroop paradigm as do anxiety -disordered patients. Relative to healthy control participants, BDD patients exhibited greater Stroop interference for positive and negative words, regardless of disorder-relevance, than for neutral words. Further analyses suggested that interference tended to be greatest for positive words related to BDD. These data suggest that BDD patients are vulnerable to distraction by emotional cues in general, and by words related to their current concerns in particular, Results suggest that BDD may indeed be related to anxiety disorders such as social phobia. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Marburg, D-35032 Marburg, Germany. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cambridge, MA USA. RP Buhlmann, U (reprint author), Massachusetts Gen Hosp East, OCD Clin, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 26 TC 48 Z9 48 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PY 2002 VL 16 IS 3 BP 289 EP 298 AR PII S0887-6185(02)00100-7 DI 10.1016/S0887-6185(02)00100-7 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 585ZW UT WOS:000177558300005 PM 12214814 ER PT J AU Oh, Y Osato, MS Han, X Bennett, G Hong, WK AF Oh, Y Osato, MS Han, X Bennett, G Hong, WK TI Folk yoghurt kills Helicobacter pylori SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article ID INFECTION; BACTERIOCINS; HUMANS AB Aims: To evaluate a traditional yoghurt used as folk medicine for its ability to kill Helicobacter pylori in vitro. Methods and Results: Micro-organisms from the yoghurt were identified and tested in different food substrates for their effects on H. pylori in a co-culture well system. Two yeasts and several strains of lactobacilli were isolated from the yoghurt, and both the yeast and the lactobacilli independently showed cidal activity against H. pylori. The microbes from the original yoghurt also retained their cidal effect when grown in corn meal and soy milk. Conclusions: The yeast and lactobacilli found in this yoghurt form a hardy symbiotic culture. The organisms secrete soluble factors capable of killing H. pylori, and these factors may include some organic by-products of fermentation. Significance and Impact of the Study: These yoghurt-derived food preparations could become simple and inexpensive therapies to suppress H. pylori infections in endemic countries. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Vet Adm Hosp, Dept Gastroenterol, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Microbiol Lab Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. Rice Univ, Dept Biochem, Houston, TX 77251 USA. RP Oh, Y (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Box 432,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672] NR 14 TC 29 Z9 32 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2002 VL 93 IS 6 BP 1083 EP 1088 DI 10.1046/j.1365-2672.2002.01779.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 618GN UT WOS:000179410500020 PM 12452966 ER PT J AU Harris, RS Willey-Courand, DB Head, CA Galletti, GG Call, DM Venegas, JG AF Harris, RS Willey-Courand, DB Head, CA Galletti, GG Call, DM Venegas, JG TI Regional V-A, Q, and V-A/Q during PLV: effects of nitroprusside and inhaled nitric oxide SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sodium nitroprusside; positron emission tomography; partial liquid ventilation; ventilation; perfusion; alveolar ventilation ID PARTIAL LIQUID VENTILATION; PULMONARY BLOOD-FLOW; RESPIRATORY-DISTRESS-SYNDROME; GAS-EXCHANGE IMPROVES; ACUTE LUNG INJURY; MECHANICAL VENTILATION; PERFUSION DISTRIBUTION; PRONE POSITION; FILLED LUNG; PERFLUOROCARBON AB Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Call, DM (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 40 TC 24 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2002 VL 92 IS 1 BP 297 EP 312 PG 16 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 510JR UT WOS:000173205400039 PM 11744673 ER PT J AU Franceschini, MA Boas, DA Zourabian, A Diamond, SG Nadgir, S Lin, DW Moore, JB Fantini, S AF Franceschini, MA Boas, DA Zourabian, A Diamond, SG Nadgir, S Lin, DW Moore, JB Fantini, S TI Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE tissue spectroscopy; frequency-domain; pulse oximetry; hemoglobin saturation ID OXYHEMOGLOBIN SATURATION; OXYGEN-CONSUMPTION; HUMAN BRAIN; OPTICAL MAMMOGRAPHY; ABSORPTION-SPECTRA; NEWBORN-INFANTS; PULSE OXIMETRY; HUMAN FOREARM; BLOOD-FLOW; SPECTROSCOPY AB We present a noninvasive method to measure the venous oxygen saturation (Sv(O2)) in tissues using near-infrared spectroscopy (NIRS). This method is based on the respiration-induced oscillations of the near-infrared absorption in tissues, and we call it spiroximetry (the prefix spiro means respiration). We have tested this method in three piglets (hind leg) and in eight human subjects (vastus medialis and vastus lateralis muscles). In the piglet study, we compared our NIRS measurements of the Sv(O2) (Sv(O2)-NIRSresp) with the Sv(O2) of blood samples. Sv(O2)-NIRSresp and Sv(O2) of blood samples agreed well over the whole range of Sv(O2) considered (20-95%). The two measurements showed an average difference of 1.0% and a standard deviation of the difference of 5.8%. In the human study, we found a good agreement between Sv(O2)-NIRSresp and the Sv(O2) values measured with the NIRS venous occlusion method. Finally, in a preliminary test involving muscle exercise, Sv(O2)-NIRSresp showed an expected postexercise decrease from the initial baseline value and a subsequent recovery to baseline. C1 Tufts Univ, Dept Elect Engn & Comp Sci, Ctr Bioengn, Medford, MA 02155 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Franceschini, MA (reprint author), Tufts Univ, Dept Elect Engn & Comp Sci, Ctr Bioengn, 4 Colby St, Medford, MA 02155 USA. OI Diamond, Solomon/0000-0002-7589-2942 FU NIMH NIH HHS [R01 MH062854, R01 MH062854-01, R01-MH-62854]; NINDS NIH HHS [R29-NS-38842] NR 56 TC 59 Z9 61 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2002 VL 92 IS 1 BP 372 EP 384 PG 13 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 510JR UT WOS:000173205400046 PM 11744680 ER PT J AU Lewandrowski, KU Bondre, SP Shea, M Untch, CM Hayes, WC Hile, DD Wise, DL Trantolo, DJ AF Lewandrowski, KU Bondre, SP Shea, M Untch, CM Hayes, WC Hile, DD Wise, DL Trantolo, DJ TI Composite poly(lactide)/hydroxylapatite screws for fixation of osteochondral osteotomies. A morphometric, histologic and radiographic study in sheep SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE bioresorbable screw; hydroxylapatite; osteotomy healing; implant osteointegration ID FOREIGN-BODY REACTIONS; POLY-L-LACTIDE; POLY(L-LACTIDE) BONE PLATES; CONTINUOUS PASSIVE MOTION; FULL-THICKNESS DEFECTS; FRACTURE FIXATION; BIODEGRADABLE IMPLANTS; MECHANICAL-PROPERTIES; ARTICULAR-CARTILAGE; INTERNAL-FIXATION AB The aim of this study was to evaluate the healing of an osteochondral fragment created in the distal sheep femur in response to fixation with a biodegradable polylactide/hydroxylapatite composite screw, Poly(L-lactide) screws were used for comparison. At follow-up times of 4 and 8 weeks, the specimens were examined with standard radiography and computed tomography, as well as with macro- and micro-histomorphometry. The intact contralateral femur served as a control, Only minimal signs of degradation of the polymer could be seen in the histologic specimens. At 8 weeks, nearly all osteotomies had healed completely and an association between implant type and delayed osteotomy healing was found. The width of the repair tissue at the tissue-implant interface was 250 48 pm. representing a clear transition zone of newly formed trabecular bone separating the implant from the surrounding plexiform bone. This study showed that large polylactide implants which are buffered with hydroxylapatite show benign tissue responses and good implant osteointegration. The osteotomy healing in a weight-bearing osteochondral fragment model in sheep utilizing a composite polylactide/hydroxylapatite screw was equivalent to a similar polylactide screw implant, indicating that hydroxylapatite-buffered screw implants could be used for similar indications in current clinical use. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Oregon Hlth Sci Univ, Dept Orthopaed & Rehabil, Portland, OR 97201 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [2 R44 AR44500-02] NR 51 TC 3 Z9 3 U1 1 U2 1 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 2002 VL 13 IS 11 BP 1241 EP 1258 DI 10.1163/156856202320892984 PG 18 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 630MW UT WOS:000180112800005 PM 12518802 ER PT J AU Friedrichs, WE Reddy, SV Bruder, JM Cundy, T Cornish, J Singer, FR Roodman, GD AF Friedrichs, WE Reddy, SV Bruder, JM Cundy, T Cornish, J Singer, FR Roodman, GD TI Sequence analysis of measles virus nucleocapsid transcripts in patients with Paget's disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Paget's disease; measles virus nucleocapsid transcripts; osteoclasts; polymerase chain reaction ID CANINE-DISTEMPER VIRUS; POLYMERASE CHAIN-REACTION; BONE TISSUE; CELLS; OSTEOCLASTS; MUTATIONS; ANTIGENS; CULTURES; ABSENCE; RNA AB It has been debated for almost 30 years whether Paget's disease of bone results from paramyxoviral infection of osteoclasts (OCs). Paramyxoviral-like nuclear inclusions are found in OCs from patients with Paget's disease, and measles virus (MV) or canine distemper virus (CDV) messenger RNA (mRNA) transcripts have been detected by in situ hybridization in bone cells from pagetic lesions. Furthermore, immunocytochemical studies have shown the presence of several paramyxoviral species in OCs from patients with Paget's disease. However, others have been unable to detect paramyxoviral transcripts in bone samples from patients with Paget's disease or marrow cultures from involved sites of patients with Paget's disease. Furthermore, no one has been able to isolate an infectious virus from pagetic bone samples or marrow cells from patients with Paget's disease, and a full-length viral gene has not been sequenced from pagetic samples. In this study, we have obtained the full-length sequence for the MV nucleocapsid (MVNP) gene in bone marrow from an involved site from a patient with Paget's disease and more than 700 base pairs (bps) of MVNP sequence in 3 other patients with Paget's disease. These sequences were undetectable in four normal marrow samples studied simultaneously. The sequences from the patients contained multiple mutations that differed from the Edmonston strain MVNP gene. These findings are consistent with the presence of a chronic MV infection in affected sites from these patients with Paget's disease. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med Endocrinol, San Antonio, TX USA. Univ Auckland, Auckland 1, New Zealand. John Wayne Canc Inst, Santa Monica, CA USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Roodman, GD (reprint author), E1152 Biomed Sci Tower,200 Lothrup, Pittsburgh, PA 15261 USA. OI Cundy, Timothy/0000-0003-4890-9400 FU NIA NIH HHS [AG13625]; NIAMS NIH HHS [AR44603]; NIDCR NIH HHS [DE12603] NR 25 TC 58 Z9 63 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2002 VL 17 IS 1 BP 145 EP 151 DI 10.1359/jbmr.2002.17.1.145 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502EH UT WOS:000172730400017 PM 11771661 ER PT J AU Ruskin, JN Camm, AJ Zipes, DP Hallstrom, AP McGrory-Usset, ME AF Ruskin, JN Camm, AJ Zipes, DP Hallstrom, AP McGrory-Usset, ME TI Implantable cardioverter defibrillator utilization based on discharge diagnoses from medicare and managed care patients SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; implant rates; utilization; ventricular tachycardia; ventricular fibrillation; sudden cardiac death; claims-based study ID COST-EFFECTIVENESS; VENTRICULAR ARRHYTHMIAS; CARDIAC DEFIBRILLATORS; SUDDEN-DEATH; HIGH-RISK; PREVENTION; AMIODARONE; DISEASE; THERAPY AB Introduction: Implantable cardioverter defibrillators (ICDs) have become an accepted therapy for patients at high risk of sudden cardiac death. To assess the current utilization of this therapy, we estimated the number of patients at risk of sudden death using an historical claims-based study and compared these results to current ICD usage volumes. Methods and Results: Managed care and Medicare databases (claims related to 4.6 million covered U.S. lives during a 12-month period) were analyzed to identify patients who had either a primary or secondary diagnosis of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest. These patients were further required to have a diagnosis code indicating a previous myocardial infarction or congestive heart failure. Patients who died during the study period or did not have medical insurance were excluded. In the base case scenario, 1,226 patients per million population were identified as potential ICD candidates. Sensitivity analyses reduced that value to a range from 736 to 1,140 ICD candidates per million population. Sensitivity factors considered included acute myocardial infarction, comorbidities, age, secondary ventricular tachycardia/ventricular fibrillation diagnosis, and varying degrees of left ventricular dysfunction. These results contrast with an ICD usage rate of 416 per million population in the United States and lower rates in other countries. Conclusion: This study suggests that, based on discharge diagnoses, many patients who could benefit from ICDs are not receiving this therapy. Diverse reasons for this underutilization should be addressed to improve access to, and appropriate use of, this therapy. C1 Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. St George Hosp, Med Sch, London, England. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Washington, AVID CTC, Seattle, WA USA. Medtronic Inc, Minneapolis, MN USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB 122 32 Fruit St, Boston, MA 02114 USA. OI Zipes, Douglas/0000-0001-7141-6829 NR 25 TC 58 Z9 58 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2002 VL 13 IS 1 BP 38 EP 43 DI 10.1046/j.1540-8167.2002.00038.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 517MA UT WOS:000173613300007 PM 11843481 ER PT J AU Chen, MH Cash, EP Danias, PG Kissinger, KV Bornstein, BA Rhodes, LM Gelman, R Harris, JR Manning, WJ AF Chen, MH Cash, EP Danias, PG Kissinger, KV Bornstein, BA Rhodes, LM Gelman, R Harris, JR Manning, WJ TI Respiratory maneuvers decrease irradiated cardiac volume in patients with left-sided breast cancer SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE cardiac magnetic resonance imaging; cardiotoxicity; breast cancer; radiation therapy; respiratory maneuvers; women ID CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; POSTOPERATIVE RADIOTHERAPY; HOLD TECHNIQUE; RADIATION-THERAPY; MEDICAL PROGRESS; MORTALITY; SURGERY; TRIAL; WOMEN AB Late cardiac morbidity and mortality among left breast cancer survivors treated with radiation therapy is related to cardiac volume included in the radiation portals. To determine if respiratory maneuvers can help decrease cardiac volume included in the radiation portals for left-sided breast cancer, 17 women with breast cancer, who had undergone left breast radiation therapy, undervent cardiac magnetic resonance imaging (MRI). Cardiac volume within the radiation portals was assessed from a transverse stack of eight, 10-mm thick, contiguous slices, covering the entire heart and obtained during breathholding at (1) endtidal volume (ETid) and (2) deep inspiration. Fourteen subjects (93% of those who completed the study) had inclusion of at least a portion of their heart within the radiation portals at ETid (median: 25.9 cm(3), range 4.2-119.1 cm(3)). In all subjects, inspiratory breathholding decreased irradiated cardiac volume [median change: - 18.1 cm(3) (-49%), p less than or equal to 0.001 vs. ETid]. In 21% of patients, the entire heart could be displaced outside the radiation field with deep inspiration. Age was not correlated with change or percentage change in cardiac volume with respiratory, maneuvers. We conclude that in breast cancer patients, deep inspiratory, maneuvers significantly decrease irradiated cardiac volume included in the left breast radiation field. Such all approach during delivery, of radiation therapy allows preservation of radiation dosage to the breast, while reducing cardiac involvement and possible associated cardiovascular toxicity. C1 Beth Israel Deaconess Med Ctr, Cardiovasc Div, Dept Med, Boston, MA USA. Harvard Univ, Med Sch, Boston, MA USA. Dana Farber Canc Inst, Boston, MA USA. Joint Ctr Radiat Therapy, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med Radiol, Boston, MA USA. RP Chen, MH (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. NR 25 TC 26 Z9 26 U1 2 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2002 VL 4 IS 2 BP 265 EP 271 DI 10.1081/JCMR-120003952 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 559ZT UT WOS:000176057200009 PM 12074141 ER PT J AU Young, BB Zhang, GY Koch, M Birk, DE AF Young, BB Zhang, GY Koch, M Birk, DE TI The roles of types XII and XIV collagen in fibrillogenesis and matrix assembly in the developing cornea SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE corneal stroma; corneal development; fibril formation; matrix assembly; extracellular matrix; collagen types XII and XIV ID TISSUE-SPECIFIC EXPRESSION; EMBRYONIC AVIAN CORNEA; EXTRACELLULAR MATRICES; MONOCLONAL-ANTIBODIES; HEPARIN-BINDING; MESSENGER-RNA; NC1 DOMAIN; FIBRILS; FIBROMODULIN; ALPHA-1(XVI) AB Corneal transparency depends on the architecture of the stromal extracellular matrix, including fibril diameter, packing, and lamellar organization. The roles of collagen types XII and XIV in regulation of corneal fibrillogenesis and development were examined. The temporal and spatial expression patterns were analyzed using semiquantitative RT-PCR, in situ hybridization, Western analysis, and immunohistochemistry. Expression of types XII and XIV collagens in cornea development demonstrated that type XII collagen mRNA levels are constant throughout development (I OD-adult) while type XIV mRNA is highest in early embryonic stages (10D-14D), decreasing significantly by hatching. The spatial expression patterns of types XII and XIV collagens demonstrated a homogeneous signal in the stroma for type XIV collagen, while type XII collagen shows segregation to the sub-epithelial and sub-endothelial stroma during embryonic stages. The type XII collagen in the anterior stroma was an epithelial product during development while fibroblasts contributed in the adult. Type XIV collagen expression was highest early in development and was absent by hatching. Both types XII and type XIV collagen have different isoforms generated by alternative splicing that may alter specific interactions important in fibrillogenesis, fibril-fibril interactions, and higher order matrix assembly. Analysis of these splice variants demonstrated that the long XII mRNA levels were constant throughout development, while the short XII NC3 mRNA levels peaked early (12D) followed by a decrease. Both type XIV collagen NC1 splice variants are highest during early stages (12D-14D) decreasing by 17D of development. These data suggest type XII collagen may have a role in development of stromal architecture and maintenance of fibril organization, while type XIV collagen may have a role in regulation of fibrillogenesis. C1 Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Birk, DE (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, 1020 Locust St,JAH 543, Philadelphia, PA 19107 USA. RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088 FU NEI NIH HHS [EY05129] NR 46 TC 50 Z9 53 U1 1 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 87 IS 2 BP 208 EP 220 DI 10.1002/jcb.10290 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 601MX UT WOS:000178451300009 PM 12244573 ER PT J AU Li, TK Baksh, S Cristillo, AD Bierer, BE AF Li, TK Baksh, S Cristillo, AD Bierer, BE TI Calcium- and FK506-independent interaction between the immunophilin FKBP51 and calcineurin SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE immunosuppression; transplantation; FKBPs; cyclosporin; rapamycin; calcineurin; immunophilin ID RECEPTOR-MEDIATED TRANSCRIPTION; CIS-TRANS-ISOMERASES; GLUCOCORTICOID RECEPTOR; BINDING-PROTEIN; FK506-BINDING PROTEIN; PROGESTERONE-RECEPTOR; PHOSPHATASE-ACTIVITY; SIGNALING PATHWAYS; HOMOLOGOUS PROTEIN; MOLECULAR-CLONING AB FKBP51 is a member of the immunophilin family having intrinsic peptidyl-prolyl cis-trans-isomerase (PPlase) activity. Its enzymatic activity is inhibited by binding either immunosuppressive agent FK506 or rapamycin. Similar to FKBP12, but at higher concentrations of FK506, FKBP51 has been shown to inhibit the serine/threonine phosphatase activity of calcineurin in the presence of calcium and calmodulin. Here we show that a glutathione S-transferase (GST) fusion protein of FKBP51 on glutathione-Sepharose beads precipitated both purified calcineurin from bovine brain and calcineurin from murine T cell lysates. Surprisingly, the binding of GST-FKBP51 to calcineurin was FK506-independent and independent of a requirement for calcium or exogenous calmodulin. Unlike FKBP12, FKBP51 transiently expressed in COS-7 cells was precipitated by calcineurin bound to calmodulin-Sepharose beads in the absence of either FK506 or rapamycin. Unlike FKBP12, however, overexpression of FKBP51 in Jurkat T cells did not significantly affect the transcriptional activation of nuclear factor of activated T cells (NFAT) upon physiological stimulation, nor did it affect the ability of FK506 to inhibit NFAT-driven transcription. We generated a series of FKBP51 mutations to map the interaction of FKBP51 with calcineurin. Deletion of the aminoterminal, FKBP12-like domain of FKBP51 did not affect the ability of FKBP51 to bind to purified calcineurin, while deletion of the FKBP51 carboxyterminal domain abrogated the ability of FKBP51 to bind to calcineurin. Taken together, these results demonstrate a novel interaction between calcineurin and the immunophilin FKBP51 that is independent of calcium, calmodulin, and drug. The binding site on calcineurin for FKBP51 is separable from the immunophilin PPlase-active and drug-binding site. Published (C) 2001 Wiley-Liss, Inc.(dagger). C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Bldg 10,Room 6C208, Bethesda, MD 20892 USA. NR 60 TC 23 Z9 24 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 VL 84 IS 3 BP 460 EP 471 DI 10.1002/jcb.10026 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 513BP UT WOS:000173358300004 PM 11813252 ER PT J AU Tse, WT Egalka, MC AF Tse, WT Egalka, MC TI Stem cell plasticity and blood and marrow transplantation: A clinical strategy SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE stem cell plasticity; transplantation; conditioning; growth factor; mobilization ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; ADULT-MOUSE BRAIN; BONE-MARROW; IN-VIVO; BODY IRRADIATION; CARDIAC-MUSCLE; HEMOPHILIA-A; MICE; CHIMERISM AB The newly described phenomenon of stem cell plasticity raises interesting biological questions and offers exciting opportunities in clinical application. This review uses the well-established practice of blood and marrow transplantation as a paradigm to explore the clinical consequences of this finding. Recently proposed non-myeloablative conditioning regimens have shown that mixed donor-host hematolymphoid chimerism can be established with relatively low toxicity in both animal studies and human trials. Hematopoietic growth factor treatment of transplanted patients can mobilize a large number of donor stem cells to migrate from marrow to non-hematopoietic organs. We propose that these advances, in conjunction with the developmental plasticity of stem cells, can constitute components of a clinical strategy to use blood and marrow transplantation as a platform to treat systemic diseases involving nonhematopoietic tissues. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tse, WT (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. NR 55 TC 2 Z9 2 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2002 SU 38 BP 96 EP 103 DI 10.1002/jcb.10038 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 550EA UT WOS:000175489600014 ER PT J AU Pitteloud, N Hayes, FJ Boepple, PA DeCruz, S Seminara, SB MacLaughlin, DT Crowley, WF AF Pitteloud, N Hayes, FJ Boepple, PA DeCruz, S Seminara, SB MacLaughlin, DT Crowley, WF TI The role of prior pubertal development, biochemical markers of testicular maturation, and genetics in elucidating the phenotypic heterogeneity of idiopathic hypogonadotropic hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; SERUM INHIBIN-B; ADRENAL HYPOPLASIA CONGENITA; LINKED KALLMANN SYNDROME; CLINICAL RESEARCH-CENTER; LUTEINIZING-HORMONE; SERTOLI CELLS; GNRH REPLACEMENT; CANDIDATE GENE; RECEPTOR AB As our knowledge of the molecular mechanisms underlying idiopathic hypogonadotropic hypogonadisin (IHH) expands, it becomes increasingly important to define the phenotypic spectrum of IHH. In this study we examined historical, clinical, biochemical, histological, and genetic features in 78 men with IHH to gain further insight into the phenotypic heterogeneity of the syndrome. We hypothesized that at least some of the spectrum of phenotypes could be explained by placing the disorder into a developmental and genetic context. Thirty-eight percent of the population had Rallmann syndrome (KS; IHH with anosmia), 54% had normosmic IHH, and 8% had acquired IHH after completion of puberty. Phenotypically, KS represented the most severe subtype (87% with complete absence of any history or signs of spontaneous pubertal development), normosmic IHH displayed the most heterogeneity (41% with some evidence of spontaneous puberty), and acquired IHH after completion of puberty clustered at the mildest end (all had complete puberty). Classification based on historical or clinical evidence of prior pubertal development, rather than the presence or absence of sense of smell, served to distinguish the population more clearly with respect to other clinical and biochemical features. Comparing IHH patients according to the absence (68%) or presence (24%) of some prior pubertal development revealed significant differences in testicular size (3.3 +/- 0.2 vs. 11.8 +/- 1.2 ml; P < 0.001), incidence of cryptorchidism (40% vs. 5%; P < 0.05), microphallus (21% vs. 0%; P < 0.05), inhibin B levels (45 :L 4 vs. 144 h 20 pg/ml; P < 0.0001), and Mullerian inhibitory substance levels (9.8 +/- 1.4 vs. 2 +/- 0.5 ng/ml). Most familial cases had no pubertal development (95% vs. 5%; P < 0.001); males with mutations in the KAL gene displayed the most severe phenotype. Mean gonadotropins levels (LH, 1.8 +/- 0.1 vs. 2.9 +/- 0.4 IU/liter, FSH, 2.2 +/- 0.2 vs. 3.3 +/- 0.3 IU/liter; P < 0.05) and the finding of apulsatile LH secretion based on frequent sampling (80% vs. 55%; P < 0.05) were statistically different between patients lacking and those exhibiting partial pubertal development, but the overlap was extensive. The use of clinical parameters (presence or absence of some evidence of prior pubertal development, cryptorchidism, and microphallus), biochemical markers of testicular growth and differentiation (inhibin B and Mullerian inhibitory substance), and genetic evidence provides insight into the time of onset and the severity of GnRH deficiency. Viewing IHH in the full context of its developmental, genetic, and biochemical complexity permits greatest insight into its phenotypic variability. C1 Massachusetts Gen Hosp, Natl Ctr Infertil Res, Pediat Surg Res Lab, Dept Med,Reprod Endocrine Unit, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Natl Ctr Infertil Res, Pediat Surg Res Lab, Dept Med,Reprod Endocrine Unit, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI PITTELOUD, Nelly/K-2709-2014 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U54 HD028138, P30 HD028138, R01 HD015788, R01-HD-15788, U54 HD029164, U54-HD-28138]; NIDDK NIH HHS [U54-DK-07027-24] NR 61 TC 89 Z9 92 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2002 VL 87 IS 1 BP 152 EP 160 DI 10.1210/jc.87.1.152 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 514PR UT WOS:000173450700025 PM 11788640 ER PT J AU Tang, SJ Nieto, JM Jensen, DM Ohning, GV Pisegna, JR AF Tang, SJ Nieto, JM Jensen, DM Ohning, GV Pisegna, JR TI The novel use of an intravenous proton pump inhibitor in a patient with short bowel syndrome SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE intravenous proton pump inhibitor; pantoprazole; short bowel syndrome ID PANTOPRAZOLE AB Recent evidence suggests that parenteral proton pump inhibitors (PPIs) can effectively control gastric acid hypersecretion. Intravenous PPI (omeprazole) can substantially reduce the risk of recurrent bleeding in patients with peptic ulcer disease. We describe a patient with short bowel syndrome who had recurrent life-threatening upper gastrointestinal bleeding from severe gastric and esophageal ulcerations. The patient had failed long-terns maximal-dose intravenous ranitidine therapy but was successfully treated and maintained on long-term therapy with an intravenous PPI (pantoprazole). To our knowledge, this is the first case report in the literature describing the use of an intravenous PPI to treat upper gastrointestinal bleeding in a patient with complete intestinal resection. Intravenous PPIs should be considered as the first line of treatment of erosive esophagitis and peptic ulcer disease in patients with short bowel syndrome and in patients who are nil per os and who fail intravenous H-2-receptor antagonist treatment. Parenteral PPI may also be the drug of choice in intensive care patients who have erosive esophagitis. Furthermore, this is the first case report describing the novel use of intravenous pantoprazole to treat erosive esophagitis in a patient with short bowel syndrome, suggesting that intravenous PPI may also be useful for the treatment of ulcer prophylaxis in patients undergoing intestinal transplantation. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, 111C,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JAN PY 2002 VL 34 IS 1 BP 62 EP 63 DI 10.1097/00004836-200201000-00012 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 506UZ UT WOS:000172991300012 PM 11743248 ER PT J AU Husain, Z Levitan, E Larsen, CE Mirza, NM Younes, S Yunis, EJ Alper, CA Dubey, DP AF Husain, Z Levitan, E Larsen, CE Mirza, NM Younes, S Yunis, EJ Alper, CA Dubey, DP TI HLA-Cw7 zygosity affects the size of a subset of CD158b(+) natural killer cells SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE natural killer cells; HLA; CD16; killer immunoglobulin like; CD94 ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; MHC CLASS-I; NK CELLS; INHIBITORY RECEPTORS; T-CELLS; HLA-C; ACTIVATION; EXPRESSION; DISEASE AB Individuals with certain HLA class 1 genotypes are highly susceptible to disease after viral infection. Natural killer (NK) cells kill virus-infected cells through a mechanism involving HLA class 1receptors. These facts may be connected if an individual's HLA genotype regulates the number and function of NK cells. We have observed that subjects homozygous for the HLA-B/C region of conserved major histocompatibility complex (MHC) extended haplotypes have lower NK cell activity and a significantly lower frequency of CD16(+)CD56(+) NK cells than heterozygotes. The proportion of CD16(-)CD56(+) NK cells was unaffected by zygosity for the HLA-B/C region. We show here that the frequency of CD16(+)CD158b(+), but not CD16(-)CD158b(+) NK cells, was significantly lower (p <0.026) in homozygotes for HLA-Cw7 (NK1 ligand) haplotypes than in heterozygotes. The frequencies of CD16(+)CD158a(+) and CD16(-)CD158a(+) and CD16(-)CD158a(+) or CD16(+)NKB1(+) and CD16(-)NKB1(+) NK cells were not different in these donor groups. These findings suggest that the proportion of NK cells coexpressing CD16 and CD158b, but not CD158a nor NKB1, is influenced by zygosity for the HLA-Cw7 (NK1 ligand) haplotype. Since NK cells are involved in protection from virus infection, a reduced size of a ligand-specific NK subset in individuals homozygous for some HLA-B/C haplotypes may help explain their increased susceptibility to virus-induced diseases. C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Dubey, DP (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583] NR 46 TC 15 Z9 16 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 2002 VL 22 IS 1 BP 28 EP 36 DI 10.1023/A:1014204519468 PG 9 WC Immunology SC Immunology GA 539RT UT WOS:000174884800005 PM 11958591 ER PT J AU Donato, JL Ko, J Kutok, JL Cheng, T Shirakawa, T Mao, XQ Beach, D Scadden, DT Sayegh, MH Adra, CN AF Donato, JL Ko, J Kutok, JL Cheng, T Shirakawa, T Mao, XQ Beach, D Scadden, DT Sayegh, MH Adra, CN TI Human HTm4 is a hematopoietic cell cycle regulator SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID S-PHASE; PROTEIN PHOSPHATASE; DEPENDENT KINASES; GENE-EXPRESSION; CDK INHIBITORS; PHORBOL ESTER; STEM-CELLS; DIFFERENTIATION; PROGRESSION; PHOSPHORYLATION AB Proper control of cell cycle progression is critical for the constant self-renewal, differentiation, and homeostasis of the hematopoietic system. Cells of all types share the common cell cycle regulators. The different expression patterns of common regulators, in a broad sense, define cell-type or lineage specificity. However, there remains the possibility of hematopoietic cell cycle regulators tailored to the demands of the hematopoietic system. Here we describe a novel protein, HTm4, which serves as a hematopoietic cell cycle regulator. Our data indicate that HTm4 is expressed in hematopoietic tissues and is tightly regulated during the differentiation of hematopoietic stem cells. It binds to cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes, and the three proteins demonstrate similar patterns of cellular expression in human lymphoid tissues. HTm4 stimulates the phosphatase activity of KAP, and its C-terminal region is required for binding to KAP-CDK2 complexes and the modulation of KAP activity. Overexpression of HTm4 can cause cell cycle arrest at the G(0)/G(1) phase. Thus, HTm4 is a novel hematopoietic modulator for the G(1)-S cell cycle transition. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Wales Swansea, Expt Med Unit, Swansea, W Glam, Wales. Kyoto Univ, Grad Sch Publ Hlth, Dept Hlth Promot & Human Behav, Kyoto, Japan. RIKEN, SNP, Typing Ctr, Tokyo, Japan. Genetica Inc, Cambridge, MA USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Div Nephrol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Adra, CN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Hematol & Oncol, 99 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [P30CA6516, P30 CA006516]; NHLBI NIH HHS [HL-44851, HL-65909, R01 HL044851, R01 HL065909]; NIAID NIH HHS [AI-33100, AI-43663, R29 AI043663]; NIDDK NIH HHS [K08 DK 02761, K08 DK002761] NR 42 TC 46 Z9 51 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2002 VL 109 IS 1 BP 51 EP 58 DI 10.1172/JCI14025 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 509RZ UT WOS:000173164600009 PM 11781350 ER PT J AU Kukreja, A Cost, G Marker, J Zhang, CH Sun, Z Lin-Su, K Ten, S Sanz, M Exley, M Wilson, B Porcelli, S Maclaren, N AF Kukreja, A Cost, G Marker, J Zhang, CH Sun, Z Lin-Su, K Ten, S Sanz, M Exley, M Wilson, B Porcelli, S Maclaren, N TI Multiple immuno-regulatory defects in type-1 diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID KILLER T-CELLS; ALPHA-CHAIN; IFN-GAMMA; NKT CELLS; INTERLEUKIN-2 PRODUCTION; SELECTIVE REDUCTION; AUTOIMMUNE-DISEASES; POSITIVE SELECTION; MONONUCLEAR-CELLS; INTERFERON-GAMMA AB Susceptibility to immune-mediated diabetes (IMD) in humans and NOD mice involves their inherently defective T cell immunoregulatory abilities. We have followed natural killer (NK) T cell numbers in patients with IMD, both by flow cytometry using mAbs to the characteristic junctions found in the T cell receptors of this cell subtype, and by semiquantitative RT-PCR for the corresponding transcripts. Both before and after clinical onset, the representation of these cells in patients' PBMCs is reduced. We also report low numbers of resting CD4(+) CD25(+) T cells in IMD patients, a subset of T cells shown to have important immunoregulatory functions in abrogating autoimmunities in 3-day thymectomized experimental mice. Whereas a biased Th1 to Th2 cytokine profile has been suggested to underlie the pathogenesis of IMD in both species, we found defective production of IFN-gamma in our patients after in vitro stimulation of their PBMCs by phorbol-myristate acetate and ionomycin and both IFN-gamma and IL-4 deficiencies in Valpha24(+) NK T-enriched cells. These data suggest that multiple immunoregulatory T (Treg) cell defects underlie islet cell autoimmunity leading to IMD in humans and that these lesions may be part of a broad T cell defect. C1 Cornell Univ, Weill Coll Med, Dept Pediat, New York, NY 10021 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Canc Immunol & AIDS Program, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. RP Maclaren, N (reprint author), Cornell Univ, Weill Coll Med, Dept Pediat, LC-623,1300 York Ave, New York, NY 10021 USA. FU NCRR NIH HHS [M01-RR06020] NR 69 TC 505 Z9 539 U1 2 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2002 VL 109 IS 1 BP 131 EP 140 DI 10.1172/JCI13605 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 509RZ UT WOS:000173164600017 PM 11781358 ER PT J AU Mauvais-Jarvis, F Ueki, K Fruman, DA Hirshman, MF Sakamoto, K Goodyear, LJ Iannacone, M Accili, D Cantley, LC Kahn, CR AF Mauvais-Jarvis, F Ueki, K Fruman, DA Hirshman, MF Sakamoto, K Goodyear, LJ Iannacone, M Accili, D Cantley, LC Kahn, CR TI Reduced expression of the murine p85 alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-KINASE-B; INDUCED GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY SUBUNIT; RECEPTOR SUBSTRATE-1; GENE-TRANSCRIPTION; GLYCOGEN-SYNTHESIS; MICE LACKING; S6 KINASE; ACTIVATION AB A critical component of insulin action is the enzyme phosphoinositide (PI) 3-kinase. The major regulatory subunits of PI 3-kinase, p85alpha and its splice variants, are encoded by the Pik3r1 gene. Heterozygous disruption of Pik3r1 improves insulin signaling and glucose homeostasis in normal mice and mice made insulin-resistant by heterozygous deletion of the Insulin receptor and/or insulin receptor substrate-1 (IRS1) genes. Reduced expression of p85 modulates the molecular balance between this protein, the p 110 catalytic subunit of PI 3-kinase, and the IRS proteins. Thus, despite the decrease in p85alpha, PI 3-kinase activation is normal, insulin-stimulated Akt activity is increased, and glucose tolerance and insulin sensitivity are improved. Furthermore, Pik3r1 heterozygosity protects mice with genetic insulin resistance from developing diabetes. These data suggest that regulation of p85alpha levels may provide a novel therapeutic target for the treatment of type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Cell Biol,Div Signal Transduct, Boston, MA USA. Columbia Univ, Diabet Res Unit, New York, NY USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Iannacone, Matteo/B-3342-2008; Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK-33201, DK-55545, R01 DK033201, R01 DK055545]; NIGMS NIH HHS [GM-41890, R01 GM041890, R37 GM041890] NR 39 TC 169 Z9 175 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2002 VL 109 IS 1 BP 141 EP 149 DI 10.1172/JCI13305 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 509RZ UT WOS:000173164600018 PM 11781359 ER PT J AU Farrell, JJ Taupin, D Koh, TJ Chen, D Zhao, CM Podolsky, DK Wang, TC AF Farrell, JJ Taupin, D Koh, TJ Chen, D Zhao, CM Podolsky, DK Wang, TC TI TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INTESTINAL TREFOIL FACTOR; PANCREATIC SPASMOLYTIC POLYPEPTIDE; EPIDERMAL GROWTH-FACTOR; CELL-MIGRATION; RECEPTOR-BINDING; TRANSGENIC MICE; DEFICIENT MICE; FACTOR-ALPHA; P-DOMAIN; EXPRESSION AB Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa. To study the physiologic role of TFF2,,we have generated TFF2-deficient mice through targeted gene disruption. Homozygous mutant mice were viable and fertile without obvious gastrointestinal abnormalities. However, quantitative measurements revealed a significant decrease in gastric mucosal thickness and in gastric mucosal proliferation rates, In addition, there was a twofold increase in activated parietal cells resulting in a twofold increase in basal and stimulated gastric acid output and an undetectable serum gastrin level. The TFF2-deficient mice also showed a significant increase in the degree of gastric ulceration after administration of indomethacin. Taken together, these results suggest a physiologic role for TFF2 to promote mucosal healing through the stimulation of proliferation and downregulation of gastric acid secretion. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Canberra Hosp, Gastroenterol Unit, Garran, Australia. Norwegian Univ Sci & Technol, Univ Trondheim Hosp, N-7034 Trondheim, Norway. RP Wang, TC (reprint author), Univ Massachusetts, Med Ctr, Div Gastroenterol, Lazare Res Bldg,Room 208,364 Plantat St, Worcester, MA 01605 USA. FU NIDDK NIH HHS [R01 DK048077, R01 DK-52778, P30 DK043351, R01 DK-48077, R01 DK052778, DK-43351, R01 DK-58889-01, DK-41577] NR 52 TC 134 Z9 148 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2002 VL 109 IS 2 BP 193 EP 204 DI 10.1172/JCI12529 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 514DP UT WOS:000173423200007 PM 11805131 ER PT J AU Cianfrocca, M Cooley, TP Lee, JY Rudek, MA Scadden, DT Ratner, L Pluda, JM Figg, WD Krown, SE Dezube, BJ AF Cianfrocca, M Cooley, TP Lee, JY Rudek, MA Scadden, DT Ratner, L Pluda, JM Figg, WD Krown, SE Dezube, BJ TI Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: A phase I AIDS malignancy consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TISSUE INHIBITOR; METASTATIC PHENOTYPE; GELATINASE-A; TUMOR-GROWTH; CELLS; DOXYCYCLINE; EXPRESSION; MELANOMA; MICE; PHARMACOKINETICS AB Purpose: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are over-expressed in Kaposi's sarcoma (KS) cells. The primary aim was to define the safety and toxicity of the MMP inhibitor COL-3 in patients with AIDS-related KS. Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). Patients and Methods: COL-3 was administered orally once daily, and doses were escalated in cohorts of three to six subjects. Patients with symptomatic visceral KS or severe tumor-associated edema were excluded. Antiretroviral therapy was permitted but not required. Study end points were grade 3 or 4 toxicity or progressive KS. Serial blood specimens were obtained for pharmacokinetics and levels of MMP-2, MMP-9, VEGF, and bFGF. Results: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg/m(2)/d. Prior KS therapy was reported by 17 patients (94%). COL-3-related grade 3 or 4 adverse events were reported by six patients and included photosensitivity, rash, and headache. There was one complete response and seven partial responses, for an overall response rate of 44%, with a median response duration of 25+ weeks. The median COL-3 half-life was 39.3 hours (range, 4.1 to 251.1 hours). There was a significant difference between responders and nonresponders with respect to the change in MMP-2 serum levels from baseline to minimum value on treatment (P = .037). Conclusion: COL-3 administered orally once daily to patients with AIDS-related KS is reasonably well tolerated. The most common adverse event was dose-related photosensitivity. Antitumor activity was noted. Further evaluation of COL-3 for the treatment of KS is warranted. (C) 2001 by American Society of Clinical Oncology. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. Washington Univ, St Louis, MO USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Clin Pharmacokinet Sect, Bethesda, MD USA. NCI, Canc Therapy Evaluat Program, Investigat Drug Branch, Bethesda, MD USA. Univ Alabama, AIDS Malignancy Consortium Operat Ctr, Birmingham, AL USA. RP Dezube, BJ (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,CC-913, Boston, MA 02215 USA. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [U01 CA 70019, U01 CA 70047, U01 CA 70054, U01 CA 70062, U01 CA 70072, U01 CA 70080, U01 CA 71375, U01 CA 83035]; NCRR NIH HHS [RR 00036, RR 00533, RR 01032] NR 33 TC 113 Z9 117 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2002 VL 20 IS 1 BP 153 EP 159 DI 10.1200/JCO.20.1.153 PG 7 WC Oncology SC Oncology GA 510XE UT WOS:000173231900020 PM 11773164 ER PT J AU LeClerc, JM Billett, AL Gelber, RD Dalton, V Tarbell, N Lipton, JM Barr, R Clavell, LA Asselin, B Hurwitz, C Schorin, M Lipshultz, SE Declerck, L Silverman, LB Cohen, HJ Sallan, SE AF LeClerc, JM Billett, AL Gelber, RD Dalton, V Tarbell, N Lipton, JM Barr, R Clavell, LA Asselin, B Hurwitz, C Schorin, M Lipshultz, SE Declerck, L Silverman, LB Cohen, HJ Sallan, SE TI Treatment of childhood acute lymphoblastic leukemia: Results of Dana-Farber ALL consortium protocol 87-01 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COGNITIVE SEQUELAE; CRANIAL RADIATION; THERAPY; RISK; CHILDREN; CANCER; INDUCTION; METHOTREXATE; PREVENTION AB Purpose: To improve efficacy and reduce toxicity of treatment for children with acute lymphoblastic leukemia. Patients and Methods: Patients from all risk groups, including infants and those with T-cell disease, were treated between 1987 and 1991. Standard-risk (SR) patients did not receive cranial irradiation, whereas high-risk (HR) and very high-risk (VHR) patients participated in a randomized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day (hyperfractionated). Results: At a median follow-up of 9.2 years, the 9-year event-free survival (EFS +/- SE) was 75% +/- 2% for all 369 patients, 77% +/- 4% for the 142 SR patients, and 73% +/- 3% for the 227 HR/VHR patients (P =.37 comparing SR and HR/VHR). The CNS, with or without concomitant bone marrow involvement, was the first site of relapse in 19 (13%) of the 142 SR patients: 16 (20%) of 79 SR boys and three (5%) of 63 SR girls. This high incidence of relapses necessitated a recall of SR boys for additional therapy. CNS relapse occurred in only two (1%) of 227 HR and VHR patients. There were no outcome differences found among randomized treatment groups. Nine-year overall survival was 84% +/- 2% for the entire population, 93% +/- 2% for SR children, and 79% +/- 3% for HR and VHR children (P <.01 comparing SR and HR/VHR). Conclusion: A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys, which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy. For HR/ VHR patients, inability to salvage after relapse (nearly all of which were in the bone marrow) remains a significant clinical problem. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Hop St Justine, Div Hematol Oncol, Montreal, PQ H3T 1C5, Canada. McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Div Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA USA. Mt Sinai Med Ctr, Dept Pediat, New York, NY 10029 USA. Univ Rochester, Med Ctr, Div Pediat Hematol Oncol, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Div Pediat Cardiol, Rochester, NY 14642 USA. San Jorge Childrens Hosp, Div Pediat Oncol, San Juan, PR USA. Maine Med Ctr, Maine Childrens Canc Program, Div Pediat Hematol Oncol, Portland, ME 04102 USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Portland, ME 04102 USA. Alton Ochsner Med Fdn & Ochsner Clin, Div Pediat Oncol, New Orleans, LA 70121 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. RP Sallan, SE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 06515, CA 68484] NR 30 TC 30 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2002 VL 20 IS 1 BP 237 EP 246 DI 10.1200/JCO.20.1.237 PG 10 WC Oncology SC Oncology GA 510XE UT WOS:000173231900031 PM 11773175 ER PT J AU Spencer, TJ Biederman, J Wilens, TE Faraone, SV AF Spencer, TJ Biederman, J Wilens, TE Faraone, SV TI Overview and neurobiology of attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Meeting on Novel Treatments for Attention-Deficit/Hyperactivity Disorder in Children and Adults CY NOV 15-17, 2001 CL BOSTON, MASSACHUSETTS ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE-D4 RECEPTOR GENE; FOLLOW-UP; PSYCHIATRIC STATUS; SCHOOL SAMPLE; CHILDREN; TWIN; ADHD; PREVALENCE; CHILDHOOD AB Although attention-deficit/hyperactivity disorder (ADHD) impairs millions of people worldwide, both the prevalence and existence of the disorder are being reevaluated at the phenotypic level. To safeguard against overdiagnosis, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), demands that individuals with ADHD have pervasive impairment, that is, impairment in more than I setting. However, the appropriateness of the DSM-IV classification of ADHD is also undergoing reevaluation. Like the symptoms of a developmental disability, the symptoms of ADHD must be evaluated in the context of age-based norms; therefore, the current criteria for ADHD, which are not age referenced, may minimize the rate of persistence of ADHD into adulthood. In an effort to better understand the pathophysiology of ADHD, recent research has focused on identifying the etiology of ADHD. These studies have revealed that the disorder is highly heritable and may be associated with neurobiological deficits in the prefrontal cortex and related subcortical systems. Etiologic studies have also identified candidate genes and prenatal and perinatal risk factors for ADHD. As the causes and course of ADHD are better understood, a new generation of medications is being developed for the disorder. Although stimulants are often effective in reducing the symptoms of the disorder, as a class they have limitations such as a lack of 24-hour-a-day coverage, unwanted side effects, potential for abuse, and lessened effectiveness in the context of some comorbidities. Therefore, the treatment characteristics of newer, more selective treatments such as atomoxetine should continue to be explored in ADHD. C1 Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02138 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, 15 Parkman St WACC 725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 61 TC 115 Z9 124 U1 7 U2 21 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 12 BP 3 EP 9 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 626UV UT WOS:000179892700001 PM 12562055 ER PT J AU Caroff, SN Mann, SC Campbell, EC Sullivan, KA AF Caroff, SN Mann, SC Campbell, EC Sullivan, KA TI Movement disorders associated with atypical antipsychotic drugs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Safety Profiles of Mood Stabilizers Antipsychotics and Broad Spectrum Psychotropics CY AUG 29-30, 2001 CL AMELIA ISLAND, FLORIDA ID NEUROLEPTIC MALIGNANT SYNDROME; PLACEBO-CONTROLLED TRIAL; CHRONIC-SCHIZOPHRENIC PATIENTS; LEVODOPA-INDUCED DYSKINESIAS; TARDIVE-DYSKINESIA; DOUBLE-BLIND; PARKINSONS-DISEASE; SCHIZOAFFECTIVE DISORDER; PSYCHOTIC DISORDERS; ACUTE EXACERBATION AB Data from clinical trials reviewed in this article fulfill predictions based on preclinical findings that atypical antipsychotic drugs are associated with a reduced potential for inducing extrapyramidal symptoms (EPS) and other movement disorders. Atypical drugs have been shown to reduce all subtypes of acute EPS, the frequency of EPS-related patient dropouts, and the need for concomitant antiparkinsonian drug use. Clozapine remains superior to other atypicals in treating psychosis without worsening motor symptoms in patients with Parkinson's disease. Atypicals may be selectively advantageous in treating schizophrenic patients with a predisposition to catatonia. Although the risk of developing lethal neuroleptic malignant syndrome may be diminished with atypical drugs, clinicians must remain alert to the signs of this disorder. Atypicals have reduced liability for inducing tardive dyskinesia (TD) and show antidyskinetic properties in patients with preexisting TD. Passive resolution of TD may be facilitated in some patients by the use of these agents. Thus, the risk of movement disorders has become only one of several considerations in choosing among antipsychotic drugs. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Caroff, SN (reprint author), Dept Vet Affairs Med Ctr, Univ Ave,Ward 7 E-116A, Philadelphia, PA 19104 USA. NR 137 TC 81 Z9 85 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 4 BP 12 EP 19 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 534TR UT WOS:000174603300002 PM 11913670 ER PT J AU Fava, M Rankin, M AF Fava, M Rankin, M TI Sexual functioning and SSRIs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Treating Sexual Dysfunction - Psychiatrys Role in the Age of Viagra CY MAY 16, 1999 CL WASHINGTON, D.C. ID SEROTONIN REUPTAKE INHIBITORS; INDUCED ANORGASMIA; GINKGO-BILOBA; OPEN TRIAL; DYSFUNCTION; FLUOXETINE; SILDENAFIL; YOHIMBINE AB This article reviews the literature concerning the relationship between sexual functioning and selective serotonin reuptake inhibitors (SSRIs). Reduced sexual functioning is a common depressive symptom that typically improves after successful antidepressant treatment. On the other hand, sexual dysfunction has been observed in a substantial proportion of patients treated with all classes of antidepressants. In particular, SSRI use has been shown to be associated with sexual dysfunction. A number of pharmacologic interventions have been found to be helpful in anecdotal case reports. Unfortunately, the lack of placebo-controlled studies in this area limits our ability to draw firm conclusions on the efficacy of such interventions. Three classes of drugs have primarily been used to counteract sexual side effects of SSRls: serotonin receptor antagonists, a(2)-adrenergic receptor antagonists, and dopaminergic agents. An open trial from our group suggests the potential usefulness of oral sildenafil in the treatment of antidepressant-associated sexual side effects, but further studies are needed. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Fruit St,ACC 815, Boston, MA 02114 USA. NR 31 TC 48 Z9 49 U1 2 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 5 BP 13 EP 16 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 542WF UT WOS:000175066700003 PM 11964136 ER PT J AU Spencer, TJ Biederman, J Wilens, TE Faraone, S AF Spencer, TJ Biederman, J Wilens, TE Faraone, S TI Novel treatments for attention-deficit/hyperactivity disorder in children SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Meeting on Novel Treatments for Attention-Deficit/Hyperactivity Disorder in Children and Adults CY NOV 15-17, 2001 CL BOSTON, MASSACHUSETTS ID DEFICIT HYPERACTIVITY DISORDER; TOURETTES-SYNDROME; COGNITIVE FUNCTION; CONDUCT DISORDER; OPEN-LABEL; METHYLPHENIDATE; DESIPRAMINE; PLACEBO; ADOLESCENTS; GUANFACINE AB Optimal medications for children with attention-deficit/hyperactivity disorder (ADHD) would be effective, well tolerated, and long acting and Dot cause mood swings or worsen comorbid conditions. Current medications work on brain dopamine and/or norepinephrine systems, which are thought to be involved in ADHD. The medication class with the most evidence of efficacy in ADHD is stimulants, but they may be abused, are effective for only 4 to 12 hours, and may cause mood swings or increase tic severity. In recent years, alternative treatments have been explored. Tricyclic antidepressants have efficacy comparable to that of stimulants but may cause constipation, dry mouth, tremors, blood pressure changes, and potentially serious side effects including cardiac conduction and repolarization delays. Monoamine oxidase inhibitors may improve ADHD symptoms but are associated with severe dietary restrictions. Serotonin reuptake inhibitors have little or no effect in ADHD but may improve comorbid depression. Bupropion, although less effective than stimulants, may improve both ADHD symptoms and comorbid depression. Antihypertensive agents may improve impulsivity, hyperactivity, and comorbid tics but cause sedation or rebound hypertension. Atomoxetine, which is being developed for ADHD, reduces symptoms of ADHD without exacerbating comorbid conditions and is associated with only minor side effects, including subtle changes in blood pressure and heart rate. Before prescribing a treatment, physicians should consider the appropriateness and effectiveness of any medication for children with ADHD, who may be less tolerant of side effects and less able to monitor and express concerns about their well-being than adults. C1 Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Spencer, TJ (reprint author), 15 Parkman St WACC 725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 43 TC 55 Z9 57 U1 3 U2 10 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 12 BP 16 EP 22 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 626UV UT WOS:000179892700003 PM 12562057 ER PT J AU Saylor, KE Buermeyer, CM Spencer, TJ Barkley, RA AF Saylor, KE Buermeyer, CM Spencer, TJ Barkley, RA TI Adaptive changes related to medication treatment of ADHD: Listening to parents of children in clinical trials of a novel nonstimulant medication SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Meeting on Novel Treatments for Attention-Deficit/Hyperactivity Disorder in Children and Adults CY NOV 15-17, 2001 CL BOSTON, MASSACHUSETTS ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CRITERION; TIME AB The DSM-IV diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD) have proved useful in providing a common language for diagnosing, treating, and researching the disorder. Despite the utility of current ADHD diagnostic criteria, sophisticated theoretical conceptualizations of the etiology of ADHD have described a much more complex disorder that includes a range of neuropsychological impairments (such as working memory deficits and other executive dysfunction) and underlying structural and functional neuropathology (e.g., caudate nucleus volume, frontal lobe activity). Inattention, hyperactivity, and impulsivity, the hallmark triumvirate symptoms of ADHD, may be better viewed as some of the many meaningful symptoms with roots in executive-functioning impairment. Outcomes of brain-imaging studies, public skepticism about diagnosis and treatment, and a demand for meaningful clinical outcomes of treatment point to a considerable need to broaden treatment-outcome criteria beyond the DSM-IV domains. The wide-ranging decrements in adaptive function and quality of life reported by Parents of children diagnosed with ADHD further support core executive dysfunction. Emerging findings concerning medication-related improvements in adaptive functioning (e.g., social, emotional, academic), as well as the rapid search for the neuropathology that may underlie these improvements, are fueling interest in the assessment of adaptive function in clinical trials. In a series of ongoing clinical trials of a novel nonstimulant medication for ADHD, many parents reported significant improvements in the lives of their children beyond the DSM-IV criteria. These parental reports, despite their inherent sources of error, underscore the importance of including broader and more meaningful clinical outcome assessment in clinical trials. Research protocols that omit parental interviews that assess adaptive and executive function may well overlook several meaningful and consequential medication-related improvements. C1 NeuroSci Inc, Bethesda, MD 20814 USA. Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. RP Saylor, KE (reprint author), NeuroSci Inc, Old Georgetown Rd Manor House,5612 Spruce Tree Av, Bethesda, MD 20814 USA. NR 29 TC 12 Z9 13 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 12 BP 23 EP 28 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 626UV UT WOS:000179892700004 PM 12562058 ER PT J AU Nonacs, R Cohen, LS AF Nonacs, R Cohen, LS TI Depression during pregnancy: Diagnosis and treatment options SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Roundtable Symsosium on Womens Issues in Antidepressant Therapy CY JUN 12, 2000 CL LOS ANGELES, CALIFORNIA ID EXPOSED IN-UTERO; INFANT DEVELOPMENT; BIRTH OUTCOMES; MATERNAL CLOMIPRAMINE; POSTNATAL DEPRESSION; PSYCHIATRIC-ILLNESS; FLUOXETINE EXPOSURE; PSYCHOTROPIC-DRUGS; PRENATAL EXPOSURE; RISK AB Women often seek clinical consultation for antidepressant use both prior to conception and during pregnancy. Some women experience a new onset of symptoms during pregnancy, while those with a history of depressive symptoms are at increased risk. Nevertheless, clinicians are faced with the challenge of treating the mother without posing risks to the fetus. This review discusses risk factors for depression during pregnancy and the consequences of untreated depression, Nonpharmacologic and pharmacologic treatment options are reviewed, and guideline,, for treating depression during pregnancy are presented. C1 Massachusetts Gen Hosp, Dept Psychiat, Clin Psychopharmacol Unit, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. RP Nonacs, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin Psychopharmacol Unit, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 71 TC 42 Z9 44 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 7 BP 24 EP 30 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 547GL UT WOS:000175324600004 PM 11995775 ER PT J AU Pato, MT Pato, CN Pauls, DL AF Pato, MT Pato, CN Pauls, DL TI Recent findings in the genetics of OCD SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 5th International Obsessive-Compulsive Disorder Conference CY MAR 29-APR 01, 2001 CL SARDINIA, ITALY ID OBSESSIVE-COMPULSIVE DISORDER; COMPLEX SEGREGATION ANALYSIS; SEROTONIN TRANSPORTER GENE; RECEPTOR GENE; SPECTRUM DISORDERS; EATING DISORDERS; ANOREXIA-NERVOSA; ASSOCIATION; POLYMORPHISM; VARIANT AB Progress in the elucidation of the genetic mechanisms involved in the expression of obsessive-compulsive disorder (OCD) has been hampered by 2 factors: heterogeneity of the clinical phenotype and lack of understanding of the Molecular mechanism of the disorder. Efforts to narrow the phenotype have included identification of 4 symptom dimensions as well as investigation into comorbid and perhaps related illnesses such as Gilles de la Tourette's syndrome, eating disorders, and impulse-control disorders. A number of familial Studies have been conducted to explore the relationship of OCD to these illnesses and the possible existence Of independently, heritable components that make (if) the more complex disorder. Candidate gene Studies are also being conducted, with the goal of understanding the molecular mechanisms of OCD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Unit Psychiat & Neurodev Genet, Charlestown, MA 02129 USA. SUNY Buffalo, Lab Psychiat & Mol Genet, Buffalo, NY 14260 USA. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Unit Psychiat & Neurodev Genet, 149 13th St,10th Floor, Charlestown, MA 02129 USA. NR 36 TC 24 Z9 26 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 6 BP 30 EP 33 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 547GK UT WOS:000175324500006 PM 12027117 ER PT J AU Zajecka, J McEnany, GW Lusk, KM AF Zajecka, J McEnany, GW Lusk, KM TI Antidepressant dosing and switching guidelines: Focus on nefazodone SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSION; DOUBLE-BLIND; OUTPATIENTS; WITHDRAWAL AB Dosing strategies form a fulcrum between patient-related and provider-related dimensions of treatment. The former focus on perceptions of efficacy and safety and adherence to the regimen, whereas the latter focus on symptom identification and appropriate drug selection. Appropriate dosing strategies may modulate adverse effects, allowing the patient to move more comfortably toward an efficacious response. Dosing also is an important dimension in switching between 2 antidepressants when the efficacy of the first agent is suboptimal, Nefazodone is effective for the management of acute, severe. and chronic major depression and relapse prevention. Response rates,with nefazodone are comparable to those of imipramine and most SSRIs. In clinical trials, the efficacy of nefazodone was most clearly established at doses between 300 and 600 mg/day. At this dose range, discontinuations because of adverse events are low. C1 Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Bristol Myers Squibb Co, Overland Pk, KS USA. RP Zajecka, J (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, 1725 W Harrison St,Ste 955, Chicago, IL 60612 USA. NR 17 TC 3 Z9 3 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 1 BP 42 EP 47 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 526AU UT WOS:000174106900005 PM 11890564 ER PT J AU Rasgon, NL Altshuler, LL Fairbanks, LA Dunkin, JJ Davtyan, C Elman, S Rapkin, AJ AF Rasgon, NL Altshuler, LL Fairbanks, LA Dunkin, JJ Davtyan, C Elman, S Rapkin, AJ TI Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Roundtable Symsosium on Womens Issues in Antidepressant Therapy CY JUN 12, 2000 CL LOS ANGELES, CALIFORNIA ID MENOPAUSAL WOMEN; BREAST-CANCER; SEROTONIN; MOOD; FLUOXETINE; STEROIDS; BRAIN; RAT AB Background: Increased vulnerability to mood disorders has been reported during perimenopause. Fluctuating estrogen levels accompany the perimenopausal transition, Thus. estrogen replacement therapy (ERT) has been proposed as a potentially effective treatment for mood disorders occurring during perimenopause. Method: We examined the efficacy of ERT in the treatment of depression in 16 perimenopausal women with DSM-IV-defined major depressive disorder who were participating in the Mood Disorders Research Program at the Department of Psychiatry of the University of California, Los Angeles. Ten antidepressant- and ERT-naive women received ERT alone. Six women who were nonresponders or partial responders to an antidepressant received ERT in addition to existing treatment with fluoxetine. The Hamilton Rating Scale for Depression (HAM-D) was administered to all patients at baseline and weekly thereafter during the 8-week open-protocol trial, Partial response was operationalized as a final HAM-D score less than or equal to 50% of the baseline score, Remission was defined as a Final HAM-D score less than or equal to 7. Results: All patients exhibited clinical improvement as measured by HAM-D scores after the first week of treatment. Of the 10 perimenopausal depressed women receiving ERT alone. 6 remitted, 3 partially responded to treatment, and I did not respond by the end of the trial. Of the 6 women receiving antidepressant treatment with ERT. I patient remitted and 5 had a partial response by the end of the trial. Conclusion: This small study suggests that for some antidepressant-naive perimenopausal women with clinical depression, ERT may have antidepressant efficacy. In depressed women who have minimal response to a selective serotonin reuptake inhibitor, ERT may augment response. Further controlled trials are needed. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90024 USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Rasgon, NL (reprint author), 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. NR 27 TC 77 Z9 81 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2002 VL 63 SU 7 BP 45 EP 48 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 547GL UT WOS:000175324600006 PM 11995778 ER PT J AU Enzweiler, CNH Wiese, TH Lembcke, AE Taupitz, M Rogalla, P Kivelitz, DE Jepsen, H Kettner, B Sheedy, PF Baumann, G Hamm, B AF Enzweiler, CNH Wiese, TH Lembcke, AE Taupitz, M Rogalla, P Kivelitz, DE Jepsen, H Kettner, B Sheedy, PF Baumann, G Hamm, B TI Electron beam tomography of interpulmonary saddle embolism: Extent and vascular distribution SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography; embolism, pulmonary; arteries, pulmonary ID DEEP VENOUS THROMBOSIS; PULMONARY-EMBOLISM; SPIRAL CT; COMPRESSION DEVICE; VEIN THROMBOSIS; THROMBOEMBOLISM; DIAGNOSIS; ANGIOGRAPHY; PREVALENCE; EVOLUTION AB Purpose: The purpose of this work was to assess morphology and secondary signs of interpulmonary emboli extending across the bifurcation of the main pulmonary artery (PA). Method: Retrospective evaluation of 780 electron beam tomographic studies of the chest yielded 17 cases of interpulmonary saddle embolism. Length, diameter, vascular distribution of the emboli, and secondary findings were prospectively assessed by two blinded reviewers. Follow-up studies were carried out in 12 of 17 patients (71%). Result: Mean total length of the emboli was 46.6 cm (range 20.9-81.5 cm). The mean diameter of the saddle embolus was significantly smaller at the level of the bifurcation than in the left or right PA (4.5, 7.7, and 7.4 mm, respectively p < 0.01). Dilatation of the right heart was found in 10 of 17 cases (59%). At follow-up, the saddle state was no longer present in 8 of 12 patients (67%). Conclusion: Interpulmonary saddle emboli appear to be a transient form of acute pulmonary embolism, the site of predilection for rupture of the embolus being the level of the bifurcation. Their frequency may therefore be underestimated. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Humboldt Univ, Dept Radiol, Berlin, Germany. Humboldt Univ, Dept Internal Med, Berlin, Germany. Humboldt Univ, Charite, Dept Nucl Med, Berlin, Germany. Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. RP Enzweiler, CNH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Bartlett Hall 510,55 Fruit St, Boston, MA 02114 USA. NR 35 TC 13 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2002 VL 26 IS 1 BP 26 EP 32 DI 10.1097/00004728-200201000-00005 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 514GP UT WOS:000173430900004 PM 11801901 ER PT J AU Jhaveri, KS Harisinghani, MG Wittenberg, J Saini, S Mueller, PR AF Jhaveri, KS Harisinghani, MG Wittenberg, J Saini, S Mueller, PR TI Right-sided colonic diverticulitis: CT findings SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE gastrointestinal system; diverticulitis; computed tomography ID ASCENDING COLON; CECAL DIVERTICULITIS; CECUM; EXPERIENCE; DIAGNOSIS AB Right-sided colonic diverticulitis is an uncommon but clinically significant condition as it closely mimics other common acute right-sided abdominal conditions like acute appendicitis and cholecystitis. CT can provide a rapid and accurate diagnosis of this condition and thereby prevent unnecessary laparotomy and surgical procedures since it is essentially a benign self-limiting condition requiring medical treatment. It is the aim of this pictorial essay to describe the CT findings and increase awareness among radiologists of this condition. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Div Abdominal & Intervent, White 270, Boston, MA 02114 USA. NR 18 TC 16 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2002 VL 26 IS 1 BP 84 EP 89 DI 10.1097/00004728-200201000-00012 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 514GP UT WOS:000173430900011 PM 11801908 ER PT J AU Sahani, D Prasad, SR Maher, M Warshaw, AL Hahn, PF Saini, S AF Sahani, D Prasad, SR Maher, M Warshaw, AL Hahn, PF Saini, S TI Functioning acinar cell pancreatic carcinoma: Diagnosis on mangafodipir trisodium (Mn-DPDP)-enhanced MRI SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pancreas; carcinoma, acinar cell; magnetic resonance imaging ID DPDP AB We describe the imaging findings of a functional pancreatic acinar cell carcinoma in a patient who presented with weight loss, hyperlipasemia, and multiple foci of subcutaneous fat necrosis. The tumor invaded the adjacent splenic and portal vein, causing isolated left-sided portal hypertension. At MRI, the tumor showed marked enhancement following administration of the hepatobiliary-specific contrast agent mangafodipir trisodium (Mn-DPDP), thereby demonstrating the functional nature of the tumor. Avid uptake of Mn-DPDP by a functioning pancreatic tumor has not been reported in the radiology literature. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 13 TC 17 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 2002 VL 26 IS 1 BP 126 EP 128 DI 10.1097/00004728-200201000-00019 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 514GP UT WOS:000173430900018 PM 11801915 ER PT J AU Hussein, MR Wood, GS AF Hussein, MR Wood, GS TI Microsatellite instability in human melanocytic skin tumors: an incidental finding or a pathogenetic mechanism? SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Editorial Material ID NONPOLYPOSIS COLON-CANCER; DNA MISMATCH REPAIR; COLORECTAL-CANCER; GASTRIC CARCINOMAS; MUTATOR PHENOTYPE; MUTATIONS; MELANOMA; HOMOLOG; REPEATS; GENES C1 Univ Wisconsin, Dept Med Dermatol, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Med Dermatol, Madison, WI 53705 USA. FU NIAMS NIH HHS [AR01326] NR 45 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2002 VL 29 IS 1 BP 1 EP 4 DI 10.1034/j.1600-0560.2002.290101.x PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 523TP UT WOS:000173971900001 PM 11841510 ER PT J AU Tanner, ACR Milgrom, PM Kent, R Mokeem, SA Page, RC Riedy, CA Weinstein, P Bruss, J AF Tanner, ACR Milgrom, PM Kent, R Mokeem, SA Page, RC Riedy, CA Weinstein, P Bruss, J TI The microbiota of young children from tooth and tongue samples SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE Streptococcus mutans; Porphyromonas gingivalis; Actinomyces; Prevotella; preschool children; dental caries; tongue samples ID PORPHYROMONAS-GINGIVALIS; MUTANS STREPTOCOCCI; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PERIODONTAL-DISEASE; CARIES PREVALENCE; DENTAL-CARIES; COLONIZATION; TEETH; AGE; SALIVARY AB This study determined the frequency with which 38 microbial species were detected in 171 randomly selected children from 6 to 36 months of age. Children were sampled and dental caries measured. Oral samples were assayed by means of a checkerboard DNA probe assay. The detection frequencies from tongue samples in children under 18 mos were: S. mutans 70%, S. sobrinus 72%, P. gingivalis 23%, B. forsythus 11%, and A. actinomycetemeomitans 30%, with similar detection frequencies in children over 18 mos. Thus, S. mutans and the periodontal pathogens, P. gingivalis and B. forsythus, were detected e, en in the youngest subjects. Species associated with caries included S. mutans (children ages 18-36 mos) and A, israelii (children ages < 18 mos), the latter species possibly reflecting increased plaque in children with caries. Species detection from tooth and tongue samples was highly associated, with most species detected more frequently from tongue than from tooth samples in children under 18 mos, suggesting that the tongue was a potential microbial reservoir. C1 Forsyth Inst, Boston, MA 02115 USA. Univ Washington, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Periodont, Seattle, WA 98195 USA. King Saud Univ, Riyadh 11691, Saudi Arabia. Dept Publ Hlth Serv, Saipan, CM 96950 USA. RP Tanner, ACR (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. OI Milgrom, Peter/0000-0003-0784-9181 FU NIDCR NIH HHS [T32 DE-07132, DE 09513, P01 DE 08555, P30 DE-09743, T35 DE 07150] NR 29 TC 83 Z9 86 U1 2 U2 5 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2002 VL 81 IS 1 BP 53 EP 57 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559JV UT WOS:000176023800012 PM 11824414 ER PT J AU Legome, EL Belton, AL Murray, RE Rao, PM Novelline, RA AF Legome, EL Belton, AL Murray, RE Rao, PM Novelline, RA TI Epiploic appendagitis: The emergency department presentation SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE epiploic; appendagitis; abdominal; CT scan; emergency AB We performed a structured retrospective chart review to describe clinical characteristics of Emergency Department (ED) patients diagnosed by history, physical examination, and abdominal computed tomography (CT) scan with epiploic appendagitis (EA). EA is a disease caused by inflammation of the appendix epiploica, subserosal adipose tissue along the colon. It may mimic surgical causes of acute abdominal pain, but is treated conservatively with pain management. There were 19 patients diagnosed with EA, with follow-up performed on 85%. All had focal, nonmigratory symptoms. Common findings included left lower quadrant pain and guarding, and a normal temperature and white cell count. No patient required operation. This preliminary work characterizes some common clinical features of ED patients diagnosed with EA. As use of emergency CT scan for abdominal pain increases, clinicians will encounter this more often. These features should also prompt the clinician to consider CT scan in patients with similar signs and symptoms. Accurate diagnosis may avoid unnecessary surgery. (C) 2002 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Emergency Med, Emergency Med Residency Off, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Legome, EL (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Emergency Med Residency Off, Founders 150, Boston, MA 02114 USA. NR 14 TC 35 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2002 VL 22 IS 1 BP 9 EP 13 DI 10.1016/S0736-4679(01)00430-9 PG 5 WC Emergency Medicine SC Emergency Medicine GA 514DN UT WOS:000173423000002 PM 11809550 ER PT J AU Zimmer, GD Brown, DFM Nadel, ES AF Zimmer, GD Brown, DFM Nadel, ES TI Blunt traumatic injuries SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID AORTIC INJURY; DIAGNOSIS; RUPTURE; CT C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115,15 Fruit St, Boston, MA 02114 USA. NR 8 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2002 VL 22 IS 1 BP 81 EP 85 DI 10.1016/S0736-4679(01)00428-0 PG 5 WC Emergency Medicine SC Emergency Medicine GA 514DN UT WOS:000173423000013 PM 11809561 ER PT J AU Akiba, Y Nakamura, M Nagata, H Kaunitz, JD Ishii, H AF Akiba, Y Nakamura, M Nagata, H Kaunitz, JD Ishii, H TI Acid-sensing pathways in rat gastrointestinal mucosa SO JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Japanese-Society-of-Gastroenterology CY OCT 19-21, 2001 CL KYOTO INT CONVENT HALL, KYOTO, JAPAN SP Japanese Soc Gastroenterol HO KYOTO INT CONVENT HALL DE vanilloid receptor; capsaicin-sensitive afferent nerves; calcitonin gene-related peptide; nitric oxide; prostaglandin; indomethacin; Na+/H+ exchanger ID GENE-RELATED PEPTIDE; GUINEA-PIG ILEUM; MUCUS GEL THICKNESS; VANILLOID RECEPTOR-1; SENSORY NERVES; LOW PH; CAPSAICIN RECEPTOR; LUMINAL ACID; DUODENUM; RELEASE AB The gastrointestinal mucosa serves as the interface between the luminal contents, including nutrients and injurious substances, and submucosal structures. Secreted gastric acid is one of the principal injurious components of the luminal contents. To be protected against harm from this acid, the epithelium has an "early warning" system that can activate potent defense mechanisms. We studied the mechanisms that defend the epithelium against luminal acid-induced injury, including the regulation of epithelial intracellular pH (pH(i)), blood flow, and mucus gel secretion in the perfused rat duodenum, and the pathways involved in the activation and regulation of these mechanisms. Physiological concentrations of luminal acid acidified the epithelial cells and increased blood flow (hyperemic response) and mucus gel thickness. The hyperemic response to acid was abolished by inhibitors of the Na+/H+ exchange, vanilloid receptors (VR), calcitonin gene-related peptide (CGRP) receptors, and nitric oxide (NO) synthase, and also by sensory afferent denervation, but not by pretreatment with a nonselective cyclooxygenase (COX) inhibitor. Mucus secretion in response to luminal acid was delayed by an interruption to the capsaicin pathway, which includes VR, capsaicin-sensitive afferent nerves, CGRP, and NO, and was abolished by COX inhibition. These observations support the hypothesis that the capsaicin pathway is an acid-sensing pathway that promotes hyperemia and mucus secretion in response to luminal acid. The COX pathway is a secondary regulatory system for mucus secretion. A similar acid-sensing capsaicin pathway is also present in the colon, suggesting that the gastrointestinal mucosa "tastes" luminal acidity through epithelial-VR communication. C1 Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan. Kitasato Inst, Ctr Clin Pharmacol, Basic Res Ctr, Tokyo, Japan. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Digest Dis Res Ctr, Los Angeles, CA USA. CURE, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Akiba, Y (reprint author), Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. FU NIDDK NIH HHS [R01 DK 54221] NR 35 TC 32 Z9 34 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PY 2002 VL 37 SU 14 BP 133 EP 138 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 617HX UT WOS:000179357200029 PM 12572881 ER PT J AU Miller, LG Liu, HH Hays, RD Golin, CE Beck, CK Asch, SM Ma, YY Kaplan, AH Wenger, NS AF Miller, LG Liu, HH Hays, RD Golin, CE Beck, CK Asch, SM Ma, YY Kaplan, AH Wenger, NS TI How well do clinicians estimate patients' adherence to combination antiretroviral therapy? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS DE adherence; compliance; HIV; clinician assessment; antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONGITUDINAL DATA; DRUG; ZIDOVUDINE; MEDICATION; NONCOMPLIANCE; SURVIVAL; REGIMEN; MODELS AB Objective: Adherence to combination antiretroviral therapy is critical for clinical and virologic success in HIV-infected patients. To combat poor adherence, clinicians must identify nonadherent patients so they can implement interventions. However, little is known about the accuracy of these assessments. We sought to describe the accuracy of clinicians' estimates of patients' adherence to combination antiretroviral therapy. Setting: Public HIV clinic. Design: Prospective cohort study. During visits, we asked clinicians (nurse practitioners, residents and fellows, and their supervising attending physicians) to estimate the percentage of antiretroviral medication taken by patients over the last 4 weeks and predicted adherence over the next 4 weeks. Adherence was measured using electronic monitoring devices, pill counts, and self-reports, which were combined into a composite adherence measure. Patients and participants: Clinicians estimated 464 episodes of adherence in 82 patients. Results: Among the 464 adherence estimates, 264 (57%) were made by principal care providers (31% by nurse practitioners, 15% by fellows, 6% by residents, and 5% by staff physicians) and 200 (43%) by supervising attending physicians. Clinicians' overestimated measured adherence by 8.9% on average (86.2% vs 77.3%). Greater clinician inaccuracy in adherence prediction was independently associated with higher CD4 count nadir (1.8% greater inaccuracy for every 100 CD4 cells, P=.005), younger patient age (3.7% greater inaccuracy for each decade of age, P=.02), and visit number (P=.02). Sensitivity of detecting nonadherent patients was poor (24% to 62%, depending on nonadherence cutoff). The positive predictive value of identifying a patient as nonadherent was 76% to 83%. Conclusions: Clinicians tend to overestimate medication adherence, Inadequately detect poor adherence, and may therefore miss important opportunities to Intervene to improve antiretroviral adherence. C1 Harbor UCLA Med Ctr, Div Infect Dis, Torrance, CA 90509 USA. Harbor UCLA Med Ctr, Div Allergy & Immunol, Torrance, CA 90509 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA. RP Miller, LG (reprint author), Harbor UCLA Med Ctr, Div Infect Dis, 1124 W Cardosn St,Box 466, Torrance, CA 90509 USA. RI Hays, Ronald/D-5629-2013 FU NIAID NIH HHS [AI28697, AI41413, P30 AI028697] NR 42 TC 108 Z9 110 U1 2 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2002 VL 17 IS 1 BP 1 EP 11 DI 10.1046/j.1525-1497.2002.09004.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 542FM UT WOS:000175032900001 PM 11903770 ER PT J AU Oneta, CM Lieber, CS Li, JJ Ruttimann, S Schmid, B Lattmann, J Rosman, AS Seitz, HK AF Oneta, CM Lieber, CS Li, JJ Ruttimann, S Schmid, B Lattmann, J Rosman, AS Seitz, HK TI Dynamics of cytochrome P4502E1 activity in man: induction by ethanol and disappearance during withdrawal phase SO JOURNAL OF HEPATOLOGY LA English DT Article DE cytochrome P4502E1; induction; dynamics of ethanol metabolism; drugs; carcinogenesis; moderate alcohol consumption; ethanol withdrawal ID GLUTATHIONE-S-TRANSFERASE; UPPER AERODIGESTIVE TRACT; HEPATOCELLULAR-CARCINOMA; GENETIC POLYMORPHISMS; COLORECTAL-CANCER; LIVER-DISEASE; 2E1; SUSCEPTIBILITY; CHLORZOXAZONE; HYDROXYLATION AB Background/Aims: Chronic ethanol consumption results in the induction of hepatic cytochrome P4502E1 (CYP2E1) in man, which is believed to play an important role in the pathogenesis of alcoholic liver disease. However, the amount and duration of alcohol intake associated with CYP2E1 induction is not known but limited information is available on the disappearance of CYP2E1 following alcohol withdrawal. Methods: To study these questions, five healthy male volunteers received ethanol daily (40 g/day) over 4 weeks. CYP2E1 induction was monitored by using the chlorzoxazone test before and every week following the start of alcohol ingestion. In addition, CYP2E1 was also determined in five alcoholics 1, 3, 8 and 15 days following ethanol withdrawal and in five patients with non-alcoholic liver disease. Results: A significant CYP2E1 induction occurred 1 week following the ingestion of 40 g ethanol per day and increased further after 4 weeks. The disappearance of CYP2E1 was found to be significant 3 days following ethanol withdrawal and further decreased up to day 8. Thereafter, no significant change occurred and CYP2E1 activities were comparable with those in patients with non-alcoholic liver disease. Conclusions: These data show a significant and quick induction of CYP2E1 activity, already at moderate alcohol consumption, which may be of importance in the pathogenesis of alcoholic liver disease, of ethanol, drug and vitamin A interactions and in alcohol associated carcinogenesis. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. C1 Salem Med Ctr, Dept Internal Med, D-69121 Heidelberg, Germany. Salem Med Ctr, Lab Alcohol Res Liver Dis & Nutr, D-69121 Heidelberg, Germany. CHU Vaudois, Dept Internal Med, Div Gastroenterol, CH-1011 Lausanne, Switzerland. PMU, CH-1011 Lausanne, Switzerland. Bronx Vet Adm Med Ctr, Alcohol Res & Treatment Ctr, Liver Dis & Nutr Sect, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Kantonsspital, Dept Internal Med & Clin Pharmacol, Schaffhausen, Switzerland. Kantonsspital, Dept Internal Med, Winterthur, Switzerland. RP Seitz, HK (reprint author), Salem Med Ctr, Dept Internal Med, Zeppelinstr 11-33, D-69121 Heidelberg, Germany. FU NIAAA NIH HHS [AA-05934, AA-11115] NR 31 TC 92 Z9 97 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2002 VL 36 IS 1 BP 47 EP 52 DI 10.1016/S0168-8278(01)00223-9 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519MU UT WOS:000173730700008 PM 11804663 ER PT J AU Parhami-Seren, B Viswanathan, M Margolies, MN AF Parhami-Seren, B Viswanathan, M Margolies, MN TI Selection of high affinity p-azophenyarsonate Fabs from heavy-chain CDR2 insertion libraries SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE phage-display; antibody engineering; saturation mutagenesis; affinity ID AZOPHENYLARSONATE-SPECIFIC ANTIBODIES; ARS-A ANTIBODIES; T-CELL EPITOPES; IMMUNE-RESPONSE; RECOMBINANT ANTIBODIES; MOLECULAR EVOLUTION; GENE SEGMENTS; GERMLINE VH; B-CELLS; PHAGE AB The length of the heavy chain complementarity-determining region two (HCDR2) of the unmutated anti-p-azophenylarsonate (Ars) monoclonal antibody (36-65 mAb) was extended by three residues in order to test whether this insertion can provide additional contacts between the Ab and the antigen. Two libraries were generated using 36-65 heavy and light chain aeries which were cloned as Fab in the phage-display vector pComb3. In the first library, three randomized amino acids were inserted between residues Gly 54 and Asn 55, which are the most solvent exposed residues in the HCDR2 loop. In the second library, in addition to the 3-mer randomized insertion, the flanking residues at positions 54 and 55 were also randomized to allow additional loop flexibility for binding to Ars. Solid-phase and solution phase affinity panning were used to select for clones that bind to Ars. Results indicate that diverse 3-mer HCDR2 insertions-can be tolerated, and affinities 10-fold higher than germline encoded 36-65 Ab can be obtained. The sequence diversity of the insertion among the selected clones from both libraries suggests that the insertion increases contact between the Ab and the protein carrier rather than the hapten alone. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Parhami-Seren, B (reprint author), Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. FU NCI NIH HHS [CA24432]; NHLBI NIH HHS [HL52282, HL47415]; NIAID NIH HHS [AI33175] NR 38 TC 8 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 1 PY 2002 VL 259 IS 1-2 BP 43 EP 53 DI 10.1016/S0022-1759(01)00488-4 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 507XT UT WOS:000173057100005 PM 11730840 ER PT J AU Treon, SP Pilarski, TM Belch, TR Kelliher, A Preffer, FI Shima, Y Mitsiades, CS Mitsiades, NS Szczepek, AJ Ellman, L Harmon, D Grossbard, ML Anderson, KC AF Treon, SP Pilarski, TM Belch, TR Kelliher, A Preffer, FI Shima, Y Mitsiades, CS Mitsiades, NS Szczepek, AJ Ellman, L Harmon, D Grossbard, ML Anderson, KC TI CD20-directed serotherapy in patients with multiple myeloma: Biologic considerations and therapeutic applications SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CD20; multiple myeloma; B cells; rituximab; interferongamma ID RECOMBINANT GAMMA-INTERFERON; ANTI-CD20 MONOCLONAL-ANTIBODY; TRANSCRIPTION FACTOR PU.1; MARROW PLASMA-CELLS; COMPLEX CLASS-I; B-CELLS; PERIPHERAL-BLOOD; BONE-MARROW; PHASE-I; UP-REGULATION AB Clonotypic B cells circulating in patients with multiple myeloma (MM) express CD20, and it has been suggested that these cells may be clonogenic. Furthermore, 20% of patients with MM express CD20 on their bone marrow plasma cells (BMPCs). Therefore, the authors began a phase 11 clinical study to determine the activity of the anti-CD20 monoclonal antibody rituximab in MM patients. Nineteen previously treated MM patients received 375 mg/m(2) rituximab per week for 4 weeks. Three months after initiation of treatment, patients were assessed for response and received a second course of therapy if their disease was stable (SD) or they achieved a partial response (PR). Six of 19 (32%) patients had either a PR (n = 1) or SD (n = 5), with a median time to treatment failure of 5.5 months (mean, 10.3 months range, 3-27+ months). All six patients who had a PR or SD had CD20(+) BMPC. Overall, rituximab therapy was well tolerated. Because most patients with MM poorly express CD20 on their BMPCs, the authors evaluated agents for their ability to induce CD20 expression and thereby facilitate rituximab binding on MM cells. These studies show that interferon-gamma (IFN-gamma) induced CD20 expression on MM BMPCs, MM B cells, and healthy donor BMPCs. In contrast, CD20 expression on chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma, healthy donor B cells, and progenitor cells was unaffected by IFN-gamma. Rituximab binding to the BMPCs of MM patients was also increased after culture with pharmacologically attainable levels of IFN-gamma ( 1-100 U/mL). In conclusion, these studies suggest that MM patients with CD20(+) BMPCs may benefit from rituximab therapy. Furthermore, IFN-gamma induces CD20 expression on MM BMPCs and B cells and facilitates rituximab binding to MM BMPCs, providing the rationale for clinical trials to examine its use with CD20-directed serotherapies in MM. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alberta, Cross Canc Inst, Dept Med Oncol, Edmonton, AB, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Max Planck Inst, Berlin, Germany. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Szczepek, Agnieszka/0000-0002-9292-6606 FU NCI NIH HHS [CA80963] NR 68 TC 102 Z9 109 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2002 VL 25 IS 1 BP 72 EP 81 DI 10.1097/00002371-200201000-00008 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 509KK UT WOS:000173146800009 PM 11924912 ER PT J AU Van Laer, A Dallalio, G McKenzie, SW Means, RT AF Van Laer, A Dallalio, G McKenzie, SW Means, RT TI Thioredoxin and protein nitrotyrosine in bone marrow supernatant from patients with human immunodeficiency virus infection SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE HIV; thioredoxin; peroxynitrite; oxidative stress; anemia ID MANGANESE SUPEROXIDE-DISMUTASE; TUMOR-NECROSIS-FACTOR; OXIDATIVE STRESS; NITRIC-OXIDE; HIPPOCAMPAL-NEURONS; PROGENITOR CELLS; IRON-METABOLISM; T-CELL; CFU-E; ACTIVATION AB Background: Balance and imbalance between oxidant stress and antioxidants contributes to the manifestations of human immunodeficiency virus (HIV) infection. Previously, we demonstrated a characteristic cytokine pattern in marrow supernatant from HIV patients who underwent diagnostic examinations. Methods: In this report, we have determined the protein nitrotyrosine (pNT) concentration (an indicator of nitric oxide-superoxide interaction) as well as the concentration of the redox enzyme thioredoxin (Trx) in marrow supernatant from HIV patients, healthy controls, and other patients, and in serum from comparable subjects. Results: pNT concentrations were similar in serum and marrow supernatant and did not differ between subject subsets. Trx concentrations in both marrow supernatant and serum were higher for HIV patients than for other subjects; serum Trx concentrations were significantly higher than marrow Trx concentrations for the non-HIV patients and controls. The ratios of pNT/Trx concentrations in serum were similar in all subsets tested. In marrow aspirate, however, these ratios differed widely and significantly, with the highest values observed in non-HIV patients and the lowest in HIV patients. Only for HIV patients were serum and marrow supernatant pNT/Trx ratios similar. In HIV patients, marrow Trx concentrations correlated with CD4 count, CD4/CD8 ratio, and marrow colony-forming unit E (CFU-E) concentration; marrow pNT concentration correlated with the concentration of tumor necrosis factor in marrow supernatant, and with platelet count. No correlations were observed in other subject subsets. Conclusions: These findings suggest that there is a degree of local regulation of the redox state of the marrow micro-environment that varies with the patients' clinical statuses, and which is associated with effects on hematopoiesis. C1 Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Div Hematol Oncol, Charleston, SC USA. Ralph H Johnson VA Med Ctr, Div Infect Dis, Charleston, SC USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL-53703] NR 55 TC 2 Z9 2 U1 0 U2 0 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2002 VL 50 IS 1 BP 10 EP 18 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 513LQ UT WOS:000173380400007 PM 11813824 ER PT J AU Chen, MH Ibrahim, JG Sinha, D AF Chen, MH Ibrahim, JG Sinha, D TI Bayesian inference for multivariate survival data with a cure fraction SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE cure rate; frailty model; Gibbs sampling; latent variables; posterior distribution; stable law ID CHAIN MONTE-CARLO; MIXTURE-MODELS; NONPARAMETRIC METHODS; REGRESSION-MODELS; LIFE-TABLES; RATES; DISTRIBUTIONS; FRAILTIES; TESTS; RISK AB We develop Bayesian methods for right censored multivariate failure time data for populations with a cure fraction, We propose a new model, called the multivariate cure rate model, and provide a natural motivation and interpretation of it. To create the correlation structure between the failure times, we introduce a frailty term, which is assumed to have a positive stable distribution. The resulting correlation structure induced by the frailty term is quite appealing and leads to a nice characterization of the association between the failure times. Several novel properties of the model are derived. First, conditional on the frailty term, it is shown that the model has a proportional hazards structure with the covariates depending naturally on the cure rate. Second, we establish mathematical relationships between the marginal Survivor functions of the multivariate cure rate model and the more standard mixture model for modelling cure rates. With the introduction of latent variables, we show that the new model is computationally appealing, and novel computational Markov chain Monte Carlo (MCMC) methods are developed to sample from the posterior distribution of the parameters. Specifically, we propose a modified version of the collapsed Gibbs technique (J.S. Liu, 1994, J. Amer. Statist Assoc. 89, 958-966) to sample from the posterior distribution. This development will lead to an efficient Gibbs sampling procedure, which would otherwise be extremely difficult. We characterize the propriety of the joint posterior distribution of the parameters using a class of noninformative improper priors. A real dataset from a melanoma clinical trial is presented to illustrate the methodology. (C) 2001 Elsevier Science. C1 Worcester Polytech Inst, Worcester, MA 01609 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Chen, MH (reprint author), Worcester Polytech Inst, Worcester, MA 01609 USA. NR 37 TC 42 Z9 44 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD JAN PY 2002 VL 80 IS 1 BP 101 EP 126 DI 10.1006/jmva.2000.1975 PG 26 WC Statistics & Probability SC Mathematics GA 520CM UT WOS:000173762800007 ER PT J AU Heckers, S Konradi, C AF Heckers, S Konradi, C TI Hippocampal neurons in schizophrenia SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE hippocampal volume; interneurons; GABA; glutamate ID MEDIAL TEMPORAL-LOBE; LOCAL CIRCUIT NEURONS; GLUTAMATE RECEPTORS; PREFRONTAL CORTEX; MESSENGER-RNAS; BINDING-SITES; EPISODE SCHIZOPHRENIA; SYNAPTIC CONNECTIVITY; VOLUME REDUCTION; NERVOUS-SYSTEM AB The hippocampus is crucial for normal brain function, especially for the encoding and retrieval of multimodal sensory information. Neuropsychiatric disorders such as temporal lobe epilepsy, amnesia, and the dementias are associated with structural and functional abnormalities of specific hippocampal neurons. More recently we have also found evidence for a role of the hippocampus in the pathophysiology of schizophrenia. The most consistent finding is a subtle, yet significant volume difference in schizophrenia. Here we review the cellular and molecular basis of smaller hippocampal volume in schizophrenia. In contrast to neurodegenerative disorders, total hippocampal cell number is not markedly decreased in schizophrenia. However, the intriguing finding of a selective loss of hippocampal interneurons deserves further study. Two neurotransmitter receptors, the GABAA and AMPA/kainate glutamate receptors, appear to be abnormal, whereas changes of the NMDA glutamate receptor are less robust. The expression of several genes, including those related to the GABAergic system, neurodevelopment, and synaptic function, is decreased in schizophrenia. Taken together, recent studies of hippocampal cell number, protein expression, and gene regulation point towards an abnormality of hippocampal architecture in schizophrenia. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Lab Neuroplast, Belmont, MA 02178 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY-9132,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIDA NIH HHS [R01 DA007134-14, DA07134, R01 DA007134]; NIMH NIH HHS [MH01763] NR 75 TC 129 Z9 132 U1 5 U2 10 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 2002 VL 109 IS 5-6 SI SI BP 891 EP 905 DI 10.1007/s007020200073 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 561MZ UT WOS:000176145900030 PM 12111476 ER PT J AU Xia, MQ Hyman, BT AF Xia, MQ Hyman, BT TI GRO alpha/KC, a chemokine receptor CXCR2 ligand, can be a potent trigger for neuronal ERK1/2 and PI-3 kinase pathways and for tau hyperphosphorylation - a role in Alzheimer's disease? SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE chemokine receptor; CXCR2; GRO alpha/KC; ERK1/2; PI-3 kinase; phosphorylated tau ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CENTRAL-NERVOUS-SYSTEM; HELICAL FILAMENT-TAU; HAMSTER OVARY CELLS; SIGNAL-TRANSDUCTION; MESSENGER-RNA; HUMAN BRAIN; DEPENDENT PHOSPHORYLATION; NEUTROPHIL MIGRATION; MEDIATED ACTIVATION AB Inflammation has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases. We have examined the potential role of some chemokine/chemokine receptors in this process. It is known that CXCR2 is a strongly expressed chemokine receptor on neurons and is strongly upregulated in AD in a subpopulation of neuritic plaques. Here, we show that one of the CXCR2 ligand GROalpha/KC can be a potent trigger for the ERK1/2 and PI-3 kinase pathways, as well as tau hyperphosphorylation in the mouse primary cortical neurons. GROalpha immunoreactivity can be detected in a subpopulation of neurons in normal and AD. Therefore, the CXCR2-ligand pair may have a potent pathophysiological role in neurodegenerative diseases. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp East, Dept Neurol,Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp East,Dept Neurol, Alzheimers Res Unit, CAGN 2009,144 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P50AG-05134] NR 75 TC 48 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2002 VL 122 IS 1-2 BP 55 EP 64 DI 10.1016/S0165-5728(01)00463-5 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 516UQ UT WOS:000173575500006 PM 11777543 ER PT J AU Shulman, MB Alexander, MP McGlinchey-Berroth, R Milberg, W AF Shulman, MB Alexander, MP McGlinchey-Berroth, R Milberg, W TI Triangular backgrounds shift the bias of line bisection performance in hemispatial neglect SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID VISUOSPATIAL NEGLECT; VISUAL NEGLECT; PERCEPTION; SEARCH AB Objective: Patients with left neglect on line bisection show normal implicit sensitivity to manipulations of both the stimulus and the visual background. Three experiments were designed to define this sensitivity more exactly. Methods: Normal controls and patients with left neglect performed a series of horizontal line bisection tasks, Independent variables were the configurations of the backgrounds for the line-rectangle, square, circle, left and right pointing isosceles triangles-and whether the background was the shape of the piece of paper or an outline drawn on a standard piece of paper. In a separate experiment different components of the triangle were outlined on a piece of paper. Deviation from true midpoint was calculated Results: Simply placing the target lines in a symmetric background such as a square or circle did not reliably reduce neglect. A triangle asymmetric in the horizontal plane caused a shift in bisection away from the triangle's vertex. With right pointing triangles the perceived midpoint shifted to the left of true centre (crossed over). The effects of the triangles were comparable in the patients and the controls when controlled for baseline bisection bias. The critical components of the triangles were the angular legs. This effect of background was not influenced by lesion site or by hemianopia. Conclusions: Patients with left visual neglect remain sensitive to covert manipulations of the visual background that implicitly shift the perceived midpoint of a horizontal line. This effect is strong enough to eliminate neglect on a bisection task. The mechanism of this effect is expressed through preattentive visual capacities. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Behav Neurol Unit, Boston, MA 02215 USA. NYU Med Ctr, Dept Neurol, New York, NY 10016 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02118 USA. VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Alexander, MP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Behav Neurol Unit, KS-2,330 Brookline Ave, Boston, MA 02215 USA. RI McGlinchey, Regina/R-1971-2016 FU NINDS NIH HHS [NS29342] NR 17 TC 4 Z9 4 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2002 VL 72 IS 1 BP 68 EP 72 DI 10.1136/jnnp.72.1.68 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 506LD UT WOS:000172973300014 PM 11784828 ER PT J AU Sasaki, H Zlatescu, MC Betensky, RA Johnk, LB Cutone, AN Cairncross, JG Louis, DN AF Sasaki, H Zlatescu, MC Betensky, RA Johnk, LB Cutone, AN Cairncross, JG Louis, DN TI Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade "oligodendroglioma" SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE astrocytoma; chromosome 1p; chromosome 19q; GFAP; histopathology; oligodendroglioma ID 19Q; 1P; PREDICTORS; SURVIVAL AB Allelic loss of chromosome 1p predicts increased chemosensitivity and better survival in oligodendroglial tumours. Clinical testing for 1p loss in oligodendroglial tumors at our hospital has allowed LIS to Postulate that certain histological appearances are associated with 1p allelic status. Forty-four cases received for genetic testing were diagnosed by referring pathologists as pure low-grade oligodendroglioma. Central neuropathological review, divided the series equally into 22 cases with classical oligodendroglioma histology and 22 with more astrocytic features. Molecular genetic analyses- demonstrated I p loss in 19 of 22 classic oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22 gliomas with astrocytic features (73%). No glial fibrillary acidic protein-positive cell type (gliofibrillary oligodendrocyte, minigemistocyte. cellular processes) was associated with I p allelic status. Fourteen of the 44 cases were treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p loss responded to PCV chemotherapy and 2 classic oligodendrogliomas that maintained both 1p alleles included a responder and a non-responder. These results suggest that histological appearance correctly predicts genotype in approximately 80% of low-grade gliomas, but that tumor genotype more closely predicts chemosensitivity, As a result, such objective molecular genetic analyses should be incorporated into patient management into clinical trials of low-grade diffuse gliomas. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol & Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Western Ontario, Dept Oncol, London, ON, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol & Neurosurg Serv, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA57683] NR 16 TC 107 Z9 111 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2002 VL 61 IS 1 BP 58 EP 63 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 508PH UT WOS:000173097300006 PM 11829344 ER PT J AU Tramo, MJ Shah, GD Braida, LD AF Tramo, MJ Shah, GD Braida, LD TI Functional role of auditory cortex in frequency processing and pitch perception SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID SUPERIOR TEMPORAL GYRUS; EVOKED MAGNETIC-FIELDS; DIPOLE MODEL ANALYSIS; TONOTOPIC ORGANIZATION; RHESUS-MONKEY; MACAQUE MONKEYS; DEVELOPMENTAL APHASIA; MISMATCH NEGATIVITY; CORTICAL-LESIONS; RESPONSES AB Microelectrode studies in nonhuman primates and other mammals have demonstrated that many neurons in auditory cortex are excited by pure tone stimulation only when the tone's frequency lies within a narrow range of the audible spectrum. However, the effects of auditory cortex lesions in animals and humans have been interpreted as evidence against the notion that neuronal frequency selectivity is functionally relevant to frequency discrimination. Here we report psychophysical and anatomical evidence in favor of the hypothesis that fine-grained frequency resolution at the perceptual level relies on neuronal frequency selectivity in auditory cortex. An adaptive procedure was used to measure difference thresholds for pure tone frequency discrimination in five humans with focal brain lesions and eight normal controls. Only the patient with bilateral lesions of primary auditory cortex and surrounding areas showed markedly elevated frequency difference thresholds: Weber fractions for frequency direction discrimination ("higher"-"lower" pitch judgments) were about eightfold higher than Weber fractions measured in patients with unilateral lesions of auditory cortex, auditory midbrain, or dorsolateral frontal cortex; Weber fractions for frequency change discrimination ("same"-"different" pitch judgments) were about seven times higher. In contrast, pure-tone detection thresholds, difference thresholds for pure tone duration discrimination centered at 500 ms, difference thresholds for vibrotactile intensity discrimination, and judgments of visual line orientation were within normal limits or only mildly impaired following bilateral auditory cortex lesions. In light of current knowledge about the physiology and anatomy of primate auditory cortex and a review of previous lesion studies, we interpret the present results as evidence that fine-grained frequency processing at the perceptual level relies on the integrity of finely tuned neurons in auditory cortex. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Tramo, MJ (reprint author), Massachusetts Gen Hosp, EDR-405,55 Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC-03382, DC-00071, DC-00117] NR 139 TC 75 Z9 76 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2002 VL 87 IS 1 BP 122 EP 139 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 509PD UT WOS:000173155700011 PM 11784735 ER PT J AU Smith, ER Ott, M Wain, J Louis, DN Chiocca, EA AF Smith, ER Ott, M Wain, J Louis, DN Chiocca, EA TI Massive growth of a meningioma into the brachial plexus and thoracic cavity after intraspinal and supraclavicular resection - Case report and review of the literature SO JOURNAL OF NEUROSURGERY LA English DT Review DE brachial plexus; thoracic cavity; meningioma; tumor recurrence ID MALIGNANT MENINGIOMAS; HEAD; NECK AB Extracranial meningiomas comprise approximately 2% of all meningiomas. Involvement of peripheral nerves by meningioma, either by a primary tumor or through secondary extension of an intraaxial lesion, is a much rarer entity; there have been only two reported primary brachial plexus meningiomas and one description of secondary involvement of the brachial plexus by extension of an intraaxial lesion. Although thoracic cavity meningiomas have been described in the literature, their pathogenesis is poorly understood. The authors present the case report of a 36-year-old man who was initially treated for a thoracic spinal meningioma that infiltrated the brachial plexus. After resection, progressive and massive growth with infiltration of the brachial plexus and pleural cavity occurred over a 5-year period despite radio- and chemotherapy. The case report is followed by a review of the literature of this rare entity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Brain Tumor Ctr,Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Chiocca, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Brain Tumor Ctr,Neurosurg Serv, Cox Bldg 315,Fruit St, Boston, MA 02114 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2002 VL 96 IS 1 SU S BP 107 EP 111 DI 10.3171/spi.2002.96.1.0107 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 509PA UT WOS:000173155100019 PM 11795697 ER PT J AU Natsume, A Mata, M Wolfe, D Oligino, T Goss, J Huang, SH Glorioso, J Fink, DJ AF Natsume, A Mata, M Wolfe, D Oligino, T Goss, J Huang, SH Glorioso, J Fink, DJ TI Bcl-2 and GDNF delivered by HSV-mediated gene transfer after spinal root avulsion provide a synergistic effect SO JOURNAL OF NEUROTRAUMA LA English DT Article DE apoptosis; Bcl-2; GDNF; gene therapy; herpes simplex; motor neuron; trauma ID MICE LACKING GDNF; NEUROTROPHIC FACTOR; MOTOR-NEURONS; CELL-DEATH; IN-VIVO; FACIAL MOTONEURONS; PERIPHERAL-NERVE; ADULT RATS; EXPRESSION; DEGENERATION AB Proximal spinal nerve injury results in the death of motor neurons in ventral horn. We have previously demonstrated this cell death can be prevented by HSV-mediated transfer of the gene coding for the antiapoptotic peptide Bcl-2 7 days prior to injury, but that expression of Bcl-2 does not preserve ChAT expression in the lesioned cells. In the current study, we examined two related issues: whether Bcl-2 delivered by HSV-mediated gene transfer 30 min after injury could similarly protect motor neurons from cell death, and whether the additional HSV-mediated expression of the glial cell derived neurotrophic factor (GDNF) could improve the result. At 30 min after avulsion of the L4, L5, and L6 spinal nerves, replication defective genomic HSV-based vectors coding for Bcl-2, GDNF, a reporter transgene (lacZ), or the Bcl-2 and GDNF vectors together were injected into spinal cord. Transduction of motor neurons with either the Bcl-2-expressing vector or the GDNF-expressing vector resulted in a substantial increase in the number of surviving motor neurons, and coinjection of the two vectors together resulted in cell survival that was similar to the result obtained with either vector alone. Neither the Bcl-2-expressing vector nor the GDNF-expressing vector delivered alone protected choline acetyltransferase (ChAT) expression in lesioned neurons. However, simultaneous injection of the Bcl-2- and the GDNF-expressing vectors together resulted in a substantial increase in the number of ChAT in cells in the lesioned ventral horn. Together, these findings suggest an approach to improving cell survival and regeneration following proximal root injury. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15240 USA. RP Fink, DJ (reprint author), S-520 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Natsume, Atsushi/I-7364-2014 OI Natsume, Atsushi/0000-0002-9113-0470 NR 29 TC 37 Z9 43 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN PY 2002 VL 19 IS 1 BP 61 EP 68 DI 10.1089/089771502753460240 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 517LD UT WOS:000173611300006 PM 11852979 ER PT J AU Counter, SA Buchanan, LH AF Counter, SA Buchanan, LH TI Neuro-ototoxicity in Andean adults with chronic lead and noise exposure SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID AUDITORY-EVOKED-POTENTIALS; BRAIN-STEM; BLOOD LEAD; OTOACOUSTIC EMISSIONS; HEARING THRESHOLDS; CHILDREN; TOXICITY; INTOXICATION; WORKERS; MONKEYS AB Brainstem auditory evoked responses and audiological thresholds were used as biomarkers for neuro-ototoxicity in adults with chronic lead (Pb) intoxication from long-term Pb exposure in ceramic-glazing work. Venous blood samples collected from 30 adults (15 men and 15 women) indicated a mean blood Pb level of 45.1 mug/dL (SD, 19.5; range, 11.2 to 80.0 mug/dL) and in excess of the World Health Organization health-based biological limits (men, 46.2 mug/dL; SD, 19.6; range, 18.3 to 80.0 mug/dL; women, 44.0 mug/dL; SD, 20.1; range, 11.2 to 74.2 mug/dL). Mean auditory thresholds at frequencies susceptible to olotoxicity (2.0, 3.0, 4.0, 6.0, and 8.0 kHz) revealed sensory-neural hearing loss in men, which may be attributable to occupational noise exposure in combination with Pb intoxication. Bilateral brainstem auditory evoked response tests on participants with elevated blood Pb levels (mean, 47.0 mug/dL) showed delayed wave latencies consistent with sensory-neural hearing impairment. The results suggest that environmental noise exposure must be considered an important factor in determining sensory-neural hearing status in occupation ally Pb-exposed adults. C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Biol Labs, Cambridge, MA 02138 USA. Harvard Univ, Dept Audiol, Hlth Serv, Shriver Ctr UAP LEND Program, Waltham, MA USA. RP Counter, SA (reprint author), Harvard Univ, Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA. NR 41 TC 21 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2002 VL 44 IS 1 BP 30 EP 38 DI 10.1097/00043764-200201000-00006 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 511QT UT WOS:000173277600006 PM 11802463 ER PT J AU Walker, WA AF Walker, WA TI Development of the intestinal mucosal barrier SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Conference of the Festschrift for Professor John Walker-Smith CY SEP 29, 2000 CL ROYAL FREE HOSP, LONDON, ENGLAND HO ROYAL FREE HOSP ID TOLL-LIKE RECEPTORS; RAT SMALL-INTESTINE; CHOLERA-TOXIN; MICROVILLUS MEMBRANE; ADENYLATE-CYCLASE; MACROMOLECULES; SENSITIVITY; TRANSPORT; DISORDERS; BINDING C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Walker, WA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Combined Program Pediat Gastroenterol & Nutr, 149 13th St, Charlestown, MA 02129 USA. NR 32 TC 37 Z9 39 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PY 2002 VL 34 SU 1 BP S33 EP S39 DI 10.1097/01.MPG.0000017295.92960.78 PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 562FG UT WOS:000176186300009 PM 12082386 ER PT J AU Alexander, SW Wade, KC Hibberd, PL Parsons, SK AF Alexander, SW Wade, KC Hibberd, PL Parsons, SK TI Evaluation of risk prediction criteria for episodes of febrile neutropenia in children with cancer SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE fever; neutropenia; high risk; low risk; pediatric oncology ID EARLY HOSPITAL DISCHARGE; FEVER; BACTEREMIA; IDENTIFICATION; MANAGEMENT; PATIENT; GRANULOCYTOPENIA; THERAPY; RULE AB Purpose: To evaluate the feasibility of risk stratification of children with cancer and febrile neutropenia using a simple set of criteria from data available to the clinician at the time of the patient's presentation. Patients and Methods: This study is a retrospective cohort study of all children with cancer admitted to a single institution with fever and neutropenia (defined as an absolute neutrophil count <500 cells/mm(3)) in a 1-year period. Patients were defined a priori as low risk if they were outpatients at the time of presentation with febrile neutropenia, had an anticipated duration of neutropenia less than 7 days, and had no significant comorbidity. All others were considered high risk. Data was analyzed by first admission for each patient and secondarily for all admissions for febrile neutropenia. Results: There were 188 admissions in 104 patients for febrile neutropenia during the study period. Of these 47% were high risk and 53% were low risk. The duration of fever was not significantly different in the two groups. However, the duration of neutropenia and the length of hospital stay were significantly longer in the high-risk group. The frequency of bacteremia, other documented infection, and serious medical complications was significantly different in the two groups. Overall, the rate of any adverse event was 4% in the low-risk group versus 41% in the high-risk group. Conclusions: Simple criteria available to the clinician at the time of evaluation of the child with cancer who has fever and neutropenia allow the selection of a population at low risk for bacteremia or serious medical complication. A prospective study is planned using these risk criteria, evaluating outpatient oral antibiotic therapy in low-risk children with cancer. C1 Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Alexander, SW (reprint author), Rainbow Babies & Childrens Hosp, Dept Pediat Hematol Oncol, 11100 Euclid Ave, Cleveland, OH 44106 USA. NR 21 TC 48 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN PY 2002 VL 24 IS 1 BP 38 EP 42 DI 10.1097/00043426-200201000-00011 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 513ZH UT WOS:000173410800011 PM 11902738 ER PT J AU Bond, B Hirota, L Fortin, J Col, N AF Bond, B Hirota, L Fortin, J Col, N TI Women like me: Reflections on health and hormones from women treated for breast cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE breast cancer; hormone replacement therapy; decision making; menopausal symptoms; risk perception ID ESTROGEN REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; RISK; DECISIONS; PROGESTIN; HEART AB Hormone replacement therapy (HRT) traditionally has been withheld from women with breast cancer to minimize their risk of recurrence. However, the benefits of HRT include relief from menopausal symptoms and protection against osteoporosis and possibly heart disease. Focus groups were conducted among women diagnosed with breast cancer to explore how the women approached health decisions, especially regarding HRT, and to identify factors that influenced their decision-making process. Factors identified included relief of symptoms, fear of cancer, side effects of treatment, attitudes toward risk, perception of risk and mastery, and physicians' recommendations. The article discusses these factors and provides suggestions, such as the following, to care providers who counsel women concerning menopause and HRT: Help patients understand areas in which the evidence is solid, address their possibly unrealistic expectations, and help them articulate their feelings and fears. C1 Tufts Univ New England Med Ctr, Dept Social Work Serv, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Decis Syst Grp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bond, B (reprint author), Tufts Univ New England Med Ctr, Dept Social Work Serv, 750 Washington St,Box 790, Boston, MA 02111 USA. NR 21 TC 3 Z9 3 U1 0 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2002 VL 20 IS 3 BP 39 EP 56 DI 10.1300/J077v20n03_03 PG 18 WC Psychology, Social SC Psychology GA 607CV UT WOS:000178774400003 ER PT J AU Perell, KL Gregor, S Kim, G Rushatakankovit, S Scremin, AME Levin, S Gregor, R AF Perell, KL Gregor, S Kim, G Rushatakankovit, S Scremin, AME Levin, S Gregor, R TI Comparison of cycling kinetics during recumbent bicycling in subjects with and without diabetes SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE bicycling; biomechanics; diabetes; peripheral neuropathy ID LOWER-EXTREMITY AMPUTATION; LIMITED JOINT MOBILITY; RISK-FACTORS; PLANTAR PRESSURES; MELLITUS; FOOT; GAIT; COMPLICATIONS; NEUROPATHY; ULCERATION AB We compared recumbent bicycle kinetics in diabetic peripheral neuropathy and nondiabetic men (nine per group). 3D kinematic and force pedal data in a linked-segment model were used. The generalized muscle moment (GMM) patterns were similar between the two groups except for (1) decreased maximum knee flexor moment, (2) increased minimum knee flexor GMM, and (3) maximum hip extensor GMM by the diabetic subjects. Similar to the walking support moment, a summation moment immutable pattern was observed, although the groups accomplished it differently. The diabetic group utilized the hip during the power phase and the knee during the recovery phase. The nondiabetic group utilized both joints together during both phases. Differences in ankle GMM were not observed, suggesting further research using the recumbent bicycle as an exercise modality for diabetic peripheral neuropathy patients to enhance ankle range of motion and strength, commonly observed walking deficits. C1 W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA USA. Georgia Inst Technol, Dept Hlth & Performance Sci, Atlanta, GA 30332 USA. RP Perell, KL (reprint author), W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 42 TC 9 Z9 9 U1 1 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN-FEB PY 2002 VL 39 IS 1 BP 13 EP 20 PG 8 WC Rehabilitation SC Rehabilitation GA 533GQ UT WOS:000174521500003 PM 11926324 ER PT J AU Williams, ME Chianchiano, D AF Williams, ME Chianchiano, D TI Medicare medical nutrition therapy: Legislative process and product SO JOURNAL OF RENAL NUTRITION LA English DT Article ID DIETARY-PROTEIN RESTRICTION; CHRONIC RENAL-DISEASE; HEMODIALYSIS-PATIENTS; PROGRESSION; PREDICTORS AB The new Medicare benefit, medical nutrition therapy (MNT), came into effect January 2002-the product of a lengthy legislative process. Over several years, evidence-based advocacy by groups such as the American Diabetic Association and the National Kidney Foundation led to a legislative product that was introduced and passed by Congress. More recently, the legislation entered an implementation process, including the most recent Coverage Determination phase. The definition of MNT and the scientific evidence supporting it are presented. Evidence-based nutrition now enters a new phase of implementation and additional analysis. (C) 2002 by the National Kidney Foundation, Inc. C1 Joslin Diabet Ctr, Renal Clin Res Ctr, Renal Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Clin Res Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JAN PY 2002 VL 12 IS 1 BP 1 EP 7 DI 10.1053/jrcn.2002.31187 PG 7 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 521KF UT WOS:000173838600001 PM 11823988 ER PT J AU Liu, CD Tilch, L Kwan, D McFadden, DW AF Liu, CD Tilch, L Kwan, D McFadden, DW TI Vascular endothelial growth factor is increased in ascites from metastatic pancreatic cancer SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE ascites; pancreatic cancer; vascular endothelial growth factor; metastasis ID EXPRESSION; RECEPTORS; ANGIOGENESIS; KDR AB Introduction. Vascular endothelial growth factor (VEGF) is an angiogenic factor that increases vascular permeability. VEGF stimulates capillary formation and has mitogenic effects on vascular endothelial cells. The development of malignant ascites causes significant morbidity. We hypothesized that increased levels of VEGF play a role in the development of malignant ascites in patients with pancreatic cancer. Methods. Athymic mice underwent orthotopic implantation of human pancreatic ductal adenocarcinoma tumors (250,000 cells) into the body of the pancreas. Tumors were allowed to grow for 12 weeks, at which time ascites develops in 50% of mice. Paracentesis was performed on mice with noticeable ascites. Saline lavage was performed in mice with equivalent pancreatic tumor masses without ascites and served as control. Both ascites and tumor masses were harvested for VEGF protein quantitation by ELISA. Results. VEGF protein levels were elevated in malignant ascites by 15-fold compared to control mice with equivalent tumors (N = 6, P < 0.001, t test). VEGF levels were slightly higher in the primary tumor masses harvested from mice without ascites. Mice with ascites also had metastatic nodules throughout the abdominal cavity. Conclusions. We are reporting for the first time that VEGF levels are increased in the ascites of nude mice with orthotopically transplanted human pancreatic cancers. VEGF increases vascular permeability and allows for extrapancreatic seeding of tumors. Irrespective of primary tumor size, intraperitoneal VEGF levels are increased when ascites and extrapancreatic nodules are present, while a paradoxical decrease is observed in VEGF levels of primary tumors. (C) 2002 Elsevier Science. C1 W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Lewis A Johnson Vet Adm Med Ctr, Clarksburg, WV 26301 USA. RP Liu, CD (reprint author), W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90095 USA. NR 11 TC 19 Z9 21 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2002 VL 102 IS 1 BP 31 EP 34 DI 10.1006/jsre.2001.6307 PG 4 WC Surgery SC Surgery GA 517MU UT WOS:000173615000005 PM 11792148 ER PT J AU Geller, DA Biederman, J Faraone, SV Cradock, K Hagermoser, L Zaman, N Frazier, JA Coffey, BJ Spencer, TJ AF Geller, DA Biederman, J Faraone, SV Cradock, K Hagermoser, L Zaman, N Frazier, JA Coffey, BJ Spencer, TJ TI Attention-deficit/hyperactivity disorder in children and adolescents with obsessive-compulsive disorder: Fact or artifact? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; pediatric; comorbidity; attention-deficit/hyperactivity disorder ID DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; TRIAL; PHENOMENOLOGY; COMORBIDITY; DESIPRAMINE; FLUOXETINE; DIAGNOSIS; CHILDHOOD AB Objective: To clarify whether the symptoms of inattention and distractibility commonly seen in children and adolescents with obsessive-compulsive disorder (OCD) represent true comorbidity with attention-deficit/hyperactivity disorder (ADHD) or a manifestation of obsessional anxiety. Method: Phenotypic features and functional correlates of ADHD-like symptoms were examined in youths with and without OCD from a large sample of pediatric psychiatry patients consecutively referred since 1997. Results: The number, frequency, and types of core ADHD symptoms as well as ADHD-associated functional indices were identical in all youths with DSM-IV-diagnosed ADHD irrespective of the presence or absence of comorbid OCD. Conclusion: These findings suggest that when ADHD-like symptoms are seen in youths with OCD, they reflect a true comorbid state of OCD plus ADHD and that the ADHD syndrome may be independent of OCD in comorbid youths. C1 McLean Hosp, OCD Clin, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, Boston, MA 02114 USA. McLean Hosp, Boston, MA 02114 USA. Pediat Psychopharmacol Clin, Boston, MA USA. RP Geller, DA (reprint author), McLean Hosp, OCD Clin, 115 Mill St, Belmont, MA 02478 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08 MH01481] NR 27 TC 50 Z9 52 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2002 VL 41 IS 1 BP 52 EP 58 DI 10.1097/00004583-200201000-00011 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 504QR UT WOS:000172867800011 PM 11800207 ER PT J AU Nurcombe, B Drell, MJ Leonard, HL McDermott, JF AF Nurcombe, B Drell, MJ Leonard, HL McDermott, JF TI Clinical problem solving: The case of Matthew, part I SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Univ Queensland, Royal Brisbane Hosp, Mental Hlth Ctr, Herston, Qld, Australia. LSU, Hlth Sci Ctr, New Orleans, LA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Hawaii, Sch Med, Honolulu, HI 96822 USA. RP Nurcombe, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2002 VL 41 IS 1 BP 92 EP 97 DI 10.1097/00004583-200201000-00017 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 504QR UT WOS:000172867800017 PM 11800214 ER PT J AU Tsao, H Kwitkiwski, K Sober, AJ AF Tsao, H Kwitkiwski, K Sober, AJ TI A single-institution case series of patients with cutaneous melanoma and non-Hodgkin's lymphoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; SKIN-CANCER; 2ND CANCERS; SUNLIGHT; DISEASE; RISK; ASSOCIATION; MORTALITY; RADIATION; TRENDS AB Background: Over the past two decades, cutaneous melanoma (CM) and non-Hodgkin's lymphoma (NHL) have both experienced unabated increases in incidence. Population-based studies have documented an elevated risk of subsequent NHL among patients with CM and vice versa. Methods: To better characterize the clinical features of patients who have had both malignancies, we retrospectively identified all patients with CM at the Massachusetts General Hospital (MGH) who subsequently had NHL and all NHL patients who later developed CM. Results: A total of 2461 CM and 2708 NHL patients were registered at MGH between 1973 and 1998. Out of these groups, 10 CM patients (0.4%) eventually developed NHL and 11 NHL patients (0.4%) subsequently had CM. The mean age at the first CM diagnosis was 56 years, whereas the mean age at the first NHL diagnosis was 67 years. The mean interval to NHL among the CM group was 119 months whereas the mean interval to CM among the NHL patients was 36 months. All primary CMs were All primary CMs were relatively thin (0.95 mm, first diagnosis; 1.07 mm second diagnosis), and most NHL subtypes were indolent in nature. Conclusion: The rates of developing a second NHL among CM patients and vice versa are low. Any interactions between CM and NHL may be due to factors such as detection bias, shared environmental ultraviolet carcinogenesis, or possibly, posttreatment effects. C1 Massachusetts Gen Hosp, Melanoma Ctr, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Melanoma Ctr, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. NR 27 TC 9 Z9 9 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2002 VL 46 IS 1 BP 55 EP 61 DI 10.1067/mjd.2001.118353 PG 7 WC Dermatology SC Dermatology GA 511YR UT WOS:000173294800006 PM 11756946 ER PT J AU Friedlander, AH AF Friedlander, AH TI The physiology, medical management and oral implications of menopause SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Review ID ESTROGEN REPLACEMENT THERAPY; HYDROXYAPATITE-COATED IMPLANTS; CORONARY HEART-DISEASE; BURNING MOUTH SYNDROME; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; RISK-FACTORS; BONE-DENSITY; RECEPTOR MODULATORS; PERIODONTAL-DISEASE AB Background. Approximately 36 million women in the United States are in the postmenopausal phase of life. The vast majority of these women experienced spontaneous cessation of menses between the ages of 47 and 55 years when the production of estrogen decreased because of an inadequate number of functioning follicles within their ovaries. Fewer warren entered menopause after surgical removal of both ovaries. This procedure usually is performed prophylactically to prevent ovarian cancer in conjunction with a hysterectomy, which is required to treat abnormal bleeding, endometriosis or pelvic inflammatory disease. The physiological changes associated with spontaneous or surgical menopause cause some women to experience uncomfortable symptoms such as hot flashes, night sweats and vagina dryness. In addition, estrogen deprivation arising from menopause in association with age-related factors disproportionately increases the risk of developing cardiovascular lease (that is, myocardial infarct, stroke), osteoporosis, Alzheimer's disease and oral lease. Hormone replacement therapy, or HRT (estrogen or estrogen and progestin), often is prescribed on a short-term basis to alleviate the uncomfortable symptoms associated with estrogen deficiency and on a long-term basis to prevent some of the chronic illnesses common to postmenopausal women. Conclusions. Dentists who treat women entering menopause need to consider the Stressful phase of life their patients are experiencing. Clinical findings of postmenopausal problems on dental examination may include a paucity of saliva, increased dental caries, prevalent prevalent dysesthesia, taste alterations, atrophic gingivitis, penodontitis and osteoporotic jaws suitable for conventional prosthetic devices or dental implants. Panoramic dental radiographs may reveal calcified rid awry atheromas. Clinical Implications. Dentists have an opportunity to refer women who are not under the care of a gynecologist for an evaluation to determine the appropriateness of HRT for its systemic and oral health benefits. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 111 TC 52 Z9 55 U1 5 U2 6 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 2002 VL 133 IS 1 BP 73 EP 81 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 513VZ UT WOS:000173402100022 PM 11811747 ER PT J AU Jones, JA Spiro, A Miller, DR Garcia, RI Kressin, NR AF Jones, JA Spiro, A Miller, DR Garcia, RI Kressin, NR TI Need for dental care in older veterans: Assessment of patient-based measures SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 78th General Session of the International-Association-for-Dental-Research CY APR 05-09, 2000 CL WASHINGTON, D.C. SP Int Assoc Dent Res DE oral health; sensitivity; outcomes; quality of life; dental care; veterans ID QUALITY-OF-LIFE; ORAL HEALTH; ADULTS AB OBJECTIVES: There is a need for brief and accurate identification of older patients in need of dental care. This study examines the sensitivity and specificity of two screening instruments. DESIGN: Cross-sectional study conducted in older community-dwelling male veterans. SETTING: Four Department of Veterans Affairs (VA) clinics in greater Boston and the VA Dental Longitudinal Study (DLS). PARTICIPANTS: Two hundred thirty-two participants from the Veterans Health Study (VHS) who were outpatients in one of four Department of Veterans Affairs clinics in greater Boston and 206 participants from the VA DLS, community-dwelling veterans who do not use VA for their health care. MEASUREMENTS: Self-report measures included a single-item global self-report of oral health (OH-1) and a six-item dental screening measure called the D-E-N-T-A-L. The D-E-N-T-A-L queries whether participants have "Dry mouth, Eating or swallowing problems, Not had a dental examination in the last 2 years, Tooth or mouth problems, Altered eating habits because of teeth or mouth, or Lesions or sores in the mouth." The criterion standard for need for treatment was determined by a clinical examination. Sensitivities and specificities were calculated and receiver operating characteristic curves plotted to identify the best cut-points for each measure. RESULTS: Need for care was nearly universal (97%) in the VHS and present in 64% of the DLS participants. The single-item self-report of oral health performed as well as the D-E-N-T-A-L in identifying persons in need of care. Compared with the clinical criterion, the OH-1 had a sensitivity of 0.75 and a specificity of 0.67 in identifying persons with severe need for denture care, whereas the D-EN-T-A-L had a sensitivity of 0.80 and a specificity of 0.62 in identifying persons with severe periodontal need. CONCLUSION: Self-reports of fair or poor oral health are useful in identifying veterans in need of dental care, especially in population,, with a large number of persons who do not usually use dental care. The D-E-N-T-A-L may also be useful as a self-screening measure and community education device to encourage older persons to seek regular dental care. C1 Edith Nourse Rogers Mem Vet Adm Hosp, VA Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Dept Hlth Policy & Hlth Serv Res, Grad Sch Dent Med, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. VA Boston Healthcare Syst, Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Jones, JA (reprint author), VA Ctr Hlth Qual Outcome & Econ Res, CHQOER 152,200 Springs Rd, Bedford, MA 01730 USA. FU NIDCR NIH HHS [K24 DE00419] NR 27 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2002 VL 50 IS 1 BP 163 EP 168 DI 10.1046/j.1532-5415.2002.50023.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 510YY UT WOS:000173236200025 PM 12028262 ER PT J AU Krakauer, EL Crenner, C Fox, K AF Krakauer, EL Crenner, C Fox, K TI Barriers to optimum end-of-life care for minority patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review DE culture; ethnicity; medical ethics; minorities; palliative care; race; trust; terminal illness ID SERIOUSLY ILL PATIENTS; AFRICAN-AMERICAN COMMUNITY; NURSING-HOME RESIDENTS; NOT-RESUSCITATE ORDERS; HEALTH-CARE; RACIAL-DIFFERENCES; VETERANS-AFFAIRS; PALLIATIVE CARE; CARDIOPULMONARY-RESUSCITATION; CARDIAC-CATHETERIZATION AB Although major efforts are underway to improve end-of-life care, there is growing evidence that improvements are not being experienced by those at particularly high risk for inadequate care: minority patients. Ethnic disparities in access to end-of-life care have been found that reflect disparities in access to many other kinds of care. Additional barriers to optimum end-of-life care for minority patients include insensitivity to cultural differences in attitudes toward death and end-of-life care and understandable mistrust of the healthcare system due to the history of racism in medicine. These barriers can be categorized as institutional, cultural, and individual. Efforts to better understand and remove each type of barrier are needed. Such efforts should include quality assurance programs to better assess inequalities in access to end-of-life care, political action to address inadequate health insurance and access to medical school for minorities, and undergraduate and continuing medical education in cultural sensitivity. C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA USA. Univ Kansas, Sch Med, Dept Hist & Philosophy Med, Kansas City, KS USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. RP Krakauer, EL (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, 55 Fruit St,Founders 600, Boston, MA 02114 USA. NR 159 TC 109 Z9 110 U1 4 U2 14 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2002 VL 50 IS 1 BP 182 EP 190 DI 10.1046/j.1532-5415.2002.50027.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 510YY UT WOS:000173236200029 PM 12028266 ER PT J AU Melhem, MF Craven, PA Liachenko, J DeRubertis, FR AF Melhem, MF Craven, PA Liachenko, J DeRubertis, FR TI alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; LIPID-PEROXIDATION; OXIDATIVE STRESS; SKELETAL-MUSCLE; VITAMIN-E; GLUCOSE-TRANSPORT; BLOOD-FLOW; ANTIOXIDANT; RATS; MELLITUS AB Previous studies demonstrated that 2 mo of dietary supple mentation with alpha -lipoic acid (LA) prevented early glomerular injury in non-insulin-treated streptozotocin diabetic rats (D). The present study examined the effects of chronic LA supplementation (30 mg/kg body wt per d) on nephropathy in D after 7 mo of diabetes. Compared with control rats. D developed increased urinary excretion of albumin and transforming growth factor beta. renal insufficiency, glomerular mesangial matrix expansion, and glomerulosclerosis in association with depletion of glutathione and accumulation of malondialdehyde in renal cortex. LA prevented or ameliorated all of these changes in D. Because chronic LA supplementation also attenuated hyperglycemia in D after 3 mo, its effects on renal injury were compared with treatment of rats with sufficient insulin to maintain a level of glycemic control for the entire 7-mo period (D-INS) equivalent to that observed with LA during, the final 4 mo. Despite superior longitudinal glycemic control in D-INS, urinary excretion of albumin and transforming growth factor beta, glomerular mesangial matrix expansion, the extent of glomerulosclerosis, and renal cortical malondialdehyde content were all significantly greater, whereas cortical glutathione content was lower than corresponding values in D given LA. Thus, the renoprotective effects of LA in D were not attributable to improved glycemic control alone but also likely reflected its antioxidant activity. The combined antioxidant and hypoglycemic actions of LA both may contribute to its utility in preventing renal injury and other complications of diabetes. C1 VA Pittsburgh Healthcare Syst, Dept Pathol, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP DeRubertis, FR (reprint author), VA Pittsburgh Healthcare Syst, Dept Pathol, 111-U Univ Dr C, Pittsburgh, PA 15240 USA. NR 51 TC 76 Z9 80 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2002 VL 13 IS 1 BP 108 EP 116 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 504ZZ UT WOS:000172887400016 PM 11752027 ER PT J AU Heffelfinger, AK Craft, S White, DA Shyken, J AF Heffelfinger, AK Craft, S White, DA Shyken, J TI Visual attention in preschool children prenatally exposed to cocaine: Implications for behavioral regulation SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE cocaine exposure; visual attention; children; neuropsychology ID IN-UTERO EXPOSURE; CEREBRAL-CORTEX; EARLY INFANCY; REACTION-TIME; HUMAN-BRAIN; DOPAMINE; RAT; CATECHOLAMINES; PERFORMANCE; COMPONENTS AB The presence of cocaine during the prenatal period disrupts the development of neural systems involved in mediating visual attention; therefore, it is possible that prenatal cocaine exposure results in impairments in visual attention in early childhood. In the current study we hypothesized that preschool children with prenatal cocaine exposure would exhibit difficulties in the disengagement operation of visual attention and in sustaining attention, particularly for targets presented in the right visual field. Fourteen cocaine-exposed children and 20 control children between 14 and 60 months of age were assessed on measures of visual attention, cognition, and behavior. Cocaine-exposed children had slower reaction times on disengagement trials in the second half of our attention task, supporting our hypotheses that impairments in disengagement and sustained attention are associated with prenatal cocaine exposure. There was a trend for slower reaction times to targets presented in the right visual field, but not to targets presented in the left visual field. Cocaine-exposed children also exhibited greater difficulties in behavioral regulation. Overall, our Findings suggest that children with prenatal cocaine exposure demonstrate specific impairments in visual attention and behavioral regulation. C1 Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. Univ Washington, VA Puget SOund Hlth Care Syst, Seattle, WA 98195 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. St Louis Univ, Dept Obstet, St Louis, MO 63103 USA. RP Heffelfinger, AK (reprint author), MCW Clin Froedtert, Div Neuropsychol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 64 TC 32 Z9 33 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2002 VL 8 IS 1 BP 12 EP 21 DI 10.1017/S1355617701020021 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 535TT UT WOS:000174663000002 PM 11843069 ER PT J AU Chen, MH Harrington, DP Ibrahim, JG AF Chen, MH Harrington, DP Ibrahim, JG TI Bayesian cure rate models for malignant melanoma: a case-study of Eastern Cooperative Oncology Group trial E1690 SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Cox model; cure rate model; Gibbs sampling; historical data; latent variables; piecewise exponential model; posterior distribution; semiparametric model ID PREDICTIVE APPROACH; SURVIVAL-DATA; SELECTION AB We propose several Bayesian models for modelling time-to-event data. We consider a piecewise exponential model, a fully parametric cure rate model and a semiparametric cure rate model. For each model, we derive the likelihood function and examine some of its properties for carrying out Bayesian inference with non-informative priors, We also examine model identifiability issues and give conditions which guarantee identifiability. Also, for each model, we construct a class of informative prior distributions based on historical data, i.e. data from similar previous studies. These priors, called power priors, prove to be quite useful in this context We examine the properties of the power priors for Bayesian inference and, in particular, we study their effect on the current analysis. Tools for model comparison and model assessment are also proposed, A detailed case study of a recently completed melanoma clinical trial conducted by the Eastern Cooperative Oncology Group is presented and the methodology proposed is demonstrated in detail. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Connecticut, Storrs, CT USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Ibrahim, JG (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 15 Z9 16 U1 2 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2002 VL 51 BP 135 EP 150 AR UNSP 0035-9254/02/5135 DI 10.1111/1467-9876.00259 PN 2 PG 16 WC Statistics & Probability SC Mathematics GA 558EY UT WOS:000175954400001 ER PT J AU Klima, UP Lee, MY Guerrero, JL LaRaia, PJ Levine, RA Vlahakes, GJ AF Klima, UP Lee, MY Guerrero, JL LaRaia, PJ Levine, RA Vlahakes, GJ TI Determinants of maximal right ventricular function: Role of septal shift SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SYSTOLIC HYPERTENSION; BLOOD-FLOW; PRESSURE; MOTION; DOGS; PERICARDIUM; ISCHEMIA; HEARTS; WALL AB Background: Right heart failure can occur after orthotopic heart transplantation and can complicate implantation of left ventricular assist devices. The functional codeterminants of right ventricular function are not fully understood. We investigated the effects of left ventricular preload and afterload, systemic pressure, and the contribution of the interventricular septum to right ventricular function. Methods and Results: In vivo studies were conducted in 12 dogs by using a highly defined, isovolumic right heart preparation. At any given arterial pressure, maximal right ventricular developed pressure was not influenced by left heart output; however, right ventricular volumes at which peak right ventricular developed pressure occurred differed significantly between the volume-loaded versus the unloaded left ventricle (P < .05). A correlation was found between peak right ventricular developed pressure and mean arterial pressure. The shift of the interventricular septum toward the left ventricle is delayed under the influence of left ventricular volume load, but the maximal interventricular septal deformation does not differ at maximal fight ventricular developed pressure. There was a substantial and significant decrease in peak right ventricular developed pressure when the interventricular septum was inactivated (P < .05). Conclusions: Right ventricular function has multiple determinants, including the right ventricular free wall, the left ventricle, and the interventricular septum. Changes in right ventricular performance caused by alterations in left ventricular volume load and mean arterial pressure are mediated partially through the interventricular septum, as well as through perfusion of the right ventricular free wall; inactivation of the interventricular septum leads to a significant decrease in right ventricular function. Maintaining left ventricular developed pressure and hence the contribution of the interventricular septum to right ventricular function may be important in the management of tight ventricular failure. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, 55 Fruit St,BUL119, Boston, MA 02114 USA. NR 31 TC 39 Z9 46 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2002 VL 123 IS 1 BP 72 EP 80 DI 10.1067/mtc.2002118683 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 515YD UT WOS:000173523500012 PM 11782758 ER PT J AU Grillo, HC Wright, CD Vlahakes, GJ MacGillivray, TE AF Grillo, HC Wright, CD Vlahakes, GJ MacGillivray, TE TI Management of congenital tracheal stenosis by means of slide tracheoplasty or resection and reconstruction, with long-term follow-up of growth after slide tracheoplasty SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID PULMONARY-ARTERY; PERICARDIAL PATCH; CHILDREN; INFANCY AB Objective: The difficult problem of congenital tracheal stenosis is infrequent and has been managed with several methods. Patch tracheoplasty has been favored in recent years. Alternative experience with a simpler program of slide tracheoplasty for long-segment stenosis or resection and reconstruction for short-segment stenosis is described and proposed as preferable. Long-term growth after slide tracheoplasty was studied. Methods: Eleven consecutive patients aged 10 days to 23 years with varied patterns of stenosis (including concurrent pulmonary artery sting, anomalous right upper lobe bronchus, and bridge bronchus) had their stenoses corrected, 8 by means of slide tracheoplasty and 3 by means of resection and anastomosis. Retrospective review was made of hospital course, complications, and long-term results, with observation of growth in 4 patients (from more than 1(1)/(2)-7(3)/(4) years). Results: All patients are alive and enjoy good airways. Only 3 patients who needed concomitant cardiovascular procedures and 1 with poor ventricular function required bypass. Eight were extubated immediately or on the day of the operation, 1 at 3 days, and 1 at 8 days. A patient with complex anomalies needed 10 days of ventilation. Three had anastomotic granulomas successfully treated by means of a single bronchoscopy. Long-term airway growth was entirely satisfactory after slide tracheoplasty in 4 infants and small children (aged 10 days, 3 months, 6 months, and 3(1)/(2) years, respectively). Conclusions: Slide tracheoplasty gives excellent short- and long-term results because long congenital stenosis is reconstructed with native tracheal tissue and is therefore immediately stable and lined with normal epithelium, and the operation is accomplished more simply and with a generally more benign postoperative course. Wholly satisfactory growth of the repaired segment occurs. Less common short congenital stenosis is effectively managed with resection and anastomosis. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570, Boston, MA 02114 USA. NR 30 TC 89 Z9 101 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2002 VL 123 IS 1 BP 145 EP 152 DI 10.1067/mtc.2002.119068 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 515YD UT WOS:000173523500022 PM 11782768 ER PT J AU Wittram, C Batt, J Rappaport, DC Hutcheon, MA AF Wittram, C Batt, J Rappaport, DC Hutcheon, MA TI Inspiratory and expiratory helical CT of normal adults - Comparison of thin section scans and minimum intensity projection images SO JOURNAL OF THORACIC IMAGING LA English DT Article DE computed tomography (CT); image processing; CT-minimum intensity projection; lung-CT ID COMPUTED-TOMOGRAPHY; LUNG DENSITY; ATTENUATION; DISEASE; MEN AB To evaluate and compare thin section CT scans (TSS) and minimum intensity projection images (MinIPs) in healthy individuals, 10 nonsmokers with normal pulmonary function tests were studied using ten 1-mm collimated, helically acquired TSS images after full inspiration and expiration at two anatomic levels. Ten-millimeter-thick MinIPs were generated from the helical scans. Two thoracic radiologists compared TSS and MinIPs for artifacts and air trapping, Hounsfield unit (HU) measurements of TSS and MinIPs were obtained. The lung parenchyma on MinIPs demonstrates a smooth anterior-to-posterior attenuation gradient, accentuated by expiration. Motion and beam-hardening artifacts on TSS images resulted in regions of high and low attenuation on MinIPs, respectively. Expiratory TSS and MinIPs demonstrated air trapping (n = 31/40 range, 0-25%; mean, 7.2%). In comparison with TSS, MinIPs improved the conspicuity of air trapping (n = 20) and appeared to detect more air trapping (n = 7). No statistical differences were found when comparing the mean HU values of TSS and MinIPs. MinIPs demonstrated a smooth anterior-to-posterior attenuation gradient. Compared with TSS, MinIPs improve the conspicuity of air trapping in healthy individuals. Therefore, expiratory MinIPs may be useful in detecting air trapping as a result of disease. C1 Toronto Hosp, Dept Med Imaging, Toronto, ON M5T 2S8, Canada. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JAN PY 2002 VL 17 IS 1 BP 47 EP 52 DI 10.1097/00005382-200201000-00006 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 519YE UT WOS:000173752400006 PM 11828212 ER PT J AU Thomas, SH Orf, J Wedel, SK Conn, AK AF Thomas, SH Orf, J Wedel, SK Conn, AK TI Hyperventilation in traumatic brain injury patients: Inconsistency between consensus guidelines and clinical practice SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 30th International Educational and Scientific Symposium of the Society-for-Critical-Care-Medicine CY FEB 11-14, 2001 CL SAN FRANCISCO, CALIFORNIA SP Soc Crit Care Med DE traumatic brain injury; hyperventilation; hypocarbia ID CEREBRAL BLOOD-FLOW; TIDAL CARBON-DIOXIDE; SEVERE HEAD-INJURY; INTRAHOSPITAL TRANSPORT; TRANSCRANIAL DOPPLER; HEMORRHAGIC-SHOCK; CHILDREN; OXYGENATION; DIFFERENCE; METABOLISM AB Background: This study assessed patients with traumatic brain injury (TBI) to determine whether prehospital and community hospital providers employed hyperventilation therapy inconsistent with consensus recommendation against its routine use. Methods: This prospective analysis of 37 intubated TBI patients without herniation, undergoing helicopter transport to an urban Level I center, entailed flight crews' noting of assisted ventilation rate (AVR) and end-tidal carbon dioxide (ETco(2)) upon their arrival at trauma scenes or community hospitals. A priori-set levels of AVR and ETco(2) were used to assess frequency of guideline-inconsistent hyperventilation, and Fisher's exact and Kruskal-Wallis tests assessed association between guideline-inconsistent hyperventilation and manual vs. mechanical ventilation mode. Results: Inappropriately high AVR and low ETco(2) were seen in 60% and 70% of patients, respectively. Manual ventilation was associated with guideline-inconsistent hyperventilation assessed by AVR (p = 0.038) and ETco(2) (p = 0.022). Conclusion: Prehospital and community hospital hyperventilation practices are not consistent with consensus recommendations for limitation of hyperventilation therapy. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston MedFlight Crit Care Transport Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA 02118 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Boston MedFlight Crit Care Transport Serv, MGH Clin Bldg,Room 115,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JAN PY 2002 VL 52 IS 1 BP 47 EP 52 DI 10.1097/00005373-200201000-00010 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 514PF UT WOS:000173449700010 PM 11791051 ER PT J AU Thomas, SH Harrison, TH Buras, WR Ahmed, W Cheema, F Wedel, SK AF Thomas, SH Harrison, TH Buras, WR Ahmed, W Cheema, F Wedel, SK TI Helicopter transport and blunt trauma mortality: A multicenter trial SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 23-25, 2000 CL SAN FRANCISCO, CALIFORNIA SP Soc Acad Emergency Med DE helicopter transport; helicopter EMS; blunt trauma ID EMERGENCY CARE; SCENE; SURVIVAL; SERVICE; IMPACT; SYSTEM; INJURY; PHYSICIAN; AIR AB Background: Despite many studies addressing potential impact of helicopter transport on trauma mortality, debate as to the efficacy of air transport continues. Methods: This retrospective study combined trauma registry data from five urban Level I adult and pediatric centers. Logistic regression assessed effect of helicopter transport on mortality while adjusting for age, sex, transport year, receiving hospital, prehospital level of care (Advanced Life Support vs. Basic Life Support), ISS, and mission type (scene vs. interfacility). Results: The study database comprised 16,699 patients. Crude mortality for Air (9.4%) was 3.4 times (95% CI, 2.9-4.0, p < 0.001) that of Ground (3.0%) patients. In adjusted analysis, helicopter transport was found to be associated with a significant mortality reduction (odds ran tio, 0.76; 95% CI, 0.59-0.98; p = 0.031). Conclusion: The results of this study are consistent with an association between helicopter transport mode and increased survival in blunt trauma patients. C1 Boston Med Flight Crit Care Transport Serv, Bedford, MA 01730 USA. Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Med Ctr, Dept Surg, Boston, MA USA. RP Thomas, SH (reprint author), Boston Med Flight Crit Care Transport Serv, Robins St,Hangar 1727, Bedford, MA 01730 USA. NR 34 TC 84 Z9 85 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JAN PY 2002 VL 52 IS 1 BP 136 EP 145 DI 10.1097/00005373-200201000-00023 PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 514PF UT WOS:000173449700025 PM 11791064 ER PT J AU Matioc, AA Wells, JA AF Matioc, AA Wells, JA TI The LMA-unique in a prehospital trauma patient: Interaction with semirigid cervical collar: A case report SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID LARYNGEAL MASK AIRWAY; LINE NECK STABILIZATION; ADULT PATIENTS; MANAGEMENT; TRANSPORT; PRESSURE C1 William S Middleton Mem Vet Adm Med Ctr, Anesthesiol Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Anesthesiol, Sch Med, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Med, Sect Pulm Med, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Med, Sect Crit Care Med, Madison, WI USA. Univ Wisconsin Hosp & Clin, Dept Med, Sect Emergency Med, Madison, WI 53792 USA. RP Matioc, AA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Anesthesiol Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 18 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JAN PY 2002 VL 52 IS 1 BP 162 EP 164 DI 10.1097/00005373-200201000-00028 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 514PF UT WOS:000173449700030 PM 11791069 ER PT J AU Gardner, BG Zietman, AL Shipley, WU Skowronski, UE McManus, P AF Gardner, BG Zietman, AL Shipley, WU Skowronski, UE McManus, P TI Late normal tissue sequelae in the second decade after high dose radiation therapy with combined photons and conformal protons for locally advanced prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; radiotherapy; treatment outcome ID BOOST THERAPY; CARCINOMA; RADIOTHERAPY; IRRADIATION; ESCALATION; EORTC AB Purpose: We determined the long-term normal tissue effects of 77.4 Gy. delivered to the prostate in patients with locally advanced prostate cancer. Methods and Materials: Between 1976 and 1992, 167 men with stages T3 to 4 prostate cancer were treated on protocol with 50.4 Gy. photons at 1.8 Gy. per fraction using a 4-field box arrangement, followed by a conformal perineal proton boost of 27 Gy. (cobalt Gy. equivalent) in 11 fractions. The chart was reviewed and 39 of the 42 surviving patients were interviewed. Median followup was 13.1 years (range 7 to 23). Normal tissue morbidity was recorded using Radiation Therapy Oncology Group criteria and the late effects normal tissue scale. Results: The actuarial incidence of grade 2 or greater genitourinary morbidity was 59% at 15 years. However, these grade 2 or greater problems persisted to the time of the interview in only 7 of 39 cases. The actuarial incidence of grade 2 or greater hematuria was 21% at 5 years and 47% at 15. For grade 3 or greater hematuria the risk was 3% and 8% at 5 and 15 years, respectively. No patient required cystectomy but 1 required diversion for morbidity. Urethral stricture and urinary incontinence with pads needed developed in 4 and 3 men, respectively. This particular morbidity was strongly associated with previous or subsequent prostate surgery. The actuarial incidence of grade 2 or greater gastrointestinal morbidity was 13% at 5 and 15 years, while grade 1 rectal bleeding occurred in another 41%. Conclusions: High dose conformal radiation to the prostate is followed by a high rate of low grade rectal bleeding but a low rate of grade 2 or higher gastrointestinal morbidity. This rate is stable and does not increase beyond 5 years. Genitourinary morbidity continues to develop well into the second decade after treatment, although high grade morbidity is uncommon. These findings do not suggest that the modern trend toward high dose prostate treatment with conformal techniques will result in a high incidence of serious and permanent late sequelae but it appears that hematuria will be common. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Harvard Cyclotron Lab, Cambridge, MA 02138 USA. RP Gardner, BG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 18 TC 67 Z9 68 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2002 VL 167 IS 1 BP 123 EP 126 DI 10.1016/S0022-5347(05)65395-5 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 502CM UT WOS:000172726200036 PM 11743288 ER PT J AU Cook, JW Malinow, MR Moneta, GL Taylor, LM Orloff, SL AF Cook, JW Malinow, MR Moneta, GL Taylor, LM Orloff, SL TI Neointimal hyperplasia in balloon-injured rat carotid arteries: The influence of hyperhomocysteinemia SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID MUSCLE CELL-PROLIFERATION; INTIMAL HYPERPLASIA; VASCULAR-DISEASE; PLASMA HOMOCYSTEINE; RISK-FACTORS; FOLLOW-UP; HYPERHOMOCYST(E)INEMIA; FOLATE; ATHEROSCLEROSIS; ENDARTERECTOMY AB Purpose: Hyperhomocyst(e)inemia (hH[e]) is a risk factor for atherosclerosis. Neointimal hyperplasia (NH) after vessel injury can contribute to atherosclerosis. In this study, we investigated the effects of hH(e) on NH formation after arterial balloon injury in rats. Methods: Lewis rats that were given a hH(e)-inducing (high methionine, low folate) or normal diet for 150 days underwent common carotid artery (CCA) balloon injury. Two and 4 weeks after injury, CCAs were formalin perfusion-fixed, sectioned, and stained for elastin. Neointimal index (NI, percent lumen occlusion) and neointima (N) and media (M) area were measured by using computer-interfaced microscopy. Results: Plasma homocyst(e)ine (H[e]) levels were elevated in rats given the study diet compared with rats given the normal diet at days 40 and 90 (69 +/- 8 and 73 +/- 9 mumol/L vs 4 +/- 0.4 and 4 +/- 0.6 pmol/L, P < .001). After balloon injury, the CCA NI and N/M ratio, but not the M area, were increased by hH(e) compared with normal plasma H(e) (2 weeks [n = 6,7]: NI = 7.3 +/- 1.7 vs 2.9 +/- 0.7, P = .002, and N/M 0.31 +/- 0.08 vs 0.08 +/- 0.02, P < .001; 4 weeks [n = 4,71: NI = 13.1 +/- 2.2 vs 6.3 +/- 1.3, P = .002, and N/M = 0.36 +/- 0.08 vs 0.17 +/- 0.03, P < .001). Conclusion: hH(e) accelerates NTH in a rat CCA balloon-injury model. The effect of hH(e) on NH may contribute to increased atherosclerosis in humans with hH(e). C1 Oregon Hlth Sci Univ, Div Liver Pancreas Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Vasc Surg, Dept Surg, Portland, OR 97201 USA. Oregon Reg Primate Res Ctr, Portland, OR USA. Portland Vet Affairs Med Ctr, Dept Surg, Portland, OR USA. RP Orloff, SL (reprint author), Oregon Hlth Sci Univ, Div Liver Pancreas Transplantat, Mail Code L-590,3181 SE Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NCRR NIH HHS [RR 00334, RR 00163] NR 41 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2002 VL 35 IS 1 BP 158 EP 165 DI 10.1067/mva.2002.118819 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 518VG UT WOS:000173688100031 PM 11802148 ER PT J AU Wall, C Rauch, SD AF Wall, C Rauch, SD TI Special section: ARO meeting 2001 - Introduction SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2002 VL 12 IS 2-3 BP 67 EP 68 PG 2 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 734LT UT WOS:000186058000001 ER PT J AU Lewis, RF Gong, WS Ramsey, M Minor, L Boyle, R Merfeld, DM AF Lewis, RF Gong, WS Ramsey, M Minor, L Boyle, R Merfeld, DM TI Vestibular adaptation studied with a prosthetic semicircular canal SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article; Proceedings Paper CT Symposium on Electrical Stimulation of the Vestibular System CY 2001 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolaryngol DE vestibular; adaptation; prosthesis; monkey ID ELECTRICAL-STIMULATION; VESTIBULOOCULAR REFLEX; SQUIRREL-MONKEY; RECOVERY AB We have developed and tested a prosthetic semicircular canal that senses angular head velocity and uses this information to modulate the rate of current pulses applied to the vestibular nerve via a stimulating electrode. In one squirrel monkey, the lateral canals were plugged bilaterally and the prosthesis was secured to the animal's head with the angular velocity sensor parallel to the axis of the lateral canals. In the first experiment, the stimulating electrode was placed near the ampullary nerve of one lateral canal. Over a period of two weeks, the gain of the horizontal VOR during yaw axis rotation gradually increased, although the response magnitude remained relatively small. In the second experiment, the stimulating electrode was placed near the ampullary nerve of the posterior canal, but the orientation of the velocity sensor remained parallel to the axis of the lateral canals. Over a one-week period, the axis of the VOR response gradually shifted towards alignment with the (yaw) axis of head rotation. Chronic patterned stimulation of the eighth nerve can therefore provide adequate information to the brain to generate a measurable VOR response, and this can occur even if the prosthetic yaw rotation cue is provided via a branch of the VIIIth nerve that doesn't normally carry yaw rotational cues. The results provided by this pilot study suggest that it may be feasible to study central adaptation by chronically modifying the afferent vestibular cue with a prosthetic semicircular canal. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Johns Hopkins Sch Med, Dept Otolaryngol, Baltimore, MD USA. NASA, Ames Res Ctr, Ctr Bioinformat, Moffett Field, CA 94035 USA. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC03066]; NINDS NIH HHS [NS27050] NR 14 TC 39 Z9 39 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2002 VL 12 IS 2-3 BP 87 EP 94 PG 8 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 734LT UT WOS:000186058000004 PM 12867667 ER PT J AU Wall, C Merfeld, DM Rauch, SD Black, FO AF Wall, C Merfeld, DM Rauch, SD Black, FO TI Vestibular prostheses: The engineering and biomedical issues SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article; Proceedings Paper CT Symposium on Electrical Stimulation of the Vestibular System CY 2001 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolaryngol DE balance; prosthetic devices; implant; sensory substitution; vibrotactile display ID INNERVATING SEMICIRCULAR CANALS; PAROXYSMAL POSITIONAL VERTIGO; SQUIRREL-MONKEY; ELECTRICAL-STIMULATION; VESTIBULOOCULAR REFLEX; ACOUSTIC NEUROMA; OTOLITH ORGANS; GALVANIC STIMULATION; NERVE STIMULATION; POSTURAL CONTROL AB Currently available data demonstrate the need for balance prostheses. Recent technological and biomedical advances now make it feasible to produce miniaturized sensors, signal processors, electric stimulators, and stimulating electrodes that are roughly analogous to a cochlear implant but which provide information about self motion, instead of sound. Many areas require work before balance prostheses become a reality. Some of these include: the development of a motion sensor array, the conversion of the sensed motion into physiologically meaningful information, the delivery of the transformed information to the CNS, the training of vestibular deficient individuals to use the prosthesis, and developing methods to evaluate the efficacy of the device. In this "white paper," we consider these issues in the context of prototype baseline prosthetic devices. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Legacy Hlth Care Syst, Portland, OR USA. Massachusetts Eye & Ear Infirm, Neural Prosthesis Res Ctr, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci Technol, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. NR 112 TC 52 Z9 56 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2002 VL 12 IS 2-3 BP 95 EP 113 PG 19 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 734LT UT WOS:000186058000005 PM 12867668 ER PT J AU Wall, C Oddsson, LI Patronik, N Sienko, K Kentala, E AF Wall, C Oddsson, LI Patronik, N Sienko, K Kentala, E TI Recovery trajectories of vestibulopathic subjects after perturbations during locomotion SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article; Proceedings Paper CT 6th Symposium on the Role of the Vestibular Organs in the Exploration of Space CY OCT, 2002 CL PORTLAND, OREGON SP NASA DE balance; postural stability; vestibular; microgravity; vestibular testing; locomotor perturbations; impulse response ID POSTURAL RESPONSES; FRONTAL-PLANE; HUMAN WALKING; BALANCE; GAIT; STABILITY; STANCE AB We compared the mediolateral (M/L) responses to perturbations during locomotion of vestibulopathic (VP) subjects to those of controls. Eight subjects with unilateral vestibular loss (100% Reduced Vestibular Response from the caloric test) resulting from surgery for vestibular schwannoma and I I controls were selected for this study. Despite their known vestibulopathy, all VP subjects scored within the normal range on computerized dynamic posturography Sensory Organization Tests. During gait, subjects were given surface perturbations of the right support-phase foot in two possible directions (forward-right and backward-left) at two possible magnitudes (5 and 10 cm) that were randomly mixed with trials having no perturbations. M/L stability was quantified by estimating the length of the M/L moment arm between the support foot and the trunk, and the M/L accelerations of the sternum and the head. The VP group had greater changes (p < 0.05) in their moment arm responses compared to controls. The number of steps that it took for the moment arm oscillations to return to normal and the variability in the moment arms were greater for the VP group. Differences in the sternum and head accelerations between VP and control groups were not as consistent, but there was a trend toward greater response deviations in the VP group for all 4 perturbation types. Increased response magnitude and variability of the VP group is consistent with an increase in their sensory noise of vestibular inputs due to the surgical lesion. Another possibility is a reduced sensitivity to motion inputs. This perturbation approach may prove useful for characterizing subtle vestibulopathies and similar changes in the human orientation mechanism after exposure to microgravity. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Boston Univ, Neuromuscular Res Ctr, Boston, MA 02215 USA. Harvard Univ, MIT, Whitaker Coll Hlth Sci & Technol, Cambridge, MA 02139 USA. Helsinki Univ Hosp, Helsinki, Finland. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 8 Z9 8 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2002 VL 12 IS 5-6 BP 239 EP 253 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 733AY UT WOS:000185978800005 PM 14501101 ER PT J AU Wild, CJ Greenlee, JJ Bolin, CA Barnett, JK Haake, DA Cheville, NE AF Wild, CJ Greenlee, JJ Bolin, CA Barnett, JK Haake, DA Cheville, NE TI An improved immunohistochemical diagnostic technique for canine leptospirosis using antileptospiral antibodies on renal tissue SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article ID OUTER-MEMBRANE PROTEIN; PATHOGENIC LEPTOSPIRA; MAMMALIAN INFECTION; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; DOGS; LIPOPROTEIN; OMPL1; ANTIGENS; FEATURES AB The purpose of this study was to compare the immunoreactivity in canine renal tissues stained with antisera specific for 3 leptospiral antigens and those processed with traditional staining methods. In addition, immunoglobulin staining was done on tissues with immunoreactivity to leptospiral antigens. Formalin-fixed renal sections from 12 dogs with chronic interstitial nephritis suspected or proven to have leptospirosis (6 dogs with silver-stained leptospires and 6 dogs in which silver-stained leptospires were not detected) were used. Antibodies consisted of a monoclonal antibody to Leptospira kirschneri serovar grippotyphosa lipopolysaccharide (LPS) and 2 polyclonal antibodies to outer membrane proteins, including OmpL1, a leptospiral porin, and LipL41, an outer membrane lipoprotein. The murine monoclonal antisera against LPS (F71C2-1) had the most abundant and consistent immunoreactivity. Immunoreactive areas were present in 6 of 6 sections positive by silver staining and included extracellular granular debris in intertubular areas, debris in macrophages, organisms in tubular lumina, and cytoplasmic granules in tubular epithelia, Antisera with specificity for the outer membrane proteins OmpL1 and LipL41 detected only intact organisms in tubular lumina. Immunoreactivity to OmpL1 (polyclonal 338) occurred in 4 of 5 sections positive by silver staining, but immunoreactivity to LipL41 (polyclonal 813) occurred in only 1 of 6 silver-positive sections. Each of the kidney sections in which leptospiral antigens were detected by immunohistochemistry also was positive by silver staining. Sections negative by silver staining were also negative by immunostaining. Although immunohistochemistry did not enhance sensitivity, amplification of signal by secondary antibody and hematoxylin counterstaining improved the case of diagnosis and allowed better evaluation of tissue morphology than did silver staining methods. IgG was the most abundant immunoglobulin. IgG immunoreactivity occurred predominantly in plasma cells within interstitial infiltrates. Interstitial infiltrates contained abundant immunoreactivity to LPS, but immunoreactivity to OmpL1 and LipL41 was not noted. C1 Iowa State Univ, Coll Vet Med, Dept Vet Pathol, Ames, IA 50011 USA. ARS, Bacterial Dis Livestock Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA 50010 USA. VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Wild, CJ (reprint author), Iowa State Univ, Coll Vet Med, Dept Vet Pathol, Ames, IA 50011 USA. FU NIAID NIH HHS [R21 AI034431, R21 AI034431-06] NR 29 TC 20 Z9 21 U1 1 U2 2 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD JAN PY 2002 VL 14 IS 1 BP 20 EP 24 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 513ZQ UT WOS:000173411600004 PM 12680639 ER PT J AU DiFronzo, NL Leung, CT Mammel, MK Georgopoulos, K Taylor, BJ Pham, QN AF DiFronzo, NL Leung, CT Mammel, MK Georgopoulos, K Taylor, BJ Pham, QN TI Ikaros, a lymphoid-cell-specific transcription factor, contributes to the leukemogenic phenotype of a mink cell focus-inducing murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; DNA-BINDING PROTEINS; DISEASE SPECIFICITY; HEMATOPOIETIC PROGENITORS; ENHANCER SEQUENCES; VIRAL SEQUENCES; GENE ENCODES; AKR MICE; IN-VIVO; 3' END AB Mink cell focus-inducing (MCF) viruses induce T-cell lymphomas in AKR/J strain mice. MCF 247, the prototype of this group of nonacute murine leukemia viruses, transforms thymocytes, in part, by insertional mutagenesis and enhancer-mediated dysregulation of cellular proto-oncogenes. The unique 3' (U3) regions in the long terminal repeats of other murine leukemia viruses contain transcription factor binding sites known to be important for enhancer function and for the induction of T-cell lymphomas. Although transcription factor binding sites important for the biological properties of MCF 247 have not been identified, pathogenesis studies from our laboratory suggested to us that binding sites for Ikaros, a lymphoid-cell-restricted transcriptional regulator, affect the biological properties of MCF 247. In this report, we demonstrate that Ikaros binds to predicted sites in U3 sequences of MCF 247 and that site-directed mutations in these sites greatly diminish this binding in vitro. Consistent with these findings, ectopic expression of Ikaros in murine cells that do not normally express this protein significantly increases transcription from the viral promoter in transient gene expression assays. Moreover, site-directed mutations in specific Ikaros-binding sites reduce this activity in T-cell lines that express Ikaros endogenously. To determine whether the Ikaros-binding sites are functional in vivo, we inoculated newborn mice with a variant MCF virus containing a mutant Ikaros-binding site. The variant virus replicated in thymocytes less efficiently and induced lymphomas with a delayed onset compared to the wild-type virus. These data are consistent with the hypothesis that the Ikaros-binding sites in the U3 region of MCF 247 are functional and cooperate with other DNA elements for optimal enhancer function in vivo. C1 George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Ctr Virol Immunol & Infect Dis Res, Washington, DC 20010 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02138 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP DiFronzo, NL (reprint author), George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Ctr Virol Immunol & Infect Dis Res, Washington, DC 20010 USA. NR 51 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2002 VL 76 IS 1 BP 78 EP 87 DI 10.1128/JVI.76.1.78-87.2002 PG 10 WC Virology SC Virology GA 500UJ UT WOS:000172644900008 PM 11739673 ER PT J AU von Gegerfelt, AS Liska, V Li, PL McClure, HM Horie, K Nappi, F Montefiori, DC Pavlakis, GN Marthas, ML Ruprecht, RM Felber, BK AF von Gegerfelt, AS Liska, V Li, PL McClure, HM Horie, K Nappi, F Montefiori, DC Pavlakis, GN Marthas, ML Ruprecht, RM Felber, BK TI Rev-independent simian immunodeficiency virus strains are nonpathogenic in neonatal macaques SO JOURNAL OF VIROLOGY LA English DT Article ID ATTENUATED VACCINE STRAINS; MESSENGER-RNA EXPORT; RHESUS MACAQUES; POSTTRANSCRIPTIONAL REGULATION; RETROVIRUS TYPE-1; MOLECULAR CLONES; VIRAL LOAD; ELEMENT; LIVE; SIV AB The viral protein Rev is essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) by the constitutive RNA transport element CTE of the simian type D retroviruses. We used neonatal macaques as a sensitive animal model to evaluate the pathogenicity of a pair of SIV mutant strains generated from Rev-independent molecular clones of SIVmac239 which differ only in the presence of the nef open reading frame. After high primary viremia, all animals remained persistently infected at levels below the threshold of detection. All macaques infected as neonates developed normally, and none showed any signs of immune dysfunction or disease during follow-up ranging from 2.3 to 4 years. Therefore, the Rev-RRE regulatory mechanism plays a key role in the maintenance of high levels of virus propagation, which is independent of the presence of nef. These data demonstrate that Rev regulation plays an important role in the pathogenicity of SIV. Replacement of Rev-RRE by the CTE provides a novel approach to dramatically lower the virulence of a pathogenic lentivirus. These data further suggest that antiretroviral strategies leading to even a partial block of Rev function may modulate disease progression in HIV-infected individuals. C1 NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Sect, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. Univ Calif Davis, Dept Vet Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Felber, BK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Pathogenesis Sect, Bldg 535,Rm 110, Frederick, MD 21702 USA. FU NCIRD CDC HHS [IP3028691-01]; NCRR NIH HHS [P51 RR000169, R01 RR014180, P51 RR000165, R01 RR14180, RR-00165, RR00169]; PHS HHS [R01 A135533-S1] NR 39 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2002 VL 76 IS 1 BP 96 EP 104 DI 10.1128/JVI.76.1.96-104.2002 PG 9 WC Virology SC Virology GA 500UJ UT WOS:000172644900010 PM 11739675 ER PT J AU Hamblin, MR Miller, JL Rizvi, I Ortel, B AF Hamblin, Michael R. Miller, Jaimie L. Rizvi, Imran Ortel, Bernhard TI Degree of substitution of chlorin e(6) on charged poly- L-lysine chains affects their cellular uptake, localization and phototoxicity towards macrophages and cancer cells SO JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY LA English DT Article DE Photodynamic therapy; photosensitizer; polymeric drug conjugate; confocal fluorescence microscopy; macrophage; cancer AB Macromolecular photosensitizer conjugates are under investigation as improved delivery vehicles for dyes used in photodynamic therapy. We have previously described the use of conjugates between photosensitizers such as chlorin(e6) (c(e6)) and poly-L-lysine (pL) chains which are versatile molecular species because the size of the chain can be varied, and the overall charge can be altered from cationic through neutral to anionic. We now report on a series of pL-c(e6) conjugates in their cationic (native), neutral (acetylated) and anionic (succinylated) forms, where the number of ce6 molecules attached to each chain was varied (pL: c(e6) ratios, 1:4, 1:8, 1:12, and 1:16). The fluorescence emissions were measured in both saline and a disaggregating solvent. We studied two cell lines (an epithelial ovarian cancer, OVCAR-5 and a mouse macrophage, J774) and measured cellular uptake, subcellular localization (by confocal fluorescence microscopy) and phototoxicity. The cellular uptake of the conjugates with four substitution ratios all delivered at 2 mu M c(e6) equivalent concentration showed a maximum at 12 c(e6) per chain for both cationic and anionic conjugates, but the uptake of the neutral conjugate was proportional to the substitution ratio. The macrophages took up several times more c(e6) than the ovarian cancer cells. Confocal fluorescence micrographs showed more cellular fluorescence with the lower substitution ratios, and more lysosomal localization with the cationic conjugates. The phototoxicity was much higher for the neutral conjugates. For the cationic and neutral conjugates the 12 c(e6) per chain was the most effective at killing cells, while for the anionic conjugate it was the 16 c(e6) per chain. The anionic conjugate was better at killing OVCAR-5 cells, while the cationic was better for J774 cells, and the neutral was approximately the same. These data will help to optimize the parameters to be used in preparing polymeric-photosensitizer conjugates for photodynamic therapy. C1 [Hamblin, Michael R.; Miller, Jaimie L.; Rizvi, Imran; Ortel, Bernhard] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.; Ortel, Bernhard] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, WEL224, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Rizvi, Imran/0000-0001-9673-4700; Hamblin, Michael/0000-0001-6431-4605 NR 28 TC 15 Z9 15 U1 2 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0895-3996 J9 J X-RAY SCI TECHNOL JI J. X-Ray Sci. Technol. PY 2002 VL 10 IS 3-4 BP 139 EP 152 PG 14 WC Instruments & Instrumentation; Optics; Physics, Applied SC Instruments & Instrumentation; Optics; Physics GA V04OC UT WOS:000207066700001 PM 22388044 ER PT J AU Thadhani, R Wolf, M West, ML Tonelli, M Ruthazer, R Pastores, GM Obrador, GT AF Thadhani, R Wolf, M West, ML Tonelli, M Ruthazer, R Pastores, GM Obrador, GT TI Patients with Fabry disease on dialysis in the United States SO KIDNEY INTERNATIONAL LA English DT Article DE end-stage renal disease; X-linked inheritance; enzyme replacement therapy; lysosomal alpha-galactosidase A ID STAGE RENAL-DISEASE; PREVALENCE; DISORDERS; THERAPY; FAILURE; GENE AB Background. Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease, Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. Methods. Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. Results. During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P = 0.03). Conclusion. End-stage renal disease is associated with Significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Dalhousie Univ, Dept Med, Div Nephrol, Halifax, NS, Canada. Tufts Univ New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA. NYU, Sch Med, Dept Neurol & Pediat, Neurogenet Program, New York, NY USA. Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Panamaricana Univ, Sch Med, Mexico City, DF, Mexico. RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Founders 036,55 Fruit St, Boston, MA 02114 USA. OI Obrador, Gregorio/0000-0003-3814-7449 FU NHLBI NIH HHS [HL-03804] NR 26 TC 121 Z9 133 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2002 VL 61 IS 1 BP 249 EP 255 DI 10.1046/j.1523-1755.2002.00097.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 505GK UT WOS:000172904900029 PM 11786107 ER PT J AU Seliger, SL Weiss, NS Gillen, DL Kestenbaum, B Ball, A Sherrard, DJ Stehman-Breen, CO AF Seliger, SL Weiss, NS Gillen, DL Kestenbaum, B Ball, A Sherrard, DJ Stehman-Breen, CO TI HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients SO KIDNEY INTERNATIONAL LA English DT Article DE hypercholesterolemia; cardiovascular disease; end-stage renal disease; USRDS Wave 2; dialysis; blood pressure; lipoprotein ID INTERMEDIATE-DENSITY LIPOPROTEIN; AVERAGE CHOLESTEROL LEVELS; CORONARY-ARTERY DISEASE; HEMODIALYSIS-PATIENTS; MAINTENANCE HEMODIALYSIS; ESTER TRANSFER; SIMVASTATIN; PRAVASTATIN; DIALYSIS; EVENTS AB Background. Patients with end-stage renal disease (ESRD) suffer from markedly higher rates of cardiovascular disease than the general population. Although therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been demonstrated to reduce the mortality from cardiovascular disease in patients without ESRD, only 10% of patients on dialysis are treated with these medications by day 60 of ESRD. We determined whether the use of statins is associated with a reduction in cardiovascular-specific death and total mortality in ESRD patients. Methods. Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Wave-2 study, a cohort of randomly selected patients who were initiating dialysis in 1996. Information about the use of statins as well as other baseline characteristics was abstracted from the patients' dialysis records by dialysis personnel. Cox proportional hazards models were developed to determine the association between use of statins at baseline and subsequent risk of mortality, with adjustment for known mortality risk factors. Results. Follow-up data were available for 3716 patients through July 1998. At baseline, 362 (9.7%) of patients were using statins. These patients had a mortality rate of 143/1000 person-years, compared with a rate of 202/1000 person-years for patients not using statins. Statin use was independently associated with a reduced risk of total mortality [relative risk (RR) = 0.68, 95% confidence interval (CI) = 0.54, 0.87] as well as cardiovascular-specific mortality (RR = 0.64, 95% CI = 0.45, 0.91). In contrast, the use of fibrates was not associated with reduced mortality (RR = 1.29). Conclusions. Statin use was associated with a reduction in cardiovascular-specific death and total mortality in patients on dialysis. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), VA Puget Sound Hlth Care Syst, Mailstop 111A,1650 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK07721-6] NR 31 TC 207 Z9 215 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2002 VL 61 IS 1 BP 297 EP 304 DI 10.1046/j.1523-1755.2002.00109.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 505GK UT WOS:000172904900034 PM 11786112 ER PT J AU Nielsen, GP Bjornsson, J Rosenberg, AE Unni, KK AF Nielsen, GP Bjornsson, J Rosenberg, AE Unni, KK TI Primary Rosai-Dorfman disease of bone. A clinicopathologic study of 13 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 69 BP 20A EP 20A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700083 ER PT J AU O'Connell, JX Nielsen, GP Rosenberg, AE AF O'Connell, JX Nielsen, GP Rosenberg, AE TI Epithelioid hemangioma of bone: A series revisited 10 years later SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Surrey Mem Hosp, Surrey, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 71 BP 20A EP 20A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700085 ER PT J AU Ogata, N Segre, GV Roth, SI AF Ogata, N Segre, GV Roth, SI TI A unique new model of osteogenesis imperfecta (OI) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 72 BP 20A EP 21A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700086 ER PT J AU Rosenberg, AE Harris, KR Keel, SB Roth, SI Nielsen, GP Mangham, C AF Rosenberg, AE Harris, KR Keel, SB Roth, SI Nielsen, GP Mangham, C TI Immunohistochemical analysis of primary osteosarcoma of bone SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Orthopaed Hosp, Birmingham B31 2AP, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 80 BP 22A EP 22A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700094 ER PT J AU Sgroi, D Gaudet, J Heike, V Ma, XJ Erlander, M AF Sgroi, D Gaudet, J Heike, V Ma, XJ Erlander, M TI In vivo gene expression profiling of human breast cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Arcturus Engn Inc, Appl Genom Div, Carlsbad, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 203 BP 51A EP 51A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700217 ER PT J AU Houser, SL McMorrow, IM LeGuern, C Schwarze, ML Fuchimoto, Y Sachs, DH Madsen, JC AF Houser, SL McMorrow, IM LeGuern, C Schwarze, ML Fuchimoto, Y Sachs, DH Madsen, JC TI The prevalence of cardiac allograft vasculopathy in miniature swine is associated with myocardial gene expression of IFN-gamma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 243 BP 61A EP 61A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700257 ER PT J AU Smith, RN Chang, Y Grazette, L Houser, SL AF Smith, RN Chang, Y Grazette, L Houser, SL TI Heart allograft patients with Quilty B lesions are at a higher risk for subsequent high grade rejetions SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 255 BP 63A EP 64A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700269 ER PT J AU Altiok, S Tambouret, R AF Altiok, S Tambouret, R TI Assessment of p16 (INK4A) immunostaining as a surrogate marker for HPV-related intraepithelial lesions of uterine cervix in cytologic specimens and surgical biopsies SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 261 BP 65A EP 65A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700275 ER PT J AU Altiok, S Cooper, TL Tambouret, R AF Altiok, S Cooper, TL Tambouret, R TI The combination of fine-needle aspiration and flow cytometric immunophenotyping in diagnosis and subclassification of primary non-Hodgkin lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Berkshire Med Ctr, Pittsfield, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 262 BP 65A EP 65A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700276 ER PT J AU Deshpande, V McKee, GT AF Deshpande, V McKee, GT TI Cytokeratin 20 (CK20): A useful adjunct to urine cytology SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 283 BP 70A EP 71A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700297 ER PT J AU Elliott, DD Faquin, WC Szyfelbein, WM Pitman, MB AF Elliott, DD Faquin, WC Szyfelbein, WM Pitman, MB TI Fine needle aspiration biopsy of Hurthle cell lesions of the thyroid: Cytologic features in a series of 91 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 287 BP 71A EP 71A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700301 ER PT J AU Geisinger, KR Pitman, MB Creager, AJ AF Geisinger, KR Pitman, MB Creager, AJ TI Cytologic features of clear cell sarcoma of soft tissue: A study of fine needle aspirates and exfoliative specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 294 BP 73A EP 73A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700308 ER PT J AU Gornstein, B Jacobs, T Bedard, Y Biscotti, C Ducatman, B Layfield, L McKee, G Sneige, N Wang, H AF Gornstein, B Jacobs, T Bedard, Y Biscotti, C Ducatman, B Layfield, L McKee, G Sneige, N Wang, H TI Interobserver agreement of a probabilistic approach to reporting breast fine needle aspirations on ThinPrep (R) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Toronto, Fac Med, Toronto, ON, Canada. Cleveland Clin Fdn, Cleveland, OH 44195 USA. W Virginia Univ, RC Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA. Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 299 BP 74A EP 74A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700313 ER PT J AU Lucey, EC Keane, J Kuang, PP Snider, GL Goldstein, RH AF Lucey, EC Keane, J Kuang, PP Snider, GL Goldstein, RH TI Severity of elastase-induced emphysema is decreased in tumor necrosis factor-alpha and interleukin-1 beta receptor-deficient mice SO LABORATORY INVESTIGATION LA English DT Article ID COLLAGEN MESSENGER-RNA; FACTOR-KAPPA-B; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; TNF RECEPTOR; PROTEINS; HAMSTERS; PATHWAYS; COPD; ACTIVATION AB A single intratracheal dose of porcine pancreatic elastase, which is cleared from the lung by 24 hours, was administered to wild-type, IL-1beta type 1 receptor-deficient, double TNF-alpha (type 1 and type 2) receptor-deficient, and combined TNF-alpha (type 1 receptor) plus IL-1beta receptor-deficient mice. The mean linear intercept (Lm) of saline-treated mice was 32(3) mum [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) mum at 21 days versus 52(5) mum at 5 days after treatment, indicating that alveolar wall remodeling occurs long after the elastase injury. At 21 days, Lm values were 67(10), 62(3), and 39(5) gm in elastase-treated mice deficient in the IL-1beta receptor, double TNF-alpha receptors, and combined receptors, respectively. The level of apoptosis assessed by a terminal deoxynucleotidyl transferase-catalyzed in situ nick end-labeling assay was increased at 5 days after elastase treatment and was markedly and similarly attenuated in the IL-10, the double TNF-alpha, and the combined receptor-deficient mice. Our results indicate that inflammatory mediators exacerbate elastase-induced emphysema. We estimate that in the combined TNF-alpha + IL-1beta receptor-deficient mice, inflammation accounts for about 80% of the emphysema that develops after elastase treatment; decreased apoptosis of lung cells likely contributes to decreased severity of emphysema. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Goldstein, RH (reprint author), Boston Univ, Sch Med, Ctr Pulm, R 304,80 E Concord St, Boston, MA 02118 USA. EM rgoldstein@lung.bumc.bu.edu OI Keane, Joseph/0000-0001-5313-385X FU NHLBI NIH HHS [HL 66547] NR 36 TC 111 Z9 115 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 BP 79 EP 85 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700009 PM 11796828 ER PT J AU Nasser, SM Faquin, WC Pitman, MB AF Nasser, SM Faquin, WC Pitman, MB TI Fine needle aspiration biopsy of pseudoangiomatous stromal hyperplasia: A series of 20 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 329 BP 81A EP 81A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700343 ER PT J AU Sheffield, MV Yee, H Fisher, DE Dorvault, CC Weibaecher, KN Eltoum, I Siegal, GP Chhieng, DC AF Sheffield, MV Yee, H Fisher, DE Dorvault, CC Weibaecher, KN Eltoum, I Siegal, GP Chhieng, DC TI Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL USA. NYU, New York, NY USA. Dana Faber Canc Inst, Boston, MA USA. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 349 BP 86A EP 86A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700362 ER PT J AU Ishizaka, N Aizawa, T Yamazaki, I Usui, S Mori, I Kurokawa, K Tang, SS Ingelfinger, JR Ohno, M Nagai, R AF Ishizaka, N Aizawa, T Yamazaki, I Usui, S Mori, I Kurokawa, K Tang, SS Ingelfinger, JR Ohno, M Nagai, R TI Abnormal iron deposition in renal cells in the rat with chronic angiotensin II administration SO LABORATORY INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; HEME OXYGENASE-1 EXPRESSION; OXIDATIVE STRESS; SKELETAL-MUSCLE; FACTOR-ALPHA; INJURY; HYPERTENSION; FIBROBLASTS; RESISTANCE; FERRITIN AB Acute experimental iron loading causes iron to accumulate in the renal tissue. The accumulation of iron may play a role in enhancing oxidant-induced tubular injury by producing increased amounts of reactive oxygen species. From findings in cells from heme oxygenase-1 (HO-1) -deficient mice, HO-1 is postulated to prevent abnormal intracellular iron accumulation. Recently, it has been reported that HO-1 is induced in the renal tubular epithelial cells, in which iron is deposited after iron loading, and that this HO-1 induction may be involved in ameliorating iron-induced renal toxicity. We previously showed that chronic administration of angiotensin II to rats induces HO-1 expression in the tubular epithelial cells. These observations led us to investigate whether there is a link between iron deposition and HO-1 induction in renal tubular cells in rats undergoing angiotensin II infusion. In the present study, rats were given angiotensin II for continuously 7 days. Prussian blue staining revealed the distinct deposits of iron in the proximal tubular epithelial cells after angiotensin II administration. Electron microscopy demonstrated that iron particles were present in the lysosomes of these cells. Histologic and immunohistochemical analyses showed that stainable iron and immunoreactive ferritin and HO-1 were colocalized in the tubular epithelial cells. Treatment of angiotensin II-infused rats with an iron chelator, deferoxamine, blocked the abnormal iron deposition in kidneys and also the induced expression of HO-1 and ferritin expression. Furthermore, deferoxamine treatment suppressed the angiotensin II-induced increase in the urinary excretion of protein and N-acetyl-beta-D-glucosaminidase, a marker of tubular injury; however, deferoxamine did not affect the angiotensin II-induced decrease in glomerular filtration rate. These results suggest that angiotensin II causes renal injury, in part, by inducing the deposition of iron in the kidney. C1 Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Tokyo 1138655, Japan. Wakayama Med Coll, Dept Pathol, Wakayama 640, Japan. Inoue Mem Hosp, Dept Pathol, Inoue, Japan. Tokai Univ, Sch Med, Dept Med, Tokai, Ibaraki, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Lab, Boston, MA USA. RP Ishizaka, N (reprint author), Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Hongo 7-3-1, Tokyo 1138655, Japan. EM nobuishizka-tky@umin.ac.jp NR 28 TC 23 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 BP 87 EP 96 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700010 PM 11796829 ER PT J AU Wilbur, DC Parker, EM Foti, JA AF Wilbur, DC Parker, EM Foti, JA TI Location guided screening of liquid-based cervical cytology specimens: A potential improvement in accuracy and productivity is demonstrated in a preclinical feasibility study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Viahlth, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 376 BP 92A EP 92A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700389 ER PT J AU Grossman, JM Mihm, MC Lyle, S AF Grossman, JM Mihm, MC Lyle, S TI Cytokeratin 15 and 19 expression in desmoplastic epitheliomas and microcystic adnexal carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 407 BP 99A EP 99A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700420 ER PT J AU North, PE Waner, M James, CA Mizeracki, A Mihm, MC AF North, PE Waner, M James, CA Mizeracki, A Mihm, MC TI Congenital nonprogressive hemangioma: A distinct clinicopathological entity unlike infantile hemangioma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 428 BP 104A EP 104A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700441 ER PT J AU Zembowicz, A Granter, SR McKee, PH Mihm, MC AF Zembowicz, A Granter, SR McKee, PH Mihm, MC TI Amelanotic cellular blue nevus: Clinico-pathological analysis of 20 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 465 BP 112A EP 113A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700478 ER PT J AU Zembowicz, A Mihm, MC AF Zembowicz, A Mihm, MC TI Pigment synthesizing melanocytic tumor: A low grade melanocytic tumor with frequent lymph node metastases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 464 BP 112A EP 112A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700477 ER PT J AU Badizadegan, K Lauwers, GY Fogt, F Fox, VL Redston, M Odze, RD AF Badizadegan, K Lauwers, GY Fogt, F Fox, VL Redston, M Odze, RD TI Loss of SMAD4/MADH4 expression in colonic juvenile polyps is associated with a multilobular or villiform growth pattern and the development of multiple juvenile polyps in children SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 511 BP 123A EP 123A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700524 ER PT J AU Bronner, M Emond, M Burgart, L Goldblum, J Greenson, J Haber, M Hart, J Lauwers, G Lazenby, A Lewin, D Robert, M Washington, K Montgomery, E AF Bronner, M Emond, M Burgart, L Goldblum, J Greenson, J Haber, M Hart, J Lauwers, G Lazenby, A Lewin, D Robert, M Washington, K Montgomery, E TI Diagnostic accuracy in ulcerative colitis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. Cleveland Clin, Cleveland, OH USA. Univ Michigan, Ann Arbor, MI 48109 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Univ S Carolina, Columbia, SC 29208 USA. Yale Univ, New Haven, CT 06520 USA. Vanderbilt Univ, Nashville, TN USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 513 BP 124A EP 124A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700526 ER PT J AU Lauwers, GY Goldblum, JR Burgart, LJ Bhan, AK Greenson, JK AF Lauwers, GY Goldblum, JR Burgart, LJ Bhan, AK Greenson, JK TI Expression of neurotrophin receptors and RET protein in duodenal gangliocytic paraganglioma: A study of 12 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 558 BP 134A EP 134A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700571 ER PT J AU Lauwers, GY Wu, CL Balis, UJ Zukerberg, LR AF Lauwers, GY Wu, CL Balis, UJ Zukerberg, LR TI Role of Cables in colonic tumorigenesis: An immunohistochemical study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 559 BP 134A EP 135A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700572 ER PT J AU Mino, M Lauwers, GY AF Mino, M Lauwers, GY TI Role of immunophenotyping in cases of duodenal mucosa with normal villous architecture and increased intraepithelial lymphocytes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 575 BP 138A EP 139A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700588 ER PT J AU Misdraji, J Yantiss, RK Graeme-Cook, FM Balis, UJ Young, RH AF Misdraji, J Yantiss, RK Graeme-Cook, FM Balis, UJ Young, RH TI Appendiceal mucinous tumors: A clinicopathological analysis of 92 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Univ Massachusetts, Mem Hlth Care, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 576 BP 139A EP 139A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700589 ER PT J AU Mueller, JD Kulke, MH Bertagnolli, MM Loda, M Odze, RD AF Mueller, JD Kulke, MH Bertagnolli, MM Loda, M Odze, RD TI VEGF, p27, skp2 and MLH1 expression in esophageal carcinoma treated by radiochemotherapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 579 BP 139A EP 140A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700592 ER PT J AU Yantiss, RK Odze, RD Farraye, FA Rosenberg, AE AF Yantiss, RK Odze, RD Farraye, FA Rosenberg, AE TI Prognostic significance of solitary versus multiple carcinoid tumors of the small intestine: A clinical and pathologic review of 75 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Massachusetts, Mem Hlth Care, Worcester, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 623 BP 150A EP 150A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700636 ER PT J AU Zukerberg, LR Mino, M Wu, CL Lauwers, GY AF Zukerberg, LR Mino, M Wu, CL Lauwers, GY TI Loss of expression of Cables, a putative tumor suppressor gene located on chromosome 18q11-12, in esophageal squamous cell carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 625 BP 150A EP 150A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700638 ER PT J AU Henley, JD Wade, CL Young, RH Ulbright, TM AF Henley, JD Wade, CL Young, RH Ulbright, TM TI Interstitial pattern of growth in seminoma: A study of 70 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 680 BP 163A EP 163A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700693 ER PT J AU Jiang, Z Wu, CL Woda, BA Dresser, K Fanger, GR Xu, J Rock, KL Yang, X AF Jiang, Z Wu, CL Woda, BA Dresser, K Fanger, GR Xu, J Rock, KL Yang, X TI P504S: A good diagnostic marker for small focus of prostatic adenocarcinoma on needle biopsy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Massachusetts, Sch Med, Worcester, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Corixa Corp, Seattle, WA USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 691 BP 166A EP 166A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700704 ER PT J AU Kallakury, BVS Sheehan, CE Fisher, DE Depowski, PL Ross, JS Jennings, TA AF Kallakury, BVS Sheehan, CE Fisher, DE Depowski, PL Ross, JS Jennings, TA TI Immunophenotypic analysis of renal and adrenal neoplasms: Utility of MiTF, inhibin, calretinin and CD10 in the differential diagnosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Albany Med Coll, Albany, NY 12208 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 693 BP 166A EP 167A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700706 ER PT J AU Krishnan, B Lechago, J Truong, L AF Krishnan, B Lechago, J Truong, L TI Intraoperative consultation (IOC) for renal lesions. Utilities and diagnostic pitfalls in 320 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 698 BP 168A EP 168A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700711 ER PT J AU Lei, J Lin, D Waltregny, D Pagano, M Loda, MF Weinstein, MH AF Lei, J Lin, D Waltregny, D Pagano, M Loda, MF Weinstein, MH TI Overexpression of the f-box protein SKP2 in aggressive prostatic cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 704 BP 169A EP 169A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700717 ER PT J AU McKenney, JK Amin, MB Young, RH AF McKenney, JK Amin, MB Young, RH TI Urothelial (transitional cell) papilloma of the urinary bladder: A clinicopathologic study of 25 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 725 BP 174A EP 174A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700738 ER PT J AU Parker, DC Folpe, AL Bell, JD Oliva, E Cohen, C Young, RH Amin, MB AF Parker, DC Folpe, AL Bell, JD Oliva, E Cohen, C Young, RH Amin, MB TI Potential utility of uroplakin III, thrombomodulin and cytokeratin 20 as a diagnostic panel for urothelial (transitional cell) differentiation SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 735 BP 176A EP 176A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700748 ER PT J AU Rossi, S Weinstein, L Graner, E Onody, T Febbo, P Loda, M AF Rossi, S Weinstein, L Graner, E Onody, T Febbo, P Loda, M TI Expression of fatty acid synthase in prostate carcinoma by oligonucleotide arrays and immunohistochemistry SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 744 BP 178A EP 178A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700757 ER PT J AU Srigley, JR Grignon, DJ Young, RH AF Srigley, JR Grignon, DJ Young, RH TI The distinction between pure carcinoid tumor and carcinoid-like adenocarcinoma of the prostate gland SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Credit Valley Hosp, Mississauga, ON, Canada. Wayne State Univ, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 28 Z9 30 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 762 BP 182A EP 183A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700775 ER PT J AU Tang, Z Zukerberg, L Young, RH Wu, CL AF Tang, Z Zukerberg, L Young, RH Wu, CL TI The role of Cables, a putative tumor suppressor gene, in urothelial carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 766 BP 183A EP 183A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700779 ER PT J AU Ulbright, TM Young, RH AF Ulbright, TM Young, RH TI Primary mucinous tumors of the testis and paratestis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 771 BP 184A EP 185A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700784 ER PT J AU Yang, X Wu, CL Amin, MB Young, R Fanger, G Jiang, Z AF Yang, X Wu, CL Amin, MB Young, R Fanger, G Jiang, Z TI P504S in diagnosis of prostate cancer: A multi-institutional analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Corixa Corp, Seattle, WA USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 783 BP 187A EP 187A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700796 ER PT J AU Yang, X Wu, CL Tretiakova, M Fanger, G Dresser, K Jiang, Z AF Yang, X Wu, CL Tretiakova, M Fanger, G Dresser, K Jiang, Z TI Expression of P504S in atypical adenomatous hyperplasia of the prostate SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Corixa Corp, Seattle, WA USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 782 BP 187A EP 187A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700795 ER PT J AU Arnell, PM Vu, Q Oliva, E AF Arnell, PM Vu, Q Oliva, E TI Beta-catenin expression in mucinous carcinomas of the ovary and metastatic colon carcinomas to the ovary: Does it have a diagnostic role? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 800 BP 191A EP 191A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700813 ER PT J AU Dionigi, A Oliva, E Clement, PB Young, RH AF Dionigi, A Oliva, E Clement, PB Young, RH TI Endometrial stromal nodules (ESNs) and endometrial stromal tumors (ESTs) with limited infiltration: A clinicopathologic study of 50 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 815 BP 195A EP 195A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700828 ER PT J AU Dong, Q Zukerberg, L Wu, CL Oliva, E AF Dong, Q Zukerberg, L Wu, CL Oliva, E TI Expression of Cables, a cyclin dependent kinase (CDK) interacting protein, in ovarian cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 816 BP 195A EP 195A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700829 ER PT J AU Eichhorn, JH Young, RH Scully, RE AF Eichhorn, JH Young, RH Scully, RE TI Transitional cell carcinoma of the ovary: A study of 100 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 818 BP 195A EP 196A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700831 ER PT J AU Lee, KR Young, RH AF Lee, KR Young, RH TI Primary vs metastatic mucinous carcinomas of the ovary differential - Diagnostic findings in 44 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 844 BP 201A EP 201A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700857 ER PT J AU Logani, S Oliva, E Amin, MB Folpe, AL Cohen, C Young, RH AF Logani, S Oliva, E Amin, MB Folpe, AL Cohen, C Young, RH TI Immunoprofile of ovarian tumors of putative transitional cell (urothelial) differentiation using novel urothelial markers: Histogenetic and diagnostic implications SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 847 BP 202A EP 202A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700860 ER PT J AU Oliva, E Vu, Q Young, RH AF Oliva, E Vu, Q Young, RH TI CD10 expression in sex cord-stromal tumors (SCSTs) and steroid cell tumors (StCTs) of the ovary SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 856 BP 204A EP 204A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700869 ER PT J AU Oliva, E Dionigi, A Young, RH AF Oliva, E Dionigi, A Young, RH TI Mixed tumors of the vagina: An immunohistochemical study of thirteen cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 857 BP 204A EP 205A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700870 ER PT J AU Pitman, ME Triratanachat, S Young, RH Oliva, E AF Pitman, ME Triratanachat, S Young, RH Oliva, E TI Hepatocyte paraffin 1 antibody cannot distinguish primary ovarian malignancies with hepatoid differentiation from metastatic hepatocellular caricnoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 864 BP 206A EP 206A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700877 ER PT J AU Gallagher, LA Faquin, WC Nielsen, GP Pilch, BZ AF Gallagher, LA Faquin, WC Nielsen, GP Pilch, BZ TI Sarcomas of the nasal cavity and paranasal sinuses: A study of 47 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 918 BP 219A EP 219A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700931 ER PT J AU Jing, W Dong, Q Wu, CL Zukerberg, L AF Jing, W Dong, Q Wu, CL Zukerberg, L TI Cables, located on chromosome 18q11-12, is frequently lost in head and neck squamous cell carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 924 BP 220A EP 220A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700937 ER PT J AU Mino, M Pilch, BZ Faquin, WC AF Mino, M Pilch, BZ Faquin, WC TI Expression of c-kit in adenoid cystic carcinomas, salivary gland tumors, and basaloid neoplasms of the head and neck SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 930 BP 221A EP 222A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700943 ER PT J AU Braaten, KM Betensky, R de Leval, L Okada, Y Hochberg, F Louis, D Harris, NL Batchelor, T AF Braaten, KM Betensky, R de Leval, L Okada, Y Hochberg, F Louis, D Harris, NL Batchelor, T TI Primary central nervous system lymphoma (PCNSL): Immunophenotypic and molecular genetic analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 975 BP 233A EP 233A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379700988 ER PT J AU Yuan, CM Vergilio, JA Harris, NL Bagg, A AF Yuan, CM Vergilio, JA Harris, NL Bagg, A TI Angioimmunoblastic T-cell lymphoma: A neoplasm of intrafollicular CD10+, BCL-6+, CD4+ memory T-cells? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1125 BP 271A EP 271A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701138 ER PT J AU Andea, AA Cheng, J Lauwers, GY Klimstra, DS Adsay, VN AF Andea, AA Cheng, J Lauwers, GY Klimstra, DS Adsay, VN TI Pancreatic intraepithelial neoplasia (PanIN) in pancreata involved by mucinous cystic neoplasms SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Wayne State Univ, Harper Hosp, Karmanos Canc Inst, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1172 BP 282A EP 282A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701185 ER PT J AU Deshpande, V Selig, MK Nielsen, GP Fernandez-del Castillo, C Lauwers, GY AF Deshpande, V Selig, MK Nielsen, GP Fernandez-del Castillo, C Lauwers, GY TI Ductulo-insular pancreatic endocrine neoplasms: Clinicopathological analysis of a unique subtype of pancreatic endocrine neoplasms SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1175 BP 283A EP 283A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701188 ER PT J AU Graeme-Cook, FM Balls, UJ Lauwers, GY Hoppin, AG Reid, AE Kaplan, LM AF Graeme-Cook, FM Balls, UJ Lauwers, GY Hoppin, AG Reid, AE Kaplan, LM TI Development and prospective validation of a pathological scoring system for NAFLD SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1184 BP 285A EP 285A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701197 ER PT J AU Hsu, HC Mountz, JD Grizzle, WE AF Hsu, HC Mountz, JD Grizzle, WE TI Glomerulosclerosis in 22-month-old BXD recombinant inbred mouse strain 22 (BXD-22) related to T cell kidney infiltration and senescence of CD4 T cells SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1269 BP 305A EP 305A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701282 ER PT J AU Beheshti, J Mino, M Mark, EJ AF Beheshti, J Mino, M Mark, EJ TI Chronic eosinophillic pneumonia, bronchiolitis obliterans organizing pneumonia overlap syndrome; Analysis of twelve cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1311 BP 315A EP 315A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701324 ER PT J AU Matsubara, O Imazeki, N Ozeki, Y Mark, EJ AF Matsubara, O Imazeki, N Ozeki, Y Mark, EJ TI Vascular endothelial growth factor and its receptors, Flt1 and KDR/Flk1, in diffuse alveolar damage and advanced pulmonary fibrosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1350 BP 324A EP 324A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701363 ER PT J AU Mino, M Zukerberg, LR Wu, CL Mark, EJ AF Mino, M Zukerberg, LR Wu, CL Mark, EJ TI Loss of expression of cables gene (located on chromosome 18q11-12) in small cell and non-small cell lung carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1354 BP 325A EP 325A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701367 ER PT J AU Murer, B Chilosi, M Barbareschi, M Macri, E Loda, M Doglioni, C AF Murer, B Chilosi, M Barbareschi, M Macri, E Loda, M Doglioni, C TI Primary vs metastatic pulmonary adenocarcinoma: Cdx-2 is a specific and sensitive marker of tumors of colonic origin SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Umberto Hosp 1, Dept Pathol, Mestre, Italy. Univ Verona, Dept Pathol, I-37100 Verona, Italy. Santa Chiara Hosp, Dept Pathol, Trent, Italy. San Martino Hosp, Dept Pathol, Belluno, Italy. Brigham & Womens Hosp, Dana Farber Canc Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1356 BP 325A EP 326A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701369 ER PT J AU Castilla, EA Staugaitis, SM Esposito, JM Prayson, RA Warshawsky, I Hartke, M Shadrach, B Chernova, O Pettay, JD Vogelbaum, MA Barnett, G Louis, DN Tubbs, RR AF Castilla, EA Staugaitis, SM Esposito, JM Prayson, RA Warshawsky, I Hartke, M Shadrach, B Chernova, O Pettay, JD Vogelbaum, MA Barnett, G Louis, DN Tubbs, RR TI Technical validation of an interphase fluorescent in-situ hybridization (FISH) method to detect epidermal growth factor receptor (EGFR) amplification in gliomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1401 BP 336A EP 336A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701414 ER PT J AU Dadras, S Balis, UJ AF Dadras, S Balis, UJ TI Fabrication of a high-resolution realtime digital projection system for microscopy using standard components SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1403 BP 337A EP 337A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701416 ER PT J AU Faquin, WC Selig, MK McKee, GT Misdraji, J Pitman, MB Tambouret, R Eichhorn, JH Nielsen, GP AF Faquin, WC Selig, MK McKee, GT Misdraji, J Pitman, MB Tambouret, R Eichhorn, JH Nielsen, GP TI The utility of electron microscopy in the evaluation of cytologic specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2002 VL 82 IS 1 MA 1450 BP 348A EP 348A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 513LJ UT WOS:000173379701463 ER PT S AU Dohlman, CH Dudenhoefer, EJ Khan, BF Dohlman, JG AF Dohlman, CH Dudenhoefer, EJ Khan, BF Dohlman, JG BE Sullivan, DA Stern, ME Tsubota, K Dartt, DA Sullivan, RM Bromberg, BB TI Corneal blindness from end-stage Sjogren's syndrome and graft-versus-host disease SO LACRIMAL GLAND, TEAR FILM, AND DRY EYE SYNDROMES 3: BASIC SCIENCE AND CLINICAL RELEVANCE, PTS A & B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Lacrimal Gland, Tear Film and Dry Eye Syndromes CY NOV 15-18, 2000 CL MAUI, HAWAII SP Alcon Lab, Minamiaoyama Eye Clin, Inspire Pharmaceut Inc, Bausch & Lomb ID PERFORATION; ULCERATION C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47282-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 506 BP 1335 EP U29 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BW22U UT WOS:000181264100193 PM 12614075 ER PT B AU Caplan, D Alpert, N Waters, G AF Caplan, D Alpert, N Waters, G BE Galaburda, AM Kosslyn, SM Christen, Y TI Brain organization for syntactic processing SO LANGUAGES OF THE BRAIN LA English DT Proceedings Paper CT Conference on the Languages of the Brain CY MAR 12-15, 1998 CL PARIS, FRANCE ID INDIVIDUAL-DIFFERENCES; AMBIGUITY RESOLUTION; WORKING MEMORY; COMPREHENSION; CONSTRAINTS; PET; LOCALIZATION; ACTIVATION C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 40 TC 0 Z9 0 U1 1 U2 1 PU HARVARD UNIV PRESS PI CAMBRIDGE PA 79 GARDEN ST, CAMBRIDGE, MA 02138 USA BN 0-674-00772-7 PY 2002 BP 57 EP 68 PG 12 WC Psychology, Biological; Psychology, Experimental SC Psychology GA BX78D UT WOS:000186423000004 ER PT S AU Hamblin, MR O'Donnell, DA Huzaira, M Zahra, T AF Hamblin, MR O'Donnell, DA Huzaira, M Zahra, T BE Jacques, SL Duncan, DD Kirkpatrick, SJ Kriete, A TI Scavenger receptor-targeted photodynamic therapy of J774 tumors in mice: Tumor response and concomitant immunity. SO LASER TISSUE INTERACTION XIII: PHOTOCHEMICAL, PHOTOTHERMAL, AND PHOTOMECHANICAL SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Laser Tissue Interaction XIII - Photochemical, Photothermal, and Photomechanical CY JAN 20-23, 2002 CL SAN JOSE, CA SP SPIE DE photodynamic therapy; macrophages; scavenger receptor; chlorin(e6); albumin conjugate; concomitant immunity ID MEDIATED DRUG DELIVERY; MALIGNANT-TUMORS; CELL-LINE; RECOGNITION; METASTASIS; ALBUMIN; ENDOCYTOSIS; SUPPRESSION; MACROPHAGES; DEGRADATION AB J774 is a cell line derived from Balb/c mice that in vitro behaves as macrophages (including scavenger-receptor expression) and has been widely used to study macrophage cell biology. In vivo it produces histiocytic lymphoma tumors that are invasive and metastatic. We report here on the response of subcutaneous J774 tumors to photodynamic therapy with scavenger-receptor targeted chlorin(e6). Bovine serum albumin was covalently conjugated with chlorin(e6), maleylated and purified by acetone precipitation and both this and free chlorin(e6) were injected IV into mice at 2 mg/kg. When tumors were illuminated with 665 nm laser-light after 24 hours there was a highly significant response (tumor volume and growth rate) for the conjugate, but this led to a relatively small survival increase due to the highly metastatic nature of the tumor. The free chlorin(e6) gave very little tumor response. When light was delivered 3 hours after injection the response from the conjugate disappeared due to insufficient time for the tumor cells to take up the photosensitizer by receptor-mediated endocytosis. Free chlorin(e6) at 3 hours however produced a total regression of the tumors due to a primarily vascular effect, but the mice died sooner than control animals. When J774 tumors were surgically removed at different times after implantation the mouse survival was proportional to the length of time they had had the tumor. We interpret this data to show that mice with J774 tumors slowly develop concomitant immunity and a PDT regimen that swiftly ablates the tumor will give worse survival results than a regimen with a slower tumor response. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 40 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 0-8194-4356-5 J9 P SOC PHOTO-OPT INS PY 2002 VL 4617 BP 1 EP 10 DI 10.1117/12.472513 PG 10 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BV05M UT WOS:000177691300001 ER PT J AU Huzaira, M Anderson, RR AF Huzaira, M Anderson, RR TI Magnetite tattoos SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE ferric oxide; ink; magnet ID Q-SWITCHED RUBY; LASER TREATMENT; MICROSCOPIC ANALYSIS; DECORATIVE TATTOOS; YAG LASER; REMOVAL; CO2-LASER; PARTICLES; ARGON AB Background and Objectives: Tattoo removal is a significant problem. The extraction of magnetite (Fe3O4) ink tattoos by a magnetic field was investigated, with and without Q-switched laser treatment. Study Design/Materials and Methods: Magnetite particles (1.4 mum) were used to make mature, black skin tattoos on hairless albino rats. A Q-switched ruby laser (QSRL) 3.5 J/cm(2) 6.5-mm spot size, 40-nanosecond pulse width was used for treatment. Permanent magnets (1.4 T, 6-mm diameter) were tested to extract, the magnetite particles, alone and after QSRL. Lightening of treated tattoos was measured from digital photographs, and the amount and distribution of magnetite in skin biopsies was scored blindly. Results: External application of magnets on mature magnetite tattoos without prior QSRL treatment, did not significantly extract, lighten, darken, or change their histologic appearance. A magnetic field applied immediately after QSRL treatment extracted some ink when epidermal injury was present, and caused significant redistribution of magnetite into the upper dermis with vertical banding along magnetic field lines. When applied for 3 weeks following QSRL, magnets caused darkening of tattoos. Conclusions: Magnetite skin tattoos can be manipulated by external magnets, especially after Q-switched laser treatment. Magnetically-extractable tattoos may be feasible. (C) 2002 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, BHX-630,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 VL 31 IS 2 BP 121 EP 128 DI 10.1002/lsm.10075 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 587VG UT WOS:000177663700007 PM 12210596 ER PT J AU Lee, S McAuliffe, DJ Kollias, N Flotte, TJ Doukas, AG AF Lee, S McAuliffe, DJ Kollias, N Flotte, TJ Doukas, AG TI Photomechanical delivery of 100-nm microspheres through the stratum corneum: Implications for transdermal drug delivery SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE drug delivery; fluorescent microspheres; shock waves; stratum corneum barrier; transdermal delivery ID GENERATED STRESS WAVES; IN-VIVO; PERMEABILIZATION; MEMBRANE; CELLS AB Background and Objectives: Photomechanical waves (PWs) render the stratum corneum permeable and allow molecules to diffuse into the epidermis. The aim of this study was to investigate the probe size that could be delivered through the stratum corneum and into the epidermis. Study Design/Materials and Methods: A single PW was applied onto the rat skin in vivo. Aqueous suspensions of fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal delivery. The presence of the microspheres in the epidermis was measured by a fiber-based spectrofluorimeter after the stratum corneum was removed by tape-stripping (TS). Results: Exposure of the rat shin to a PW permeabilized the stratum corneum and allowed the fluorescent microspheres to diffuse into the epidermis. Conclusions: The experiments show that PWs can facilitate the delivery of very large molecules and probes into the epidermis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Mail Stop WEL224,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 27 Z9 31 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 VL 31 IS 3 BP 207 EP 210 DI 10.1002/lsm.10099 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 598EQ UT WOS:000178262800009 PM 12224095 ER PT J AU Tachihara, R Farinelli, WA Anderson, RR AF Tachihara, R Farinelli, WA Anderson, RR TI Low intensity light-induced vasodilation in vivo SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 37 BP 11 EP 11 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500036 ER PT J AU Huzaira, M Anderson, RR AF Huzaira, M Anderson, RR TI Magnetite tattoos SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 77 BP 23 EP 23 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500075 ER PT J AU Yaroslavsky, AN Anderson, RR AF Yaroslavsky, AN Anderson, RR TI Multi-spectral reflectance imaging for the assessment of nonmelanoma skin tumor margins SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 91 BP 27 EP 27 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500089 ER PT J AU Manstein, D Poureshagh, M Yaroslavsky, I Altshuler, G Anderson, RR AF Manstein, D Poureshagh, M Yaroslavsky, I Altshuler, G Anderson, RR TI Spatially confined photothermolysis of dermal targets using an IR-fiberlaser in combination with focusing and contact cooling SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Palomar Med Technol, Burlington, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 92 BP 28 EP 28 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500090 ER PT J AU Gupta, S Taneja, A Racette, A Trehan, M Taylor, CR AF Gupta, S Taneja, A Racette, A Trehan, M Taylor, CR TI 308 nm excimer laser vs 595 nm flashlamp pulsed-dye laser for the treatment of plaque psoriasis SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gange Photomed Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 116 BP 35 EP 35 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500114 ER PT J AU Yaroslavsky, L Altshuler, GB Manstein, D Anderson, RR AF Yaroslavsky, L Altshuler, GB Manstein, D Anderson, RR TI Skin pigmentation index as a predictive parameter for optimizing laser and light treatments SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Palomar Med Technol Inc, Burlington, MA USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 117 BP 35 EP 35 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500115 ER PT J AU Lim, KH Anderson, RR AF Lim, KH Anderson, RR TI Robotic treatment of microvascular lesions SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 123 BP 37 EP 37 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500121 ER PT J AU Tachihara, R Farinelli, WA Yung, PKL Anderson, RR AF Tachihara, R Farinelli, WA Yung, PKL Anderson, RR TI Percutaneous drug delivery using Er : YAG laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Lab Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 129 BP 39 EP 39 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500126 ER PT J AU Suthamjariya, K Farinelli, WA Anderson, RR AF Suthamjariya, K Farinelli, WA Anderson, RR TI Treatment of telangiectases and reticular veins of lower extremities with long-pulsed Nd : YAG laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 136 BP 41 EP 41 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500133 ER PT J AU Manstein, D Poureshagh, M Erofeev, AV Altshuler, GB Anderson, RR AF Manstein, D Poureshagh, M Erofeev, AV Altshuler, GB Anderson, RR TI Effects of diode laser versus flashlamp exposure on hair follicles SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Palomar Med Technol, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 150 BP 44 EP 44 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500146 ER PT J AU Nigri, GR Fungaloi, P Waterman, P Kossodo, SE Stahl, GL LaMuraglia, GM AF Nigri, GR Fungaloi, P Waterman, P Kossodo, SE Stahl, GL LaMuraglia, GM TI Anti-neutrophil antibody or anti-C5 antibody allows inhibition of acute vein graft thrombosis after photochemical therapy SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 167 BP 48 EP 48 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500161 ER PT J AU Yun, P Tsao, S AF Yun, P Tsao, S TI Successful treatment of discoid lupus erythematosus utilizing the 595 nm pulsed dye laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2002 SU 14 MA 317 BP 85 EP 85 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 536XE UT WOS:000174726500293 ER PT J AU Gaudet, G Friedberg, JW Weng, A Pinkus, GS Freedman, AS AF Gaudet, G Friedberg, JW Weng, A Pinkus, GS Freedman, AS TI Breast lymphoma associated with breast implants: Two case-reports and a review of the literature SO LEUKEMIA & LYMPHOMA LA English DT Review DE breast lymphoma; silicone breast implants; T-cell lymphoma; non-Hodgkin's lymphoma ID T-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; SILICONE LYMPHADENOPATHY; MALIGNANT-LYMPHOMA; CANCER; GEL AB Breast lymphoma is a rare entity consisting mostly of B-cell lymphomas that affects older women. Very few cases of breast lymphomas of T-cell origin have been reported. Even fewer cases of breast lymphomas have been reported in women who have received breast implants. Silicone, a frequent component of breast implants, has been extensively investigated as a possible etiologic agent for some neoplasias and autoimmune disorders, including non-Hodgkin's lymphoma. We herein report two unusual cases of anaplastic large cell lymphoma of T-cell phenotype developing in the breasts of women who had received breast implants. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Gaudet, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Weng, Andrew/I-5015-2014 NR 26 TC 55 Z9 55 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2002 VL 43 IS 1 BP 115 EP 119 DI 10.1080/10428190290000392 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 561XF UT WOS:000176167800015 PM 11908714 ER PT J AU Wu, CJ Neuberg, D Chillemi, A McLaughlin, S Hochberg, EP Galinsky, I Deangelo, D Soiffer, RJ Alyea, EP Capdeville, R Stone, RM Ritz, J AF Wu, CJ Neuberg, D Chillemi, A McLaughlin, S Hochberg, EP Galinsky, I Deangelo, D Soiffer, RJ Alyea, EP Capdeville, R Stone, RM Ritz, J TI Quantitative monitoring of BCR/ABL transcript during STI-571 therapy SO LEUKEMIA & LYMPHOMA LA English DT Article DE chronic myelocytic leukemia; PCR; STI-571; quantitative ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; POLYMERASE CHAIN-REACTION; BONE-MARROW TRANSPLANTATION; BCR-ABL TRANSCRIPTS; STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; TYROSINE KINASE; PHILADELPHIA-CHROMOSOME; RT-PCR AB PCR for the BCR / ABL fusion transcript provides a highly sensitive and specific method for detecting minimal residual disease in patients with chronic myeloid leukemia (CML). We sought to determine if quantitative PCR measurement of peripheral blood BCR / ABL transcript can be used to monitor response in CML patients with clinically evident disease while receiving the protein tyrosine kinase inhibitor STI-571. Serial bone marrow cytogenetics and peripheral blood BCR / ABL mRNA levels were measured in 17 patients [9 with chronic phase (CP) and 8 with accelerated phase or blast crisis (AP/BC)] during 1 year of treatment. Overall, quantitative PCR BCR / ABL transcript level decreased by a median of 0.9 log during the first 3 months, and by 1.6 logs by 12 months. Among cytogenetic responders (6 CP and 2 AP/BC), median BCR / ABL copy number was 0.9 and 2.1 logs lower than baseline after 3 and 12 months of treatment, respectively. No patient became PCR-negative for BCR / ABL . Among cytogenetic non-responders, BCR / ABL transcript level decreased by 0.4 logs after 3 months, with no subsequent reductions. At study entry, BCR / ABL expression in cytogenetic responders and non-responders was similar. However, BCR / ABL expression became significantly different 3 months after treatment ( p =0.02), and increasingly different with continued therapy ( p =0.04, 0.005, 0.0008 at 6, 9 and 12 months, respectively). Our results demonstrate that PBMC BCR / ABL mRNA levels correlate well with response to STI-571. This non-invasive, rapid and sensitive PCR-based assay can be used to monitor response to STI-571. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Dana Farber Canc Inst,Ctr Hematol Oncol, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996]; NHLBI NIH HHS [KO8 HL04293]; NIAID NIH HHS [AI29530] NR 40 TC 10 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2002 VL 43 IS 12 BP 2281 EP 2289 DI 10.1080/1042819021000039992 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 609MW UT WOS:000178910400006 PM 12613514 ER PT J AU Rosen, HR Fontana, RJ Brown, RS Wiesner, RH Schiano, TD Bass, NM Bloomer, JR Kaplan, L AF Rosen, HR Fontana, RJ Brown, RS Wiesner, RH Schiano, TD Bass, NM Bloomer, JR Kaplan, L TI Curricular guidelines, for training in transplant hepatology SO LIVER TRANSPLANTATION LA English DT Article C1 Amer Soc Transplantat, Liver & Intraabdominal Subcomm, Moorestown, NJ 08057 USA. Amer Assoc Study Liver Dis, Training & Workforce Comm, Thorofare, NJ 08086 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland VA Med Ctr, POB 1034,P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 4 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JAN PY 2002 VL 8 IS 1 BP 85 EP 87 DI 10.1053/jlts.2002.29759 PG 3 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 512EE UT WOS:000173307500015 PM 11799493 ER PT J AU Cooper, GS Parks, CG Treadwell, EL St Clair, EW Gilkeson, GS Cohen, PL Roubey, RAS Dooley, MA AF Cooper, GS Parks, CG Treadwell, EL St Clair, EW Gilkeson, GS Cohen, PL Roubey, RAS Dooley, MA TI Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States SO LUPUS LA English DT Article DE lupus; demographics; age; sex; race; autoantibodies ID GENDER DIFFERENCES; REVISED CRITERIA; MANIFESTATIONS; ONSET; CLASSIFICATION; EXPRESSION; PROGNOSIS; CHINESE; COHORT; MALES AB We examined the prevalence of clinical and immunologic features of systemic lupus erythematosus (SLE) by race, sex and age in a population-based study of 265 SLE patients. Patients fulfilled the American College of Rheumatology classification criteria. The median time between diagnosis and study enrollment was 13 months. The clinical and hematologic data were limited to occurrences up to 6 months after the diagnosis date, as documented in medical records. We used sera collected at study enrollment from 244 (92%) patients for serologic testing of autoantibodies. The associations between clinical and immunological features of SLE and age, sex and race were examined using logistic regression. The effect of each of these variables was examined adjusting for the other two demographic factors, Mean age at diagnosis was 6 years younger among African-Americans and other minorities compared with white patients (P < 0.01). Discoid lupus, proteinuria, anti-Sm and anti-RNP autoantibodies were more commonly seen in African-American patients, with odds ratios higher than 3.0. Photosensitivity and mucosal ulcers were noted less often in African-American patients. Proteinuria, leukopenia, lymphopenia and thrombocytopenia were approximately three times more common in men compared with women. The prevalence of oral or nasal ulcers and anti-DNA autoantibodies declined with age. The extent to which the differences we observed reflect genetic or environmental influences on the disease process should be investigated. C1 NIEHS, Epidemiol Branch, Durham, NC 27709 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Univ N Carolina, Div Rheumatol & Immunol, Thurston Arthritis Res Ctr, Chapel Hill, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Durham, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 25 TC 114 Z9 115 U1 0 U2 3 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2002 VL 11 IS 3 BP 161 EP 167 DI 10.1191/0961203302lu161oa PG 7 WC Rheumatology SC Rheumatology GA 541DW UT WOS:000174970800005 PM 11999880 ER PT S AU Ochoa, ER Vacanti, JP AF Ochoa, ER Vacanti, JP BE Rockson, SG TI An overview of the pathology and approaches to tissue engineering SO LYMPHATIC CONTINUUM: LYMPHATIC BIOLOGY AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Lymphatic Continuum CY MAY 03-04, 2002 CL NIH NATCHER CTR, BETHESDA, MARYLAND HO NIH NATCHER CTR DE tissue engineering; bone cartilage; cardiovascular; MEMS; gastrointestinal; liver; microfabrication ID BIODEGRADABLE POLYMER; PULMONARY-ARTERY; TRANSPLANTATION; HEPATOCYTES; FABRICATION; CARTILAGE; CHANNELS AB In tissue engineering, there is an attempt to culture living tissues for surgical transplantation. In vitro and in vivo approaches have produced vascular and cardiovascular components, cartilage, bone, intestine, and liver. Attempts to microdesign cell-culture support scaffolds have used a new generation of biocompatible and bioabsorbable polymers. Suspensions of donor cells are seeded onto protein-coated polymer scaffolds and grown to confluence in dynamic bioreactors. In vitro techniques produce monolayers of tissues. Denser masses are achieved by implanting monolayers onto a host, or by culturing cell/polymer constructs in vivo. Existing techniques have produced functioning heart valves from sheep endothelial cells and myofibroblasts. Cultured ovine arterial cells have replaced 2-cm segments of pulmonary artery in lambs. Chondrocyte cultures have produced a human-ear-shaped construct, temporo-mandibular joint discs, meniscal replacement devices, and human-phalange-shaped constructs, complete with a joint. The culture of composite tissue types has recently been reported. Intestinal organoid units containing a mesenchymal core with surrounding polarized epithelia have been used in lieu of an ileal pouch in Lewis rats, and the long-term culture of rat hepatocytes has revealed cellular differentiation and neomorphology resembling elements of a biliary drainage system. To sustain the in vitro culture of dense tissues prior to implantation, micro-electro-mechanical systems (MEMS) fabrication technologies have been adapted to create wafers of polymer containing sealed, branching, vascular-type spaces. After seeding with rat lung endothelial cells, followed by 5 days of bioreactor culture, the result is an endothelial network with controlled blood flow rates, pressure, and hematocrit. When these customized vascular systems can be used to support in vitro culture, a new generation of dense, composite, morphologically complex tissues will be available for clinical development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. RP Vacanti, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Warren 11,14 Fruit St, Boston, MA 02114 USA. NR 39 TC 44 Z9 45 U1 0 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-414-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 979 BP 10 EP 26 PG 17 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BW05J UT WOS:000180751900003 PM 12543712 ER PT S AU Choi, EK Buxbaum, JD Wasco, W AF Choi, EK Buxbaum, JD Wasco, W BE Mizuno, Y Fisher, A Hanin, I TI Calsenilin-presenilin interaction in Alzheimer's disease SO MAPPING THE PROGRESS OF ALZHEIMER'S AND PARKINSON'S DISEASE SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT 5th International Conference on the Progress in Alzheimers and Parkinsons Disease/9th International Catecholamine Symposium CY MAR 31-APR 05, 2001 CL KYOTO, JAPAN ID PROTEINS; APOPTOSIS; FAMILY; ASSOCIATION; EXPRESSION; CASPASE-3; FRAGMENT; CLEAVAGE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. RP Choi, EK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0099-9962 BN 0-306-46763-1 J9 ADV BEHAV BIOL PY 2002 VL 51 BP 105 EP 110 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA BV16K UT WOS:000178038700018 ER PT S AU Schlossmacher, MG Frosch, MP Gai, WP Sharma, N Medina, M Ochiishi, T Shimura, H Hattori, N Mizuno, Y Hyman, BT Selkoe, DJ Kosik, KS AF Schlossmacher, MG Frosch, MP Gai, WP Sharma, N Medina, M Ochiishi, T Shimura, H Hattori, N Mizuno, Y Hyman, BT Selkoe, DJ Kosik, KS BE Mizuno, Y Fisher, A Hanin, I TI Colocalization of parkin with alpha-synuclein in the Lewy bodies of Parkinson disease SO MAPPING THE PROGRESS OF ALZHEIMER'S AND PARKINSON'S DISEASE SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT 5th International Conference on the Progress in Alzheimers and Parkinsons Disease/9th International Catecholamine Symposium CY MAR 31-APR 05, 2001 CL KYOTO, JAPAN ID UBIQUITIN; MUTATION C1 Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Unit, Boston, MA 02115 USA. Flinders Univ S Australia, Dept Physiol, Bedford Pk, SA 5042, Australia. Flinders Univ S Australia, Ctr Neurosci, Bedford Pk, SA 5042, Australia. Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. RP Schlossmacher, MG (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. RI Gai, Wei-Ping/A-3700-2008 NR 11 TC 1 Z9 1 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0099-9962 BN 0-306-46763-1 J9 ADV BEHAV BIOL PY 2002 VL 51 BP 297 EP 300 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA BV16K UT WOS:000178038700050 ER PT J AU Johnson, ML Gordon, HS Petersen, NJ Wray, NP Shroyer, AL Grover, FL Geraci, JM AF Johnson, ML Gordon, HS Petersen, NJ Wray, NP Shroyer, AL Grover, FL Geraci, JM TI Effect of definition of mortality on hospital profiles SO MEDICAL CARE LA English DT Article DE coronary disease; mortality; outcome assessment; quality of care; surgery ID ADMINISTRATIVE DATA; VETERANS-AFFAIRS; CARDIAC-SURGERY; QUALITY; CARE; RATES; INDICATOR; AREA AB BACKGROUND: Hospitals are ranked based on risk-adjusted measures of postoperative mortality, but definitions differ about which deaths following surgery should be included. OBJECTIVE: To determine whether varying the case definition of deaths following surgery that are included in coronary artery bypass surgery quality assessment affects the identification of outlier hospitals. RESEARCH DESIGN: The study used a prospective cohort design. SUBJECTS: A total of 15,288 patients undergoing coronary artery bypass surgery without other cardiac procedures from October 1993 to March 1996 at all (N = 43) Veterans Affairs hospitals that conduct cardiac surgery. MEASURES: The first measure included any death occurring within 30 days after surgery, regardless of cause, in or out of the hospital (30-day mortality). The second measure included 30-day mortality plus any death occurring 30 days to 6 months after surgery that was judged to be a direct result of a perioperative complication of the surgery (all procedure-related mortality). RESULTS: Hospital performance as assessed by the two different definitions of death varied substantially. The rankings of hospitals differed for 86% (37/43) of hospitals. Twenty-one percent (9/43) changed their quartile of rank and five hospitals changed their outlier status. The correlation of observed-to-expected ratios was high (r = 0.96), but there was disagreement of outlier status (kappa = 0.71). CONCLUSIONS: judgments regarding the quality of a hospital's performance of coronary artery bypass surgery vary depending on the definition of postoperative mortality that is used. Further research is needed to assess what definition is most appropriate to identify quality of care problems. C1 Houston VAMC, Ctr Qual Care, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, Dept Gen Internal Med, Houston, TX 77030 USA. RP Johnson, ML (reprint author), Houston VAMC, Ctr Qual Care, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Gordon, Howard/E-4420-2010; Shroyer, Annie Laurie/B-8836-2016 OI Gordon, Howard/0000-0002-6712-5954; Shroyer, Annie Laurie/0000-0001-6461-0623 NR 29 TC 38 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 BP 7 EP 16 DI 10.1097/00005650-200201000-00003 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 507DD UT WOS:000173011000003 PM 11748422 ER PT J AU Dominitz, JA Maynard, C Billingsley, KG Boyko, EJ AF Dominitz, JA Maynard, C Billingsley, KG Boyko, EJ TI Race, treatment, and survival of veterans with cancer of the distal esophagus and gastric cardia SO MEDICAL CARE LA English DT Article DE esophageal neoplasms; epidemiology; racial stocks; blacks; surgery; survival; chemotherapy, adjuvant; radiation oncology; veterans ID COLORECTAL-CANCER; PROSTATE-CANCER; MEDICAL SYSTEM; COLON-CANCER; AFFAIRS; ACCESS; RATES; STATISTICS; CARCINOMA; PHYSICIAN AB CONTEXT. Prior studies have found racial differences in the use of invasive procedures and in cancer survival. OBJECTIVE. To assess the influence of race on the treatment and survival of patients with distal esophageal cancer. DESIGN. Retrospective cohort study. SETTING. All Veterans Affairs Medical Centers. PATIENTS. One thousand two hundred ninety white and 231 black male veterans with a new diagnosis of distal esophageal cancer during 1993 to 1997. MAIN OUTCOME MEASURES. Utilization of surgical resection, chemotherapy, radiation therapy, and survival. RESULTS. Black patients with esophageal adenocarcinoma were less likely to undergo surgery (OR, 0.54; 95% Cl, 0.30-0.96) but had similar odds of undergoing chemotherapy and radiation therapy. Black patients with squamous cell carcinoma (SCC) were less likely to undergo surgical resection (OR, 0.45; 95% Cl, 0.29-0.70), but were more likely to undergo radiation therapy (OR, 1.72; 95% CI, 1.21-2.47) and chemotherapy (OR, 1.74; 95% CL 1.19-2.54). Mortality was increased for black patients with SCC (adjusted risk ratio 1.33; 95% CI, 1.10-1.61) but not adenocarcinoma. Among those veterans who underwent surgical resection (n = 502), similar results were found. CONCLUSIONS. Black veterans with distal SCC are less likely than white veterans to undergo surgical resection, whereas the use of radiation therapy and chemotherapy, as well as mortality, is increased. Black patients with distal esophageal adenocarcinoma have lower odds of undergoing surgical resection but have similar utilization of radiation therapy and chemotherapy and similar survival. Despite the presence of an equal access medical system, treatment and outcomes differ for black and white veterans with distal esophageal cancer. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Seattle Epidemiol Res & Informat Ctr, 111-S Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 35 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 14 EP 26 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000003 ER PT J AU Collins, TC Clark, JA Petersen, LA Kressin, NR AF Collins, TC Clark, JA Petersen, LA Kressin, NR TI Racial differences in how patients perceive physician communication regarding cardiac testing SO MEDICAL CARE LA English DT Article DE communication; cardiac testing ID OF-VETERANS-AFFAIRS; CORONARY HEART-DISEASE; HEALTH-CARE SYSTEM; AFRICAN-AMERICANS; BLACK POPULATIONS; MEDICAL-RESEARCH; RACE; SATISFACTION; COMMUNITY; BEHAVIORS AB OBJECTIVES. Recent studies documenting racial variation in the use of cardiac procedures highlight the need to understand if there are racial differences in processes of communication and decision making. Investigations of patients' perceptions of their interaction with providers regarding cardiac testing were conducted. METHODS. Four focus groups were convened with 13 patients who had undergone cardiac stress testing with positive results, stratified by race (white vs. black). Verbatim transcripts of discussions of their interactions with providers relating to their cardiac problems were analyzed qualitatively by a team of behavioral scientists and general internists to identify significant dimensions of communication and patient-provider relationships. RESULTS. Four domains of communication were identified that appeared to bear on patients' comfort and preferences regarding cardiac procedures. First, the substance of the information that was provided by physicians and other providers was described as incomplete, vague, ambiguous, and unclear. Second, some recommendations either were inconsistent with expectations or awakened fears based on distressing previous experiences. Third, patients said they needed to be convinced of the need for additional, invasive tests and therapeutic procedures, and in some cases providers' arguments failed in this regard. Fourth, the patients highlighted the importance of trusting their provider. Although there were no apparent differences by race in patients' perception of the information they received, black patients consistently expressed a preference for building a relationship with physicians (trust) before agreeing to an invasive cardiac procedure, and just as consistently complained that trust was lacking. Conversely, white patients tended to emphasize that they were inadequately convinced of the need for recommended procedures. CONCLUSIONS. This study provided qualitative information regarding patients' perceptions of physician-patient communication and racial differences in such perceptions. For both black and white patients, we found problematic aspects of the patients' experiences regarding communication about cardiac testing. Our findings suggest that although patients desire clarity from physicians, they are often confused regarding the information received. Both a lack of substance and vagueness of the information received may be linked to feelings of mistrust toward physicians when considering further diagnostic testing. Mistrust may be a source of some of the documented racial variation in health care utilization. C1 Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. RP Collins, TC (reprint author), Dept Vet Affairs, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 41 TC 40 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 27 EP 34 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000004 ER PT J AU Horner, RD Oddone, EZ Stechuchak, KM Grambow, SC Gray, J Khuri, SF Henderson, WG Daley, J AF Horner, RD Oddone, EZ Stechuchak, KM Grambow, SC Gray, J Khuri, SF Henderson, WG Daley, J TI Racial variations in postoperative outcomes of carotid endarterectomy - Evidence from the veterans affairs national surgical quality improvement program SO MEDICAL CARE LA English DT Article DE blacks; carotid endarterectomy; health care utilization and outcomes; cerebrovascular disease ID TRANSIENT ISCHEMIC ATTACK; RISK ADJUSTMENT; PREDICTING COMPLICATIONS; DECISION-MAKING; CARE; STENOSIS; STROKE AB CONTEXT. Black patients and Hispanic patients receive carotid endarterectomy (CEA) at lower rates than white patients. It is unclear whether worse surgical outcomes are influencing clinical decision-making regarding use of the operation among minority group patients. OBJECTIVE. To determine if there are racial differences in postoperative outcomes for patients undergoing CEA at Veterans Affairs (VA) medical centers. DESIGN. Secondary analysis of data from an ongoing, prospective study on surgical quality and outcomes in the VA health care system. SETTING. One hundred thirty-two VA Medical Centers that were part of the VA National Surgical Quality Improvement Program. PATIENTS. A cohort of 6551 men (91.4% white, 5.3% black, and 3.3% Hispanic) who had CEA performed between October 1, 1994 and September 30, 1997. MAIN OUTCOME MEASURES. Primary outcomes were stroke or death and stroke, myocardial infarction (MI), or death within 30 days of the operation. RESULTS. Thirty-day postoperative rates of stroke or death and of stroke, MI, or death were generally low for all racial/ethnic groups, ranging between 2.6% and 6.5%. Within clinical states that define indications for CEA, rates were also low (1.6% to 3.2%) among asymptomatic patients across racial/ethnic groups. However, among patients with transient ischemic attack (TIA), Hispanic patients had significantly worse outcomes than white patients with a postoperative rate of stroke or death of 10.5% (P <0.05) and stroke, MI, or death of 13.2% (P <0.05) compared with 3.1% to 3.5% for white patients. Hispanic patients did not differ from black patients for stroke, death/stroke, death, or MI. CONCLUSION. Rates of major postoperative complications after CEA are low within the VA and similar across racial/ethnic groups with the possible exception of Hispanic men with TIA. Further investigation of this elevated complication rate among Hispanic men with TIA may be warranted. C1 Durham VA Med Ctr, VA Epidemiol Res & Informat Ctr, Durham, NC USA. Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Durham VA Med Ctr, Stroke QUERI Program, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Brockton W Roxbury VA Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Hines VA Cooperat Studies Coordinat Ctr, Hines, IL USA. Durham VA Med Ctr, Surg Serv, Durham, NC USA. RP Horner, RD (reprint author), Vet Adm Med Ctr, HSR&D 152, 508 Fulton St, Durham, NC 27705 USA. NR 39 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 35 EP 43 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000005 ER PT J AU Ibrahim, SA Siminoff, LA Burant, CJ Kwoh, CK AF Ibrahim, SA Siminoff, LA Burant, CJ Kwoh, CK TI Understanding ethnic differences in the utilization of joint replacement for osteoarthritis - The role of patient-level factors SO MEDICAL CARE LA English DT Article DE health disparities; osteoarthritis; joint replacement therapy; patient factors ID TOTAL HIP-ARTHROPLASTY; RHEUMATOID-ARTHRITIS; RACIAL-DIFFERENCES; VALIDATION; DEPRESSION; PREFERENCES; POPULATION; SURGERY; HEALTH; BLACKS AB BACKGROUND. There is a marked difference between black patients and white patients in the utilization of joint replacement therapy. The reasons behind this disparity remain unknown. OBJECTIVES. To examine how black and white potential candidates for joint replacement compare with respect to their overall familiarity with joint replacement as an option, as well as their perceptions of the risks/benefits of this procedure. METHODS. Cross-sectional survey of 596 elderly patients with symptomatic osteoarthritis of the knee or hip or both attending primary care clinics at Cleveland VAMC. RESULTS. Black (44%) and white (56%) patients in this cohort were comparable with respect to age and clinical factors. However, black patients were less likely to be employed (8% vs. 15%, P = 0.017) or to be married (39% vs. 56%, P = 0.000), but more likely to report an annual household income of less than $10,000 (41% vs. 20%, P = 0.000) and less than high school education (43% vs. 29%, P = 0.001). Black patients were less likely than white patients to have had family or friends who had had joint replacement (OR, 0.39 [0.26-0.61]), or to report a good understanding of joint replacement as a form of treatment (OR, 0.62 [0.42-0.92]). They were more likely than white patients to expect longer hospital course (OR, 4.09 [2.57-6.54]), moderate to extreme pain (OR, 2.61 [1.74-3.89]), and moderate to extreme difficulty walking after replacement surgery (OR, 2.76 [1.83-4.16]). CONCLUSION. Black patients were less likely than white patients to be familiar with joint replacement surgery and more likely to express concerns about postsurgical pain and difficulty walking. C1 Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Div Gen Med, Dept Med, Louis Stokes Dept VAMC, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Div Hlth Care Res, Dept Med, Louis Stokes Dept VAMC, Cleveland, OH 44106 USA. Univ Pittsburgh, Div Clin Immunol & Rheumatol, Pittsburgh, PA 15260 USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Hlth Care Syst, Ctr Hlth Equity Res & Promot, Univ Dr C,11-E,130 A-U, Pittsburgh, PA 15264 USA. RI Siminoff, Laura /H-6277-2012 NR 32 TC 52 Z9 52 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 44 EP 51 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000006 ER PT J AU Kressin, NR Clark, JA Whittle, J East, M Peterson, ED Chang, BH Rosen, AK Ren, XS Alley, LG Kroupa, L Collins, TC Petersen, LA AF Kressin, NR Clark, JA Whittle, J East, M Peterson, ED Chang, BH Rosen, AK Ren, XS Alley, LG Kroupa, L Collins, TC Petersen, LA TI Racial differences in health-related beliefs, attitudes, and experiences of VA cardiac patients - Scale development and application SO MEDICAL CARE LA English DT Article DE psychology; applied psychometrics; decision making; race relations ID CORONARY-ARTERY SURGERY; MYOCARDIAL-INFARCTION; CARE UTILIZATION; DECISION-MAKING; OLDER ADULTS; RELIABILITY; ASSOCIATION; SURVIVAL; AMERICAN; RACE AB OBJECTIVES. To determine whether there are racial differences in patients' health-related attitudes, beliefs, and experiences regarding invasive cardiac procedures, and to develop psychometrically and conceptually valid scales and single items to assess these dimensions. METHODS. A survey was designed and administered to 854 white and black patients with ischemic heart disease at five VA medical centers. Patients were queried about the domains proposed to be important to treatment decision making by the Health Decision Model: sociodemographic characteristics, social interactions, health care experiences, patient preferences for care, knowledge about diseases and potential treatments, and health beliefs. Using multitrait analysis, the psychometric properties of scales assessing these domains were examined. It was then assessed whether there were racial differences in scale or individual item scores using chi(2) and t test analyses. RESULTS. The analyses yielded eight psychometrically valid scales: disease severity, patient evaluation of physician's interpersonal style, patient evaluations of VA care, satisfaction with treatment decision making, perceived urgency of catheterization, vulnerability to catheterization, bodily impact of catheterization, and attitudes toward religion. There were only racial differences on mean scores for the latter scale. Individual item analyses indicated that black patients were less likely to have been encouraged by friends or family to have cardiac catheterization, and had less personal or familial experiences with this or other surgical procedures. In contrast to expectations, white patients were more likely to be skeptical of medical care. CONCLUSIONS. The multiple dimensions of white and black patients' health-related attitudes, beliefs, and experiences were examined, and few differences were found. These results suggest that racial differences in patients' attitudes, beliefs, and experiences are not a likely source of racial disparities in cardiac care. Future research will examine the association of beliefs, attitudes and experiences with actual use of invasive cardiac procedures. C1 Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, VA Hlth Serv Res & Dev, Natl Ctr Excellence, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. Pittsburgh VA Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA USA. Pittsburgh VA Healthcare Syst, Gen Internal Med Sect, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. VA Med Ctr, Ctr Hlth Serv Res & Dev, Durham, NC USA. Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. Emory Univ, Rehabil R&D Ctr, Atlanta VA Med Ctr, Atlanta, GA 30322 USA. Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. St Louis Univ, Sch Med, St Louis VA Med Ctr, St Louis, MO USA. St Louis Univ, Sch Med, Dept Med, St Louis, MO 63104 USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, VA Hlth Serv Res & Dev, Natl Ctr Excellence, Houston, TX USA. Baylor Coll Med, Dept Med, Div Hlth Serv Res, Houston, TX 77030 USA. RP Kressin, NR (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, VA Hlth Serv Res & Dev, Natl Ctr Excellence, 200 Springs Rd,Bldg 70,152, Bedford, MA 01730 USA. NR 29 TC 21 Z9 21 U1 14 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 72 EP 85 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000009 ER PT J AU Petersen, LA Wright, SM Peterson, ED Daley, J AF Petersen, LA Wright, SM Peterson, ED Daley, J TI Impact of race on cardiac care and outcomes in veterans with acute myocardial infarction SO MEDICAL CARE LA English DT Article DE blacks; health services accessibility; acute myocardial infarction; heart catheterization; coronary artery bypass graft surgery; angioplasty, percutaneous transluminal coronary; ethnology; physicians' practice patterns; comparative study; veterans hospitals ID COOPERATIVE CARDIOVASCULAR PROJECT; CORONARY REVASCULARIZATION PROCEDURES; RACIAL-DIFFERENCES; MEDICARE PATIENTS; ELDERLY PATIENTS; AFFAIRS; QUALITY; CATHETERIZATION; MANAGEMENT; SURVIVAL AB OBJECTIVES. The goal of this study was to assess racial differences in process of care and outcome for acute myocardial infarction in the VA health care system. DESIGN. Retrospective cohort study using clinical data. SETTING. Eighty-one acute care VA hospitals. PATIENTS. Four thousand seven hundred sixty veterans discharged with a confirmed diagnosis of acute myocardial infarction. The analysis was restricted to 606 black and 4005 white patients. MAIN OUTCOME MEASURES. Comparison of use of guideline-based medications, invasive cardiac procedures, and all-cause mortality at 30 days, 1 year, and 3 years. RESULTS. Black patients were equally likely to receive beta-blockers, more likely than white patients to receive aspirin (86.8% vs. 82.0%; P <0.05), and marginally more likely to receive angiotensin converting enzyme inhibitors (55.7% vs. 49.6%; P = 0.07) at the time of discharge. In contrast, black patients were less likely than white patients to receive thrombolytic therapy at the time of arrival (32.4% vs. 48.2%; P <0.01). There was no significant difference in refusal of angiography or percutaneous transluminal coronary angioplasty between black patients and white patients, or in crude rates of either of these procedures. There was also no difference overall in the percentage of patients who refused coronary artery bypass graft surgery. However, black patients were less likely than white patients to undergo bypass surgery (6.9% vs. 12.5% by 90 days; P <0.001). Black patients remained less likely to undergo bypass surgery even when high-risk specific coronary anatomy subgroups were examined. There was no difference in mortality in the two groups. CONCLUSIONS. In this integrated health care system, no significant racial disparities in use of noninterventional therapies, diagnostic coronary angiography, or short- or long-term mortality was found. Disparities in use of thrombolytic therapy and coronary artery bypass surgery existed, however, even after accounting for differences in clinical indications for treatment and patient refusals. Further work should assess the role of the medical interaction and physician behavior in racial disparities in use of health care. C1 Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Duke Univ, Med Ctr, Clin Res Inst, Durham, NC USA. Massachusetts Gen Hosp, Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Inst Hlth Policy, Boston, MA 02114 USA. VA Headquarters, Off Qual & Performance, Washington, DC USA. RP Petersen, LA (reprint author), Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 44 TC 46 Z9 46 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 86 EP 96 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000010 ER PT J AU Conigliaro, J Whittle, J Good, CB Skanderson, M Kelley, M Goldberg, K AF Conigliaro, J Whittle, J Good, CB Skanderson, M Kelley, M Goldberg, K TI Delay in presentation for cardiac care by race, age, and site of care SO MEDICAL CARE LA English DT Article DE access; race; cardiac disease; bypass grafts; angioplasty ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; OF-VETERANS-AFFAIRS; BLACK-AND-WHITE; UNITED-STATES; REVASCULARIZATION PROCEDURES; RACIAL VARIATION; PREHOSPITAL DELAY; ARTERY DISEASE; MEDICAL-CARE AB BACKGROUND. Racial differences exist in the management of coronary artery disease. One hypothesis is that black patients delay seeking care and that this delay may influence the management of coronary artery disease. OBJECTIVES. To assess delay in seeking care for heart disease. RESEARCH DESIGN. Cross-sectional survey. SUBJECTS. One thousand six hundred and fifty-two patients awaiting coronary angiography at three VA and one non-VA Medical Center. MEASURES. Patients were asked to retrospectively report the time between symptom onset and presentation for medical care and what if any were the reasons for delay. RESULTS. One thousand five hundred eleven patients (12% VA & 43% non-VA) answered questions regarding delay in treatment. Overall, 73% reported delaying 1 month or more and 16% reported delaying more than 6 months. Black patients and white patients were equally likely to delay as were older persons (greater than or equal to65) compared with younger. Patients at the VA hospitals reported longer delays and patients with prior revascularization were less likely to report delays. We used ordinal logistic regression to predict delay using site type and prior revascularization as covariates. VA site of care independently predicted longer delays whereas prior revascularization predicted less delay. Among patients who reported at least a 1 month delay, patients at the non-VA hospital were more likely to cite ignoring symptoms as their reason for delay (72% vs. 61%; P = 0.03) as were those with at least a high school education 69% versus 50%; P = 0.003). Black patients reported that they ignored their symptom more often but this was marginally significant (77% vs. 63%; P = 0.053). CONCLUSIONS. Race was not associated with delay in seeking care among patients awaiting coronary angiography. Non-VA patients, and those with past revascularization, were less likely to delay. Ignoring symptoms was the most common reason for delays greater than 1 month. Further study of the sequence of patient and provider decisions that ultimately lead to revascularization is needed. C1 VA Pittsburgh Hlth Care Syst, Sect Gen Internal Med 11E120, Pittsburgh, PA 15240 USA. VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. VA Pittsburgh Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Duke Univ, Med Ctr, Durham Vet Affairs Med Ctr, Durham, NC USA. RP Conigliaro, J (reprint author), VA Pittsburgh Hlth Care Syst, Sect Gen Internal Med 11E120, Univ Dr C, Pittsburgh, PA 15240 USA. NR 29 TC 12 Z9 12 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 97 EP 105 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000011 ER PT J AU Collins, TC Johnson, M Henderson, W Khuri, SF Daley, J AF Collins, TC Johnson, M Henderson, W Khuri, SF Daley, J TI Lower extremity nontraumatic amputation among veterans with peripheral arterial disease - Is race an independent factor? SO MEDICAL CARE LA English DT Article DE race; peripheral arterial disease; amputation ID AFFAIRS SURGICAL RISK; INTERMITTENT CLAUDICATION; MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES; HEART-DISEASE; MORTALITY; QUALITY; CARE; PREVALENCE; ADJUSTMENT AB OBJECTIVES. To determine if race/ethnicity is independently associated with an increased risk for nontraumatic lower extremity amputation versus lower extremity bypass revascularization among patients with peripheral arterial disease (PAD). METHODS. Data were analyzed from the National VA Surgical Quality Improvement Program (NSQIP) and from the Veterans Affairs Patient Treatment File (PTF). Race/ethnicity was defined as non-Hispanic white, black, or Hispanic. Variables that were univariately associated (P less than or equal to0.05) with the outcome of amputation were placed into a multiple logistic regression model to determine independent predictors for the dependent variable, lower extremity amputation versus lower extremity bypass revascularization. RESULTS. Three thousand eighty-five lower extremity amputations and 8409 lower extremity bypass operations were identified. Among all cases included, there were 416 Hispanic patients (3.6%), 2337 black patients (20.3%), and 8741 non-Hispanic white patients (76.1%). Among all variables within the model, Hispanic and black race were each associated with a greater risk for amputation than a history of rest pain/gangrene (Hispanic race 1.4, 95% Cl 1.1, 1.9; black race 1.5, 95% Cl 1.4, 1.7; rest pain/gangrene 1.1, 95% CI 1.0, 1.3). The final model had a c statistic of 0.83. CONCLUSION. Hispanic race and black race were independent risk factors for lower extremity amputation in patients with PAD. Although the burden of certain atherosclerotic risk factors (eg, diabetes and hypertension) is higher in minority patients, the impact of this burden does not account for the increased risk for the outcome of lower extremity amputation in these two populations. Further research is needed to better understand the reason(s) why race/ethnicity is independently associated with poor outcomes in PAD. C1 Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX USA. Hines VA Cooperat Studies Program Coordinat Ctr, Hines, IL USA. W Roxbury VA Med Ctr, W Roxbury, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Partners Hlth Care Syst,Ctr Hlth Syst Design & Ev, Massachusetts Gen Hosp,Inst Hlth Policy, Boston, MA USA. RP Collins, TC (reprint author), Dept Vet Affairs, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 44 TC 34 Z9 34 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 106 EP 116 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000012 ER PT J AU Harada, ND Damron-Rodriguez, J Villa, VM Washington, DL Dhanani, S Shon, H Chattopadhyay, M Fishbein, H Lee, M Makinodan, T Andersen, R AF Harada, ND Damron-Rodriguez, J Villa, VM Washington, DL Dhanani, S Shon, H Chattopadhyay, M Fishbein, H Lee, M Makinodan, T Andersen, R TI Veteran identity and race/ethnicity - Influences on VA outpatient care utilization SO MEDICAL CARE LA English DT Article DE veteran; race; access ID MILITARY SERVICE AB BACKGROUND. "Veteran identity" is defined as veterans' self-concept that derives from his/her military experience within a sociohistorical context. Veteran identity may vary by race/ethnicity because the sociohistorical context of the military experience varies by race. OBJECTIVES. To explore veteran identity and how it varies by race/ethnicity, and to identify aspects of veteran identity that significantly influence preferences for, and use of, VA outpatient care. RESEARCH DESIGN. Focus groups were conducted at community sites to explore concepts related to veteran identity, race/ethnicity, military experience, and health services use. The focus groups informed the development of a telephone survey, which was administered to veterans of four racial/ethnic groups in Southern California and Southern Nevada. SUBJECTS. One hundred seventy-eight veterans participated in the focus groups, and 3,227 veterans completed the telephone survey. MEASURES. Dependent variables include: (1) preference for VA health services, (2) VA-only outpatient use, (3) Any VA outpatient use, and (4) number of outpatient visits within the previous 12 months. Independent variables include veteran identity, sociodemographic, and health-related characteristics. RESULTS. All veteran identity variables were significantly associated with race/ethnicity. Race/ethnicity, eg, being black or Hispanic, in addition to veteran identity factors, significantly influenced preferences for VA outpatient care. Veteran identity factors, however, had less influence on VA outpatient service utilization than socioeconomic factors. CONCLUSIONS. Minority veterans who highly identify with their veteran status may prefer the VA to other systems of care. Factors associated with veteran identity may be useful for incorporation into interventions to improve access to VA care. C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Policy & Social Welfare, Los Angeles, CA USA. Gallup Org Inc, Princeton, NJ USA. VA Greater Los Angeles Healthcare, Ctr Study Healthcare Provider Behavior, Sepulveda Ambulatory Care Ctr, Los Angeles, CA USA. RP Harada, ND (reprint author), VA Greater Los Angeles Hlth Care Syst, Bldg 115,Rm 328,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM nharada@ucla.edu NR 30 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2002 VL 40 IS 1 SU S BP 117 EP 128 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 508DC UT WOS:000173072000013 ER PT J AU Schackman, BR Goldie, SJ Freedberg, KA Losina, E Brazier, J Weinstein, MC AF Schackman, BR Goldie, SJ Freedberg, KA Losina, E Brazier, J Weinstein, MC TI Comparison of health state utilities using community and patient preference weights derived from a survey of patients with HIV/AIDS SO MEDICAL DECISION MAKING LA English DT Article DE HIV; AIDS; utilities; preference weights; cost-effectiveness ID QUALITY-OF-LIFE; HUMAN-IMMUNODEFICIENCY-VIRUS; NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; SERVICES UTILIZATION; HIV COST; ANTIRETROVIRAL THERAPY; CONTROLLED TRIAL; PLUS INDINAVIR; UNITED-STATES AB Objectives. The authors compare health state utilities derived from a national survey of patients with HIV/AIDS to represent community-based preferences with utilities derived from the same survey representing patient preferences; explore the relationships between these utilities and the dimensions of the SF-6D health state classification; and examine the implications of differences in the source of utilities for a cost-effectiveness analysis of early treatment of patients with HIV/AIDS. Methods. The authors derived community-based standard gamble (SG) utilities using an algorithm developed for the SF-6D health state classification system. The authors derived patient SG utilities from HIV/AIDS patient rating scale self-assessments using a power transformation. Data were from the HIV Cost and Services Utilization Study, a probability sample of 2864 HIV-infected adults receiving care in the United States in 1996. Results. Patient SG utilities were higher than community SG utilities by 4% to 9% (0.979 vs. 0.937, 0.910 vs. 0.841, and 0.845 vs. 0.778; P < 0.001 for all comparisons). In regression analyses, patient SG utilities were less influenced by physical functioning, pain, and mental health dimensions of the SF-6D. The base case results of a cost-effectiveness analysis comparing early antiretrovdral therapy to deferred therapy were unaffected by the choice between community ($20,100 per quality-adjusted life year) and patient ($18,400 per quality-adjusted life year) perspectives. The impact of the choice of utilities remained small in sensitivity analyses that varied the influence of treatment side effects on utilities and the initial symptom status of Patients. Conclusion. There are differences between community and patient utilities for HIV/AIDS health states, although even when treatment side effects are important, these differences may not affect cost-effectiveness ratios. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Univ Sheffield, Sch Hlth & Related Res, Sheffield Hlth Econ Grp, Sheffield, S Yorkshire, England. RP Schackman, BR (reprint author), Cornell Univ, Weill Med Coll, Dept Publ Hlth, Div Outcomes & Effectiveness Res, 411 E 69th St, New York, NY 10021 USA. FU NIAID NIH HHS [R01AI42006, R01 AI042006]; NLM NIH HHS [LM07092-07, T15 LM007092]; ODCDC CDC HHS [U64/CCU114927, U64/CCU119525] NR 43 TC 76 Z9 76 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2002 VL 22 IS 1 BP 27 EP 38 DI 10.1177/02729890222062892 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 513JW UT WOS:000173375600003 PM 11833663 ER PT J AU Armstrong, K Schwartz, JS Fitzgerald, G Putt, M Ubel, PA AF Armstrong, K Schwartz, JS Fitzgerald, G Putt, M Ubel, PA TI Effect of framing as gain versus loss on understanding and hypothetical treatment choices: Survival and mortality curves SO MEDICAL DECISION MAKING LA English DT Article DE decision making; framing effect; risk communication ID TREATMENT PREFERENCES; HEALTH-CARE; DECISIONS; EXPLANATIONS; PHYSICIANS AB Background. Presentation of information using survival or mortality(i.e., incidence) curves offers a potentially powerful method of communication because such curves provide information about risk over time in a relatively simple graphic format. However, the effect of framing as survival versus mortality, on understanding and treatment choice is not known. Methods. In this study, 451 individuals awaiting jury duty at the Philadelphia City Courthouse were randomized to receive 1 of 3 questionnaires: (1) survival curves, (2) mortality curves, or (3) both survival and mortality curves. Each questionnaire included a brief description of a hypothetical treatment decision, survival curve graphs and/or mortality curve graphs presenting the outcome of the treatment, and questions measuring understanding of the information contained in the graphs and preference for undergoing treatment. After completing a brief practice exercise, participants were asked to answer questions assessing their ability to interpret single points on a cure and the difference between curves, and then to decide whether they would choose to undergo preventive surgery for 3 different scenarios in which the benefit of surgery varied. Results. Participants who received only survival curves or who received both survival and mortality curves were significantly more accurate in answering questions about the information than participants who received only mortality, curves (P < 0.05). For 2 of the 3 treatment presentations, participants who received only mortality curves were significantly less likely to prefer preventive surgery than participants who received survival curves only or both survival and mortality curves (P < 0.05). The effect of framing on understanding was greatest among participants with less than a college education and among non-Caucasian participants. Conclusion. Framing graphic risk information as chance of death over time results in lower levels of understanding and less interest in preventive surgery than framing as chance of survival over time. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 17 TC 67 Z9 67 U1 0 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2002 VL 22 IS 1 BP 76 EP 83 DI 10.1177/02729890222062946 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 513JW UT WOS:000173375600008 PM 11833668 ER PT S AU Cotin, S Stylopoulos, N Ottensmeyer, M Neumann, P Rattner, D Dawson, S AF Cotin, S Stylopoulos, N Ottensmeyer, M Neumann, P Rattner, D Dawson, S BE Dohi, T Kikinis, R TI Metrics for laparoscopic skills trainers: The weakest link! SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION-MICCAI 2002, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 5th International Conference on Medical Image Computing and Computer-Assisted Intervention CY SEP 25-28, 2002 CL TOKYO, JAPAN ID SURGICAL SKILLS; SIMULATION; EDUCATION; MODEL AB Metrics are widely employed in virtual environments and provide a yardstick for performance measurement. The current method of defining metrics for medical simulation remains more an art than a science. Herein, we report a practical scientific approach to defining metrics, specifically aimed at computer-assisted laparoscopic skills training. We also propose a standardized global scoring system usable across different laparoscopic trainers and tasks. The metrics were defined in an explicit way based on the relevant skills that a laparoscopic surgeon should master. We used a five degree of freedom device and a software platform capable of 1) tracking the motion of two laparoscopic instruments 2) real time information processing and feedback provision. A validation study was performed. The results show that our metrics and scoring system represent a technically sound approach that can be easily incorporated in a computerized trainer for any task, enabling a standardized performance assessment method. C1 Massachusetts Gen Hosp, Simulat Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cotin, S (reprint author), Massachusetts Gen Hosp, Simulat Grp, Boston, MA 02114 USA. EM scotin@partners.org NR 17 TC 68 Z9 68 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44224-3 J9 LECT NOTES COMPUT SC PY 2002 VL 2488 BP 35 EP 43 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Robotics SC Computer Science; Engineering; Robotics GA BY57N UT WOS:000189412100005 ER PT S AU Golland, P Fischl, B Spiridon, M Kanwisher, N Buckner, RL Shenton, ME Kikinis, R Dale, A Grimson, WEL AF Golland, P Fischl, B Spiridon, M Kanwisher, N Buckner, RL Shenton, ME Kikinis, R Dale, A Grimson, WEL BE Dohi, T Kikinis, R TI Discriminative analysis for image-based studies SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION-MICCAI 2002, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 5th International Conference on Medical Image Computing and Computer-Assisted Intervention CY SEP 25-28, 2002 CL TOKYO, JAPAN ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; COORDINATE SYSTEM; CORTEX AB In this paper, we present a methodology for performing statistical analysis for image-based studies of differences between populations and describe our experience applying the technique in several different population comparison experiments. Unlike traditional analysis tools, we consider all features simultaneously, thus accounting for potential correlations between the features. The result of the analysis is a classifier function that can be used for labeling new examples and a map over the original features indicating the degree to which each feature participates in estimating the label for any given example. Our experiments include shape analysis of subcortical structures in schizophrenia, cortical thinning in healthy aging and Alzheimer's disease and comparisons of fMRI activations in response to different visual stimuli. C1 MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab, Boston, MA USA. Harvard Univ, Sch Med, VAMC Brockton, Dept Psychiat,Clin Neurosci Div,Lab Neurosci, Brockton, MA 02401 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63130 USA. Washington Univ, Dept Radiol, St Louis, MO 63130 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Golland, P (reprint author), MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. RI Dale, Anders/A-5180-2010 NR 18 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44224-3 J9 LECT NOTES COMPUT SC PY 2002 VL 2488 BP 508 EP 515 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Robotics SC Computer Science; Engineering; Robotics GA BY57N UT WOS:000189412100063 ER PT S AU Pohl, KM Wells, WM Guimond, A Kasai, K Shenton, ME Kikinis, R Grimson, WEL Warfield, SK AF Pohl, KM Wells, WM Guimond, A Kasai, K Shenton, ME Kikinis, R Grimson, WEL Warfield, SK BE Dohi, T Kikinis, R TI Incorporating non-rigid registration into expectation maximization algorithm to segment MR images SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION-MICCAI 2002, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 5th International Conference on Medical Image Computing and Computer-Assisted Intervention CY SEP 25-28, 2002 CL TOKYO, JAPAN ID BRAIN AB The paper introduces an algorithm which allows the automatic segmentation of multi channel magnetic resonance images. We extended the Expectation Maximization-Mean Field Approximation Segmenter, to include Local Prior Probability Maps. Thereby our algorithm estimates the bias field in the image while simultaneously assigning voxels to different tissue classes under prior probability maps. The probability maps were aligned to the subject using non-rigid registration. This allowed the parcellation of cortical sub-structures including the superior temporal gyrus. To our knowledge this is the first description of an algorithm capable of automatic cortical parcellation incorporating strong noise reduction and image intensity correction. C1 MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Clin Neurosci Div, Dept Psychiat,Lab Neurosci, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02301 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Neurol Imaging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Surg Planning Lab, Boston, MA 02115 USA. RP Pohl, KM (reprint author), MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. EM kpohl@ai.mit.edu; welg@ai.mit.edu; guimond@bwh.harvard.edu; kasaik@bwh.harvard.edu; martha_shenton@hms.harvard.edu; kikinis@bwh.harvard.edu; welg@ai.mit.edu; sw@bwh.harvard.edu; kikinis@bwh.harvard.edu RI Warfield, Simon/B-3352-2009 NR 17 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44224-3 J9 LECT NOTES COMPUT SC PY 2002 VL 2488 BP 564 EP 571 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Robotics SC Computer Science; Engineering; Robotics GA BY57N UT WOS:000189412100070 ER PT S AU Ntziachristos, V Ripoll, J Graves, E Weissleder, R AF Ntziachristos, V Ripoll, J Graves, E Weissleder, R BE Dohi, T Kikinis, R TI In-vivo molecular investigations of live tissues using diffracting sources SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION-MICCAI 2002, PT 1 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 5th International Conference on Medical Image Computing and Computer-Assisted Intervention CY SEP 25-28, 2002 CL TOKYO, JAPAN ID MICROSCOPY; APPROXIMATION AB We present novel technologies based on reconstructions employing diffracting sources in fluorescent mode that resolve molecular function in deep tissues. To facilitate time-efficient three-dimensional reconstructions we have employed fast analytical solutions of the diffusion equation to allow for close to real-time volumetric imaging of fluorescent near-infrared beacons that activate (fluoresce) with high specificity in the presence of specific molecular targets. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM vasilis@helix.mgh.harvard.edu; ripoll@helix.mgh.harvard.edu; graves@helix.mgh.harvard.edu; weissleder@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 16 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44224-3 J9 LECT NOTES COMPUT SC PY 2002 VL 2488 BP 739 EP 745 PG 7 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Robotics SC Computer Science; Engineering; Robotics GA BY57N UT WOS:000189412100091 ER PT S AU Guimond, A Egorova, S Killiany, RJ Albert, MS Guttmann, CRG AF Guimond, A Egorova, S Killiany, RJ Albert, MS Guttmann, CRG BE Dohi, T Kikinis, R TI Automatic statistical identification of neuroanatomical abnormalities between different populations SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION-MICCAI 2002, PT 1 SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 5th International Conference on Medical Image Computing and Computer-Assisted Intervention CY SEP 25-28, 2002 CL TOKYO, JAPAN ID BRAIN ATLAS AB We present a completely automatic method to identify abnormal anatomical configurations of the brain resulting from various pathologies. The statistical framework developed here is applied to identify regions that significant differ from normal anatomy in two groups of patients, namely subjects who subsequently converted to Alzheimer's Disease (AD) and subjects with mild AD. The regions identified are consistent with post-mortem pathological findings in AD. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Imaging, Cambridge, MA 02138 USA. Boston Univ, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. RP Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Imaging, Cambridge, MA 02138 USA. EM guimond@bwh.harvard.edu; egorova@bwh.harvard.edu; rkilliany@cajal-1.bu.edu; albert@psych.mgh.harvard.edu; guttmann@bwh.harvard.edu NR 31 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44224-3 J9 LECT NOTES COMPUT SC PY 2002 VL 2488 BP 785 EP 792 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Robotics SC Computer Science; Engineering; Robotics GA BY57N UT WOS:000189412100097 ER PT J AU Crispino, JD Orkin, SH AF Crispino, JD Orkin, SH TI The use of altered specificity mutants to probe specific protein-protein interactions involved in the activation of GATA-1 target genes SO METHODS LA English DT Article DE transcription factors; yeast two-hybrid; altered specificity mutants ID TRANSCRIPTION FACTOR GATA-1; REVERSE 2-HYBRID; HYBRID SYSTEMS; DIFFERENTIATION; YEAST; ASSOCIATION AB With the increasing popularity of the yeast two-hybrid screen, a large number, of protein-protein interactions have been identified. In many cases, single proteins have been found to associate with a large number of cofactors. For example, the hematopoietic transcription factor GATA-1 interacts with a multitude of other nuclear proteins, including Friend of GATA-1 (FOG-1), EKLF, CBP/p300, and Lmo2. Furthermore, p300, besides associating with GATA-1, interacts with at least seven other hematopoietic transcription factors. Despite the numerous pairwise and higher-order interactions identified, assessment of their contribution to transcriptional control has been lacking. Here we describe a strategy that can be applied to assess the functional relevance of any protein-protein association. This approach involves the creation of altered specificity mutants though the use of a combination of two yeast two-hybrid screens. Once altered specificity factors are obtained, a researcher can then proceed to functional assays that address the role of a specific protein-protein interaction. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Childrens Hosp, Dept Pediat, Dana Farber Canc Ctr, Div Hematol & Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Crispino, JD (reprint author), Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. OI Crispino, John/0000-0002-8182-8306 NR 19 TC 4 Z9 4 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 1046-2023 J9 METHODS JI Methods PD JAN PY 2002 VL 26 IS 1 BP 84 EP 92 AR PII 1046-2023(02)00010-5 DI 10.1016/S1046-2023(02)00010-5 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 551QM UT WOS:000175572600010 PM 12054907 ER PT J AU Achtmeyer, CE Payne, TH Anawalt, BD AF Achtmeyer, CE Payne, TH Anawalt, BD TI Computer order entry system decreased use of sliding scale insulin regimens SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE medical records systems; computerized; diabetes mellitus; physicians practice patterns; insulin ID DECISION-SUPPORT SYSTEMS; PRACTICE GUIDELINES; DIABETES-MELLITUS; MANAGEMENT; INTERVENTION; PERFORMANCE; OUTCOMES; ERRORS; TRIAL; PAPER AB Objectives: Despite evidence documenting their ineffectiveness, sliding scale insulin is a commonly used regimen for glucose management for hospitalized patients with diabetes, mellitus. At the Veterans Affairs Puget Sound Medical Center, where computer order entry has been mandated, we tested the hypothesis that an evidence-based minimal intervention order (supplemental insulin only when fasting serum glucoses exceeded 400 mg/dl) would decrease the use of sliding scale insulin orders. Methods. Using a computerized order entry system, providers were initially offered a traditional sliding scale order or their own ad hoc orders for glycemic control of inpatients. After 34 weeks providers were offered a third option; a "minimal intervention order" with supplemental insulin only for glucose >400 mg/dl. We extracted all regular insulin orders and performed a retrospective review of insulin sliding scale orders written between December 1, 1998 and November 16, 1999. We compared the frequency of traditional insulin sliding scale orders before and after the introduction of the minimal intervention order. Results. Nearly all orders in the first 34 weeks were traditional insulin sliding scales. We found a significant decrease in the number of traditional insulin sliding scale orders in the 16 weeks after the introduction of a computerized quick order for minimal intervention. from 978/1007 (97.1%) to 254/398 (63.8%) (P < 0.001). Conclusions. A simple evidenced based quick-order in a computer order entry system rapidly and significantly reduced use of sliding scale insulin regimens for glycemic control of inpatients. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Achtmeyer, CE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, S-111,1660 S Columbian Way, Seattle, WA 98108 USA. NR 26 TC 11 Z9 11 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2002 VL 41 IS 4 BP 277 EP 281 PG 5 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 607GL UT WOS:000178783700005 PM 12425238 ER PT S AU Moses, AV Jarvis, MA Raggo, C Bell, YC Ruhl, R Luukkonen, BGM Griffith, DJ Wait, CL Druker, BJ Heinrich, MC Nelson, JA Fruh, K AF Moses, AV Jarvis, MA Raggo, C Bell, YC Ruhl, R Luukkonen, BGM Griffith, DJ Wait, CL Druker, BJ Heinrich, MC Nelson, JA Fruh, K BE Aujame, L Burdin, N Dodet, B Vicari, M TI A functional genomics approach to Kaposi's sarcoma SO MICROARRAYS, IMMUNE RESPONSES AND VACCINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Microarrays, Immune Responses and Vaccines CY MAY 26-29, 2002 CL VEYRIER DU LAC, FRANCE SP Fdn Merieux DE Kaposi's sarcoma-associated herpesvirus; microarray; c-kit; antisense ID STEM-CELL FACTOR; C-KIT RECEPTOR; EPSTEIN-BARR-VIRUS; ENDOTHELIAL-CELLS; SPINDLE CELLS; DNA-SEQUENCES; SURFACE-ANTIGENS; GENE-EXPRESSION; HERPESVIRUS; COEXPRESSION AB Kaposi's sarcoma (KS) is the most frequent malignancy afflicting acquired immune-deficiency syndrome (AIDS) patients. Tumor lesions are characterized by spindle cells of vascular origin and vascularization. Kaposi's sarcoma-associated herpes virus (KSHV) is consistently found in all forms of KS. Infection of dermal microvascular endothelial cells (DMVEC) with KSHV recapitulates spindle cell formation in vitro. We studied this transformation process by DNA microarray analysis comparing the RNA expression profiles of KSHV-infected and mock-infected DMVEC. Genes involved in tumorigenesis, angiogenesis, host defense, cell growth and differentiation, transcription, and metabolism were observed to change significantly upon infection with KSHV. One of the most consistently KSHV-induced genes was the receptor tyrosine kinase and proto-oncogene c-Kit. Inhibition of c-Kit activity with the pharmacological inhibitor of c-Kit signaling ST1571 reversed the KSHV-induced morphological transformation of DMVEC. Moreover, overexpression studies showed that c-Kit was sufficient to induce spindle cell formation (Moses et al. J. Virol. 76(16): 8383-8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis. C1 Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RW Johnson Pharmaceut Res Inst, San Diego, CA 92121 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Moses, AV (reprint author), 505 NW 185th Ave, Beaverton, OR 97006 USA. NR 45 TC 18 Z9 18 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-446-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 975 BP 180 EP 191 PG 12 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BW05G UT WOS:000180751500015 PM 12538164 ER PT J AU Gerard, HC Freise, J Wang, Z Roberts, G Rudy, D Krauss-Patz, B Kohler, L Zeidler, H Schumacher, HR Whittum-Hudson, JA Hudson, AP AF Gerard, HC Freise, J Wang, Z Roberts, G Rudy, D Krauss-Patz, B Kohler, L Zeidler, H Schumacher, HR Whittum-Hudson, JA Hudson, AP TI Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection SO MICROBES AND INFECTION LA English DT Article DE Chlamydia trachomatis; ATP production; glycolysis; pentose phosphate pathway ID REACTIVE ARTHRITIS; REITERS-SYNDROME; HUMAN-MONOCYTES; PNEUMONIAE; VIABILITY; INVITRO; CULTURE AB The Chlamydia trachomatis genome encodes glycolysis and pentose phosphate pathway enzymes, two ATP/ADP exchange proteins, and other energy transduction-related components. We asked if and when chlamydial genes specifying products related to energy transduction are expressed during active vs. persistent infection in in vitro models and in synovia from Chlamydia-associated arthritis patients. Hep-2 cells infected with K serovar were harvested from 0-48 h post-infection (active infection). Human monocytes identically infected were harvested at 1, 2, 3, 5 days post-infection (persistent). RNA from each preparation and from synovial samples PCR-positive/-negative for Chlamydia DNA was subjected to RT-PCR targeting (a) chlamydial primary rRNA transcripts and adt1 mRNA, (b) chlamydial mRNA encoding enzymes of the glycolysis (pyk, gap, pgk) and pentose phosphate (gnd, tal) pathways, the TCA cycle (mdhC, fumC), electron transport system (cydA, cydB), and sigma factors (rpoD, rpsD, rpoN). Primary rRNA transcripts and adt1 mRNA were present in each infected preparation and patient sample; controls were negative for chlamydial RNA. In infected Hep-2 cells, all energy transduction-related genes were expressed by approximate to 11 h post-infection. In monocytes, pyk, gap, pgk, gnd, tal, cydA mRNA were present in 1-2-day-infected cells but absent at 3 days and after; cydB, mdhC, fumC were expressed through 5 days post-infection. RT-PCR targeting mRNA from sigma factor genes indicated that lack of these gene products cannot explain selective transcriptional down-regulation during persistence. Analyses of RNA from synovial tissues mirrored those from the monocyte system. These data suggest that in the first phase of active chlamydial infection, ADP/ATP exchange provides energy required for metabolism; in active growth, glycolysis supplements host ATP. In persistence host, rather than bacterially produced, ATP is the primary energy source. Metabolic rate in persistent C. trachomatis is lower than in actively growing cells, as judged from assays for relative chlamydial primary rRNA transcript levels in persistent vs. actively growing cells. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Med Hochschule Hannover, Abt Rheumatol, D-30625 Hannover, Germany. Wayne State Univ, Sch Med, Dept Internal Med, Div Rheumatol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48201 USA. Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Detroit, MI 48201 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NIAID NIH HHS [AI-44493]; NIAMS NIH HHS [AR-42541, AR-47186] NR 38 TC 56 Z9 57 U1 0 U2 7 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2002 VL 4 IS 1 BP 13 EP 22 AR PII S1286-4579(01)01504-0 DI 10.1016/S1286-4579(01)01504-0 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 522UV UT WOS:000173916100002 PM 11825770 ER PT J AU Abou-Elenin, K Xydakis, A Hamdy, O Economides, PA Horton, ES Veves, A AF Abou-Elenin, K Xydakis, A Hamdy, O Economides, PA Horton, ES Veves, A TI The effect of aspirin and various iontophoresis solution vehicles on skin microvascular reactivity SO MICROVASCULAR RESEARCH LA English DT Article DE iontophoresis; aspirin; deionized water ID PULMONARY VASCULAR-RESISTANCE; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; SODIUM-NITROPRUSSIDE; IN-VIVO; ACETYLCHOLINE; VASODILATION; DILATATION; MECHANISMS; RESPONSES AB The two main objectives of this study were: (1) to examine the effect of aspirin on the endothelial function in healthy subjects and (2) to examine the effect of deionized water and 5% NaCl as iontophoresis solution vehicles. The skin microcirculation was evaluated at the forearm level of healthy subjects. A laser Doppler scanner was employed to measure vasodilation in response to the iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). In the first experiment, nine healthy subjects were given 500 mg aspirin daily for 3 days. The microvascular reactivity was measured at the beginning and the end of the study. In the second experiment, the response to iontophoresis of acetylcholine and sodium nitroprusside as 1% solutions of deionized water was compared to the responses that were achieved after the iontophoresis of deionized water or 5% NaCl solution. After 3 days of aspirin intake, there were no changes in the vasodilatory response to acetylcholine (endothelium-dependent vasodilation) [81 +/- 11 vs 77 +/- 10 (% of increase over baseline at the beginning vs the end of the study, mean +/- SE), P NS] or sodium nitroprusside (endothelium-independent vasodilation) (69 +/- 8 vs 64 +/- 12, P = NS). There was also a negligible response after the iontophoresis of 5% NaCl (3 +/- 4) and deionized water (6 +/- 4) in anodal mode (the mode employed for the iontophoresis of acetylcholine). in cathodal mode, employed for the iontophoresis of sodium nitroprusside, the response to 5% NaCl was still negligible but a considerable response was found after the iontophoresis of deionized water. In normal healthy subjects, aspirin administration has no effect on forearm skin microvascular reactivity, including both endothelium-dependent and endothelium-independent vasodilation. In addition, a NaCl solution would be preferable to deionized water as the iontophoresis solution vehicle. (C) 2001 Elsevier Science. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Clin Res Ctr,Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab,Dept Surg, Boston, MA 02215 USA. RP Abou-Elenin, K (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Clin Res Ctr,Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. NR 17 TC 26 Z9 26 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JAN PY 2002 VL 63 IS 1 BP 91 EP 95 DI 10.1006/mvre.2001.2369 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 510EY UT WOS:000173196800010 PM 11749076 ER PT J AU Blumenthal, D AF Blumenthal, D TI Doctors in a wired world: Can professionalism survive connectivity? SO MILBANK QUARTERLY LA English DT Article ID HEALTH-CARE INTERNET; INFORMATION; QUALITY; SYSTEM AB The information revolution has the potential to reduce the asymmetry of information between patients and doctors and thereby to undermine a central pillar of physicians' claim to professional status: the possession of distinctive competence based on technical know-how selflessly applied and collectively monitored. A close analysis of the information revolution's likely effects suggests that for some patients with some conditions, their access to more and better information will indeed reduce the magic, mystery, and power of the medical profession. However, the information revolution also offers opportunities for physicians to bolster the cognitive and moral bases of professionalism. To seize those opportunities, physicians must master new roles and skills and avoid unacceptable conflicts of interest. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St, Boston, MA 02114 USA. NR 31 TC 57 Z9 59 U1 0 U2 3 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0887-378X J9 MILBANK Q JI Milbank Q. PY 2002 VL 80 IS 3 BP 525 EP + DI 10.1111/1468-0009.00021 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 591VC UT WOS:000177900100003 PM 12233248 ER PT J AU Bolton, EE Litz, BT Glenn, DM Orsillo, S Roemer, L AF Bolton, EE Litz, BT Glenn, DM Orsillo, S Roemer, L TI The impact of homecoming reception on the adaptation of peacekeepers following deployment SO MILITARY PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VETERANS; SOMALIA; SCALE; PTSD AB Not unlike combat soldiers, peacekeepers are at risk for the development of significant symptoms of posttraumatic stress disorder (PTSD; Litz, Orsillo, Freidman, Ehlich, & Batres, 1997). Previous studies have demonstrated that the response of family and community members at homecoming has a significant restorative role in the adaptation of combat soldiers (e.g., Fontana & Rosenheck, 1994). This study assesses this potential effect in the postdeployment adjustment of peacekeepers. As part of a larger investigation, 1,023 U.S. military personnel who served as peacekeepers in Somalia were administered a comprehensive psychosocial questionnaire that included measures of exposure to negative and potentially traumatic peacekeeping experiences, homecoming reception, and PTSD symptom severity. Adjustment to peacekeeping was positively related to homecoming reception. C1 Boston Dept Vet Affairs, Ctr Med, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div,Psychiat Serv, Boston, MA 02130 USA. Duke Univ, Ctr Med, Dept Psychiat, Durham, NC 27706 USA. Boston Univ, Sch Med, Womens Hlth Sci Div, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston VA Hlth Care Syst, Boston, MA 02215 USA. Univ Massachusetts, Boston, MA 01003 USA. RP Litz, BT (reprint author), Boston Dept Vet Affairs, Ctr Med, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div,Psychiat Serv, 116B-5 150 S Huntington Ave, Boston, MA 02130 USA. OI Roemer, Lizabeth/0000-0002-2453-5435 NR 18 TC 26 Z9 26 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0899-5605 J9 MIL PSYCHOL JI Milit. Psychol. PY 2002 VL 14 IS 3 BP 241 EP 251 DI 10.1207/S15327876MP1403_4 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 593ML UT WOS:000177995200004 ER PT J AU Nielsen, GP Bjornsson, J Rosenberg, AE Unni, KK AF Nielsen, GP Bjornsson, J Rosenberg, AE Unni, KK TI Primary Rosai-Dorfman disease of bone. A clinicopathologic study of 13 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 69 BP 20A EP 20A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900086 ER PT J AU O'Connell, JX Nielsen, GP Rosenberg, AE AF O'Connell, JX Nielsen, GP Rosenberg, AE TI Epithelioid hemangioma of bone: A series revisited 10 years later SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Surrey Mem Hosp, Surrey, BC, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 71 BP 20A EP 20A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900088 ER PT J AU Ogata, N Segre, GV Roth, SI AF Ogata, N Segre, GV Roth, SI TI A unique new model of osteogenesis imperfecta (OI) SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 72 BP 20A EP 21A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900089 ER PT J AU Rosenberg, AE Harris, KR Keel, SB Roth, SI Nielsen, GP Mangham, C AF Rosenberg, AE Harris, KR Keel, SB Roth, SI Nielsen, GP Mangham, C TI Immunohistochemical analysis of primary osteosarcoma of bone SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal Orthopaed Hosp, Birmingham B31 2AP, W Midlands, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 80 BP 22A EP 22A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900097 ER PT J AU Sgroi, D Gaudet, J Heike, V Ma, XJ Erlander, M AF Sgroi, D Gaudet, J Heike, V Ma, XJ Erlander, M TI In vivo gene expression profiling of human breast cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Arcturus Engn Inc, Appl Genom Div, Carlsbad, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 203 BP 51A EP 51A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900220 ER PT J AU Houser, SL McMorrow, IM LeGuern, C Schwarze, ML Fuchimoto, Y Sachs, DH Madsen, JC AF Houser, SL McMorrow, IM LeGuern, C Schwarze, ML Fuchimoto, Y Sachs, DH Madsen, JC TI The prevalence of cardiac allograft vasculopathy in miniature swine is associated with myocardial gene expression of IFN-gamma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 243 BP 61A EP 61A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900260 ER PT J AU Smith, RN Chang, Y Grazette, L Houser, SL AF Smith, RN Chang, Y Grazette, L Houser, SL TI Heart allograft patients with quilty B lesions are at a higher risk for subsequent high grade rejetions SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 255 BP 63A EP 64A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900272 ER PT J AU Altiok, S Tambouret, R AF Altiok, S Tambouret, R TI Assessment of p16 (INK4A) immunostaining as a surrogate marker for HPV-related intraepithelial lesions of uterine cervix in cytologic specimens and surgical biopsies SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 261 BP 65A EP 65A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900278 ER PT J AU Altiok, S Cooper, TL Tambouret, R AF Altiok, S Cooper, TL Tambouret, R TI The combination of fine-needle aspiration and flow cytometric immunophenotyping in diagnosis and subclassification of primary non-Hodgkin lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Berkshire Med Ctr, Pittsfield, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 262 BP 65A EP 65A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900279 ER PT J AU Deshpande, V McKee, GT AF Deshpande, V McKee, GT TI Cytokeratin 20 (CK20): A useful adjunct to urine cytology SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 283 BP 70A EP 71A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900300 ER PT J AU Elliott, DD Faquin, WC Szyfelbein, WM Pitman, MB AF Elliott, DD Faquin, WC Szyfelbein, WM Pitman, MB TI Fine needle aspiration biopsy of Hurthle cell lesions of the thyroid: Cytologic features in a series of 91 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 287 BP 71A EP 71A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900304 ER PT J AU Geisinger, KR Pitman, MB Creager, AJ AF Geisinger, KR Pitman, MB Creager, AJ TI Cytologic features of clear cell sarcoma of soft tissue: A study of fine needle aspirates and exfoliative specimens SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 294 BP 73A EP 73A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900311 ER PT J AU Gornstein, B Jacobs, T Bedard, Y Biscotti, C Ducatman, B Layfield, L McKee, G Sneige, N Wang, H AF Gornstein, B Jacobs, T Bedard, Y Biscotti, C Ducatman, B Layfield, L McKee, G Sneige, N Wang, H TI Interobserver agreement of a probabilistic approach to reporting breast fine needle aspirations on ThinPrep (R) SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Toronto, Fac Med, Toronto, ON, Canada. Cleveland Clin Fdn, Cleveland, OH 44195 USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 299 BP 74A EP 74A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900316 ER PT J AU Nasser, SM Faquin, WC Pitman, MB AF Nasser, SM Faquin, WC Pitman, MB TI Fine needle aspiration biopsy of pseudoangiomatous stromal hyperplasia: A series of 20 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 329 BP 81A EP 81A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900346 ER PT J AU Sheffield, MV Yee, H Fisher, DE Dorvault, CC Weibaecher, KN Eltoum, I Siegal, GP Chhieng, DC AF Sheffield, MV Yee, H Fisher, DE Dorvault, CC Weibaecher, KN Eltoum, I Siegal, GP Chhieng, DC TI Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. NYU, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 349 BP 86A EP 86A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900366 ER PT J AU Wilbur, DC Parker, EM Foti, JA AF Wilbur, DC Parker, EM Foti, JA TI Location guided screening of liquid-based cervical cytology specimens: A potential improvement in accuracy and productivity is demonstrated in a preclinical feasibility study SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Viahealth, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 376 BP 92A EP 92A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900393 ER PT J AU Grossman, JM Mihm, MC Lyle, S AF Grossman, JM Mihm, MC Lyle, S TI Cytokeratin 15 and 19 expression in desmoplastic epitheliomas and microcystic adnexal carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 407 BP 99A EP 99A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900424 ER PT J AU North, PE Waner, M James, CA Mizeracki, A Mihm, MC AF North, PE Waner, M James, CA Mizeracki, A Mihm, MC TI Congenital nonprogressive hemangioma: A distinct clinicopathological entity unlike infantile hemangioma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 428 BP 104A EP 104A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900445 ER PT J AU Zembowicz, A Granter, SR McKee, PH Mihm, MC AF Zembowicz, A Granter, SR McKee, PH Mihm, MC TI Amelanotic cellular blue nevus: Clinico-pathological analysis of 20 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 465 BP 112A EP 113A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900482 ER PT J AU Zembowicz, A Mihm, MC AF Zembowicz, A Mihm, MC TI Pigment synthesizing melanocytic tumor: A low grade melanocytic tumor with frequent lymph node metastases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 464 BP 112A EP 112A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900481 ER PT J AU Badizadegan, K Lauwers, GY Fogt, F Fox, VL Redston, M Odze, RD AF Badizadegan, K Lauwers, GY Fogt, F Fox, VL Redston, M Odze, RD TI Loss of SMAD4/MADH4 expression in colonic juvenile polyps is associated with a multilobular or villiform growth pattern and the development of multiple juvenile polyps in children SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Presbyterian Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 511 BP 123A EP 123A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900528 ER PT J AU Bronner, M Emond, M Burgart, L Goldblum, J Greenson, J Haber, M Hart, J Lauwers, G Lazenby, A Lewin, D Robert, M Washington, K Montgomery, E AF Bronner, M Emond, M Burgart, L Goldblum, J Greenson, J Haber, M Hart, J Lauwers, G Lazenby, A Lewin, D Robert, M Washington, K Montgomery, E TI Diagnostic accuracy in ulcerative colitis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Univ S Carolina, Columbia, SC 29208 USA. Yale Univ, New Haven, CT 06520 USA. Vanderbilt Univ, Nashville, TN USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 513 BP 124A EP 124A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900530 ER PT J AU Lauwers, GY Wu, CL Balis, UJ Zukerberg, LR AF Lauwers, GY Wu, CL Balis, UJ Zukerberg, LR TI Role of Cables in colonic tumorigenesis: An immunohistochemical study SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 559 BP 134A EP 135A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900576 ER PT J AU Lauwers, GY Goldblum, JR Burgart, LJ Bhan, AK Greenson, JK AF Lauwers, GY Goldblum, JR Burgart, LJ Bhan, AK Greenson, JK TI Expression of neurotrophin receptors and RET protein in duodenal gangliocytic paraganglioma: A study of 12 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 558 BP 134A EP 134A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900575 ER PT J AU Mino, M Lauwers, GY AF Mino, M Lauwers, GY TI Role of immunophenotyping in cases of duodenal mucosa with normal villous architecture and increased intraepithelial lymphocytes SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 575 BP 138A EP 139A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900592 ER PT J AU Misdraji, J Yantiss, RK Graeme-Cook, FM Balis, UJ Young, RH AF Misdraji, J Yantiss, RK Graeme-Cook, FM Balis, UJ Young, RH TI Appendiceal mucinous tumors: A clinicopathological analysis of 92 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Univ Massachusetts, Mem Hlth Care, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 576 BP 139A EP 139A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900593 ER PT J AU Mueller, JD Kulke, MH Bertagnolli, MM Loda, M Odze, RD AF Mueller, JD Kulke, MH Bertagnolli, MM Loda, M Odze, RD TI VEGF, p27, skp2 and MLH1 expression in esophageal carcinoma treated by radiochemotherapy SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 579 BP 139A EP 140A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900596 ER PT J AU Yantiss, RK Odze, RD Farraye, FA Rosenberg, AE AF Yantiss, RK Odze, RD Farraye, FA Rosenberg, AE TI Prognostic significance of solitary versus multiple carcinoid tumors of the small intestine: A clinical and pathologic review of 75 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Massachusetts, Mem Hlth Care, Worcester, MA 01605 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 623 BP 150A EP 150A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900640 ER PT J AU Zukerberg, LR Mino, M Wu, CL Lauwers, GY AF Zukerberg, LR Mino, M Wu, CL Lauwers, GY TI Loss of expression of Cables, a putative tumor suppressor gene located on chromosome 18q11-12, in esophageal squamous cell carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 625 BP 150A EP 150A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900642 ER PT J AU Henley, JD Wade, CL Young, RH Ulbright, TM AF Henley, JD Wade, CL Young, RH Ulbright, TM TI Interstitial pattern of growth in seminoma: A study of 70 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 680 BP 163A EP 163A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900697 ER PT J AU Jiang, Z Wu, CL Woda, BA Dresser, K Fanger, GR Xu, J Rock, KL Yang, X AF Jiang, Z Wu, CL Woda, BA Dresser, K Fanger, GR Xu, J Rock, KL Yang, X TI P504S: A good diagnostic marker for small focus of prostatic adenocarcinoma on needle biopsy SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Corixia Corp, Seattle, WA USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 691 BP 166A EP 166A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900708 ER PT J AU Kallakury, BVS Sheehan, CE Fisher, DE Depowski, PL Ross, JS Jennings, TA AF Kallakury, BVS Sheehan, CE Fisher, DE Depowski, PL Ross, JS Jennings, TA TI Immunophenotypic analysis of renal and adrenal neoplasms: Utility of MiTF, inhibin, calretinin and CD10 in the differential diagnosis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Albany Med Coll, Albany, NY 12208 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 693 BP 166A EP 167A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900710 ER PT J AU Krishnan, B Lechago, J Truong, L AF Krishnan, B Lechago, J Truong, L TI Intraoperative consultation (IOC)for renal lesions. Utilities and diagnostic pitfalls in 320 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 698 BP 168A EP 168A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900715 ER PT J AU Lei, J Lin, D Waltregny, D Pagano, M Loda, MF Weinstein, MH AF Lei, J Lin, D Waltregny, D Pagano, M Loda, MF Weinstein, MH TI Overexpression of the F-box protein SKP2 in aggressive prostatic cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 704 BP 169A EP 169A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900721 ER PT J AU McKenney, JK Amin, MB Young, RH AF McKenney, JK Amin, MB Young, RH TI Urothelial (transitional cell) papilloma of the urinary bladder: A clinicopathologic study of 25 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 725 BP 174A EP 174A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900742 ER PT J AU Parker, DC Folpe, AL Bell, JD Oliva, E Cohen, C Young, RH Amin, MB AF Parker, DC Folpe, AL Bell, JD Oliva, E Cohen, C Young, RH Amin, MB TI Potential utility of uroplakin III, thrombomodulin and cytokeratin 20 as a diagnostic panel for urothelial (transitional cell) differentiation SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 735 BP 176A EP 176A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900752 ER PT J AU Rossi, S Weinstein, L Graner, E Onody, T Febbo, P Loda, M AF Rossi, S Weinstein, L Graner, E Onody, T Febbo, P Loda, M TI Expression of fatty acid synthase in prostate carcinoma by oligonucleotide arrays and immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Graner, Edgard/K-4411-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 744 BP 178A EP 178A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900761 ER PT J AU Srigley, JR Grignon, DJ Young, RH AF Srigley, JR Grignon, DJ Young, RH TI The distinction between pure carcinoid tumor and carcinoid-like adenocarcinoma of the prostate gland SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Credit Valley Hosp, Mississauga, ON, Canada. Wayne State Univ, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 28 Z9 30 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 762 BP 182A EP 183A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900786 ER PT J AU Tang, Z Zukerberg, L Young, RH Wu, CL AF Tang, Z Zukerberg, L Young, RH Wu, CL TI The role of Cables, a putative tumor suppressor gene, in urothelial carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 766 BP 183A EP 183A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900790 ER PT J AU Ulbright, TM Young, RH AF Ulbright, TM Young, RH TI Primary mucinous tumors of the testis and paratestis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 771 BP 184A EP 185A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900795 ER PT J AU Yang, XJ Wu, CL Amin, MB Young, R Fanger, G Jiang, Z AF Yang, XJ Wu, CL Amin, MB Young, R Fanger, G Jiang, Z TI P504S in diagnosis of prostate cancer: A multi-institutional analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Corixa Corp, Seattle, WA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 783 BP 187A EP 187A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900807 ER PT J AU Yang, XJ Wu, CL Tretiakova, M Fanger, G Dresser, K Jiang, Z AF Yang, XJ Wu, CL Tretiakova, M Fanger, G Dresser, K Jiang, Z TI Expression of P504S in atypical adenomatous hyperplasia of the prostate SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Corixa Corp, Seattle, WA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 782 BP 187A EP 187A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900806 ER PT J AU Arnell, PM Vu, Q Oliva, E AF Arnell, PM Vu, Q Oliva, E TI Beta-catenin expression in mucinous carcinomas of the ovary and metastatic colon carcinomas to the ovary: Does it have a diagnostic role? SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 800 BP 191A EP 191A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900824 ER PT J AU Dionigi, A Oliva, E Clement, PB Young, RH AF Dionigi, A Oliva, E Clement, PB Young, RH TI Endometrial stromal nodules (ESNs) and endometrial stromal tumors (ESTs) with limited infiltration: A clinicopathologic study of 50 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 815 BP 195A EP 195A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900839 ER PT J AU Dong, Q Zukerberg, L Wu, CL Oliva, E AF Dong, Q Zukerberg, L Wu, CL Oliva, E TI Expression of Cables, a cyclin dependent kinase (CDK) interacting protein, in ovarian cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 816 BP 195A EP 195A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900840 ER PT J AU Eichhorn, JH Young, RH Scully, RE AF Eichhorn, JH Young, RH Scully, RE TI Transitional cell carcinoma of the ovary: A study of 100 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 818 BP 195A EP 196A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900842 ER PT J AU Lee, KR Young, RH AF Lee, KR Young, RH TI Primary vs metastatic mucinous carcinomas of the ovary differential diagnostic findings in 44 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 844 BP 201A EP 201A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900867 ER PT J AU Logani, S Oliva, E Amin, MB Folpe, AL Cohen, C Young, RH AF Logani, S Oliva, E Amin, MB Folpe, AL Cohen, C Young, RH TI Immunoprofile of ovarian tumors of putative transitional cell (urothelial) differentiation using novel urothelial markers: Histogenetic and diagnostic implications SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 847 BP 202A EP 202A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900870 ER PT J AU Oliva, E Vu, Q Young, RH AF Oliva, E Vu, Q Young, RH TI CD10 expression in sex cord-stromal tumors (SCSTs) and steroid cell tumors (StCTS) of the ovary SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 856 BP 204A EP 204A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900879 ER PT J AU Oliva, E Dionigi, A Young, RH AF Oliva, E Dionigi, A Young, RH TI Mixed tumors of the Vagina: An immunohistochemical study of thirteen cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 857 BP 204A EP 205A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900880 ER PT J AU Pitman, NB Triratanachat, S Young, RH Oliva, E AF Pitman, NB Triratanachat, S Young, RH Oliva, E TI Hepatocyte paraffin 1 antibody cannot distinguish primary ovarian malignancies with hepatoid differentiation from metastatic hepatocellular caricnoma SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 864 BP 206A EP 206A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900887 ER PT J AU Gallagher, LA Faquin, WC Nielsen, GP Pilch, BZ AF Gallagher, LA Faquin, WC Nielsen, GP Pilch, BZ TI Sarcomas of the nasal cavity and paranasal sinuses: A study of 47 cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 918 BP 219A EP 219A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900941 ER PT J AU Jing, W Dong, Q Wu, CL Zukerberg, L AF Jing, W Dong, Q Wu, CL Zukerberg, L TI Cables, located on chromosome 18q11-12, is frequently lost in head and neck squamous cell carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 924 BP 220A EP 220A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900947 ER PT J AU Mino, M Pilch, BZ Faquin, WC AF Mino, M Pilch, BZ Faquin, WC TI Expression of c-kit in adenoid cystic carcinomas, salivary gland tumors, and basaloid neoplasms of the head and neck SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 930 BP 221A EP 222A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388900953 ER PT J AU Braaten, KM Betensky, R de Leval, L Okada, Y Hochberg, F Louis, D Harris, NL Batchelor, T AF Braaten, KM Betensky, R de Leval, L Okada, Y Hochberg, F Louis, D Harris, NL Batchelor, T TI Primary central nervous system lymphoma (PCNSL): Immunophenotypic and molecular genetic analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 975 BP 233A EP 233A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388900998 ER PT J AU Yuan, CM Vergilio, JA Harris, NL Bagg, A AF Yuan, CM Vergilio, JA Harris, NL Bagg, A TI Angioimmunoblastic T-cell lymphoma: A neoplasm of intrafollicular CD10+, BCL-6+, CD4+ memory T-cells? SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1125 BP 271A EP 271A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901148 ER PT J AU Andea, AA Cheng, J Lauwers, GY Klimstra, DS Adsay, VN AF Andea, AA Cheng, J Lauwers, GY Klimstra, DS Adsay, VN TI Pancreatic Intraepithelial neoplasia (PanIN) in pancreata involved by mucinous cystic neoplasms SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Wayne State Univ, Harper Hosp, Karmanos Canc Inst, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1172 BP 282A EP 282A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901195 ER PT J AU Deshpande, V Selig, MK Nielsen, GP Castillo, CF Lauwers, GY AF Deshpande, V Selig, MK Nielsen, GP Castillo, CF Lauwers, GY TI Ductulo-insular pancreatic endocrine neoplasms: Clinicopathological analysis of a unique subtype of pancreatic endocrine neoplasms SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1175 BP 283A EP 283A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901198 ER PT J AU Graeme-Cook, FM Balis, UJ Lauwers, GY Hoppin, AG Reid, AE Kaplan, LM AF Graeme-Cook, FM Balis, UJ Lauwers, GY Hoppin, AG Reid, AE Kaplan, LM TI Development and prospective validation of a pathological scoring system for NAFLD SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1184 BP 285A EP 285A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901207 ER PT J AU Hsu, HC Mountz, JD Grizzle, WE AF Hsu, HC Mountz, JD Grizzle, WE TI Glomerulosclerosis in 22-month-old BXD recombinant inbred mouse strain 22 (BXD-22) related to T cell kidney infiltration and senescence of CD4 T cells SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1269 BP 305A EP 305A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901292 ER PT J AU Beheshti, J Mino, M Mark, EJ AF Beheshti, J Mino, M Mark, EJ TI Chronic eosinophillic pneumonia, bronchiolitis obliterans organizing pneumonia overlap syndrome; Analysis of twelve cases SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1311 BP 315A EP 315A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901333 ER PT J AU Matsubara, O Imazeki, N Ozeki, Y Mark, EJ AF Matsubara, O Imazeki, N Ozeki, Y Mark, EJ TI Vascular endothelial growth factor and its receptors, Flt1 and KDR/Flk1, in diffuse alveolar damage and advanced pulmonary fibrosis SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1350 BP 324A EP 324A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901372 ER PT J AU Mino, M Zukerberg, LR Wu, CL Mark, EJ AF Mino, M Zukerberg, LR Wu, CL Mark, EJ TI Loss of expression of Cables gene (located on chromosome 18q11-12) in small cell and non-small cell lung carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1354 BP 325A EP 325A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901376 ER PT J AU Murer, B Chilosi, M Barbareschi, M Macri, E Loda, M Doglioni, C AF Murer, B Chilosi, M Barbareschi, M Macri, E Loda, M Doglioni, C TI Primary vs metastatic pulmonary adenocarcinoma: Cdx-2 is a specific and sensitive marker of tumors of colonic origin SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 UmbertoI Hosp, Dept Pathol, Mestre, Italy. Univ Verona, Dept Pathol, I-37100 Verona, Italy. Santa Chiara Hosp, Dept Pathol, Trento, Italy. San Martino Hosp, Dept Pathol, Belluno, Italy. Brigham & Womens Hosp, Dana Farber Canc Ctr, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1356 BP 325A EP 326A PG 2 WC Pathology SC Pathology GA 513QD UT WOS:000173388901378 ER PT J AU Castilla, EA Staugaitis, SM Esposito, JM Prayson, RA Warshawsky, I Hartke, M Shadrach, B Chernova, O Pettay, JD Vogelbaum, MA Barnett, GH Louis, DN Tubbs, RR AF Castilla, EA Staugaitis, SM Esposito, JM Prayson, RA Warshawsky, I Hartke, M Shadrach, B Chernova, O Pettay, JD Vogelbaum, MA Barnett, GH Louis, DN Tubbs, RR TI Technical validation of an interphase fluorescent in-situ hybridization (FISH) method to detect epidermal growth factor receptor (EGFR) amplification in gliomas SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1401 BP 336A EP 336A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901422 ER PT J AU Dadras, S Balis, UJ AF Dadras, S Balis, UJ TI Fabrication of a high-resolution realtime digital projection system for microscopy using standard components SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1403 BP 337A EP 337A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901424 ER PT J AU Faquin, WC Selig, MK McKee, GT Misdraji, J Pitman, MB Tambouret, R Eichhorn, JH Nielsen, GP AF Faquin, WC Selig, MK McKee, GT Misdraji, J Pitman, MB Tambouret, R Eichhorn, JH Nielsen, GP TI The utility of electron microscopy in the evaluation of cytologic specimens SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2002 VL 15 IS 1 MA 1450 BP 348A EP 348A PG 1 WC Pathology SC Pathology GA 513QD UT WOS:000173388901471 ER PT B AU Caycomb, RJ Forman, SA Raines, DE AF Caycomb, RJ Forman, SA Raines, DE BE Urban, BW Barann, M TI Inhibition of alpha(4)beta(2) rat neuronal nicotinic acetylcholine receptors by nonhalogenated alkane anesthetics and perhalogenated alkane nonimmobilizers SO MOLECULAR AND BASIC MECHANISMS OF ANESTHESIA LA English DT Proceedings Paper CT 6th International Conference on Molecular and Basic Mechanisms of Anesthesia CY JUN 28-30, 2001 CL BONN, GERMANY DE alkanes; neuronal nicotinic acetylcholine receptor; nonimmobilizer ID GENERAL-ANESTHESIA; MECHANISMS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Caycomb, RJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU PABST SCIENCE PUBLISHERS PI D-49525 LENGERICH PA EICHENGRUND 28, D-49525 LENGERICH, GERMANY BN 3-936142-41-6 PY 2002 BP 115 EP 119 PG 5 WC Anesthesiology; Biochemistry & Molecular Biology; Neurosciences SC Anesthesiology; Biochemistry & Molecular Biology; Neurosciences & Neurology GA BX07A UT WOS:000184178900017 ER PT J AU Mundy, CL Patenge, N Matthews, AGW Oettinger, MA AF Mundy, CL Patenge, N Matthews, AGW Oettinger, MA TI Assembly of the RAG1/RAG2 synaptic complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RECOMBINATION SIGNAL SEQUENCES; MOBILITY GROUP PROTEINS; V(D)J RECOMBINATION; MU-TRANSPOSASE; TRANSPOSITIONAL RECOMBINATION; RETROVIRAL INTEGRATION; RAG2 PROTEINS; CLEAVAGE; DNA; INITIATION AB Assembly of antigen receptor genes by V(D)J recombination requires the site-specific recognition of two distinct DNA elements differing in the length of the spacer DNA that separates two conserved recognition motifs. Under appropriate conditions, V(D)J cleavage by the purified RAG1/RAG2 recombinase is similarly restricted. Double-strand breakage occurs only when these proteins are bound to a pair of complementary signals in a synaptic complex. We examine here the binding of the RAG proteins to signal sequences and find that the full complement of proteins required for synapsis of two signals and coupled cleavage can assemble on a single signal. This complex, composed of a dimer of RAG2 and at least a trimer of RAG1, remains inactive for double-strand break formation until a second complementary signal is provided. Thus, binding of the second signal activates the complex, possibly by inducing a conformational change. If synaptic complexes are formed similarly in vivo, one signal of a recombining pair may be the preferred site for RAG1/RAG2 assembly. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM48026, R01 GM048026] NR 35 TC 77 Z9 80 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 1 BP 69 EP 77 DI 10.1128/MCB.22.1.69-77.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501LK UT WOS:000172686000007 PM 11739723 ER PT J AU Wurster, AL Withers, DJ Uchida, T White, MF Grusby, MJ AF Wurster, AL Withers, DJ Uchida, T White, MF Grusby, MJ TI Stat6 and IRS-2 cooperate in interleukin 4 (IL-4)-induced proliferation and differentiation but are dispensable for IL-4-dependent rescue from apoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RECEPTOR-ALPHA-CHAIN; IL-4 RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; INSULIN-RECEPTOR; B-CELLS; LYMPHOCYTE-PROLIFERATION; TYROSINE-PHOSPHATASE; TRANSCRIPTION FACTOR; AKT PROTOONCOGENE AB Stat6 and IRS-2 are two important signaling proteins that associate with the cytoplasmic tail of the interleukin 4 (IL-4) receptor. Data from numerous in vitro experiments have led to a model for IL-4 signal transduction in which the Stat6 signaling pathway is responsible for the IL-4 induced changes in gene expression and differentiation events, while the IRS-2 signaling pathway provides mitogenic and antiapoptotic signals. In order to determine the relative contributions of these signaling molecules in primary lymphocytes, we have examined IL-4 responses in T cells from mice deficient for either Stat6 or IRS-2 as well as from mice doubly deficient for both genes. Both IRS-2 and, especially, Stat6 are shown to be critically involved in IL-4-induced proliferation of T cells, presumably through the cooperative regulation of the Cdk inhibitor p27kip1. Like Stat6-deficient Th cells, IRS-2-deficient cells are also compromised in their ability to secrete Th2 cytokines, revealing a previously unrecognized role for IRS-2 in Th2 cell development. Although Stat6 and/or IRS-2 expression is required for IL-4-induced proliferative and differentiative responses, both signaling proteins are dispensable for the antiapoptotic effect of IL-4. However, treatment of lymphocytes with a protein tyrosine phosphatase inhibitor is able to block the antiapoptotic effect of IL-4 specifically in Stat6- or IRS-2-deficient cells and not in wild-type cells. Our results suggest that Stat6 and IRS-2 cooperate in promoting both IL-4-induced proliferative and differentiating responses, while an additional signaling mediator that depends on protein tyrosine phosphatase activity contributes to the antiapoptotic activities of IL-4 in primary T cells. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Grusby, MJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave, Boston, MA 02115 USA. RI Withers, Dominic/D-7671-2014 OI Withers, Dominic/0000-0002-8009-7521 FU NIAID NIH HHS [AI40171, R01 AI040171] NR 48 TC 63 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 1 BP 117 EP 126 DI 10.1128/MCB.22.1.117-126.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501LK UT WOS:000172686000011 PM 11739727 ER PT J AU Ko, L Cardona, GR Henrion-Caude, A Chin, WW AF Ko, L Cardona, GR Henrion-Caude, A Chin, WW TI Identification and characterization of a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RING FINGER PROTEIN; STEROID-HORMONE RECEPTORS; ANDROGEN-RECEPTOR; DEPENDENT TRANSACTIVATION; MOLECULAR-CLONING; GROWTH-FACTOR; CANCER CELLS; TRANSCRIPTION; BRCA1; GENE AB Gene activation mediated by nuclear receptors is regulated in a tissue-specific manner and requires interactions between nuclear receptors and their cofactors. Here, we identified and characterized a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors. GT198 was originally described as a genomic transcript that mapped to the human breast cancer susceptibility locus 17q12-q21 with unknown function. We show that GT198 exhibits a tissue-specific expression pattern in which its mRNA is elevated in testis, spleen, thymus, pituitary cells, and several cancer cell lines. GT198 is a 217-amino-acid nuclear protein that contains a leucine zipper required for its dimerization. In vitro binding and yeast two-hybrid assays indicated that GT198 interacted with nuclear receptors through their DNA-binding domains. GT198 potently stimulated transcription mediated by estrogen receptor alpha and beta, thyroid hormone receptor beta1, androgen receptor, glucocorticoid receptor, and progesterone receptor. However, the action of GT198 was distinguishable from that of the ligand-binding domain-interacting nuclear receptor coactivators, such as TRBP, CBP, and SRC-1, with respect to basal activation and hormone sensitivity. Furthermore, protein kinase A, protein kinase C, and mitogen-activated protein kinase can phosphorylate GT198 in vitro, and cotransfection of these kinases regulated the transcriptional activity of GT198. These data suggest that GT198 is a tissue-specific, kinase-regulated nuclear receptor coactivator that interacts with the DNA-binding domains of nuclear receptors. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Dept Gene Regulat Bone & Inflammat Res, Indianapolis, IN 46285 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Hop Enfants Armand Trousseau, INSERM, U515, Paris, France. RP Ko, L (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Dept Gene Regulat Bone & Inflammat Res, Bldg 98-C,Drop Code 0434, Indianapolis, IN 46285 USA. RI Henrion Caude, Alexandra/I-2778-2016 NR 58 TC 57 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 1 BP 357 EP 369 DI 10.1128/MCB.22.1.357-369.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501LK UT WOS:000172686000031 PM 11739747 ER PT J AU Chestukhin, A Litovchick, L Rudich, K DeCaprio, JA AF Chestukhin, A Litovchick, L Rudich, K DeCaprio, JA TI Nucleocytoplasmic shuttling of p130/RBL2: Novel regulatory mechanism SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LARGE-T-ANTIGEN; RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE REGULATION; E2F TRANSCRIPTION FACTORS; NUCLEAR EXPORT SIGNAL; PRB-RELATED PROTEINS; BINDING-SITE; IN-VIVO; FAMILY MEMBERS; GROWTH-REGULATION AB The retinoblastoma-related pocket proteins pRb, p107, and p130 are implicated in the control of cell proliferation, differentiation, and transformation. The function of pocket proteins is in part mediated by their ability to inhibit specific E2F transcription factors. The transcriptional activity of E2Fs is controlled by alteration of their nucleocytoplasmic localization during the cell cycle. p130 was observed to shuttle between the nucleus and cytoplasm in a heterokaryon fusion assay, suggesting the presence of nuclear and cytoplasmic localization signals. Two independent nuclear localization signals (NLS) that could target reporter proteins to the nucleus in transient transfection and microinjection experiments were identified in the C terminus of p130. In addition to the C-terminal NLS, the intact pocket domain of p130 itself was sufficient for nuclear translocation. Moreover, an additional functional NLS was mapped within the unique Loop region of p130. An N-terminal domain that conferred cytoplasmic localization was identified. Removal of the entire N terminus did not affect the ability of p130 to interact with E2F and to induce growth arrest. A model suggesting that the activity of pRb family members can be regulated by intracellular trafficking of the proteins is proposed. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Mayer 457,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA063113, F32 CA084752, 1 F32 CA84752-01, R01-CA63113] NR 92 TC 46 Z9 47 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 453 EP 468 DI 10.1128/MCB.22.2.453-468.2002 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900007 PM 11756542 ER PT J AU Liang, GG Chan, MF Tomigahara, Y Tsai, YC Gonzales, FA Li, E Laird, PW Jones, PA AF Liang, GG Chan, MF Tomigahara, Y Tsai, YC Gonzales, FA Li, E Laird, PW Jones, PA TI Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CPG ISLAND; CELLS; REPLICATION; TISSUES; GENE; HYPERMETHYLATION; OVEREXPRESSION; EPIGENETICS; GENOME; TUMORS AB We used mouse embryonic stem (ES) cells with systematic gene knockouts for DNA methyltransferases to delineate the roles of DNA methyltransferase 1 (Dnmt1) and Dumt3a and -3b in maintaining methylation patterns in the mouse genome. Dnmt1 alone was able to maintain methylation of most CpG-poor regions analyzed. In contrast, both Dnmt1 and Dnmt3a and/or Dumt3b were required for methylation of a select class of sequences which included abundant murine LINE-1 promoters. We used a novel hemimethylation assay to show that even in wild-type cells these sequences contain high levels of hemimethylated DNA, suggestive of poor maintenance methylation. We showed that Dnmt3a and/or -3b could restore methylation of these sequences to pretreatment levels following transient exposure of cells to 5-aza-CdR, whereas Dnmt1 by itself could not. We conclude that ongoing de novo methylation by Dnmt3a and/or Dnmt3b compensates for inefficient maintenance methylation by Dnmt1 of these endogenous repetitive sequences. Our results reveal a previously unrecognized degree of cooperativity among mammalian DNA methyltransferases in ES cells. C1 Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90089 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Jones, PA (reprint author), Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, 1441 Eastlake Ave,MS 8302L, Los Angeles, CA 90089 USA. RI Laird, Peter/G-8683-2012; OI Liang, Gangning/0000-0001-8664-922X FU NCI NIH HHS [R01 CA075090] NR 31 TC 320 Z9 333 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 480 EP 491 DI 10.1128/MCB.22.2.480-491.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900009 PM 11756544 ER PT J AU Bardeesy, N Morgan, J Sinha, M Signoretti, S Srivastava, S Loda, M Merlino, G DePinho, RA AF Bardeesy, N Morgan, J Sinha, M Signoretti, S Srivastava, S Loda, M Merlino, G DePinho, RA TI Obligate roles for p16(Ink4a) and p19(Arf)-p53 in the suppression of murine pancreatic neoplasia SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; ARF TUMOR-SUPPRESSOR; TRANSGENIC MICE; FACTOR-ALPHA; P53-DEPENDENT APOPTOSIS; INK4A LOCUS; PLASMACYTOMA SUSCEPTIBILITY; CELL-PROLIFERATION; CYSTIC TUMORS; TGF-ALPHA AB Epithelial tumors of the pancreas exhibit a wide spectrum of histologies with varying propensities for metastasis and tissue invasion. The histogenic relationship among these tumor types is not well established; moreover, the specific role of genetic lesions in the progression of these malignancies is largely undefined. Transgenic mice with ectopic expression of transforming growth factor alpha (TGF-alpha) in the pancreatic acinar cells develop tubular metaplasia, a potential premalignant lesion of the pancreatic ductal epithelium. To evaluate the cooperative interactions between TGF-ci and signature mutations in pancreatic tumor genesis and progression, TGF alpha transgenic mice were crossed onto Ink4a/Arf and/or p53 mutant backgrounds. These compound mutant mice developed a novel pancreatic neoplasm, serous cystadenoma (SCA), presenting as large epithelial tumors bearing conspicuous gross and histological resemblances to their human counterpart. TGF alpha animals heterozygous for both the Ink4a/Arf and the p53 mutation showed a dramatically increased incidence of SCA, indicating synergistic interaction of these alleles. Inactivation of p16(Ink4a) by loss of heterozygosity, intragenic mutation, or promoter hypermethylation was a common feature in these SCAs, and correspondingly, none of the tumors expressed wild-type p16(Ink4a). kll tumors sustained loss of p53 or Arf, generally in a mutually exclusive fashion. The tumor incidence data and molecular profiles establish a pathogenic role for the dual inactivation of p16(Ink4a) and p19(Arf)-p53 in the development of SCA in mice, demonstrating that p16(Ink4a) is a murine tumor suppressor. This genetically defined model provides insights into the molecular pathogenesis of SCA and serves as a platform for dissection of cell-specific programs of epithelial tumor suppression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NCI, Mol Biol Lab, Mol Genet Sect, Bethesda, MD 20892 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St M413, Boston, MA 02115 USA. FU NCI NIH HHS [5R01-CA81755, 5K08CA72744-05] NR 61 TC 48 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2002 VL 22 IS 2 BP 635 EP 643 DI 10.1128/MCB.22.2.635-643.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506QU UT WOS:000172983900023 PM 11756558 ER PT J AU Zhang, XA Kazarov, AR Yang, XW Bontrager, AL Stipp, CS Hemler, ME AF Zhang, XA Kazarov, AR Yang, XW Bontrager, AL Stipp, CS Hemler, ME TI Function of the tetraspanin CD151-alpha 6 beta 1 integrin complex during cellular morphogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ALPHA-3-BETA-1 INTEGRIN; TRANSMEMBRANE-4 SUPERFAMILY; BRANCHING MORPHOGENESIS; EXTRACELLULAR-MATRIX; CYTOPLASMIC DOMAIN; ENDOTHELIAL-CELLS; TM4SF PROTEINS; CD151; MIGRATION; ASSOCIATION AB Upon plating on basement membrane Matrigel, NIH3T3 cells formed an anastomosing network of cord-like structures, inhibitable by anti-alpha6beta1 integrin antibodies. For NIH3T3 cells transfected with human CD151 protein, the formation of a cord-like network was also inhibitable by anti-CD151 antibodies. Furthermore, CD151 and alpha6beta1 were physically associated within NIH3T3 cells. On removal of the short 8-amino acid C-terminal CD151 tail (by deletion or exchange), exogenous CD151 exerted a dominant negative effect, as it almost completely suppressed alpha6beta1-dependent cell network formation and NIH3T3 cell spreading on laminin-1 (an alpha6beta1 ligand). Importantly, mutant CD151 retained alpha6beta1 association and did not alter alpha6beta1-mediated cell adhesion to Matrigel. In conclusion, the CD151-alpha6beta1 integrin complex acts as a functional unit that markedly influences cellular morphogenesis, with the CD151 tail being of particular importance in determining the "outside-in" functions of alpha6beta1-integrin that follow ligand engagement. Also, antibodies to alpha6beta1 and CD151 inhibited formation of endothelial cell cord-like networks, thus pointing to possible relevance of CD151-alpha6beta1 complexes during angiogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 42368, R01 CA042368, CA 86712] NR 45 TC 93 Z9 111 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2002 VL 13 IS 1 BP 1 EP 11 DI 10.1091/mbc.01-10-0481 PG 11 WC Cell Biology SC Cell Biology GA 513VY UT WOS:000173402000001 PM 11809818 ER PT J AU Tan, MW Ausubel, FM AF Tan, MW Ausubel, FM TI Alternative models in microbial pathogens SO MOLECULAR CELLULAR MICROBIOLOGY SE METHODS IN MICROBIOLOGY LA English DT Review ID AERUGINOSA VIRULENCE FACTORS; PSEUDOMONAS-AERUGINOSA; CAENORHABDITIS-ELEGANS; LEGIONELLA-PNEUMOPHILA; DICTYOSTELIUM-DISCOIDEUM; MOLECULAR MECHANISMS; GENETIC-ANALYSIS; HOST; DROSOPHILA; SYSTEM C1 Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Tan, MW (reprint author), Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. NR 41 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0580-9517 J9 METHOD MICROBIOL PY 2002 VL 31 BP 461 EP 475 DI 10.1016/S0580-9517(02)31026-2 PG 15 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BT76G UT WOS:000173973000025 ER PT J AU Tawfeek, HAW Qian, F Abou-Samra, AB AF Tawfeek, HAW Qian, F Abou-Samra, AB TI Phosphorylation of the receptor for PTH and PTHrP is required for internalization and regulates receptor signaling SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; HORMONE-RELATED PEPTIDE; AGONIST-DEPENDENT PHOSPHORYLATION; CULTURED BONE-CELLS; PARATHYROID-HORMONE; DOWN-REGULATION; KIDNEY-CELLS; KINASE-C; RAPID DESENSITIZATION; OSTEOSARCOMA CELLS AB We have previously shown that agonist-dependent phosphorylation of the PTH/PTHrP receptor occurs on its carboxyl-terminal tail. Using site-directed mutagenesis, phosphopeptide mapping, and direct sequencing of cyanogen bromide-cleaved fragments of phosphoreceptors, we report here that PTH-dependent phosphorylation occurs on the serine residues at positions 491, 492, 493, 495, 501, and 504, and that the serine residue at position 489 is required for phosphorylation. When these seven sites were mutated to alanine residues, the mutant receptor was no longer phosphorylated after PTH stimulation. The phosphorylation-deficient receptor, stably expressed in LLCPK-1 cells, was impaired in PTH-dependent internalization and showed an increased sensitivity to PTH stimulation; the EC50 for PTH-stimulated cAMP accumulation was decreased by 7-fold. Furthermore, PTH stimulation of the phosphorylation-deficient PTH/PTHrP receptor caused a sustained elevation in intracellular cAMP levels. These data indicate that agonist-dependent phosphorylation of the PTH/PTHrP receptor plays an important role in receptor function. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-10087-01, DK-11794-26] NR 49 TC 49 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2002 VL 16 IS 1 BP 1 EP 13 DI 10.1210/me.16.1.1 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 507HJ UT WOS:000173020700001 PM 11773434 ER PT J AU Padera, TP Stoll, BR So, PTC Jain, RK AF Padera, Timothy P. Stoll, Brian R. So, Peter T. C. Jain, Rakesh K. TI Conventional and High-Speed Intravital Multiphoton Laser Scanning Microscopy of Microvasculature, Lymphatics, and Leukocyte-Endothelial Interactions SO MOLECULAR IMAGING LA English DT Article DE Fluorescence microscopy; multiphoton laser scanning microscopy; tumor pathophysiology; angiogenesis; lymphatics; leukocyte-endothelial interaction ID INTERSTITIAL FLUID PRESSURE; GREEN FLUORESCENT PROTEIN; HUMAN TUMOR XENOGRAFT; IN-VIVO MEASUREMENT; DENDRITIC SPINES; HYPERTENSION; ANGIOGENESIS; CAPILLARIES; CELLS; METASTASIS AB The ability to determine various functions of genes in an intact host will be an important advance in the postgenomic era. Intravital imaging of gene regulation and the physiological effect of the gene products can play a powerful role in this pursuit. Intravital epifluorescence microscopy has provided powerful insight into gene expression, tissue pH, tissue pO(2), angiogenesis, blood vessel permeability, leukocyte-endothelial (L-E) interaction, molecular diffusion, convection and binding, and barriers to the delivery of molecular and cellular medicine. Multiphoton laser scanning microscopy (MPLSM) has recently been applied in vivo to overcome three drawbacks associated with traditional epifluorescence microscopy: (i) limited depth of imaging due to scattering of excitation and emission light; (ii) projection of three-dimensional structures onto a two-dimensional plane; and (iii) phototoxicity. Here, we use MPLSM for the first time to obtain high-resolution images of deep tissue lymphatic vessels and show an increased accuracy in quantifying lymphatic size. We also demonstrate the use of MPLSM to perform accurate calculations of the volume density of angiogenic vessels and discuss how this technique may be used to assess the potential of antiangiogenic treatments. Finally, high-speed MPLSM, applied for the first time in vivo, is used to compare L-E interactions in normal tissue and a rhabdomyosarcoma tumor. Our work demonstrates the potential of MPLSM to noninvasively monitor physiology and pathophysiology both at the tissue and cellular level. Future applications will include the use of MPLSM in combination with fluorescent reporters to give novel insight into the regulation and function of genes. C1 [Padera, Timothy P.; Stoll, Brian R.; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Padera, Timothy P.; Jain, Rakesh K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Padera, Timothy P.; Stoll, Brian R.; So, Peter T. C.; Jain, Rakesh K.] MIT, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. OI Padera, Timothy/0000-0002-3453-9384 FU NCI Outstanding Investigator Grant [R35-CA 56591]; Bioengineering Research Partnership Grant [R24 CA85140]; National Foundation for Cancer Research Project [ACS RPG9805801CCE, NIH R29GM56486-01]; Whitaker Health Sciences Fund Fellowship FX The authors thank Y. Chen, C. Dong, K. King, D. Fukumura, T. Gohongi, A. Kadambi, and J. Kahn for their technical expertise. They also thank E. Brown, K. Burton, E. di Tomaso, and L. Munn for their insightful criticism of the manuscript. This work was supported by an NCI Outstanding Investigator Grant (R35-CA 56591), a Bioengineering Research Partnership Grant (R24 CA85140), and National Foundation for Cancer Research Project Grant to RKJ, and grants ACS RPG9805801CCE and NIH R29GM56486-01 to PTCS. TPP is a recipient of the Whitaker Health Sciences Fund Fellowship. NR 39 TC 54 Z9 54 U1 0 U2 4 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 EI 1536-0121 J9 MOL IMAGING JI Mol. Imaging PD JAN PY 2002 VL 1 IS 1 BP 9 EP 15 DI 10.1162/153535002753395662 PG 7 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA V38CE UT WOS:000209320700001 PM 12920856 ER EF