FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Scully, R AF Scully, R TI Role of BRCA gene dysfunction in breast and ovarian cancer predisposition SO BREAST CANCER RESEARCH LA English DT Review DE breast cancer; DNA repair; homologous recombination; ovarian cancer; tumor suppressor genes ID ATOMIC-BOMB SURVIVORS; EMBRYONIC CELLULAR PROLIFERATION; WILD-TYPE CHROMOSOME; DNA-DAMAGE RESPONSE; SUSCEPTIBILITY GENE; TRANSCRIPTIONAL ACTIVATION; BRCA1-DEFICIENT MICE; TARGETED DISRUPTION; GERMLINE MUTATIONS; EPITHELIAL-CELLS AB Tumor suppressor genes that perform apparently generic cellular functions nonetheless cause tissue-specific syndromes in the human population when they are mutated in the germline. The two major hereditary breast/ovarian cancer predisposition genes, BRCA1 and BRCA2, appear to participate in a common pathway that is involved in the control of homologous recombination and in the maintenance of genomic integrity. How might such functions translate into the specific suppression of cancers of the breast and ovarian epithelia? Recent advances in the study of BRCA1 and BRCA2, discussed herein, have provided new opportunities to address this question. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Scully, R (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [K01 CA079576] NR 84 TC 43 Z9 43 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 5 BP 324 EP 330 DI 10.1186/bcr76 PG 7 WC Oncology SC Oncology GA 408QJ UT WOS:000167338900002 PM 11250724 ER PT J AU Haiman, CA Hankinson, SE Spiegelman, D Colditz, GA Willett, WC Speizer, FE Brown, M Hunter, DJ AF Haiman, CA Hankinson, SE Spiegelman, D Colditz, GA Willett, WC Speizer, FE Brown, M Hunter, DJ TI Polymorphic repeat in AIB1 does not alter breast cancer risk SO BREAST CANCER RESEARCH LA English DT Review DE AIB1 polymorphism; breast cancer; genetic susceptibility; molecular epidemiology ID PLASMA-HORMONE LEVELS; POSTMENOPAUSAL WOMEN; OVARIAN-CANCER; RECEPTOR GENE; CAG REPEAT; AGE 40; ESTROGEN; LENGTH; CYP17 AB We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Haiman, CA (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [R01 CA065725, CA40356, CA49449, CA57374, CA65725, R01 CA040356, R01 CA049449, U01 CA049449] NR 23 TC 20 Z9 20 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 5 BP 378 EP 385 PG 8 WC Oncology SC Oncology GA 408QJ UT WOS:000167338900008 PM 11056690 ER PT J AU Peiro, G Bornstein, BA Connolly, JL Gelman, R Hetelekidis, S Nixon, AJ Recht, A Silver, B Harris, JR Schnitt, SJ AF Peiro, G Bornstein, BA Connolly, JL Gelman, R Hetelekidis, S Nixon, AJ Recht, A Silver, B Harris, JR Schnitt, SJ TI The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; lobular; ductal; conservative surgery; radiation therapy ID CONSERVATION THERAPY; PATHOLOGIC FINDINGS; CANCER; MULTICENTRICITY; VARIANT; TUMORS AB Background: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal-lobular histology. Methods: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and greater than or equal to 6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular feature these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. Results: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and l3% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. Conclusions: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Connolly, JL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, E Campus,330 Brookline Ave, Boston, MA 02215 USA. NR 24 TC 60 Z9 60 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2000 VL 59 IS 1 BP 49 EP 54 DI 10.1023/A:1006384407690 PG 6 WC Oncology SC Oncology GA 288DK UT WOS:000085546400005 PM 10752679 ER PT J AU Del Governatore, M Hamblin, MR Piccinini, EE Ugolini, G Hasan, T AF Del Governatore, M Hamblin, MR Piccinini, EE Ugolini, G Hasan, T TI Targeted photodestruction of human colon cancer cells using charged 17.1A chlorin(e6) immunoconjugates SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; photoimmunotherapy; photosensitizer; polylysine; laser ID INTRAPERITONEAL PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODY 17-1A; LIVER METASTASIS MODEL; COLORECTAL-CANCER; OVARIAN-CANCER; HEPATIC METASTASES; CARCINOMA; PHOTOIMMUNOTHERAPY; BIODISTRIBUTION; ENDOCYTOSIS AB The goal of this study was to develop a strategy for the selective destruction of colorectal cancer cells. Towards this end, photoimmunoconjugates were prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorin, (c(e6)). Polylysine linkers bearing several c(e6) molecules were covalently attached in a site-specific manner to partially reduced IgG molecules, which allowed photoimmunoconjugates to bear either cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies with native antibody. The overall charge on the photoimmunoconjugate was an important determinant of PS delivery. The cationic photoimmunoconjugate delivered 4 times more c(e6) to the cells than the anionic photoimmunoconjugate, and both 17.1A conjugates showed, in comparison to non-specific rabbit IgG conjugates, selectivity for antigen-positive target cells. Illumination with only 3 J cm(-2) of 666 nm light reduced the number of colony forming cells by more than 90% for the cationic 17.1A conjugate and by 73% for the anionic 17.1A conjugate after incubation with 1 mu M c(e6) equivalent of the respective conjugates. By contrast. 1 mu M free c(e6) gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required. (C) 2000 Cancer Research Campaign. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Osped Policlin S Orsola, Dept Chirurg 3, I-40100 Bologna, Italy. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU NIAMS NIH HHS [R01 AR 40352] NR 48 TC 51 Z9 54 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 2000 VL 82 IS 1 BP 56 EP 64 PG 9 WC Oncology SC Oncology GA 267CA UT WOS:000084335900012 PM 10638967 ER PT J AU Tonini, M De Giorgio, R De Ponti, F Sternini, C Spelta, V Dionigi, P Barbara, G Stanghellini, V Corinaldesi, R AF Tonini, M De Giorgio, R De Ponti, F Sternini, C Spelta, V Dionigi, P Barbara, G Stanghellini, V Corinaldesi, R TI Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE human gastric fundus; VIP- and NOS-immunohistochemistry; NADPH-diaphorase histochemistry; NANC inhibitory nerves; electrically-induced relaxations; mechanically-induced relaxations ID NONADRENERGIC NONCHOLINERGIC RELAXATION; PIG SMALL-INTESTINE; GUINEA-PIG; CIRCULAR MUSCLE; INHIBITORY TRANSMISSION; TAENIA-COLI; L-ARGININE; CHOLINERGIC TRANSMISSION; NADPH-DIAPHORASE; MYENTERIC PLEXUS AB 1 The morphological pattern and motor correlates of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) innervation in the human isolated gastric fundus was explored. 2 By using the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-diaphorase and specific rabbit polyclonal NO-synthase (NOS) and VIP antisera, NOS- and VIP-containing varicose nerve fibres were identified throughout the muscle layer or wrapping ganglion cell bodies of the myenteric plexus. NOS-immunoreactive (IR) neural cell bodies were more: abundant than those positive for VIP-IR. The majority of myenteric neurones containing VIP coexpressed NADPH-diaphorase. 3 Electrical stimulation of fundus strips caused frequency-dependent NANC relaxations. N-G-nitro-L-arginine (L-NOARG: 300 mu M) enhanced the basal tone, abolished relaxations to 0.3-3 Hz (5 s) and those to 1 Hz (5 min), markedly reduced (similar to 50%) those elicited by 10-50 Hz, and unmasked or potentiated excitatory cholinergic responses at frequencies greater than or equal to 1 Hz. L-NOARG-resistant relaxations were virtually abolished by VIP (100 nM) desensitization at all frequencies. 4 Relaxations to graded low mechanical distension (less than or equal to 1 g) were insensitive to tetrodotoxin (TTX: 1 mu M) and L-NOARG (300 mu M), while those to higher distensions (2 g) were slightly inhibited by both agents to the same extent (similar to 25%). 5 In the human gastric fundus, NOS- and VIP immunoreactivities are colocalized in the majority of myenteric neurones; NO and VIP mediate electrically evoked relaxations: low frequency stimulation, irrespective of the duration, caused NO release only, whereas shortlasting stimulation at high frequencies induced NO and VIP release. Relaxations to graded mechanical distension were mostly due to passive viscoelastic properties, with a slight NO-mediated neurogenic component at 2 g distension. The difference between NO and VIP release suggests that in human fundus accommodation is initiated by NO. C1 Univ Pavia, Dept Internal Med & Therapeut, Div Expt & Clin Pharmacol, I-27100 Pavia, Italy. Univ Bologna, Dept Internal Med & Gastroenterol, I-40138 Bologna, Italy. Univ Bologna, Inst Pharmacol, I-40126 Bologna, Italy. Univ Calif Los Angeles, Dept Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Pavia, Policlin San Matteo, Dept Surg, IRCCS, I-27100 Pavia, Italy. RP Tonini, M (reprint author), Univ Pavia, Dept Internal Med & Therapeut, Div Expt & Clin Pharmacol, Piazza Botta 10, I-27100 Pavia, Italy. OI DIONIGI, PAOLO/0000-0002-0768-9395; De Giorgio, Roberto/0000-0003-0867-5873; De Ponti, Fabrizio/0000-0002-0367-9595 FU NIDDK NIH HHS [R01 DK054155, P30 DK041301, R56 DK054155] NR 56 TC 55 Z9 57 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2000 VL 129 IS 1 BP 12 EP 20 DI 10.1038/sj.bjp.0702977 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 276UB UT WOS:000084894800002 PM 10694197 ER PT J AU Shah, J Prasad, S Patkar, D Kothari, S AF Shah, J Prasad, S Patkar, D Kothari, S TI Intrathoracic extension of aggressive fibromatoses SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID DESMOID TUMORS AB Intrathoracic extension or primary thoracic origin of fibromatoses is distinctly uncommon. We describe the imaging features in three patients with this condition. C1 Dr Balabhai Nanavati Hosp, Dept Radiol, Bombay, Maharashtra, India. King Edward Mem Hosp, Dept Radiol, Bombay, Maharashtra, India. RP Prasad, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Radiol, Ellison 234,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 5 Z9 6 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD JAN PY 2000 VL 73 IS 865 BP 66 EP 68 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 283ED UT WOS:000085262400012 PM 10721322 ER PT J AU Rao, A Avni, O AF Rao, A Avni, O TI Molecular aspects of T-cell differentiation SO BRITISH MEDICAL BULLETIN LA English DT Article ID CYTOKINE GENE-EXPRESSION; TRANSCRIPTION FACTOR; C-MAF; LINEAGE COMMITMENT; HELPER DEVELOPMENT; TH1 CELLS; INTERLEUKIN-4; GATA-3; STAT6; IL-4 AB Differentiated T helper 1 (Th 1) and T helper 2 (Th2) T-cells show striking differences in their patterns of cytokine expression. This process is initiated by stimulation with antigen and the cytokines IL-12 and IL-4, respectively, and requires antigen-induced transcription factors such as NFAT and cytokine-induced transcription factors such as STAT4, induced by IL-12, and STAT6, induced by IL-4. This results in induction and maintained expression of subset-specific transcription factors including T-bet in Th1 cells and GATA3 in Th2 cells, which are involved in ensuring the commitment of T-cells to Th1 or Th2 lineages. Here we review the signalling pathways and transcription factors that mediate T-cell differentiation, and describe the epigenetic changes in chromatin structure, locus accessibility and DNA methylation that are known to accompany this process. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI44432] NR 50 TC 76 Z9 84 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0007-1420 J9 BRIT MED BULL JI Br. Med. Bull. PY 2000 VL 56 IS 4 BP 969 EP 984 DI 10.1258/0007142001903634 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 434NK UT WOS:000168822400009 PM 11359632 ER PT J AU Arjmandi, BH Birnbaum, RS Juma, S Barengolts, E Kukreja, SC AF Arjmandi, BH Birnbaum, RS Juma, S Barengolts, E Kukreja, SC TI The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE estrogens; isoflavones; osteoporosis; ovariectomy; rats ID OVARIECTOMIZED RAT MODEL; BREAST-CANCER CELLS; POSTMENOPAUSAL WOMEN; IN-VITRO; OSTEOPOROSIS; PROGESTERONE; DENSITY; MASS AB Ipriflavone (IP), a synthetic isoflavone has been reported to prevent bone loss in both postmenopausal women and ovariectomized (ovx) rats. The purpose of this study was to compare and contrast some of the bone protective mechanisms of TP to those of 17 beta-estradiol (E-2) in ovarian hormone deficiency. Forty-eight 95-day-old Sprague-Dawley rats were assigned to four groups: sham, ovx, ovx+IP, and ovx+E-2. The doses of IP and E-2 were 100 mg and 10 mu g/kg body weight per day, respectively. Rats were fed a diet that contained 0.4% calcium, 0.3% phosphorus, and 0.195 nmol vitamin D-3/g diet. After sacrifice, left femoral bone densities were measured and bone histomorphometry was performed on the proximal tibial metaphysis. Ipriflavone as well as E-2 treatment completely prevented the ovx-induced femoral bone density loss. How ever, in contrast to E-2, IP did not lower the ovx-induced rise in serum alkaline phosphatase (ALP) activity or insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 concentrations. On histomorphometry analysis, the ovariectomy-induced increase (P < 0.09) in bone formation rate (BFR) was significantly (P < 0.05) suppressed by E-2 treatment, whereas this higher BFR was maintained in IF-treated animals. These findings indicate that IP is effective in preventing the ovx-associated bone loss. The bone protective mechanisms of IF in ovarian hormone deficiency may be different from those of E-2 and may involve increased rates of bone formation. C1 Oklahoma State Univ, Dept Nutr Sci, Stillwater, OK 74078 USA. VA Puget Sound Healthcare Syst, Amer Lake Div, Tacoma, WA 98493 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. W Side Vet Adm Med Ctr, Dept Med, Chicago, IL 60612 USA. RP Arjmandi, BH (reprint author), Oklahoma State Univ, Dept Nutr Sci, Stillwater, OK 74078 USA. NR 32 TC 31 Z9 38 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 2000 VL 66 IS 1 BP 61 EP 65 DI 10.1007/s002230050012 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 266HF UT WOS:000084294000012 PM 10602847 ER PT J AU Major, PP Lipton, A Berenson, J Hortobagyi, G AF Major, PP Lipton, A Berenson, J Hortobagyi, G TI Oral bisphosphonates - A review of clinical use in patients with bone metastases SO CANCER LA English DT Review DE bisphosphonates; metastases; bone; trials ID BREAST-CANCER; MULTIPLE-MYELOMA; DOUBLE-BLIND; DICHLOROMETHYLENE-DIPHOSPHONATE; PAGETS-DISEASE; CONTROLLED TRIAL; PROSTATE-CANCER; PHARMACOLOGICAL PROPERTIES; THERAPEUTIC EFFICACY; SKELETAL METASTASES AB BACKGROUND. This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients. METHODS. Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology. RESULTS. Etidronate, alendronate, pamidronate, risedronate, and tiludronate currently are available in the U.S. as either intravenous and/or oral formulations. Although newer bisphosphonates are more potent, oral bioavailability remains < 1%. Oral etidronate has been found to be ineffective in patients with multiple myeloma and prostate carcinoma bone metastases, Pamidronate has been found to be effective in reducing skeletal morbidity associated with bone metastases in both multiple myeloma and breast carcinoma patients when given intravenously, but is ineffective orally in multiple myeloma patients. To the authors' knowledge, there are no double blind, placebo-controlled trials of oral pamidronate in patients with breast carcinoma and bone metastases. Several clinical trials with clodronate, a bisphosphonate that is not available in the U.S., have shown mixed results in patients with myeloma and breast carcinoma bone metastases. To the authors' knowledge, there are no published trials evaluating oral alendronate, tiludronate, or risedronate in patients with metastases to bone. CONCLUSIONS. Oral bisphosphonates do not appear to be as effective as intravenous administration in reducing skeletal complications in patients with metastases to bone lesions. Low oral bioavailability is the most likely reason for this difference. Oral dosing should not be substituted for intravenous administration in the treatment of malignant osteolysis. Cancer 2000;88:6-14. (C) 2000 American Cancer Society. C1 Hamilton Reg Canc Ctr, Hamilton, ON L8V 5C2, Canada. Penn State Univ, Milton S Hershey Med Ctr, Div Hematol & Oncol, Hershey, PA 17033 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Hematol & Oncol, Los Angeles, CA USA. Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. RP Major, PP (reprint author), Hamilton Reg Canc Ctr, 699 Concess St, Hamilton, ON L8V 5C2, Canada. NR 76 TC 78 Z9 79 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2000 VL 88 IS 1 BP 6 EP 14 DI 10.1002/(SICI)1097-0142(20000101)88:1<6::AID-CNCR3>3.0.CO;2-D PG 9 WC Oncology SC Oncology GA 270YW UT WOS:000084565600003 PM 10618600 ER PT J AU Ryan, DP Lynch, TJ Grossbard, ML Seiden, MV Fuchs, CS Grenon, N Baccala, P Berg, D Finkelstein, D Mayer, RJ Clark, JW AF Ryan, DP Lynch, TJ Grossbard, ML Seiden, MV Fuchs, CS Grenon, N Baccala, P Berg, D Finkelstein, D Mayer, RJ Clark, JW TI A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors SO CANCER LA English DT Article DE clinical trials; Phase I; gemcitabine; docetaxel; taxotere; pancreatic neoplasms ID CELL LUNG-CANCER; DOSE-ESCALATION; 2',2'-DIFLUORODEOXYCYTIDINE; PHARMACOLOGY; SCHEDULE; TRIAL AB BACKGROUND. A Phase I study was initiated to determine the maximum tolerated dose of weekly gemcitabine combined with monthly, fixed-dose docetaxel. METHODS. Patients with metastatic solid tumors were treated with docetaxel, 60 mg/m(2), on Day 1 every 28 days. Gemcitabine was administered on Days 1, 8, and 15 and underwent dose adjustment in cohorts of 3-6 patients. At the maximum tolerated dose, 11 additional patients were enrolled. RESULTS. Twenty-six patients treated at this dose level experienced dose-limiting toxicities (DLTs) requiring the reduction of gemcitabine to 600 mg/m(2) per dose and the administration of ciprofloxacin, 500 mg orally twice daily, on Days 8-18. At the second dose level the first 3 patients experienced no DLTs and the dose of gemcitabine was increased to 700 mg/m(2). Two of the 6 patients treated at the 700 mg/m(2) dose level experienced DLTs. Eleven additional patients were enrolled at the recommended Phase II dose of gemcitabine (600 mg/m(2)). At this dose level, Grade 3/4 (according the National Cancer Institute's common toxicity criteria) neutropenia and thrombocytopenia occurred in 12.5% and 2.1% of cycles, respectively. Grade 3 and 4 nonhematologic toxicities were uncommon. Three of seven evaluable patients with pancreatic carcinoma had evidence of significant antineoplastic activity (three partial responses). In addition, two complete responses (one patient with gastric carcinoma and one patient with ovarian carcinoma) and one partial response (patient with hepatocellular carcinoma) were noted in patients with other solid tumors. CONCLUSIONS. The regimen comprised of docetaxel, 60 mg/m(2), on Day 1 and gemcitabine, 600 mg/m(2), on Days 1, 8, and 15 with ciprofloxacin on Days 8-18 every 28 days is safe, well tolerated, and active. Cancer 2000;88:180-5. (C) 2000 American Cancer Society. C1 Dana Farber Partners CancerCare, Gastrointestinal Canc Clin, Boston, MA USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 26 TC 20 Z9 21 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 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2000 VL 88 IS 1 BP 180 EP 185 DI 10.1002/(SICI)1097-0142(20000101)88:1<180::AID-CNCR25>3.0.CO;2-Q PG 6 WC Oncology SC Oncology GA 270YW UT WOS:000084565600025 PM 10618622 ER PT J AU Kroning, R Lichtenstein, AK Nagami, GT AF Kroning, R Lichtenstein, AK Nagami, GT TI Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE cisplatin; nephrotoxicity; amino acids; cytotoxicity; uptake; transport ID RATS; NEPHROTOXICITY AB Purpose: Nephrotoxicity is one of the major dose-limiting side-effects of cisplatin (DDP). The disproportionate accumulation of cisplatin in kidney tissue may play an important role; however, therapeutic measures to prevent this prime cause of nephrotoxicity are not available. Because certain amino acids (AAs) have been reported to modulate DDP nephrotoxicity in vivo, we explored the potential of all 20 protein AAs, N-acetylcysteine and DL-homocysteine to reduce DDP cytotoxicity and uptake in S-1, S-3 (proximal tubule), and DCT (distal convoluted tubule) cell lines. Methods: Immortalized but non-transformed renal tubule epithelial cell lines, derived from specific portions of the nephron of an SV40 transgenic mouse, were grown to confluency and exposed to various concentrations of DDP for 1 h with or without concurrent exposure to AAs in an otherwise AA-free Krebs-Ringer buffer (I(RB). After 1 h, cell layers were washed and replenished with medium for cytotoxicity assays, or processed immediately for the determination of DDP accumulation. Cytotoxicity was assessed 48 h later by an MTT assay, and DDP uptake after Ih was determined by atomic absorption spectroscopy. Results: In an initial screening where the cells were concurrently incubated with 0.25 mM DDP and 1 mM AA for I h in KRB, only cysteine (Cys), me-thionine (Met), N-acetylcysteine and DL-homocysteine reduced DDP toxicity. This effect was enhanced at 5 mM AA and most potent for Cys, which reduced DDP cytotoxicity by 79 +/- 3% in S3 cells, by 78 +/- 12.2% in DCT cells, and by 19 +/- 3.6% in S-1 cells (P < 0.05). Reduction of cytotoxicity was less for Met, DL-homocysteine, and N-acetylcysteine, in decreasing order. All four AAs also inhibited DDP uptake in renal cells, with Cys as the strongest inhibitor. Inhibition of DDP accumulation by 1 mM Cys after 1 h was 39% in S-3 cells, 38% in DCT cells, and 28% in S-1 cells. Again, reduction of uptake was less for the three other AAs. Pre-complexing of DDP with Cys for 16 h increased its uptake by 8- to 30-fold compared with native DDP, but markedly inhibited its toxicity. Thus, pre-complexing of DDP with Cys could not explain the reduced uptake of DDP, but could partly account for the reduction in cytotoxicity. Double-reciprocal Lineweaver-Burk plots of DDP concentration-versus-uptake rates at a constant concentration of Cys suggested that: Cys competitively inhibited DDP uptake in S-1 and DCT cells, and in a more complex fashion in S-3 cells. Conclusions: We conclude that Cys, Met, N-acetylcysteine, and DL-homocysteine differentially inhibit DDP toxicity and uptake in cultured S-1, S-3, and DCT cells, and that the inhibition of uptake, as well as the complexation of DDP with Cys within the cell, may prevent toxicity. The structural element R-CH(NH2)-[CH2](1-2)-S-R, which is common to all four molecules, may play a crucial role in blocking the transport of DDP, and could have future clinical applications. C1 Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Hematol Oncol Sect, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Nephrol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Kroning, R (reprint author), Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Bldg 304,Room E2-218,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 19 TC 54 Z9 60 U1 1 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2000 VL 45 IS 1 BP 43 EP 49 DI 10.1007/PL00006741 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 269FJ UT WOS:000084465800007 PM 10647500 ER PT J AU Li, FP Kantor, A AF Li, FP Kantor, A TI Progress report from the editor 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 6 Z9 6 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 2000 VL 9 IS 1 BP 1 EP 1 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279QJ UT WOS:000085056400001 ER PT J AU Emmons, KM Kalkbrenner, KJ Klar, N Light, T Schneider, KA Garber, JE AF Emmons, KM Kalkbrenner, KJ Klar, N Light, T Schneider, KA Garber, JE TI Behavioral risk factors among women presenting for genetic testing SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; PHYSICAL-ACTIVITY; POPULATION; SMOKING; PREVENTION; PROJECT; BRCA1; TRIAL AB Considerable research attention has been given to the impact of genetic testing on psychological outcomes. Participation in genetic testing also may impact on health behaviors that increase the risk of cancer and other chronic diseases. The purpose of this study is to describe behavioral cancer risk factors of women who requested genetic testing for breast and ovarian cancer susceptibility (BRCA1, BRCA2), Before participation in a genetic testing program, 119 women completed a series of questionnaires designed to assess their health behaviors, perception of risk, and depressive symptomatology. Eight percent of participants were current smokers, 27% did not engage in at least moderate exercise, 46% did not regularly protect themselves from the sun, 39% did not consume at least five servings of fruits and vegetables per day, and 9% drank at least one alcoholic beverage per day. Poisson regression analysis revealed that age was the only predictor of behavioral risk profiles, with older women having fewer cancer risk behaviors. These patients who presented for genetic testing generally had better health behaviors than the general population. However, given their possible high-risk status, these patients should consider further improving their preventable cancer risk factors and, in particular, their diet, sun protection, and physical activity levels, Inclusion of behavioral risk factor counseling in the context of the genetic testing process may be an important opportunity to reach this at-risk population. C1 Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Div Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NHGRI NIH HHS [2R01HG01244] NR 41 TC 23 Z9 23 U1 1 U2 1 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 2000 VL 9 IS 1 BP 89 EP 94 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279QJ UT WOS:000085056400010 PM 10667468 ER PT J AU Paulino, AC Latona, C AF Paulino, AC Latona, C TI Unresectable adenocarcinoma of the pancreas: Patterns of failure and treatment results SO CANCER INVESTIGATION LA English DT Article ID THERAPY; RADIATION; GEMCITABINE; CARCINOMA; CANCER AB We retrospectively reviewed the outcome of 36 consecutive patients seen in our department with nonmetastatic unresectable adenocarcinoma of the pancreas. There were 28 men and 8 women with a mean age of 63.7 years (range, 43-78 years). Radiation therapy (RT) was given to all patients. 5-Fluorouracil (5-FU) was given as a bolus (500-1000 mg/m(2)/day) was given to 3 patients. The median survival for all patients was 10 months. Overall survival for all patients at 1 and 3 years was 47.2% and 19.1%, respectively. The pancreas, peritoneum, liver, and lungs were components of failure in 66.7%, 33.3%, 14.8%, and 14.8%, respectively. Local control was a major problem in patients treated for unreseceptable pancreatic cancer. The results of this study confirm the dismal prognosis of these patients. C1 Loyola Univ, Cardinal Bernardin Canc Ctr, Dept Radiotherapy, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Radiotherapy, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Paulino, AC (reprint author), Univ Iowa Hosp & Clin, 200 Hawkins Dr,Room W 189Z GH, Iowa City, IA 52242 USA. NR 16 TC 11 Z9 14 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 2000 VL 18 IS 4 BP 309 EP 313 DI 10.3109/07357900009012173 PG 5 WC Oncology SC Oncology GA 305PK UT WOS:000086549300003 PM 10808366 ER PT J AU Jeyapalan, SA Batchelor, TT AF Jeyapalan, SA Batchelor, TT TI Diagnostic evaluation of neurologic metastases SO CANCER INVESTIGATION LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; LEPTOMENINGEAL METASTASES; CARCINOMATOUS MENINGITIS; INTRACRANIAL METASTASES; PROGNOSTIC-SIGNIFICANCE; CEREBROSPINAL-FLUID; CEREBRAL METASTASES; CLINICAL-FEATURES; BREAST-CARCINOMA; BRAIN METASTASIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr, Boston, MA 02114 USA. Columbia Presbyterian Med Ctr, Neurol Inst, New York, NY 10032 USA. RP Batchelor, TT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr, Cox 315, Boston, MA 02114 USA. NR 40 TC 11 Z9 12 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 2000 VL 18 IS 4 BP 381 EP 394 DI 10.3109/07357900009012181 PG 14 WC Oncology SC Oncology GA 305PK UT WOS:000086549300011 PM 10808374 ER PT J AU Kopans, DB AF Kopans, DB TI Should postoperative mammograms be obtained routinely following the surgical excision of a breast cancer? SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Editorial Material ID MARGIN C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 2000 VL 6 IS 1 BP 11 EP 12 PG 2 WC Oncology SC Oncology GA 281NA UT WOS:000085166100002 PM 10696732 ER PT J AU Shapiro, GI Edwards, CD Rollins, BJ AF Shapiro, GI Edwards, CD Rollins, BJ TI The physiology of p16(INK4A)-mediated G1 proliferative arrest SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 9th Conference on DNA Topoisomerases in Therapy CY OCT, 1998 CL NEW YORK, NEW YORK DE p16; INK4A; ARF; cell cycle; cancer ID TUMOR-SUPPRESSOR GENE; P53-DEPENDENT G(1) ARREST; CELL-CYCLE INHIBITION; RETINOBLASTOMA-PROTEIN; PANCREATIC-CANCER; DEPENDENT KINASES; LUNG CANCERS; DNA-DAMAGE; RB; INACTIVATION AB Phosphorylation of the product of the retinoblastoma susceptibility gene (Rb) physiologically inactivates its growth-suppressive properties. Rb phosphorylation is mediated by cyclin-dependent kinases (CDKs), whose activity is enhanced by cyclins and inhibited by CDK inhibitors. p16(INK4A) is a member of a family of inhibitors specific for CDK4 and CDK6. p(16INK4A) is deleted and inactivated in a wide variety of human malignancies, including familial melanomas and pancreatic carcinoma syndromes, indicating that it is an authentic human tumor suppressor. Although one mechanism for its tumor suppression may be prevention of Rb phosphorylation, thereby causing G1 arrest, many normal cell types express p16(INK4A), and are still able to traverse the cell cycle. In a search for other mechanisms, we have found that p16(INK4A) is required for p53-independent G1 arrest in response to DNA-damaging agents, including topoisomerase I and II inhibitors. Thus, like other tumor suppressors, p16(INK4A) plays an essential role in a DNA-damage checkpoint that leads to cell cycle arrest. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 44 TC 48 Z9 54 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2000 VL 33 IS 2 BP 189 EP 197 DI 10.1385/CBB:33:2:189 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 397MY UT WOS:000166700500007 PM 11325039 ER PT J AU Gregory, PG Connolly, CK Toner, M Sullivan, SJ AF Gregory, PG Connolly, CK Toner, M Sullivan, SJ TI In vitro characterization of porcine hepatocyte function SO CELL TRANSPLANTATION LA English DT Article DE porcine hepatocytes; collagen; matrix ID ADULT-RAT HEPATOCYTES; BIOARTIFICIAL LIVER; SANDWICH CONFIGURATION; COLLAGEN-SANDWICH; IN-VITRO; SUPPORT; CULTURE; MATRIX; CELLS; EXPERIENCE AB The clinical consequences of acute liver failure are associated with high mortality. Intensive medical intervention is required to treat the symptoms of liver failure, including coagulopathy, metabolic instability, and encephalopathy. Providing temporary liver support with an extracorporeal liver assist device could stabilize the patient until a donor liver became available or the patient's own liver was able to recover. The use of human hepatocytes as the biologic component of the assist device is precluded by the scarcity of available tissue and the limited proliferative potential of adult hepatocytes in vitro. Consequently, porcine hepatocytes are being evaluated as a cell source for liver assist devices. Maintaining differentiated function in isolated hepatocytes, however, remains a challenge in the development of this technology and is complicated by the fact that the key therapeutic functions for short-term survival have not been well defined. Several approaches have been effective in prolonging rodent hepatocyte function in vitro, including manipulation of extracellular matrix. Here, we have investigated porcine hepatocyte function in vitro with a specific emphasis on the response to exogenous collagen matrix. In control cultures, albumin secretion increased during the first 7-10 days of culture to an average of 50 +/- 17 mu g/day/10 degrees cells and then decreased over the next 2 weeks. The pattern of urea synthesis was slightly different in that it was highest in the first 1-3 days postisolation (140 +/- 19 mu g/day/10(6) cells) and then decreased by about 50% to a plateau level that was stable during the next 3-4 weeks of culture. Cytochrome P450-mediated activities were the most labile with time in culture and were undetectable after the first week in the absence of pharmacological inducers. In contrast to results reported for rat cells. porcine hepatocytes exhibited differentiated function in the absence of any modification of the culture dish surface and function was not increased or prolonged in the presence of exogenous collagen. C1 Organogenesis Inc, Canton, MA 02021 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Sullivan, SJ (reprint author), Organogenesis Inc, 150 Dan Rd, Canton, MA 02021 USA. NR 23 TC 33 Z9 33 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JAN-FEB PY 2000 VL 9 IS 1 BP 1 EP 10 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 304KL UT WOS:000086482600001 PM 10784060 ER PT J AU Trivedi, N Steil, GM Colton, CK Bonner-Weir, S Weir, GC AF Trivedi, N Steil, GM Colton, CK Bonner-Weir, S Weir, GC TI Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor SO CELL TRANSPLANTATION LA English DT Article DE transplantation; immunobarrier; Lispro; angiogenesis; encapsulation ID BLOOD-FLOW; DIABETIC MICE; IN-VITRO; ANGIOGENESIS; ISLETS; NEOVASCULARIZATION; XENOGRAFTS; CELLS; MICROARCHITECTURE; EXPRESSION AB Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System(TM)) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 mu l) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day thigh dose: n = 7 for 10 days into devices implanted SC in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 mu l of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices. C1 Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-50657, DK-36836, DK-35449] NR 41 TC 41 Z9 42 U1 0 U2 5 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JAN-FEB PY 2000 VL 9 IS 1 BP 115 EP 124 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 304KL UT WOS:000086482600014 PM 10784073 ER PT S AU Duke-Cohan, JS Tang, W Schlossman, SF AF Duke-Cohan, JS Tang, W Schlossman, SF BE Langner, J Ansorge, S TI Attraction: A cub-family protease involved in T cell-monocyte/macrophage interactions SO CELLULAR PEPTIDASES IN IMMUNE FUNCTIONS AND DISEASES 2 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Conference on Cellular Peptidases in Immune Functions and Diseases II CY SEP 12-14, 1999 CL MAGDEBURG, GERMANY SP Deutsch Forschungsgemeinsch, Minist Kultur Landes Sachsen Anhalt, Otto VonGuericke Univ Magdeburg, Martin Luther Univ Halle Wittenberg, Becton Dickinson GmbH Heidelberg, Biochrom Beteilig GmbH & Co Centeon Liederbach, Karl Roth GmbH & Co KG, NEN Life Sci Prod GmbH, R & D Syst, Roche Diagnost GmbH DE attractin; CD26; dipeptidyl peptidase IV; mahogany; T cells; chemokines; cytokines ID DIPEPTIDYL PEPTIDASE-IV; HUMAN SERUM; EXTRACELLULAR-MATRIX; DPPT-L; CD26; ACTIVATION; LYMPHOCYTES; MAHOGANY; DOMAIN; RANTES AB Attractin is a rapidly upregulated membrane-associated molecule on activated T cells. It is a member of the CUB family of extracellular guidance and development proteins, sharing with them a protease activity similar to that of Dipeptidyl peptidase TV (DPPIV/CD26). Most remarkably, and in sharp contrast to CD26, it is released from the T cell and is presumed to be a major source of a soluble serum-circulating attractin. Genomic sequencing reveals that the soluble form is not a proteolytic product of the membrane form, but is in fact the result of alternative splicing. Recent results prove that the loss of murine membrane attractin results in the mahogany mutation with severe repercussions upon skin pigmentation and control of energy metabolism. In each of these latter instances, there is a strong likelihood that attractin is moderating the interaction of cytokines with their respective receptors. We propose that attractin is performing a similar function in the immune system through capture and proteolytic modification of the N-terminals of several cytokines and chemokines. This regulatory activity allows cells to interact and form immunoregulatory clusters and subsequently aids in downregulating chemokine/cytokine activity once a response has been initiated. These two properties are likely to be affected by the balance of membrane-expressed to soluble attractin. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA USA. RP Duke-Cohan, JS (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA USA. OI Duke-Cohan, Jonathan/0000-0002-9478-9609 NR 41 TC 36 Z9 38 U1 1 U2 2 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46383-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2000 VL 477 BP 173 EP 185 PG 13 WC Cell Biology; Immunology; Medicine, Research & Experimental SC Cell Biology; Immunology; Research & Experimental Medicine GA BQ32C UT WOS:000087923000020 PM 10849745 ER PT J AU Halgren, E Raij, T Marinkovic, K Jousmaki, V Hari, R AF Halgren, E Raij, T Marinkovic, K Jousmaki, V Hari, R TI Cognitive response profile of the human fusiform face area as determined by MEG SO CEREBRAL CORTEX LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; POSITRON EMISSION TOMOGRAPHY; DEPTH-RECORDED POTENTIALS; MEDIAL TEMPORAL-LOBE; HUMAN VISUAL-CORTEX; SPATIOTEMPORAL STAGES; CEREBRAL-LESIONS; MACAQUE MONKEY; HUMAN BRAIN; PROSOPAGNOSIA AB Activation in or near the fusiform gyrus was estimated to faces and control stimuli. Activation peaked at 165 ms and was strongest to digitized photographs of human faces, regardless of whether they were presented in color or grayscale, suggesting that face- and color-specific areas are functionally separate. Schematic sketches evoked similar to 30% less activation than did face photographs. Scrambling the locations of facial features reduced the response by similar to 25% in either hemisphere, suggesting that configurational versus analytic processing is not lateralized at this latency. Animal faces evoked similar to 50% less activity, and common objects, animal bodies or sensory controls evoked similar to 80% less activity than human faces. The (small) responses evoked by meaningless control images were stronger when they included surfaces and shading, suggesting that the fusiform gyrus may use these features in constructing its face-specific response. Putative fusiform activation was not significantly related to stimulus repetition, gender or emotional expression. A midline occipital source significantly distinguished between faces and control images as early as 110 ms, but was more sensitive to sensory qualities. This source significantly distinguished happy and sad faces from those with neutral expressions. We conclude that the fusiform gyrus may selectively encode faces at 165 ms, transforming sensory input for further processing. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. INSERM E9926, Marseille, France. Helsinki Univ Technol, Low Temp Lab, Brain Res Unit, Helsinki, Finland. RP Halgren, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Jousmaki, Veikko/H-6008-2012; Hari, Riitta/J-1880-2012 OI Jousmaki, Veikko/0000-0003-1963-5834; Hari, Riitta/0000-0002-3142-2703 FU NINDS NIH HHS [R01 NS018741, NS18741] NR 77 TC 330 Z9 336 U1 0 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2000 VL 10 IS 1 BP 69 EP 81 DI 10.1093/cercor/10.1.69 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 269ZM UT WOS:000084510700008 PM 10639397 ER PT J AU Bennett, CL Schwartz, DN Parada, JP Sipler, AM Chmiel, JS DeHovitz, JA Goetz, MB Weinstein, RA AF Bennett, CL Schwartz, DN Parada, JP Sipler, AM Chmiel, JS DeHovitz, JA Goetz, MB Weinstein, RA TI Delays in tuberculosis isolation and suspicion among persons hospitalized with HIV-related pneumonia SO CHEST LA English DT Article; Proceedings Paper CT 2nd Annual Midwestern Health Services Research Meeting CY MAR, 1998 CL CHICAGO, IL DE nosocomial outbreak of tuberculosis; patterns of care; quality of care ID RESISTANT MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; HIGH-RISK; OUTBREAK; EPIDEMIOLOGY; TRANSMISSION; INFECTION AB Background: Despite awareness of HIV-related tuberculosis (TB), nosocomial outbreaks of multidrug-resistant TB among HIV-infected individuals occur. Objective: To investigate delays in TB isolation and suspicion among HIV-infected inpatients discharged with TB or Pneumocystis carinii pneumonia (PCP), common HIV-related pneumonias. Design: Cohort study during 1995 to 1997, Setting: For PCP, 1,227 persons who received care at 44 New York City, Chicago, and Los Angeles hospitals, For TB, 89 patients who reteived care at five Chicago hospitals, Measurements: Two-day rates of TB isolation/suspicion, Results: For HIV-related PCP, Los Angeles hospitals had the lon est 2-day rates of isolation/suspicion of TB (24.3%/26.6% vs 65.5%/66.4% for New York City and 62.8%/58.3% for Chicago, respectively; p < 0.001 for overall comparison by chi(2) test for each outcome measure). within cities, hospital isolation/suspicion rates varied from < 35 to > 70% (p < 0.001 for interhospital comparisons in each city). The Chicago hospital with a nosocomial outbreak of multidrug-resistant TB from 1991 to 1995 isolated 60% of HIV-infected individuals who were discharged with a diagnosis of HIV-related TB and 52% discharged with HIV-related PCP, rates that were among the lowest of all Chicago hospitals in both data sets. Conclusion: Low 2-day races of TB isolation/suspicion among HIV-related PCP patients were frequent. One Chicago hospital with low 2-day rates of TB isolation/suspicion,among persons with. HIV-related PCP also had low 2-day rates of isolation/suspicion among confirmed TB patients. That hospital experienced a nosocomial multidrug-resistant TB outbreak. Educational efforts on the benefits of early TB suspicion/isolation among HIV-infected pneumonia patients are needed. C1 Chicago VA Hlth Care Syst, Lakeside Div, Chicago, IL USA. Chicago VA Hlth Care Syst, Westside Div, Chicago, IL USA. Loyola Univ, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Evanston, IL USA. Northwestern Univ, Sch Med, Dept Internal Med, Evanston, IL USA. Cook Cty Hosp, Chicago, IL 60612 USA. W Los Angeles VA, Los Angeles, CA USA. SUNY Brooklyn, Allied Program, Brooklyn, NY USA. RP Bennett, CL (reprint author), Lakeside VA, 400 E Ontariao St,Suite 205, Chicago, IL 60611 USA. EM cbenne@nwu.edu RI Bennett, Charles/C-2050-2008; OI Goetz, Matthew/0000-0003-4542-992X FU NIDA NIH HHS [5RO1DA10628-02] NR 21 TC 17 Z9 18 U1 0 U2 0 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 2000 VL 117 IS 1 BP 110 EP 116 DI 10.1378/chest.117.1.110 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 274PN UT WOS:000084774400022 PM 10631207 ER PT J AU Hoo, GWS Hakimian, N Santiago, SM AF Hoo, GWS Hakimian, N Santiago, SM TI Hypercapnic respiratory failure in COPD patients - Response to therapy SO CHEST LA English DT Article DE COPD; hypercapnia; mechanical ventilation; respiratory failure ID OBSTRUCTIVE PULMONARY-DISEASE; POSITIVE-PRESSURE VENTILATION; ACUTE EXACERBATIONS; MECHANICAL VENTILATION; LUNG-DISEASE; SURVIVAL; REAPPRAISAL; MANAGEMENT; PROGNOSIS; MORTALITY AB Introduction: The clinical course of patients with acute exacerbations of underlying COPD presenting with hypercapnic respirator failure was reviewed. : of 138 episodes of hyercapnic respiratory failure Methods: This was a retrospective review (Paco(2) greater than or equal to 50 mm Hg and pH less than or equal to 7,35), Patients were admitted to the West Los Angeles VAMC Medical Intensive Care Unit between 1990 and 1994, Results: Of the 138 hypercapnic episodes, 74 (54%) required intubation, Comparison was made with the 64 cases in which patients responded to medical therapy, Patients requiring intubation had a greater severity of illness, with a higher APACHE II (Acute Physiology and Chronic Health Evaluation II) score (18 +/- 5 vs 16 +/- 4; p < 0,01), higher W'BC, higher serum BUN, and greater acidosis (pH, 7.26 +/- 0.07 vs 7.28 +/- 0.06; p = 0,08), Those with the most severe acidosis (pH < 7,20) had the highest intubation rate (70%) and shortest time to intubation (2 +/- 2 h), and they required the longest period of time to respond to medical therapy (69 +/- 60 h). With an initial pH of < 7.25, there was a consistently higher intubation rate. Conversely, those with an initial pH of 7.31 to 7.35 were less likely to be intubated (45%), had a longer time to intubation (13 +/- 18 h), and had a more rapid response to medical therapy (30 +/- 18 h). Of those patients requiring intubation, most (78%) were intubated within 8 h of presentation, and the vast majority (93%) by 24 h. Of those patients responding to medical therapy, half(52%) recovered within 24 h and the vast majority (92%) recovered within 72 h, Conclusions: This study provides a better characterization of the response to therapy of COPD patients with hypercapnic respiratory failure. This should be useful in limiting or omitting medical therapy in high-risk patients, thereby avoiding delays in intubation as well as providing a framework for continued therapy in those more likely to improve. C1 W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Hoo, GWS (reprint author), W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Sect, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 25 TC 28 Z9 30 U1 0 U2 0 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 2000 VL 117 IS 1 BP 169 EP 177 DI 10.1378/chest.117.1.169 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 274PN UT WOS:000084774400031 PM 10631216 ER PT J AU Ferreyra, G Goddon, S Fujino, Y Kacmarek, RM AF Ferreyra, G Goddon, S Fujino, Y Kacmarek, RM TI The relationship between gas delivery patterns and the lower inflection point of the pressure-volume curve during partial liquid ventilation SO CHEST LA English DT Article DE compliance; gas delivery pattern; lower inflection point; partial liquid ventilation; resistance ID RESPIRATORY-DISTRESS SYNDROME; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; LUNG INJURY; PERFLUOROCARBON; EXCHANGE; FAILURE AB Study question: To determine whether a positive end-expiratory pressure (PEEP) level equivalent to the lower inflection point (LIP) could be identified by evaluation of the airway pressure, flow (V), and volume vs time waveforms during partial liquid ventilation (PLV). Design: Prospective application of PEEP during PLV: in a healthy animal model. Setting: University hospital animal laboratory. Participants: Five healthy sheep weighing 30 kg each. Interventions: The sequential application of 0 to 20 cm H2O PEEP in 2.5-cm H2O steps during PLV with both pressure and volume ventilation, Measurements: Analysis of the pressure, volume, and V waveforms as PEEP is sequentially increased. Results: At 0 cm H2O PEEP, VT was markedly reduced compared with PEEP VT at greater than or equal to 7.5 cm H2O (p < 0.05) in pressure control ventilation (PCV), and peak inspiratory pressure minus PEEP was markedly increased compared with PEEP at greater than or equal to 5.0 cm H2O (p < 0.05) in volume control ventilation, At 10 cm H2O PEEP, all waveforms began to stabilize, and no significant differences in any variable assessed were measured at > 12.5 cm H2O PEEP, Conclusions: The application of PEEP during PLV markedly alters airway waveforms. Low PEEP decreases VT in PCV and increases airway pressure in VCV, The PEEP level equal to the LIP during PLV can be grossly estimated from airway waveforms. PEEP at greater than or equal to 10 cm H2O is needed to normalize gas delivery to functional residual capacity in the uninjured lung that is partially filled with perfluorocarbon. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Resp Care, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Resp Care, Ellison 401, Boston, MA 02114 USA. NR 19 TC 9 Z9 9 U1 0 U2 0 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 2000 VL 117 IS 1 BP 191 EP 198 DI 10.1378/chest.117.1.191 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 274PN UT WOS:000084774400034 PM 10631219 ER PT J AU Caruana-Montaldo, B Gleeson, K Zwillich, CW AF Caruana-Montaldo, B Gleeson, K Zwillich, CW TI The control of breathing in clinical practice SO CHEST LA English DT Review DE carotid body; chemoreceptors; control of ventilation; pulmonary receptors ID OBSTRUCTIVE PULMONARY-DISEASE; SLEEP-APNEA SYNDROME; POSITIVE AIRWAY PRESSURE; CONGESTIVE-HEART-FAILURE; NOCTURNAL NASAL VENTILATION; INSPIRATORY MUSCLE FATIGUE; CHEYNE-STOKES RESPIRATION; LUNG IRRITANT RECEPTORS; CAROTID-BODY RESECTION; EYE-MOVEMENT SLEEP AB The control of breathing results from a complex interaction involving the respiratory centers, which feed signals to a central control mechanism that, in turn, provides output to the effector muscles, In this review, we describe the individual elements of this system, and what is known about their function in man. We outline clinically relevant aspects of the integration of human ventilatory control system, and describe altered function in response to special circumstances, disorders, and medications. We emphasize the clinical relevance of this topic by employing case presentations of active patients from our practice. C1 Penn State Geisinger Hlth Syst, Pulm Allergy & Crit Care Sect, Hershey, PA 17036 USA. St Vincents Hosp, St Verona, Malta. Denver VA Med Ctr, Denver, CO USA. RP Gleeson, K (reprint author), Penn State Geisinger Hlth Syst, Pulm Allergy & Crit Care Sect, 500 Univ Dr, Hershey, PA 17036 USA. NR 126 TC 54 Z9 56 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2000 VL 117 IS 1 BP 205 EP 225 DI 10.1378/chest.117.1.205 PG 29 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 274PN UT WOS:000084774400036 PM 10631221 ER PT J AU Heckers, S Konradi, C AF Heckers, S Konradi, C TI Anatomic and molecular principles of psychopharmacology - A primer for psychiatrists SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GLUTAMATE RECEPTORS; DOPAMINE-RECEPTORS; ALZHEIMERS-DISEASE; GABA(B) RECEPTORS; BRAIN-FUNCTION; SEROTONIN; MEMORY; DRUGS; PHARMACOLOGY AB Modulation of neuronal activity by neurotransmitters is a fundamental mechanism of brain function. Perturbations of neurotransmission in disease states can be targeted therapeutically through the administration of psychotropic drugs. This article reviews three mechanisms that explain the therapeutic and adverse effects of psychotropic agents. First, the location and projection of neurons determines their behavioral affiliation. Second, neurotransmitter receptors lead to changes in the electrical properties (i.e., membrane potential) or the biochemical properties (i.e., protein function) of neurons. Third, intracellular signaling pathways lead to immediate or delayed, longer-term effects on neuronal function. These three principles and their clinical implications are reviewed for the glutamatergic, GABAergic, cholinergic, serotonergic, noradrenergic, and dopaminergic systems. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp E, CNY-9132,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 42 TC 1 Z9 1 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 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2000 VL 9 IS 1 BP 1 EP + PG 23 WC Psychiatry SC Psychiatry GA 281AU UT WOS:000085136600003 PM 10674188 ER PT J AU Spencer, T Biederman, J Wilens, T AF Spencer, T Biederman, J Wilens, T TI Pharmacotherapy of attention deficit hyperactivity disorder SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID AGGRESSIVE NONCOMPLIANT FEATURES; STIMULANT MEDICATION; TOURETTES-SYNDROME; CONDUCT DISORDER; ADHD CHILDREN; COMBINING METHYLPHENIDATE; PHARMACOLOGICAL TREATMENT; PSYCHIATRIC COMORBIDITY; HOSPITALIZED CHILDREN; THREO-METHYLPHENIDATE AB The pharmacotherapy of attention-deficit hyperactivity disorder has evolved parallel to the understanding of the disorder. Over the decades, treatment concerns have expanded from a primarily behavioral focus to include prosocial interactions and cognitive and executive functions. Although the bulk of the vast literature documents the short-term efficacy of stimulants, recent studies have begun to examine long-term effects. In addition to the stimulants, there is a considerable amount of literature indicating an important role for other catecholaminergic agents and promising new findings in cholinergic agents. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. NR 178 TC 67 Z9 68 U1 3 U2 4 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 2000 VL 9 IS 1 BP 77 EP + PG 22 WC Psychiatry SC Psychiatry GA 281AU UT WOS:000085136600006 PM 10674191 ER PT J AU Ramirez-Montagut, T Andrews, DM Ihara, A Pervaiz, S Pandolfi, F Van den Elsen, PJ Waitkus, R Boyle, LA Hishii, M Kurnick, JT AF Ramirez-Montagut, T Andrews, DM Ihara, A Pervaiz, S Pandolfi, F Van den Elsen, PJ Waitkus, R Boyle, LA Hishii, M Kurnick, JT TI Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): effect of differential expression of Melan-A/MART-1 SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE tumour-infiltrating lymphocytes; melanoma; T cell receptor; cytotoxic T lymphocytes; PCR-SSCP; Melan-A; MART-1 ID CELL-RECEPTOR; IN-VIVO; METASTATIC MELANOMA; POSSIBLE MECHANISMS; IMMUNE-RESPONSE; GENE USAGE; PCR-SSCP; GP100; LINES; CLONES AB We have isolated, from an individual patient with metastatic melanoma, a series of eight TIL clones capable of lysing autologous melanoma cell targets. Six of the eight clones expressed TCRAV2S1 and lysed targets expressing HLA-A2 and the Melan-A/MART-1 peptide: AAGIGILTV. Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis showed that the Melan-A/MART-1-specific clones were predominant in the bulk culture prior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell-lytic clones. Using the anti-Melan-A/MART-1 MoAb (A-103), we noted that Melan-A/MART-1 expression on three melanoma cell lines varied considerably during in vitro culture, in the absence of T cell immunoselection, relative to cell density. Tumour cells which spontaneously decreased Melan-A/MART-1 expression were less susceptible to specific TIL lysis. Melan-A/MART-1 expression and susceptibility to lysis increased in cells cultured at lower density. These data suggest that modulation of tumour antigen may account for tumour progression in the presence of tumour cell-lytic T lymphocytes. The observations suggest a possible explanation for the common finding of Melan-A/MART-1-specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention. C1 Massachusetts Gen Hosp, Pathol Res Lab, Boston, MA 02114 USA. Catholic Univ, Chair Semeiot Med, Rome, Italy. Leiden Univ, Med Ctr, Dept Immunohaematol & Blood Bank, Leiden, Netherlands. RP Kurnick, JT (reprint author), Massachusetts Gen Hosp, Immunopathol Lab, COX 5, Boston, MA 02114 USA. RI Pervaiz, Shazib/C-4188-2015 FU NHLBI NIH HHS [HL-43793] NR 46 TC 13 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2000 VL 119 IS 1 BP 11 EP 18 DI 10.1046/j.1365-2249.2000.01089.x PG 8 WC Immunology SC Immunology GA 271ZG UT WOS:000084625100003 PM 10606959 ER PT J AU Schutzer, WE Watts, VJ Chapman, J Cumbay, MG Neve, KA Neve, RL Mader, SL AF Schutzer, WE Watts, VJ Chapman, J Cumbay, MG Neve, KA Neve, RL Mader, SL TI Viral-mediated gene delivery of constitutively activated G alpha s alters vasoreactivity SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE cAMP; gene transfer; G-protein; Herpes simplex virus; vascular tone; vasorelaxation ID VASCULAR SMOOTH-MUSCLE; RAT AORTA; PROTEIN; AGE; OVEREXPRESSION; EXPRESSION; DESENSITIZATION; MECHANISMS; RELAXATION; RESPONSES AB 1. Decline in beta-adrenoceptor (beta-AR)-mediated function occurs with increasing age, as well as in multiple disease conditions. The mechanisms responsible for this decline include alterations in beta-AR itself, beta-AR coupling proteins, such as G-proteins, or other beta-AR-linked proteins, such as G-protein receptor kinases and/or phosphatases. 2. The present study examines the physiological effects of n vitro transfer of constitutively activated G alpha s (G alpha s-U227L) to both cultured vascular smooth muscle cells (VSMC) and whole aortic tissue of 6-month-old (adult) animals via a replication-deficient Herpes simplex virus (HSV) vector. These studies were conducted to provide a model for future examination of the role of G alpha s in the age-related decline in beta-AR-mediated vasorelaxation. 3. Gene transfer was confirmed by western blotting for specific proteins. Aortic tissue infected with HSV-G alpha s-Q227L had reduced phenylephrine-induced contraction and enhanced isoproterenol-stimulated vasorelaxation, Infection of cultured VSMC with HSV-G alpha s-Q227L increased both basal- and isoproterenol-stimulated cAMP accumulation, whereas forskolin-stimulated cAMP production was unchanged. 4. These results implicate G alpha s as a target for further investigation in age-related changes in vascular reactivity and support the use of viral-mediated gene transfer as an effective tool to study adrenergic signal transduction and physiology in vascular tissue. C1 Portland VA Med Ctr, Res Serv, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Harvard Univ, Sch Med, Dept Genet, Belmont, MA 02178 USA. RP Mader, SL (reprint author), Portland VA Med Ctr, Res Serv, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. RI Watts, Val/A-4633-2012; OI Neve, Kim/0000-0003-0109-7345 FU NIDA NIH HHS [T32 DA07262] NR 24 TC 14 Z9 14 U1 1 U2 1 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD JAN-FEB PY 2000 VL 27 IS 1-2 BP 9 EP 13 DI 10.1046/j.1440-1681.2000.03210.x PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 284WA UT WOS:000085354800002 PM 10696522 ER PT J AU Alexanian, R Anderson, K Barlogie, B Berenson, J Dalton, WS Kyle, RA AF Alexanian, R Anderson, K Barlogie, B Berenson, J Dalton, WS Kyle, RA TI Sydney E. Salmon SO CLINICAL CANCER RESEARCH LA English DT Biographical-Item C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Barlogie, B (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2000 VL 6 IS 1 BP 316 EP 316 PG 1 WC Oncology SC Oncology GA 276YP UT WOS:000084906200040 ER PT J AU Molano, ID Wloch, MK Alexander, AA Watanabe, H Gilkeson, GS AF Molano, ID Wloch, MK Alexander, AA Watanabe, H Gilkeson, GS TI Effect of a genetic deficiency of terminal deoxynucleotidyl transferase on autoantibody production by C57BL6 Fas(lpr) mice SO CLINICAL IMMUNOLOGY LA English DT Article DE terminal deoxynucleotidyl transferase; lpr; autoimmunity; autoantibodies; Ig sequence ID ANTI-DNA ANTIBODIES; HEAVY-CHAIN; AUTOIMMUNE ANTIBODIES; SOMATIC MUTATION; BACTERIAL-DNA; LPR MICE; REGION; SPECIFICITY; SEQUENCES; DIVERSITY AB Terminal deoxynucleotidyl transferase (TdT) adds nontemplate coded nucleotides (N additions) between the recombining ends of immunoglobulin and T cell receptor genes. These nucleotides add significant diversity to the Ig and TCR repertoires. Amino acids coded for by these nucleotides play a key role in the binding of self antigens by autoantibodies and autoreactive T cells. To determine the effect of a lack: of N additions on autoantibody production, we bred the TdT knockout genotype onto the autoimmune C57BL/6-Fas(lpr) background. TdT-deficient mice had significantly lower sera anti-DNA and rheumatoid factor activity than their TdT-producing littermates. C57BL/6Fas(lpr) TdT-deficient mice had shorter VH CDR3 regions and fewer VH CDR3 arginines [0.6% versus 4.7%] than their TdT-producing littermates. These data indicate that the absence of TdT limited the production of anti-DNA antibodies and rheumatoid factors in C57BL/6-Fas(lpr) mice, likely due to constraints on Ig diversity secondary to the lack of TdT-derived N additions. (C) 2000 Academic Press. C1 Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. RP Molano, ID (reprint author), Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC 29425 USA. NR 30 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2000 VL 94 IS 1 BP 24 EP 32 DI 10.1006/clim.1999.4797 PG 9 WC Immunology SC Immunology GA 273ZJ UT WOS:000084739000004 PM 10607487 ER PT J AU Gordon, LK Eggena, M Targan, SR Braun, J AF Gordon, LK Eggena, M Targan, SR Braun, J TI Mast cell and neuroendocrine cytoplasmic autoantigen(s) detected by monoclonal pANCA antibodies SO CLINICAL IMMUNOLOGY LA English DT Article DE inflammatory bowel disease; pANCA; mast cell; autoimmunity ID INFLAMMATORY BOWEL-DISEASE; PRIMARY SCLEROSING CHOLANGITIS; HLA CLASS-II; ULCERATIVE-COLITIS; CROHNS-DISEASE; NEUTROPHIL AUTOANTIBODIES; SUSCEPTIBILITY LOCUS; INCREASING PROTEIN; ANTIGEN RETRIEVAL; ANCA AB pANCA is a marker antibody expressed in most patients with ulcerative colitis, and its cognate antigen is potentially an immunologic target in this disease; This study evaluates whether pANCA detects an autoantigen that is expressed in the colonic mucosa. Immunohistochemistry of colon specimens with human pANCA monoclonal antibodies (Fab 5-2 and 5-3) revealed a minor population of immunoreactive mucosal cells bearing a cytoplasmic vesicle antigen. By distribution, morphology, and tryptase expression, these were identified as mast cells. Immunofluorescent analysis revealed similar immunoreactivity of mouse mast cell lines and human KU812. western analysis or mouse mast cell lines revealed immunoreactive proteins, and these were distinct from previously proposed pANCA antigens (histone H1, HMG 1 and 2, and neutrophil vesicle antigens). Cognate antigen for Fab 5-2 and 5-3 was also expressed in other tissue mast cells, cerebellar neurons, and pancreatic islet cells. These findings identify a novel cytoplasmic autoantigen(s) associated with UC by its presence in colonic mucosa and recognition by a disease-associated marker antibody. (C) 2000 Academic Press. C1 Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90099 USA. Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, Los Angeles, CA 90048 USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P01-CA12800]; NEI NIH HHS [K08-EY00360]; NIDDK NIH HHS [P01-DK46763] NR 57 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2000 VL 94 IS 1 BP 42 EP 50 DI 10.1006/clim.1999.4805 PG 9 WC Immunology SC Immunology GA 273ZJ UT WOS:000084739000006 PM 10607489 ER PT J AU Graybill, JR Sobel, J Saag, M van der Horst, C Powderly, W Cloud, G Riser, L Hamill, R Dismukes, W AF Graybill, JR Sobel, J Saag, M van der Horst, C Powderly, W Cloud, G Riser, L Hamill, R Dismukes, W CA NIAID Mycoses Study Grp AIDS Cooperative Treatment Grp TI Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TUBERCULOUS MENINGITIS; AMPHOTERICIN-B; CEREBROSPINAL-FLUID; ITRACONAZOLE; FLUCONAZOLE; THERAPY; TISSUE AB This study was undertaken to characterize the laboratory and clinical course of patients with AIDS and cryptococcal meningitis who had normal or elevated cerebrospinal fluid (CSF) pressure. Data were obtained retrospectively from a randomized multicenter quasifactorial phase III study comparing amphotericin B with or without flucytosine in primary treatment of cryptococcal meningitis. CSF pressure was measured before treatment and at 2 weeks. Repeated lumbar punctures were done to drain CSF and to reduce pressure, Patients with the highest baseline opening pressures (greater than or equal to 250 mm H2O) were distinguished by higher titers of cryptococcal capsular polysaccharide antigen in CSF; more frequently positive India ink smears of CSF; and more frequent headache, meningismus, papilledema, hearing loss, and pathological reflexes. After receiving antifungal therapy, those patients whose CSF pressure was reduced by >10 mm or did not change had more frequent clinical response at 2 weeks than did those whose pressure increased >10 mm (P <.001), Patients with pretreatment opening pressure greater than or equal to 250 mm H2O had increased short-term survival compared with those with higher pressure, We recommend that opening pressures greater than or equal to 250 mm H2O be treated with large-volume CSF drainage. C1 Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Infect Dis Sect 111F, San Antonio, TX 78284 USA. Houston Vet Adm Hosp, Houston, TX USA. Wayne State Univ, Detroit, MI USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Washington Univ, St Louis, MO USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Infect Dis Sect 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM graybill@uthscsa.edu FU NIAID NIH HHS [AI-65296, AI-15082] NR 32 TC 202 Z9 219 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 2000 VL 30 IS 1 BP 47 EP 54 DI 10.1086/313603 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 278TJ UT WOS:000085004800011 PM 10619732 ER PT J AU Craig, WA AF Craig, WA TI Pharmacokinetics of antibiotics with special emphasis on cephalosporins SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article; Proceedings Paper CT Cephalosporins - The Golden Jubilee, 1949-1998 CY DEC 11-13, 1998 CL CAGLIARI, ITALY ID PHARMACODYNAMICS; PENETRATION; FLUID; MODEL C1 William S Middleton Mem Vet Hosp, Dept Med, Madison, WI 53711 USA. Univ Wisconsin, Dept Med, Madison, WI USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Hosp, Dept Med, 2500 Overlook Terrace, Madison, WI 53711 USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PY 2000 VL 6 SU 3 BP 46 EP 49 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 399LG UT WOS:000166812100011 PM 11449649 ER PT J AU Holloway, R Shoulson, I Fahn, S Kieburtz, K Lang, A Marek, K McDermott, M Seibyl, J Weiner, W Welsh, M Kamp, C Day, D Pahwa, R Smith, D McGuire, D Barclay, L Sutherland, L Hildebrand, K Hubble, J Weeks, C LeWitt, P Mistura, K Bloomfield, W Miyasaki, J Duff, J Sime, E Suchowersky, O Argatoff, P Andreas, Y Kurth, M Brewer, M Russell, D Fussell, B Ford, B Dillon, S Hammerstad, J Stone, C Riley, D Rainey, P Standaert, D Tennis, M Wooten, F Rost-Ruffner, E Factor, S Brown, D Jankovic, J Beach, J Kurlan, R Gardiner, I Panisset, M Amyot, D Hall, J Rajout, A Wilson, W McCullan, L Brown, K Clark, R Rodnitzky, R Dobson, J Shults, C Fontaine, D Waters, C Welsh, M Pfeiffer, R Rast, S Bujak, G Casaceli, C Freimuth, A Hodgeman, K Honsinger, K Watts, A Hall, WJ Leventhal, CM Reich, S Tariot, P Balgoyen, D Corak, D Corrigan, M Driver, M Fraser, TJ Lai, PY Gomez-Mancilla, B Munting, J Peters, G Rowland, C Sullivan, H Trasky, R Wright, G Berber, E Morris, J Mills, D Hallak, L Rines, S AF Holloway, R Shoulson, I Fahn, S Kieburtz, K Lang, A Marek, K McDermott, M Seibyl, J Weiner, W Welsh, M Kamp, C Day, D Pahwa, R Smith, D McGuire, D Barclay, L Sutherland, L Hildebrand, K Hubble, J Weeks, C LeWitt, P Mistura, K Bloomfield, W Miyasaki, J Duff, J Sime, E Suchowersky, O Argatoff, P Andreas, Y Kurth, M Brewer, M Russell, D Fussell, B Ford, B Dillon, S Hammerstad, J Stone, C Riley, D Rainey, P Standaert, D Tennis, M Wooten, F Rost-Ruffner, E Factor, S Brown, D Jankovic, J Beach, J Kurlan, R Gardiner, I Panisset, M Amyot, D Hall, J Rajout, A Wilson, W McCullan, L Brown, K Clark, R Rodnitzky, R Dobson, J Shults, C Fontaine, D Waters, C Welsh, M Pfeiffer, R Rast, S Bujak, G Casaceli, C Freimuth, A Hodgeman, K Honsinger, K Watts, A Hall, WJ Leventhal, CM Reich, S Tariot, P Balgoyen, D Corak, D Corrigan, M Driver, M Fraser, TJ Lai, PY Gomez-Mancilla, B Munting, J Peters, G Rowland, C Sullivan, H Trasky, R Wright, G Berber, E Morris, J Mills, D Hallak, L Rines, S CA Parkinson Study Grp TI A randomized controlled trial comparing pramipexole with levodopa in early Parkinson's disease: Design and methods of the CALM-PD study SO CLINICAL NEUROPHARMACOLOGY LA English DT Review ID DOUBLE-BLIND; FOLLOW-UP; BROMOCRIPTINE; RELIABILITY; PLACEBO; 5-YEAR AB CALM-PD (Comparison of the agonist pramipexole with levodopa on motor complications of Parkinson's disease) is a randomized, multicenter, double-blind, controlled clinical trial designed to compare the policy of initial treatment of pramipex ole with the policy of initial treatment with levodopa in early, symptomatic Parkinson's disease with regard to the development of dopamineragic motor complications. At 22 American and Canadian sites, 301 eligible subjects requiring antiparkinsonian therapy to treat emerging disability were enrolled in CALM-PD and randomized to (i) active pramipexole and placebo levodopa or (ii) placebo pramipexole and active levodopa. Subjects are being evaluated systematically at regular intervals during a 23.5-month period to determine if and when dopaminergic motor complications (wearing off, dyskinesias, "on-off " effects) occur. In addition, quality-of-life outcomes, economic outcomes, and functional imaging outcomes are being assessed in standard fashion with [I-123]beta-CIT and SPECT imaging throughout the trial. The study design contains many provisions to approximate routine clinical practice and to produce data about clinical effectiveness, tolerability, and cost to facilitate the evidence-based practice of neurology. C1 Univ Rochester, Dept Neurol, Rochester, NY 14620 USA. Columbia Univ, New York, NY USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Yale Univ, Sch Med, New Haven, CT USA. Univ So Calif, Los Angeles, CA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Ottawa Civic Hosp, Ottawa, ON K1Y 4E9, Canada. Ohio State Univ, Columbus, OH 43210 USA. Sinai Clin Neurosci Ctr, W Bloomfield, MI USA. Toronto Hosp, Western Div, Toronto, ON M5T 2S8, Canada. Univ Calgary, Med Clin, Calgary, AB, Canada. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Mt Sinai Med Ctr, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Albany Med Coll, Albany, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Douglas Hosp, McGill Ctr Studies Aging, Verdun, PQ, Canada. Univ Saskatchewan, Royal Univ Hosp, Saskatoon, SK, Canada. Univ Iowa Hosp, Iowa City, IA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Alzheimers Res Ctr, La Jolla, CA USA. Univ Tennessee, Memphis, TN USA. Johns Hopkins Univ, Baltimore, MD USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. Canadian Pharmacia & Upjohn, Don Mills, ON, Canada. Coviance Labs Inc, Indianapolis, IN USA. RP Holloway, R (reprint author), Univ Rochester, Dept Neurol, 1351 Mt Hope Ave,Suite 220, Rochester, NY 14620 USA. NR 42 TC 75 Z9 76 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JAN-FEB PY 2000 VL 23 IS 1 BP 34 EP 44 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 281PX UT WOS:000085170900006 ER PT J AU Rivas-Vazquez, RA Carrazana, EJ Rey, GJ Blais, MA Racher, DA AF Rivas-Vazquez, RA Carrazana, EJ Rey, GJ Blais, MA Racher, DA TI Alzheimer's disease: Pharmacological treatment and management SO CLINICAL NEUROPSYCHOLOGIST LA English DT Review ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED TRIAL; DOUBLE-BLIND; ELDERLY PATIENTS; BEHAVIORAL DISTURBANCES; AGGRESSIVE-BEHAVIOR; PHYSICAL AGGRESSION; REUPTAKE INHIBITORS; TARDIVE-DYSKINESIA; COGNITIVE DEFICITS AB The expected rise in prevalence rates of Alzheimer's disease over the next several decades has generated a great deal of attention at all levels of society, including governmental and scientific communities. These concerns have resulted in a vast number of research studies which have yielded medications focusing primarily on the symptomatic relief of the cognitive, neuropsychiatric and behavioral alterations felt to be pathognomic of the disease. Medical and pharmacological interventions which impact the onset or delay the progression of the illness are not yet readily available. We review and discuss the medications which are currently used for the symptomatic treatment and management of the disease, as well as discuss new pharmacological strategies which are under investigation and development. C1 Univ Miami, Sch Med, Neurol Ctr S Florida, Coral Gables, FL 33124 USA. Univ Miami, Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rivas-Vazquez, RA (reprint author), 8940 N Kendall Dr,Suite 802-E, Miami, FL 33176 USA. NR 141 TC 2 Z9 2 U1 1 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2000 VL 14 IS 1 BP 93 EP 109 DI 10.1076/1385-4046(200002)14:1;1-8;FT093 PG 17 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 324XB UT WOS:000087645700010 PM 10855063 ER PT J AU Ring, D Jupiter, JB AF Ring, D Jupiter, JB TI Reconstruction of posttraumatic elbow instability SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID RADIAL HEAD; JOINT; DISLOCATION; REPLACEMENT; STABILITY; LIGAMENT; EXCISION AB Successful reconstruction of posttraumatic elbow instability depends on restoration of the anatomic contributors to stability, The osseous and articular structures are paramount. The radial head and coronoid should be repaired or reconstructed and the olecranon (proximal ulna) should be repaired in anatomic alignment so that the contour and dimensions of the trochelar notch are restored and the radiocapitellar joint is aligned appropriately. The lateral collateral ligament complex is commonly disrupted and usually can be reattached to its origin from the lateral epicondyle. Patients with longstanding subluxation or dislocation may require temporary hinged external fixation or reconstruction of the collateral ligaments with tendon grafts. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 64 TC 36 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2000 IS 370 BP 44 EP 56 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 278TR UT WOS:000085005500006 PM 10660701 ER PT J AU Rosenbaum, JF AF Rosenbaum, JF TI Expanding the use of anxiolytics in clinical practice - Introduction SO CLINICAL THERAPEUTICS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2000 VL 22 SU A BP A1 EP A2 DI 10.1016/S0149-2918(00)89069-4 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 311YF UT WOS:000086913700001 ER PT J AU Ticker, JB Warner, JJP AF Ticker, JB Warner, JJP TI Selective capsular shift technique for anterior and anterior-inferior glenohumeral instability SO CLINICS IN SPORTS MEDICINE LA English DT Article ID ARTHROSCOPIC BANKART REPAIR; SHOULDER INSTABILITY; MULTIDIRECTIONAL INSTABILITY; SUTURE ANCHORS; RECONSTRUCTION; DISLOCATION; STABILIZATION; ANESTHESIA; MANAGEMENT; LESION AB The diagnosis and treatment of patients with unstable shoulders present unique challenges. In the setting of recurrent anterior and anterior-inferior glenohumeral instability, treatment options vary. Ln acute, traumatic episodes of instability, especially in young individuals, labral detachment usually occurs(6, 30) and can be associated with abnormal capsular laxity. In this case, the diagnosis is usually more apparent than in the case of repetitive microtrauma or atraumatic instability, in which abnormal capsular laxity is the primary problem. When a surgical approach is chosen, however, the operative technique must allow for complete flexibility to address all aspects of the surgical pathology, especially when intraoperative decisions deviate from the preoperative plan. Traditional procedures that were recommended to address anterior patterns of glenohumeral instability were considered successful if the operation eliminated additional instability. A new, broader definition of "success" after instability surgery takes into account the specific functional demands of individuals, especially athletes whose sports require overhead motion. A successful surgical procedure for glenohumeral anterior and anterior-inferior glenohumeral instability is often successfully treated with nonoperative measures, particularly in atraumatic instability. In the case of traumatic instability, especially when the labrum is detached from the anterior-inferior glenoid rim, surgery is often necessary to stabilize the shoulder and restore function. An anatomic repair, such as the selective capsular shift that addresses any capsular or labral pathology is essential for a successful outcome. C1 Isl Orthpaed & Sports Med PC, Massapequa, NY 11758 USA. Columbia Univ Coll Phys & Surg, Dept Orthopaed Surg, New York, NY 10032 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA 02114 USA. RP Ticker, JB (reprint author), Isl Orthpaed & Sports Med PC, 660 Broadway, Massapequa, NY 11758 USA. NR 55 TC 7 Z9 7 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 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD JAN PY 2000 VL 19 IS 1 BP 1 EP + DI 10.1016/S0278-5919(05)70293-3 PG 18 WC Sport Sciences SC Sport Sciences GA 277AT UT WOS:000084911100002 PM 10652662 ER PT J AU Warner, JJP AF Warner, JJP TI Management of the unstable shoulder - Arthroscopic approaches for the next millennium - Preface SO CLINICS IN SPORTS MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Profess Off Bldg,Suite 403, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD JAN PY 2000 VL 19 IS 1 BP IX EP X DI 10.1016/S0278-5919(05)70292-1 PG 2 WC Sport Sciences SC Sport Sciences GA 277AT UT WOS:000084911100001 ER PT J AU Cole, BJ Warner, JJP AF Cole, BJ Warner, JJP TI Arthroscopic versus open bankart repair for traumatic anterior shoulder instability SO CLINICS IN SPORTS MEDICINE LA English DT Review ID INFERIOR CAPSULAR SHIFT; 5-YEAR FOLLOW-UP; SUTURE REPAIR; STAPLE CAPSULORRHAPHY; CAPSULOLABRAL REPAIR; DISLOCATION; RECONSTRUCTION; STABILIZATION; MANAGEMENT; LESION AB Techniques for the arthroscopic treatment of patients with recurrent shoulder instability have flourished despite several early reports indicating greater failure rates compared with traditional open stabilization techniques. Proponents of arthroscopic stabilization cite its advantages as including more accurate identification of intra-articular pathology, less morbidity, improved cosmesis, faster recovery, and, possibly, greater returns in postoperative motion. Disadvantages include complications inherent to the technique applied, requisite technical skill, a potential lack of versatility to treat a spectrum of pathology, and generally higher failure rates. As the knowledge of the basic science behind the pathophysiology of shoulder instability improves and as more clinical reports emerge, the exact indications for arthroscopic stabilization are gradually being refined. Techniques for the arthroscopic stabilization treatment of patients with recurrent shoulder instability have flourished despite several early reports indicating greater failure rates compared with traditional open stabilization techniques. Proponents cite advantages including more accurate identification of intra-articular pathology, less morbidity, improved cosmesis, faster recovery, and, possibly, greater return of postoperative motion. Disadvantages include complications inherent to the applied techniques, requisite technical skill, a potential lack of versatility to treat a spectrum of pathology, and generally higher failure rates. As knowledge of the basic science of the pathophysiology of shoulder instability improves, and as more clinical reports emerge, the exact indications for arthroscopic stabilization gradually are being refined. C1 Rush Univ, Rush Med Coll, Dept Orthopaed, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Sect Sports Med, Chicago, IL 60612 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA USA. RP Cole, BJ (reprint author), 1725 W Harrison,Suite 1063, Chicago, IL 60612 USA. NR 150 TC 67 Z9 73 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD JAN PY 2000 VL 19 IS 1 BP 19 EP + DI 10.1016/S0278-5919(05)70294-5 PG 32 WC Sport Sciences SC Sport Sciences GA 277AT UT WOS:000084911100003 PM 10652663 ER PT J AU Higgins, LD Warner, JJP AF Higgins, LD Warner, JJP TI Arthroscopic Bankart repair - Operative technique and surgical pitfalls SO CLINICS IN SPORTS MEDICINE LA English DT Article ID ANTERIOR SHOULDER DISLOCATIONS; INFERIOR GLENOHUMERAL LIGAMENT; CLOSURE AB This article reviews the pathoanatomy of shoulder instability and the indications for arthroscopic Bankart repair. A technical analysis of the arthroscopic technique includes discussion of the critical steps and potential pitfalls in this surgical approach to shoulder instability. Recent techniques are highlighted to achieve fully arthroscopic shoulder stabilization. C1 Duke Univ, Med Ctr, Div Orthopaed Surg, Dept Surg, Durham, NC 27708 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Higgins, LD (reprint author), Duke Univ, Med Ctr, Div Orthopaed Surg, Dept Surg, Box 3615,Finch Yeager Bldg,Room 317, Durham, NC 27708 USA. NR 27 TC 8 Z9 8 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 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD JAN PY 2000 VL 19 IS 1 BP 49 EP + DI 10.1016/S0278-5919(05)70295-7 PG 15 WC Sport Sciences SC Sport Sciences GA 277AT UT WOS:000084911100004 PM 10652664 ER PT S AU Cariani, P AF Cariani, P BE Chandler, JLR VandeVijver, G TI Regenerative process in life and mind SO CLOSURE: EMERGENT ORGANIZATIONS AND THEIR DYNAMICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Workshop on Closure - Emergent Organizations and Their Dynamics CY MAY 03-05, 1999 CL GHENT, BELGIUM SP Fund Sci Res, Res Community Evolut & Complex, Washington Evolutionary Syst Soc ID THRESHOLD; COGNITION AB The functional organization of the nervous system is discussed from the standpoint of organizational closure and regenerative process in order to draw parallels between life and mind. Li,Sng organization entails continual regeneration of material parts and functional relations (self-production), Similarly, dynamic stability of informational states in brains may entail coherent self-regenerating patterns of neural signals. If mind is the functional organization of the nervous system, then mental states can be seen as switchings between alternative sets of stable, self-regenerative neural signal productions, In networks of neurons, signaling resonances can be created through recurrent, reentrant neural circuits that are organized to implement a heterarchy of correlational operations. Neural representations are dynamically built-up through an interplay between externally-impressed, incoming sensory signals and internally-generated circulating signals to form pattern-resonances, Semiotic aspects of resonance states involve semantic: sensori-motor linkages to and through the external environment and pragmatic linkages to evaluative mechanisms that implement internal goal states. It is hypothesized that coherent regenerative signaling may be an organizational requirement for a material system to support conscious awareness. In this view general anesthetics and seizures abolish awareness by temporarily disrupting the organizational coherence of regenerative neural signaling. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Cariani, P (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC03054] NR 78 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-248-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 901 BP 26 EP 34 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BQ61S UT WOS:000088969000003 PM 10818554 ER PT J AU Ferguson, DO Sekiguchi, JM Frank, KM Gao, Y Sharpless, NE Gu, Y Manis, J DePinho, RA Alt, FW AF Ferguson, DO Sekiguchi, JM Frank, KM Gao, Y Sharpless, NE Gu, Y Manis, J DePinho, RA Alt, FW TI The interplay between nonhomologous end-joining and cell cycle checkpoint factors in development, genomic stability, and tumorigenesis SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID STRAND-BREAK REPAIR; HOMOLOGOUS RECOMBINATIONAL REPAIR; DNA-LIGASE-IV; V(D)J RECOMBINATION; EMBRYONIC LETHALITY; VERTEBRATE CELLS; MAMMALIAN-CELLS; C-ABL; ATM; PATHWAY C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ferguson, DO (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 NR 46 TC 15 Z9 17 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 395 EP 403 DI 10.1101/sqb.2000.65.395 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800042 PM 12760055 ER PT J AU Wu, X Rathbun, G Lane, WS Weaver, DT Livingston, DM AF Wu, X Rathbun, G Lane, WS Weaver, DT Livingston, DM TI Interactions of the Nijmegen breakage syndrome protein with ATM and BRCA1 SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID DNA-DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; CELL-CYCLE CHECKPOINTS; ATAXIA-TELANGIECTASIA; SACCHAROMYCES-CEREVISIAE; FHA DOMAIN; DEPENDENT PHOSPHORYLATION; MEIOTIC RECOMBINATION; BUDDING YEAST; REPAIR GENE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Harvard Microchem Facil, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Wu, X (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 49 TC 7 Z9 7 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 535 EP 545 DI 10.1101/sqb.2000.65.535 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800058 PM 12760071 ER PT J AU Kahn, JG Becker, BJ Maclsaa, L Amory, JK Neuhaus, J Olkin, I Creinin, MD AF Kahn, JG Becker, BJ Maclsaa, L Amory, JK Neuhaus, J Olkin, I Creinin, MD TI The efficacy of medical abortion: A meta-analysis SO CONTRACEPTION LA English DT Review DE abortion; medical abortion; meta-analysis; mifepristone; methotrexate ID EARLY-PREGNANCY TERMINATION; SURGICAL VACUUM ASPIRATION; VAGINAL MISOPROSTOL; PROSTAGLANDIN ANALOG; MIFEPRISTONE RU-486; ORAL METHOTREXATE; MULTICENTER TRIAL; CLINICAL-TRIAL; UNITED-STATES; RU486 AB Multiple clinical studies demonstrate the efficacy of medical abortion with mifepristone or methotrexate followed by a prostaglandin analogue. However, assessing predictors of success, including regimen, is difficult because of regimen variability and a lack of direct comparisons. This meta-analysis estimates rates of primary clinical outcomes of medical abortion (successful abortion, incomplete abortion, and viable pregnancy) and compares them by regimen and gestational age. We identified 54 studies published from 1991 to 1998 using mifepristone with misoprostol (18), mifepristone with other prostaglandin analogues (23), and methotrexate with misoprostol (13). Data abstracted from studies included regimen details and clinical outcomes by gestational age. We found that efficacy decreases with increasing gestational age (p <0.001), and differences by regimen are not statistically significant except at gestational age greater than or equal to 57 days. For gestations less than or equal to 49 days, mean rates of complete abortion were 94-96%, incomplete abortion 2-4%, and ongoing (viable) pregnancy 1-3%. For gestations of 50-56 days, the mean rate of complete abortion was 91% (same for all regimens), incomplete abortion 5-8%, and ongoing pregnancy 3-5%. For greater than or equal to 57 days, success was lower for mifepristone/misoprostol (85%, 95% confidence interval 78-91%) than for mifepristone/other prostaglandin analogues 95% (CI 91-98%, p = 0.006). For mifepristone/misoprostol, using greater than or equal to 2 prostaglandin analogue doses seems to be better than a single dose for certain outcomes acid gestational ages. We conclude that both mifepristone and methotrexate, when administered with misoprostol, have high levels of success at less than or equal to 49 days gestation but may have lower efficacy at longer gestation. CONTRACEPTION 2000;61:29-40 (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Michigan State Univ, Coll Educ, Program Measurement & Quantitat Methods, E Lansing, MI 48824 USA. NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. RP Kahn, JG (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, Box 0936, San Francisco, CA 94143 USA. OI Becker, Betsy Jane/0000-0003-3438-560X NR 71 TC 60 Z9 67 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JAN PY 2000 VL 61 IS 1 BP 29 EP 40 DI 10.1016/S0010-7824(99)00115-8 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 302ND UT WOS:000086370900005 PM 10745067 ER PT J AU Chirgwin, JM Guise, TA AF Chirgwin, JM Guise, TA TI Molecular mechanisms of tumor-bone interactions in osteolytic metastases SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE PTHrP; TGF-beta; osteolysis; bone metastasis; breast cancer ID HORMONE-RELATED PROTEIN; HUMAN BREAST-CANCER; PROSTATE-SPECIFIC ANTIGEN; GROWTH-FACTOR-BETA; CELLS IN-VIVO; OSTEOCLASTOGENESIS-INHIBITORY FACTOR; MESSENGER-RIBONUCLEIC-ACID; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR RECEPTOR; N-TERMINAL KINASE AB In patients with advanced disease, several cancer types frequently metastasize to the skeleton, where they cause bone destruction. Osteolytic metastases are incurable and cause pain, hypercalcemia, fracture, and nerve compression syndromes. It was proposed over a century ago that certain cancers, such as that of the breast, preferentially metastasize to the favorable microenvironment provided by bone. Bone matrix is a rich store of immobilized growth factors that are released during bone resorption. Histological analysis of osteolytic bone metastases indicates that the bone destruction is mediated by the osteoclast rather than directly by the tumor cells. These observations suggest a vicious cycle driving the formation of osteolytic metastases: tumor cells secrete factors stimulating osteoclasts through adjacent bone marrow stromal cells; osteoclastic resorption in turn releases growth factors from the bone matrix; finally, locally released growth factors activate the tumor cells. This vicious cycle model has now been confirmed at the molecular level. In particular, transforming growth factor beta (TGF beta) is abundant in bone matrix and released as a consequence of osteoclastic bone resorption. Bone-derived TGF beta plays an integral role in promoting the development and progression of osteolytic bone metastases by inducing tumor production of parathyroid hormone-related protein (PTHrP), a known stimulator of osteoclastic bone resorption. In breast cancer cells TGF beta appears to stimulate PTHrP secretion by a posttranscriptional mechanism through both Smad and p38 mitogen activated protein (MAP) kinase signaling pathways. Osteolytic metastases can be suppressed in vivo by inhibition of bone resorption, blockade of TGF beta signaling in tumor cells, and by neutralization of PTHrP. Other factors released from bone matrix may also act on tumor cells in bone. which in turn may produce other factors that stimulate bone resorption, following the vicious cycle paradigm established for TGF beta and PTHrP. An understanding at the molecular level of the mechanisms of osteolytic metastasis will result in more effective therapies for this devastating complication of cancer. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol, San Antonio, TX 78229 USA. Vet Adm Med Ctr, Res Serv, San Antonio, TX 78229 USA. RP Chirgwin, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol, Mail Code 7877,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA40035, CA69158] NR 139 TC 143 Z9 151 U1 1 U2 3 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 2000 VL 10 IS 2 BP 159 EP 178 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 372HV UT WOS:000165229000005 PM 11186331 ER PT J AU Nagler-Anderson, C AF Nagler-Anderson, C TI Tolerance and immunity in the intestinal immune system SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE oral tolerance; T-cell anergy; regulatory T cells; mucosal adjuvants ID CD4(+) T-CELLS; DOSE ORAL TOLERANCE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; DENDRITIC CELLS; IN-VIVO; ACTIVE SUPPRESSION; ANTIBODY-RESPONSES; EPITHELIAL-CELLS; CLONAL EXPANSION AB The intestinal immune system must guard the body against invasion by pathogens while avoiding a response to the many potential antigens present in food. In the absence of the inflammatory stimuli necessary to elicit an immune response, oral administration of soluble protein antigens induces antigen-specific systemic nonresponsiveness. Recent studies have shown that peripheral nonresponsiveness to orally administered antigen is preceded by transient T-cell activation and is due primarily to the induction of functional T-cell anergy. The microenvironment of the gut-associated lymphoid tissue plays a central role in orally induced nonresponsiveness by supporting the growth of regulatory T cells that maintain intestinal homeostasis in the face of constant antigenic challenge. The transfer of nonresponsiveness by peripheral T cells from antigen-fed mice suggests that these gut-derived regulatory cells also function in peripheral sites. When oral antigens are presented with adjuvants (microbial products that activate the innate immune system) an adaptive immune response is induced to this normally tolerogenic form of antigen. This review examines recent work that has provided new insight into the regulation of tolerance and immunity in the intestinal immune system. C1 Massachusetts Gen Hosp East, Mucosal Immunol Lab, Boston, MA 02129 USA. RP Nagler-Anderson, C (reprint author), Massachusetts Gen Hosp East, Mucosal Immunol Lab, Room 3308,Pediat G-I,3 West,Bldg 149,13th St, Boston, MA 02129 USA. FU NIDDK NIH HHS [DK 35506, DK 47017, DK 40561] NR 89 TC 55 Z9 56 U1 0 U2 4 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2000 VL 20 IS 2 BP 103 EP 120 PG 18 WC Immunology SC Immunology GA 323UL UT WOS:000087583300002 PM 10872893 ER PT J AU Sattler, M Pisick, E Morrison, PT Salgia, R AF Sattler, M Pisick, E Morrison, PT Salgia, R TI Role of the cytoskeletal protein paxillin in oncogenesis SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE paxillin; focal adhesion; cell motility; BCR/ABL; E6; lung cancer ID FOCAL ADHESION KINASE; STIMULATES TYROSINE PHOSPHORYLATION; SMOOTH-MUSCLE CELLS; SWISS 3T3 CELLS; HUMAN PAPILLOMAVIRUS TYPE-16; RETINOBLASTOMA GENE-PRODUCT; GROWTH-FACTOR; E6 ONCOPROTEIN; SERINE PHOSPHORYLATION; LIM DOMAINS AB The focal adhesion is an important cellular structure that: is involved in cell signaling, cell motility, and oncogenic transformation. Paxillin is a unique adapter protein that is localized to the focal adhesion and is involved in regulating various functions of the focal adhesion. The predicted amino acid structure for paxillin shows at the amino-terminus five LD motifs, a proline-rich domain, several potential phosphorylation sites and four carboxy-terminal LIM domains. Paxillin interacts with cell surface receptors and the actin cytoskeleton and activates several signal transduction pathways that are known to regulate normal cell physiology. Because paxillin is a central protein within the focal adhesion, it is a common target of many different oncoproteins, such as BCR/ABL, v-Src, and E6. Zn this review we summarize the current knowledge about the structure/function of paxillin and its family members, its role in integrin, cytokine signaling, and oncogenic transformation. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Mol Biol Core Facil, Boston, MA 02115 USA. RP Salgia, R (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75348-03] NR 72 TC 46 Z9 52 U1 0 U2 1 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 2000 VL 11 IS 1 BP 63 EP 76 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA 306WL UT WOS:000086620700003 PM 10795627 ER PT J AU El-Shabrawi, Y Christen, WG Foster, CS AF El-Shabrawi, Y Christen, WG Foster, CS TI Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1 beta, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis SO CURRENT EYE RESEARCH LA English DT Article DE uveitis; matrix metalloproteinases; interleukin-1 beta; interleukin-1 receptor antagonists; interleukin-12; proinflammatory cytokines; human ID MATRIX METALLOPROTEINASES; ARTHRITIS; DISEASE; RELEASE; CELLS AB Purpose. Matrix metalloproteinases have been shown to play a role in active uveitis. Transcription of MMPs is induced by a number of growth factors and cytokines. This study investigates the role of MMPs in chronic uveitis and correlates the amounts of MMP-2 and -9 in intraocular samples to the intraocular levels of proinflammatory cytokines (Interleukin-1 [IL-1], Interleukin-12 [IL-12] and Interleukin-1 receptor antagonist [IL-1ra]). Methods. Aqueous humor of 16 patients was collected during surgical or diagnostic procedures (control group: cataract patients). MMP-2 and -9 were measured using zymography. IL-1, IL-12 and IL-1ra were evaluated by ELISA. Results. We found MMP-2 and -9 in all of our uveitis patients. In the control group only MMP-2 was seen. Higher levels of MMP-2 and -9 were found in patients with higher activity of uveitis (p < 0.014 for MMP-2, p < 0.0054 for MMP-9). The amounts of IL-1, IL-12 and IL-1ra detected in our uveitis patients correlated with levels of MMP-2 (p < 0.07, p < 0.0004, p < 0.03) and MMP-9 (p < 0.003, p < 0.0001, p < 0.002), and IL-12 (p < 0.004, p < 0.0001). Patients with moderately active uveitis presented with twice the level of MMP-2 as the control group; MMP-9 levels reached up to 92% of the amounts found in patients with active uveitis. Two patients in remission for almost one year still had detectable intraocular MMP-9 levels. Conclusion. Our data suggests that the high levels of MMPs found in patients with chronic uveitis might contribute to the damage often seen in these eyes. Since MMPs are capable of releasing proinflammatory cytokines bound to components of the extracellular matrix, and facilitate the secretion of active TNF-alpha by cleavage of the membrane bound form, it is conceivable that MMPs contribute to the chronicity of some uveitis cases. C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 45 Z9 50 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2000 VL 20 IS 3 BP 211 EP 214 DI 10.1076/0271-3683(200003)20:3;1-9;FT211 PG 4 WC Ophthalmology SC Ophthalmology GA 291VZ UT WOS:000085760500009 PM 10694897 ER PT J AU Marder, SR AF Marder, SR TI Newer antipsychotics SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID TREATMENT-RESISTANT SCHIZOPHRENIA; VS. HALOPERIDOL; CLOZAPINE; OLANZAPINE AB Newer antipsychotics have been widely used in schizophrenia for the past 5 years. During this period, controlled clinical trials have improved our understanding of the effectiveness of these agents in different populations of patients with schizophrenia. Other studies have enhanced our understanding of how improvement on these agents is associated with the occupancy of central nervous system receptors, The best understood of the newer agents is clozapine, although clinically important information has become available for risperidone, olanzapine, quetiapine and amisulpride. Curr Opin Psychiatry 13:11-14. (C) 2000 Lippincott Williams & Wilkins. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, W Los Angeles Hlth Ctr, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Hlth Care Ctr, MIRECC-210A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 17 TC 7 Z9 7 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2000 VL 13 IS 1 BP 11 EP 14 DI 10.1097/00001504-200001000-00003 PG 4 WC Psychiatry SC Psychiatry GA 273RQ UT WOS:000084721500003 ER PT J AU Wirshing, DA Erhart, SM Pierre, JM Boyd, JA AF Wirshing, DA Erhart, SM Pierre, JM Boyd, JA TI Nonextrapyramidal side effects of novel antipsychotics SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID NEUROLEPTIC MALIGNANT SYNDROME; DIABETIC-KETOACIDOSIS; CLOZAPINE TREATMENT; RISPERIDONE; OLANZAPINE; MEDICATIONS; FERTILITY; PREGNANCY; SEROTONIN; GLUCOSE AB The novel antipsychotic drugs offer significant advantages over conventional antipsychotic drugs because of their favorable extrapyramidal side-effect profiles, These medications do have some side effects that are clinically significant to our patients with psychotic disorders, however. We summarized the literature from July 1998 through September 1999 on nonextrapyramidal side effects of these medications, focusing on cardiac effects, weight gain, diabetes and impaired glucose tolerance, prolactin elevation, sexual side effects and neuroleptic malignant syndrome, Curr Opin Psychiatry 13:45-50. (C) 2000 Lippincott Williams & Wilkins. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Dept Vet Affairs, Vet Integrated Serv Network 22, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. RP Wirshing, DA (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Dept Psychiat, 11301 Wilshire Blvd,Bldg 210,Room 15 B-151H, Los Angeles, CA 90073 USA. NR 49 TC 14 Z9 15 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2000 VL 13 IS 1 BP 45 EP 50 DI 10.1097/00001504-200001000-00008 PG 6 WC Psychiatry SC Psychiatry GA 273RQ UT WOS:000084721500008 ER PT J AU Spencer, T Biederman, J Wozniak, J Wilens, T AF Spencer, T Biederman, J Wozniak, J Wilens, T TI Attention deficit hyperactivity disorder and affective disorders in childhood: continuum, comorbidity or confusion SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID LA-TOURETTES SYNDROME; DEPRESSIVE-DISORDERS; STIMULANT MEDICATION; GENETIC-RELATIONSHIP; PSYCHIATRIC STATUS; ADHD CHILDREN; FOLLOW-UP; ANXIETY; METHYLPHENIDATE; ADOLESCENTS AB An increasing awareness of the importance of comorbidity in psychiatric disorders has emerged. Over the past decade numerous reports on the overlap of attention deficit hyperactivity disorder and depression have been published. A growing number of reports have now addressed the overlap of childhood mania and attention deficit hyperactivity disorder. Clinical, epidemiological and family genetic studies have provided evidence supporting the coexistence of these conditions. Curr Opin Psychiatry 13:73-79. (C) 2000 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA. NR 60 TC 3 Z9 3 U1 6 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2000 VL 13 IS 1 BP 73 EP 79 DI 10.1097/00001504-200001000-00013 PG 7 WC Psychiatry SC Psychiatry GA 273RQ UT WOS:000084721500013 ER PT J AU Aramburu, J Rao, A Klee, CB AF Aramburu, J Rao, A Klee, CB TI Calcineurin: From structure to function SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 36 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID DEPENDENT PROTEIN PHOSPHATASE; NF-KAPPA-B; ACTIVATED T-CELLS; TRANSCRIPTION FACTOR NFAT1; LONG-TERM DEPRESSION; VACUOLAR H+-ATPASE; IMMUNOPHILIN-IMMUNOSUPPRESSANT COMPLEXES; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; SIGNAL-TRANSDUCTION PATHWAY; CYCLOPHILIN-CYCLOSPORINE-A C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Univ Pompeu Fabra, Fac Ciencies Salut Vida, Barcelona 08002, Spain. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Aramburu, J (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 NR 352 TC 203 Z9 212 U1 1 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 J9 CURR TOP CELL REGUL PY 2000 VL 36 BP 237 EP 295 PG 59 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BQ27H UT WOS:000087771600011 PM 10842755 ER PT J AU White, RA Pasztor, LM Richardson, PM Zon, LI AF White, RA Pasztor, LM Richardson, PM Zon, LI TI The gene encoding TBC1D1 with homology to the tre-2/USP6 oncogene, BUB2, and cdc16 maps to mouse chromosome 5 and human chromosome 4 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CELL-CYCLE; CYTOKINESIS; MITOSIS; YEAST AB TBC1D1 is the founding member of a family of related proteins with homology to (t) under bar re-2/UPS6, (B) under bar UB2, and (c) under bar dc16 and containing the tbc box motif of 180-220 amino acids. This protein family is thought to have a role in differentiation and in regulating cell growth. We set out to map the TBC1D1 gene in mouse and human. Segregation analysis of a TBC1D1 RFLP in two independent mouse RI (recombinant inbred) lines reveals that mouse Tbc1d1 is closely linked to Pgm1 on chromosome 5. The human TBC1D1 gene was assigned to human chromosome 4p15.1 --> 4q21 using Southern blot analyses of genomic DNAs from rodent-human somatic cell lines. A human-specific genomic fragment was observed in the somatic cell lines containing human chromosome 4 or the 4p15.1 --> 4q21 region of the chromosome. TBC1D1 maps to the region containing the ortholog of mouse Pgr,ll adding another locus to this long region of conserved synteny between mouse and man. Copyright (C) 2000 S. Karger AG, Basel. C1 Childrens Mercy Hosp, Biomol Lab, UMKC Sch Med, Sect Med Genet & Mol Med, Kansas City, MO 64108 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP White, RA (reprint author), Childrens Mercy Hosp, Biomol Lab, UMKC Sch Med, Sect Med Genet & Mol Med, 2801 Wyandotte Ave, Kansas City, MO 64108 USA. FU NHLBI NIH HHS [HL32262] NR 12 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 3-4 BP 272 EP 275 DI 10.1159/000015632 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 346ZK UT WOS:000088901600039 PM 10965142 ER PT J AU Chiaur, DS Murthy, S Cenciarelli, C Parks, W Loda, M Inghirami, G Demetrick, D Pagano, M AF Chiaur, DS Murthy, S Cenciarelli, C Parks, W Loda, M Inghirami, G Demetrick, D Pagano, M TI Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 4th International Chromosome 6 Workshop CY JUN 10-12, 1999 CL CAMBRIDGE, ENGLAND ID BETA-CATENIN; CELL-CYCLE; DEGRADATION; IDENTIFICATION; UBIQUITINATION; PROTEOLYSIS; COMPLEX; FAMILY; CANCER; P27 AB Members of the F-box protein (Fbp) family are characterized by an approximately 40 amino acid F-box motif. SCF complexes (formed by Skp1, cullin, and one of many Fbps) act as protein-ubiquitin ligases that control the G(1)/S transition of the eukaryotic cell cycle. The substrate specificity of SCF complexes is determined by the presence of different Fbp subunits that recruit specific substrates for ubiquitination. Unchecked degradation of cellular regulatory proteins has been observed in certain tumors and it is possible that deregulated ubiquitin ligases play a role in the altered degradation of cell cycle regulators. We have recently identified a family of human Fbps. As a first step aimed at determining if FBP genes could be involved in human neoplasia, we have mapped the chromosome positions of 5 FBP genes by fluorescence in situ hybridization (FISH) to 10q24 (BTRC alias beta-TRCP/FBW1a), 9q34 (FBXW2 alias FBW2), 13q22 (FBXL3A alias FBL3a), 5p12 (FBXO4 alias FBX4) and 6q25 -->q26 (FBXO5 alias FBX5). Since most of these are chromosomal loci frequently altered in tumors, we have screened 42 human tumor cell lines and 48 human tumor samples by Southern hybridization and FISH. While no gross alterations of the genes encoding beta-Trcp/Fbw1a, Fbw2, Fbx4 and Fbx5 were found, heterozygous deletion of the FBXL3A gene was found in four of 13 small cell carcinoma cell lines. This is the first evaluation of genes encoding Fbps in human tumors. Copyright (C) 2000 S. Karger AG,Basel. C1 NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. Univ Calgary, Dept Pathol, Calgary, AB, Canada. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Pagano, M (reprint author), NYU, Sch Med, Dept Pathol, MSB 548,550 1st Ave, New York, NY 10016 USA. FU NCI NIH HHS [CA76584, CA66229]; NIGMS NIH HHS [GM57587] NR 17 TC 20 Z9 22 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 88 IS 3-4 BP 255 EP 258 DI 10.1159/000015532 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 319PV UT WOS:000087351100023 PM 10828603 ER PT J AU Haile, DJ AF Haile, DJ TI Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q32 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 4th International Chromosome 6 Workshop CY JUN 10-12, 1999 CL CAMBRIDGE, ENGLAND ID INSITU HYBRIDIZATION C1 Univ Texas, Hlth Sci Ctr, Audie Murphy Vet Adm Hosp, San Antonio, TX USA. RP Haile, DJ (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 88 IS 3-4 BP 328 EP 329 DI 10.1159/000015522 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 319PV UT WOS:000087351100043 PM 10828623 ER PT J AU Kienke, AS Rosenbaum, JF AF Kienke, AS Rosenbaum, JF TI Efficacy of venlafaxine in the treatment of severe depression SO DEPRESSION AND ANXIETY LA English DT Review DE severe depression; venlafaxine; melancholia; inpatient; antidepressant ID MAJOR DEPRESSION; NEWER ANTIDEPRESSANTS; MELANCHOLIA; DESIPRAMINE; FLUOXETINE AB Although the efficacy of available antidepressants has been well established ist the treatment of mld to moderate depression, clinical research literature olt severe depression is mor-e limited, due to lack of a standardized definition for the condition and the resulting inconsistent data, Given the heterogeneous nature of severe depression, reports suggesting noradrenergic as well as serotonergic system involvement in depressive disorders, and tbe substantive capability of both clomipramine and TCA-SSRI combination to treat severe depression, investigation of dual-action antidepressant agent efficacy ist the treatment of severe depression is warranted. The merit of one such combined-action agent, venlafaxine, is reviewed. Efficacy findings from the limited number of comparative clinical trials conducted in the severely depressed patient population suggest that, while venlafaxine has beer evaluated ist a broad range of depressed patients, this compound may be pn particularly effective for the severely ill. Pharmacological features of venlafaxine, which may benefit the patient with severe depression, include the possibility of a rapid onset of action and a dose-response curve. Based upon studies comparing venlafaxine with both placebo and other fir-sr-line antidepressants, it is concluded that venlafaxine is safe, tolerable, and effective for the treatment of severe depression. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Mood & Anxiety Disorders Inst, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, Mood & Anxiety Disorders Inst, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM jrosenbaum@partners.org NR 36 TC 16 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 12 SU 1 BP 50 EP 54 DI 10.1002/1520-6394(2000)12:1+<50::AID-DA6>3.0.CO;2-4 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 373CC UT WOS:000165269900006 PM 11098414 ER PT J AU Nobler, MS Teneback, CC Nahas, Z Bohning, DE Shastri, A Kozel, FA George, MS AF Nobler, MS Teneback, CC Nahas, Z Bohning, DE Shastri, A Kozel, FA George, MS TI Structural and functional neuroimaging of electroconvulsive therapy and transcranial magnetic stimulation SO DEPRESSION AND ANXIETY LA English DT Article DE cerebral blood flow; cerebral metabolic rate; PET; SPECT ID CEREBRAL-BLOOD-FLOW; ELECTRICALLY-INDUCED SEIZURES; POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; MOTOR CORTEX; ANTIDEPRESSANT RESPONSE; COMPUTED-TOMOGRAPHY; EPILEPTIC SEIZURES; DEPRESSED-PATIENTS; TMS AB Neuroimaging has long been utilized to provide a measure of the effects of electroconvulsive therapy (ECT) on brain structure and function as well as to better understand its mechanisms of action. In a similar-fashion, functional neuroimaging may provide the means to elucidate both the underlying neurobiological effects and therapeutic potential of transcranial magnetic stimulation (TMS). This article will review findings of neuroimaging studies of both TMS and ECT; concentrating on how such studies may help guide treatment. (C) 2000 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, Dept Biol Psychiat, New York, NY 10032 USA. Med Univ S Carolina, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, Room D297,171 Ashley Ave, Charleston, SC 29425 USA. EM georgem@musc.edu RI Kozel, Frank/I-5366-2012 FU NIMH NIH HHS [K08 MH01244] NR 69 TC 18 Z9 20 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 12 IS 3 BP 144 EP 156 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 379MA UT WOS:000165644800006 PM 11126189 ER PT J AU Manfro, GG Pollack, MH Otto, MW Worthington, JJ Rosenbaum, JF Scott, EL Kradin, RL AF Manfro, GG Pollack, MH Otto, MW Worthington, JJ Rosenbaum, JF Scott, EL Kradin, RL TI Cell-surface expression of L-selectin (CD62L) by blood lymphocytes: Correlates with affective parameters and severity of panic disorder SO DEPRESSION AND ANXIETY LA English DT Article DE panic disorder; immunity; CD45RA; CD62L; lymphocyte traffic ID T-CELLS; PSYCHOIMMUNOENDOCRINE ASPECTS; NORADRENERGIC FUNCTION; ADHESION MOLECULES; DOWN-REGULATION; RECEPTOR; SUBSETS; ANXIETY; RECIRCULATION; INTERLEUKIN-2 AB The surface immune phenotype of peripheral blood lymphocytes (PBL) was examined in 30 patients meeting DSM-III-R criteria for panic disorder and in 10 normal controls by immunostaining and cytofluorimetry. Patients with panic disorder and controls showed comparable numbers of PBL and no differences in the percentages of blood T-cells, B-cells, or NK-cells. The PBL in panic disorder patients showed a trend toward enrichment for "naive" CD45RA+ T-lymphocytes (35.0 +/- 1.6 vs. 28.7 +/- 9.8, P = 0.09) and significant enrichment for cells expressing CD62L (L-selectin, 22.9 +/- 5.9 vs. 14.6 +/- 63, P = 0.002), a lymphocyte homing receptor that mediates binding to lymph node endothelium. Increased expression of CD62L correlated directly With the global severity of illness, Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) scores. Although in the normal range, plasma cortisol levels were significantly increased in patients with panic disorder (P = 0.003) with respect to controls and correlated with the expression of CD62L by PBL. We conclude that the peripheral blood in panic disorder shows phenotypic changes that may reflect diminished cell activation in vivo. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunopathol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Pollack, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychopharmacol Unit, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Manfro, Gisele/B-7020-2009 NR 56 TC 16 Z9 16 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 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 11 IS 1 BP 31 EP 37 DI 10.1002/(SICI)1520-6394(2000)11:1<31::AID-DA5>3.0.CO;2-O PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 290AX UT WOS:000085655100005 PM 10723633 ER PT J AU Geller, D Biederman, J Faraone, SV Frazier, J Coffey, BJ Kim, G Bellordre, CA AF Geller, D Biederman, J Faraone, SV Frazier, J Coffey, BJ Kim, G Bellordre, CA TI Clinical correlates of obsessive compulsive disorder in children and adolescents referred to specialized and non-specialized clinical settings SO DEPRESSION AND ANXIETY LA English DT Article DE obsessive compulsive disorder; correlates; comorbidity; referral bias; ascertainment source ID PROSPECTIVE FOLLOW-UP; COMMUNITY SAMPLE; CHILDHOOD; 2-YEAR; PHENOMENOLOGY; RELIABILITY; SYMPTOMS; BEHAVIOR AB The objective of this study was to assess the extent of referral bias by comparing children and adolescents with Obsessive Compulsive Disorder (OCD) ascertained through a specialized pediatric OCD and a general child psychiatry clinic. Subjects were juveniles meeting DSM-III-R and DSM IV criteria for OCD referred to a general pediatric psychopharmacology clinic and to a specialized OCD clinic within the same academic medical center. Subjects were evaluated clinically and with structured diagnostic interviews using the Kiddie SADS-E. OCD was identified in 8.6% of the general psychiatry clinic subjects. The only differences between ascertainment sources in clinical or sociodemographic characteristics of OCD subjects were higher rates of social phobia and ADHD in the non-specialized clinic, while specialty clinic subjects had a greater lifetime severity of OCD and were more likely to have received treatment of their OCD. Because we found limited evidence for referral biases, oar results suggest that findings from studies using either of these sources may generalize to the other. It also suggests that pooling subjects from the two sources is justified. Nevertheless, because some group differences did emerge, researchers should acknowledge referral bias as a potential limitation of their work. (C) 2000 Wiley-Liss, Inc. C1 McLean Hosp, Pediat Psychopharmacol Clin, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Joint Pediat Psychopharmacol Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Geller, D (reprint author), McLean Hosp, Pediat Psychopharmacol Clin, 115 Mill St, Belmont, MA 02478 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 38 TC 30 Z9 31 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 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 11 IS 4 BP 163 EP 168 DI 10.1002/1520-6394(2000)11:4<163::AID-DA3>3.0.CO;2-3 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 338UH UT WOS:000088441300003 PM 10945136 ER PT J AU Schatz, J Craft, S Koby, M DeBaun, MR AF Schatz, J Craft, S Koby, M DeBaun, MR TI A lesion analysis of visual orienting performance in children with cerebral vascular injury SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID EARLY INFANCY; ATTENTION; DEFICITS; STROKE AB Anterior brain insults during development have been shown to result in visual orienting deficits; however, the type of orienting deficit has varied across studies. Performance on an orienting task was examined in relation to the location and volume of injury on magnetic resonance exams in 15 children with cerebral infarction and 32 control children. Contralateral lesions including the parietal lobe were associated with larger validity effects, suggesting difficulties disengaging attention. A similar trend was found for the middle-frontal gyrus. Basal ganglia injury contralateral to a given hemifield was associated with less facilitation of attention. Lesion volume in each hemisphere did not show a significant relation with contralateral validity effects. The data suggest that variability in the type of visual orienting deficits shown in prior studies of children with anterior brain insults may be related in part to the specific location of lesions within the frontal lobe. C1 Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Schatz, J (reprint author), Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2000 VL 17 IS 1 BP 49 EP 61 DI 10.1207/S15326942DN1701_03 PG 13 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 337CN UT WOS:000088340000003 PM 10916574 ER PT J AU Hickman, SE Howieson, DB Dame, A Sexton, G Kaye, J AF Hickman, SE Howieson, DB Dame, A Sexton, G Kaye, J TI Longitudinal analysis of the effects of the aging process on neuropsychological test performance in the healthy young-old and oldest-old SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; INTELLECTUAL-DEVELOPMENT; COGNITIVE PERFORMANCE; SENILE DEMENTIA; LATER LIFE; MEMORY; ADULTS; AGE; POPULATION; IMPAIRMENT AB A sample of 33 young-old (ages 65 to 74) and 20 oldest-old (ages 84 to 93) healthy elderly without dementia were assessed with neuropsychological tests annually over a 4-year period to examine longitudinal changes in cognitive functioning. Significant age-group differences existed at baseline in participants' performances on tests of immediate memory and visuospatial skills. There were no age-group differences in the rate of change over the 4-year interval on any neuropsychological tests. Within each age-group, the amount of change over time was minimal for most tests though some practice effects were apparent, and on some tests mild decline was observed. Results suggest that healthy old adults, including the oldest-old, do not experience measurable declines in cognitive functioning over a 4-year period. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Div Mental Hlth, Portland, OR USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Publ Hlth, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Prevent Med, Portland, OR 97201 USA. RP Howieson, DB (reprint author), Oregon Hlth Sci Univ, Dept Neurol, CR131,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AGO8017] NR 49 TC 32 Z9 33 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2000 VL 17 IS 3 BP 323 EP 337 DI 10.1207/S15326942DN1703_3 PG 15 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 362AY UT WOS:000089757500003 PM 11056847 ER PT J AU Verney, C Takahashi, T Bhide, PG Nowakowski, RS Caviness, VS AF Verney, C Takahashi, T Bhide, PG Nowakowski, RS Caviness, VS TI Independent controls for neocortical neuron production and histogenetic cell death SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE cell death; apoptosis; cell cycle; cell proliferation; TUNEL; neocortex ID DEVELOPING CEREBRAL-CORTEX; PRIMARY VISUAL-CORTEX; SOMATOSENSORY CORTEX; QUANTITATIVE CYTOARCHITECTONICS; PROLIFERATIVE EPITHELIUM; POSTNATAL-DEVELOPMENT; THALAMIC PROJECTIONS; CORTICAL-NEURONS; LINEAGE ANALYSIS; NERVOUS-SYSTEM AB We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm(2) was calculated and the proportionate cell death for each day of the 2-week interval was estimated, The data sh ow th at cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the 'inside-out' neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity. Copyright (C) 2000 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Hop La Pitie Salpetriere, INSERM, U106, Paris, France. Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149 13th St, Boston, MA 02129 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS12005, NS32657, NS33433] NR 71 TC 59 Z9 59 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD JAN-APR PY 2000 VL 22 IS 1-2 BP 125 EP 138 DI 10.1159/000017434 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 288QG UT WOS:000085574300014 PM 10657705 ER PT J AU Warram, JH Scott, LJ Hanna, LS Wantman, M Cohen, SE Laffel, LMB Ryan, L Krolewski, AS AF Warram, JH Scott, LJ Hanna, LS Wantman, M Cohen, SE Laffel, LMB Ryan, L Krolewski, AS TI Progression of microalbuminuria to proteinuria in type 1 diabetes - Nonlinear relationship with hyperglycemia SO DIABETES LA English DT Article ID CONVERTING ENZYME-INHIBITION; BLOOD-GLUCOSE CONTROL; RENAL-FUNCTION; URINE SAMPLES; FOLLOW-UP; NEPHROPATHY; MELLITUS; PRESSURE; CAPTOPRIL; DISEASE AB While small clinical trials have shown that improved glycemic control reduces the risk of progression of microalbuminuria to proteinuria, two recent clinical trials did not confirm this finding. We sought to reconcile the contradictory evidence by examining the dose-response relationship between hyperglycemia and progression of microalbuminuria to proteinuria in individuals with type 1 diabetes and microalbuminuria (n = 312) who were followed for 4 years with repeated assessments of urinary albumin excretion. Since 33 patients did not participate in follow-up (10.6%), data for 279 patients mere analyzed. Urinary albumin excretion level worsened to proteinuria in 40 (4.1 per 100 person-years). To examine the dose- response relationship, baseline WA,, was divided into four roughly equal groups using the cut points 8, 9, and 10%. The incidence rate varied significantly among the four groups (P = 0.008). Among those with HbA(1c) <8.0%, the incidence rate of progression was only 1.3 per 100 person-years, while it was 5.1, 4.2, and 6.7 per 100 person-years in the three other groups, We used generalized additive models to examine the dose-response curve using HbA(1c) as a continuous variable and found that the risk of progression rises steeply between an HbA(1c) of 7.5-8.5% and then remains approximately constant across higher levels. In conclusion, the results of this study suggest that, in patients with microalbuminuria, the risk of progression to overt proteinuria can be reduced by improved glycemic control only if the HbA(1c) is maintained below 8.5%. Moreover, below that value, the risk declines as the level of HbA(1c) decreases. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA USA. RP Warram, JH (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM james.warram@joslin.harvard.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIDDK NIH HHS [R01-DK41526] NR 43 TC 66 Z9 66 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JAN PY 2000 VL 49 IS 1 BP 94 EP 100 DI 10.2337/diabetes.49.1.94 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270PD UT WOS:000084543800014 PM 10615955 ER PT J AU Gavin, JR Abrahamson, MJ Blonde, L Celebi, D Donovan, DS Kanzer-Lewis, G Kuschner, PR Mulcahy, K Reasner, CA Rodbard, H Zimmerman, B AF Gavin, JR Abrahamson, MJ Blonde, L Celebi, D Donovan, DS Kanzer-Lewis, G Kuschner, PR Mulcahy, K Reasner, CA Rodbard, H Zimmerman, B TI New treatment paradigm for managing outcomes in type 2 diabetes SO DIABETES EDUCATOR LA English DT Article ID METFORMIN; MELLITUS; ADULTS AB Diabetes education is at the core of quality diabetes care. Like other chronic diseases, diabetes requires many difficult lifestyle adaptations. The role of the diabetes educator is to help individuals with type 2 diabetes and those who are at risk for diabetes make these adaptations through Diabetes Self-Management Education (DSME) and care management. This is a complex role with varied responsibilities. DSME is an interactive, collaborative, ongoing process involving the person with diabetes and the diabetes educator Diabetes educators need the skill and experience necessary to promote effective self-management in the person with diabetes. Self-management skills lead to appropriate behavior changes and improved adherence to medication and blood glucose monitoring. These and other self care behaviors help delay and/or prevent chronic complications associated with diabetes. Many new treatments for diabetes have been introduced in the past several years; however; diabetes management is still frequently not aggressive enough to meet the ADA treatment goals designed to prevent the onset and progression of complications.(1) All too often, the clinical diagnosis of type 2 diabetes is made 9 to 12 years after the onset of the disease.(1) Indeed, by the time diabetes is diagnosed, 15% to 20% of patients have developed retinopathy and 5% to 10% have proteinuria.(1) It is now known that the atherogenic pattern of risk factors associated with insulin resistance has been found even before the onset of type 2 diabetes, underscoring the need for early diagnosis and treatment.(2) An estimated 16 million people in the United States are affected by diabetes.(3) This chronic disease accounts for $100 billion in health cave costs per year causes a widespread decline in patients' quality of life, and leads to high rates of disability, disease-related complications, and death.(4-7) To address these concerns, a multidisciplinary panel of leading US diabetes experts convened to review the traditional approach to diabetes treatment and to suggest a new treatment paradigm that provides earlier diagnosis and more effective management of the patient with diabetes. C1 NIH, Res Scholars Program, HHM1, Chevy Chase, MD 20815 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Clin, Boston, MA 02215 USA. Alton Ochsner Med Fdn & Ochsner Clin, Dept Internal Med, Cardiol Sect, New Orleans, LA 70121 USA. Columbia Univ, Columbia Presbyterian Med Ctr, Coll Phys & Surg, Diabetes Management Serv, New York, NY 10032 USA. GKL Associates, Pomona, NY USA. Amer Assoc Diabet Educ, Chicago, IL 60603 USA. Univ Calif Irvine, Irvine Med Ctr, Osteoporosis Diagnost Ctr, Long Beach, CA USA. Inova Diabetes Ctr, Fairfax, VA USA. Univ Texas, Hlth Sci Ctr, Texas Diabetes Inst, San Antonio, TX USA. Amer Assoc Clin Endocrinologists, Rockville, MD USA. Mayo Clin & Mayo Grad Sch Med, Rochester, MN 55901 USA. RP Gavin, JR (reprint author), NIH, Res Scholars Program, HHM1, Chevy Chase, MD 20815 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 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. PY 2000 SU S BP 2 EP 6 PG 7 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 358BW UT WOS:000089538200001 ER PT J AU Burgess, DS Hastings, RW Summers, KK Hardin, TC Rinaldi, MG AF Burgess, DS Hastings, RW Summers, KK Hardin, TC Rinaldi, MG TI Pharmacodynamics of fluconazole, itraconazole, and amphotericin B against Candida albicans SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article; Proceedings Paper CT Focus on Fungal Infection 7 CY MAR 13-15, 1997 CL SAN ANTONIO, TEXAS ID FUNGAL INFECTION; RISK-FACTORS; EPIDEMIOLOGY AB The objective of this study was to evaluate the pharmacodynamic activity of fluconazole, itraconazole, and amphotericin B against Candida albicans. Susceptibilities were determined according to the NCCLS guidelines (M27). Time-kill studies were performed using antifungal concentrations of 0.25-32 X MIC. Samples were withdrawn at predetermined timepoints, then plated using a spiral plater. Colony counts were determined after incubation at 35 degrees C for 24 h. The AUKC(0-48) was plotted against the concentration/MIC ratio. Candida isolates (95-2672, 96-15, and 95-2542) were classified as susceptible, susceptible-dose dependent, and resistant to fluconazole and itraconazole (MIC = 0.25 and 0.03 mu g/mL, 32 and 0.5 mu g/mL, 64 and 1 mu g/mL; respectively). All three isolates were susceptible to amphotericin B (MIC = 0.13 mu g/mL). Fluconazole inhibited the growth of the susceptible and S-DD isolates and was ineffective at all concentrations against the resistant isolate. Itraconazole, on the other hand, inhibited growth of the susceptible isolate, but was ineffective for the S-DD and resistant isolates. Maximal effectiveness was noted at the concentration 8 X MIC and 2 X MIC for fluconazole and itraconazole, respectively. Amphotericin B demonstrated concentration-dependent antifungal activity. The times necessary for the colony counts to fall below the limit of quantification were inversely related to increasing concentrations of amphotericin B. The maximal effect for amphotericin B was recorded at 2 X MIG. In summary, the triazoles inhibit growth of susceptible C. albicans; however, careful consideration should be given to the MIC for S-DD isolates because itraconazole may not be active if the MIC is reported in the higher susceptible-dose dependency range. In reference to amphotericin B, optimal activity may be achieved by maximizing the peak drug concentration/MIC ratio. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Coll Pharm, Austin, TX 78712 USA. Univ Texas, Hlth Sci Ctr, Dept Pharm, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Burgess, DS (reprint author), Univ Texas, Coll Pharm, Austin, TX 78712 USA. NR 13 TC 32 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JAN PY 2000 VL 36 IS 1 BP 13 EP 18 DI 10.1016/S0732-8893(99)00097-8 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 286QJ UT WOS:000085456400003 PM 10744363 ER PT J AU Anand, BS Velez, M AF Anand, BS Velez, M TI Influence of chronic alcohol abuse on hepatitis C virus replication SO DIGESTIVE DISEASES LA English DT Article DE hepatitis C; alcohol; viremia; HCV-RNA ID LIVER-DISEASE; RNA LEVELS; INFECTION; TRANSFUSION; ANTIBODY AB Background: Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection, Several workers have shown that HCV-infected alcoholics have more severe biochemical and histological evidence of liver disease than anti-HCV-negative patients, One possible mechanism for the increased liver damage is that alcohol may have a stimulatory effect on HCV replication. The present study was carried out to examine this issue in detail. Methods: Sixty-eight HCV-infected patients, comprising of 50 chronic alcoholics, consuming 80 g or more of alcohol daily for at least 5 years, and 18 completely abstinent subjects were included in the study. Quantitative HCV-RNA was performed by the branched chain DNA (bDNA) technique. Results: There was no significant difference in the mean serum HCV titers in chronic alcoholics compared to nonalcoholic subjects. Linear regression analysis showed no correlation between the daily ethanol consumption and HCV titers. Seven of the chronic alcoholics, 4 of whom were continuing to drink and 3 who had become abstinent, were retested after 6 months. There was no definite trend in the viral titers, either in abstinent individuals or in those who continued to drink. Conclusions:These findings suggest that chronic alcohol abuse does not influence the HCV load in the serum. Therefore, the observation that alcoholics with HCV infection have more severe liver damage requires some other explanation than increased HCV viral titers. Copyright (C) 2000 S. Karger AG, Basel. C1 VA Med Ctr, Digest Dis Sect 111D, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Anand, BS (reprint author), VA Med Ctr, Digest Dis Sect 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 21 Z9 21 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2000 VL 18 IS 3 BP 168 EP 171 DI 10.1159/000051390 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 412MM UT WOS:000167559000007 PM 11279335 ER PT J AU Dore, MP Leandro, G Realdi, G Sepulveda, AR Graham, DY AF Dore, MP Leandro, G Realdi, G Sepulveda, AR Graham, DY TI Effect of pretreatment antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy - A meta-analytical approach SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE meta-analysis; metronidazole; clarithromycin; resistance; Helicobacter pylori; therapy ID LANSOPRAZOLE-QUADRUPLE THERAPY; COLLOIDAL BISMUTH SUBCITRATE; PEPTIC-ULCER DISEASE; TRIPLE THERAPY; DUODENAL-ULCER; ERADICATION THERAPY; COMBINATION THERAPY; CLINICAL RELEVANCE; DOUBLE-BLIND; INFECTION AB Our purpose was to define the effect of pretreatment Helicobacter pylori resistance to metronidazole or to clarithromycin on the success of antimicrobial therapy. We used 75 key words to perform a literature search in MEDLINE as well as manual searches to identify clinical treatment trials that provided results in relation to H, pylori susceptibility to metronidazole and clarithromycin or both during the period 1984-1997 (abstracts were not included). Meta-analysis was done with both fixed- and random-effect models; results were shown using Galbraith's radial plots. We identified 49 papers with 65 arms for metronidazole (3594 patients, 2434 harboring H. pylori strains sensitive to metronidazole and 1160 harboring resistant strains). Metronidazole resistance reduced effectiveness by an average of 37.7% (95% CI = 29.6-45.7%). The variability in the risk difference for metronidazole was 122.0 to -90.6 and the chi-square value for heterogeneity was significant (P < 0.001). Susceptibility tests for clarithromycin were performed in 12 studies (501 patients, 468 harboring H. pylori strains sensitive to clarithromycin and 33 harboring resistant strains). Clarithromycin resistance reduced effectiveness by an average of 55% (95% CI = 33-78%). We found no common factors that allowed patients to be divided into subgroups with additional factors significantly associated with resistance. In conclusion, metronidazole or clarithromycin pretreatment resistant Pi. pylori are the main factors responsible for treatment failure with regimens using these compounds. If H. pylori antibiotic resistance continues to increase, pretherapy antibiotic sensitivity testing might become necessary in many regions. C1 Univ Sassari, Ist Clin Med, Dept Internal Med, I-07100 Sassari, Italy. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. IRCCS S De Bellis, Bari, Italy. RP Dore, MP (reprint author), Univ Sassari, Ist Clin Med, Dept Internal Med, Viale San Pietro 8, I-07100 Sassari, Italy. NR 71 TC 145 Z9 152 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2000 VL 45 IS 1 BP 68 EP 76 DI 10.1023/A:1005457226341 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 286WG UT WOS:000085471400012 PM 10695616 ER PT J AU Gerweck, LE AF Gerweck, LE TI The pH difference between tumor and normal tissue offers a tumor specific target for the treatment of cancer SO DRUG RESISTANCE UPDATES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiat Biol, Boston, MA 02114 USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Biol, Cox 7, Boston, MA 02114 USA. NR 8 TC 24 Z9 26 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 2000 VL 3 IS 1 BP 49 EP 50 DI 10.1054/drup.2000.0122 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307CE UT WOS:000086635200008 ER PT J AU Fisher, DE AF Fisher, DE TI Turning p53 on or off: either way may treat cancer SO DRUG RESISTANCE UPDATES LA English DT Review ID TUMOR-SUPPRESSOR GENE; P53-DEPENDENT APOPTOSIS; ACTIVATION; THERAPY; MDM2; TUMORIGENESIS; DEGRADATION; INDUCTION; PATHWAYS; PROMOTES AB The p53 tumor suppressor gene is likely the most commonly mutated tumor suppressor gene in human cancer. Its functions include modulation of both cell cycle arrest and apoptosis. Animal models and human clinical data suggest that in some settings, p53 may be prognostically significant, reflecting its role as a key regulator of cell death during cancer therapy. Two recent strategies have been proposed to exploit p53's unique death-regulating activity in opposite directions and improve cancer treatment. One approach seeks to inhibit p53 in normal cells thereby diminishing therapy-related, p53-dependent toxicity. The other utilizes a peptide derived from the C-terminus of p53 to activate wild-type or mutant p53 proteins, triggering apoptosis with selectivity for transformed cells. These novel approaches hold promise for targeting p53 in cancer therapy and may shed light on mechanisms underlying the role of p53 in cancer cell survival. (C) 2000 Harcourt Publishers Ltd. C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 2000 VL 3 IS 2 BP 77 EP 79 DI 10.1054/drup.2000.0128 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 320NG UT WOS:000087406800003 ER PT J AU Duan, ZF Lamendola, DE Seiden, MV AF Duan, ZF Lamendola, DE Seiden, MV TI CDNA Technologies and their application to drug resistance research: power, potential and problems SO DRUG RESISTANCE UPDATES LA English DT Review ID DIFFERENTIALLY EXPRESSED GENES; SERIAL ANALYSIS; CANCER-CELLS; LUNG-CANCER; IDENTIFICATION; LINE AB The effectiveness of systemic chemotherapy is dramatically limited by both intrinsic and acquired drug resistance. Several new technologies have been developed over the last decade to more rapidly identify underlying genetic alterations that impart a drug-resistant phenotype. Techniques such as cDNA-based subtraction technologies, SAGE analysis, and most recently cDNA array and high-density micro-array technologies have rapidly expanded our ability to detect changes in RNA transcription in drug-resistant tumors. These technologies are currently being applied to generate a large number of new hypotheses regarding the regulatory molecules underlying the drug-resistance phenotype. These techniques suggest that there is a large number of transcriptional changes which occur in the drug-resistance phenotype and future work will need to focus on dissecting which of these transcriptional changes are central to the drug resistance phenotype, both in vitro, and more importantly within clinical neoplasia. (C) 2000 Harcourt Publishers Ltd. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 2000 VL 3 IS 5 BP 277 EP 282 DI 10.1054/drup.2000.0163 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 380EN UT WOS:000165686400004 ER PT J AU Graybill, JR AF Graybill, JR TI The role of murine models in the development of antifungal therapy for systemic mycoses SO DRUG RESISTANCE UPDATES LA English DT Review ID LIPOSOMAL AMPHOTERICIN-B; EXPERIMENTAL CRYPTOCOCCAL MENINGITIS; COLONY-STIMULATING FACTOR; EXPERIMENTAL DISSEMINATED CANDIDIASIS; EXPERIMENTAL PULMONARY ASPERGILLOSIS; TUMOR-NECROSIS-FACTOR; IN-VITRO ACTIVITY; OBOVOIDEUM RAMICHLORIDIUM-MACKENZIEI; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PERSISTENTLY NEUTROPENIC RABBITS AB Animal testing is crucial to the development of new antifungal compounds. This review describes the role that murine and other animal models have played in the development of three classes of antifungal agents: the polyenes, the triazoles and the echinocandins and the ways in which these models have been either the positive link in the path from in vitro studies to the patient, or have foreclosed later clinical evaluation. Efficacy studies in particular mycoses are discussed, as well as studies designed to determine whether combinations of antifungal drugs may have value over single agents. (C) 2000 Harcourt Publishers Ltd. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Graybill, JR (reprint author), Audie Murphy Vet Adm Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 234 TC 17 Z9 18 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 2000 VL 3 IS 6 BP 364 EP 383 DI 10.1054/drup.2000.0171 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 397ER UT WOS:000166680800006 ER PT B AU Hall, JE Welt, CK AF Hall, JE Welt, CK BE Filicori, M TI Inhibin and female reproduction SO ENDOCRINE BASIS OF REPRODUCTIVE FUNCTION LA English DT Proceedings Paper CT Conference on Endocrine Basis of Reproductive Function CY JAN 20-22, 2000 CL TAMPA, FL DE follicle stimulating hormone; luteinizing hormone; gonadotropins; hypothalamic-pituitary-ovarian axis ID HUMAN MENSTRUAL-CYCLE; FOLLICLE-STIMULATING-HORMONE; GONADOTROPIN-RELEASING-HORMONE; 2-SITE ENZYME-IMMUNOASSAY; TOTAL ACTIVIN-A; DIMERIC INHIBIN; IMMUNOREACTIVE INHIBIN; SERUM CONCENTRATIONS; LUTEINIZING-HORMONE; PRECURSOR PROTEINS AB The differential regulation of LH and FSH secretion from a single cell type within the pituitary can be explained in part by differential responses to GnRH pulse frequency and gonadal steroid feedback. In addition, there is increasing evidence that the inhibin system plays a Key role in differential gonadotropin secretion in women. The application of specific assays for dimeric inhibin A and inhibin B to careful observational studies have revealed that both dimeric inhibins are secreted in women. The pattern of inhibin B secretion across the menstrual cycle suggests that it is produced by small and developing follicles while the pattern of inhibin A suggests production by the mature preovulatory follicle and corpus luteum. Studies in GnRH-deficient women in whom FSH levels can be manipulated by changes in GnRH pulse frequency indicate that early follicular phase levels of inhibin B are profoundly sensitive to small changes in the pattern of FSH secretion within the normal range. 'In vitro' studies suggest that these changes result from development of an increasing complement of granulosa cells rather than from an FSH induced increase in inhibin B synthesis and/or secretion from individual cells. Inhibin B does not correlate with increasing size of the dominant follicle while there is a strong correlation of inhibin A with follicle size. GnRH antagonist studies provide evidence of gonadotropin control of inhibin A secretion from the mature follicle. GnRH antagonist studies also indicate that inhibin A is dependent on GnRH-induced gonadotropin secretion in the luteal phase and that it's secretion can be maintained by hCG, but not FSH. In women with regular reproductive cycles, inhibin B levels are lower in those >35 compared with <35 in conjunction with a small, but significant increase in FSH, but no change in estradiol. These studies provide evidence for an endocrine negative feedback role of inhibin B on FSH. Decreased levels of inhibin A occur at a more advanced stage of reproductive aging, but evidence of an endocrine rob of inhibin A in control of FSH is less compelling. In summary: I) the patterns of inhibin A and inhibin B secretion across the menstrual cycle suggest differential synthesis dependent on the stage of follicular development; 2) there is strong evidence for the control of inhibin secretion by gonadotropins, however the specific inhibin affected depends on the stage of follicle maturation; and 3) there is some evidence for a negative feedback role of inhibin B in the control of I;SH secretion in normal women, while that of inhibin A has yet to be established. C1 Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 48 TC 0 Z9 0 U1 0 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0120-2 PY 2000 BP 151 EP 167 PG 17 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA BR08M UT WOS:000165612300009 ER PT B AU Taylor, AE Hall, JE AF Taylor, AE Hall, JE BE Filicori, M TI Insulin, weight, and gonadotropin dynamics SO ENDOCRINE BASIS OF REPRODUCTIVE FUNCTION LA English DT Proceedings Paper CT Conference on Endocrine Basis of Reproductive Function CY JAN 20-22, 2000 CL TAMPA, FL ID POLYCYSTIC-OVARY-SYNDROME; WOMEN; SECRETION; DISEASE C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0120-2 PY 2000 BP 205 EP 214 PG 10 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA BR08M UT WOS:000165612300013 ER PT J AU Robles, R Morita, Y Mann, KK Perez, GI Yang, S Matikainen, T Sherr, DH Tilly, JL AF Robles, R Morita, Y Mann, KK Perez, GI Yang, S Matikainen, T Sherr, DH Tilly, JL TI The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse SO ENDOCRINOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; OOCYTE APOPTOSIS; MICE LACKING; AH RECEPTOR; DESTRUCTION; EXPRESSION; OOGENESIS; BCL-2 AB The aryl hydrocarbon receptor (AhR), so-designated based on the ability of the protein to bind with and be activated by polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons, is part of an emerging family of ligand-activated transcriptional regulators that are distinct from the steroid-thyroid hormone receptor superfamily. Once bound by ligand, the AhR interacts with the AhR nuclear translocator (ARNT) protein to form the aryl hydrocarbon receptor complex (AHRC). Both subunits of the AHRC contain sequences corresponding to basic helix-loop-helix domains, a motif that is shared by a number of other dimeric transcription factors. Although the natural ligand(s) for the AhR remains to be elucidated, to date over fifteen genes, including enzymes, growth factors and other transcription factors, have been identified as potential targets for transcriptional regulation by the chemically-activated AHRC. In the ovary, PAH exposure is known to cause destruction of oocytes within immature follicles, implying that one function of the AhR is to mediate cell death signaling in the female germ line. To assess this possibility, we explored AhR expression patterns in the murine ovary, and then determined the impact of AhR-deficiency (gene knockout) on female germ cell dynamics. Immunohistochemical analysis of ovaries of wild-type female mice indicated that AhR protein was abundantly and exclusively expressed in oocytes and granulosa cells of follicles at all stages of development. Histomorphometric analysis of serial ovarian sections revealed a two-fold higher number of primordial follicles in Ahr-null versus wild-type females at day 4 postpartum. This phenotype likely results from a cell-intrinsic death defect in the developing germ line since AhR-deficiency attenuated the magnitude of oocyte apoptosis in fetal ovaries cultured without hormonal support for 72 h. We propose that the AhR, activated by an as yet unknown endogenous ligand(s), serves to regulate the size of the oocyte reserve endowed at birth by affecting germ cell death during female gametogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Environm Hlth, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. EM jtilly@partners.org FU NIEHS NIH HHS [P42-ES07381, R01-ES06086, R01-ES08430] NR 24 TC 113 Z9 114 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2000 VL 141 IS 1 BP 450 EP 453 DI 10.1210/en.141.1.450 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 267AJ UT WOS:000084332200054 PM 10614669 ER PT J AU Cole, AJ AF Cole, AJ TI Is epilepsy a progressive disease? The neurobiological consequences of epilepsy SO EPILEPSIA LA English DT Article; Proceedings Paper CT 1999 Annual Course on Complications of Epilespy at the American-Epilespy-Society Meeting CY DEC 05, 1999 CL ORLANDO, FLORIDA SP Amer Epilespy Soc DE neuronal injury; signal transduction; second messenger; gene expression; synaptic reorganization; plasticity ID FIBER SYNAPTIC REORGANIZATION; FACTOR MESSENGER-RNA; GRANULE CELL NEUROGENESIS; TEMPORAL-LOBE EPILEPSY; CULTURED MOUSE CELLS; ADULT-RAT FOREBRAIN; NERVE GROWTH-FACTOR; HIPPOCAMPAL-NEURONS; INDUCED SEIZURES; LIMBIC SEIZURES AB While primary, or idiopathic, epilepsies may exist, in the vast majority of cases epilepsy is a symptom of an underlying brain disease or injury. In these cases, it is difficult if not impossible to dissociate the consequences of epilepsy from the consequences of the underlying disease, the treatment of either the disease or the epilepsy, or the actual seizures themselves. Several cases of apparent complications of epilepsy are presented to illustrate the range of consequences encountered in clinical practice and the difficulty in assigning blame for progressive symptomatology in individual cases. Because of the difficulty in interpreting clinical material, many investigators have turned to epilepsy models in order to address the potential progressive consequences of recurrent seizures. The authors review experimental data, mainly from animal models, that illustrate short-, medium-, and long-term morphological and biochemical changes in the brain occurring after seizures, and attempt to relate these observations to the human condition. C1 Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, VBK 830,Fruit St, Boston, MA 02114 USA. NR 71 TC 24 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2000 VL 41 SU 2 BP S13 EP S22 DI 10.1111/j.1528-1157.2000.tb01520.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 323YW UT WOS:000087593600004 PM 10885736 ER PT J AU Fujikawa, DG Shinmei, SS Cai, BY AF Fujikawa, DG Shinmei, SS Cai, BY TI Seizure-induced neuronal necrosis: Implications for programmed cell death mechanisms SO EPILEPSIA LA English DT Article; Proceedings Paper CT 5th Workshop on the Neurobiology of Epilepsy (WONOEP V) CY SEP 08-10, 1999 CL CESKY KRUMLOV, CZECH REPUBLIC SP Hoechst Marion Roussell, Parke Davis, Div Warner Lambert Co, Abbott Labs, Danippon Pharmaceut Co, Astra Charnwood, Daiichipharmaceut, Ortho McNeil Pharmaceut, UCB Pharma & Sanolfi DE apoptosis; status epilepticus; necrosis; DNA laddering; TUNEL stain ID INDUCED STATUS EPILEPTICUS; NMDA RECEPTOR ANTAGONIST; KAINIC ACID TREATMENT; RAT-BRAIN; HIPPOCAMPAL-NEURONS; DNA FRAGMENTATION; CYCLIN D1; DAMAGE; APOPTOSIS; KAINATE AB Purpose: To determine definitively the morphology of neuronal death from lithium-pilocarpine (LPC)-and kainic acid (KA)-induced status epilepticus (SE), and to correlate this with markers of DNA fragmentation that have been associated with cellular apoptosis. Endogenous glutamate release is probably responsible for neuronal death in both seizure models, because neuronal death in both is N-methyl-D-aspartate receptor-mediated. Methods: SE was induced for 3 hours in adult male Wistar rats with either LPC or KA, and 24 or 72 hours later the rats were killed. One group of rats had brain sections, stained with hematoxylin and eosin and the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, examined by light microscopy and by electron microscopy. A separate,group of rats had DNA extracted from the same brain regions examined by electron microscopy in the first group. The extracted DNA was electrophoresed on an agarose gel with ethidium bromide and was examined for the presence or absence of internucleosomal DNA cleavage (DNA "laddering"). Results: Twenty-four and 72 hours after 3 hours of LPC- or KA-induced SE, neuronal death in the hippocampus, amygdala, and piriform, entorhinal, and frontal cortices was morphologically necrotic, in spite of DNA laddering in these regions 24 and 72 hours after SE and positive TUNEL staining in some of the regions 72 hours after SE. Ultrastructurally, necrotic neurons were dark and shrunken, with cytoplasmic vacuoles and pyknotic nuclei with small, irregular, dispersed chromatin clumps. Conclusions: Our results, together with those of other reports, suggest that programmed cell death-promoting mechanisms are activated by SE in neurons that become necrotic rather than apoptotic and point to the possibility that such mechanisms may contribute to SE-induced neuronal necrosis. C1 VA Greater Los Angeles Healthcare Syst, Dept Neurol, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. VA Greater Los Angeles Healthcare Syst, Nursing Home Care Unit, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90024 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, Sepulveda Ambulatory Care Ctr, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 32 TC 54 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2000 VL 41 SU 6 BP S9 EP S13 DI 10.1111/j.1528-1157.2000.tb01549.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 351KN UT WOS:000089156500003 PM 10999512 ER PT J AU Sankar, R Shin, D Liu, HT Katsumori, H Wasterlain, CG AF Sankar, R Shin, D Liu, HT Katsumori, H Wasterlain, CG TI Granule cell neurogenesis after status epilepticus in the immature rat brain SO EPILEPSIA LA English DT Article; Proceedings Paper CT 5th Workshop on the Neurobiology of Epilepsy (WONOEP V) CY SEP 08-10, 1999 CL CESKY KRUMLOV, CZECH REPUBLIC SP Hoechst Marion Roussell, Parke Davis, Div Warner Lambert Co, Abbott Labs, Danippon Pharmaceut Co, Astra Charnwood, Daiichipharmaceut, Ortho McNeil Pharmaceut, UCB Pharma & Sanolfi DE hippocampus; dentate granule cells; development; neurogenesis; lithium-pilocarpine; status epilepticus; epilepsy; synaptic plasticity ID DENTATE GYRUS; SYNAPTIC REORGANIZATION; ADULT-RAT; TREATED RATS; SEIZURES; CONSEQUENCES; PROLIFERATION; HIPPOCAMPUS AB Purpose: Several experimental paradigms of seizure induction that produce epilepsy as a consequence have been shown to be associated with the proliferation of dentate granule cells. In developing animals, the acute sequela of hilar damage and the chronic sequelae of spontaneous seizures and mossy fiber synaptic reorganization, in response to status epilepticus, occur in an age-dependent manner. We investigated seizure-induced granule cell neurogenesis in developing rat pups to study the association between hilar injury, granule cell neurogenesis, and epilepsy. Methods: Rat pups of 2 and 3 weeks postnatal age were subjected to lithium-pilocarpine status epilepticus (LiPC SE). Rats were given bromodeoxyuridine (BrdU; 50 mg/kg intraperitoneal) twice daily for 4 days beginning 3 days after SE to label dividing cells. Routine immunocytochemistry and quantification of BrdU labeling image analysis were performed. Results were compared with previously reported data on cellular injury, mossy fiber sprouting, and spontaneous seizures in rat pups of these ages after LiPC SE. Results: In 3-week-old pups, which demonstrate SE-induced hilar damage and develop spontaneous seizures accompanied by mossy fiber sprouting, the BrdU-immunoreactive area (percent) in the subgranular proliferative zone increased to 10.6 +/- 2.5 compared with 1.4 +/- 0.5 in the control animals (p < 0.05). The 2-week-old animals, which show neither hilar damage nor sprouting and rarely develop spontaneous seizures, also showed a comparable extent of SE-induced neurogenesis [8.0 +/- 1.4 (LiPC SE) versus 0.4 +/- 0.2 (control), p < 0.05]. Conclusions: Seizure-induced granule cell neurogenesis does not appear to be a function of seizure-induced hilar cellular damage. Granule cell neurogenesis induced by SE does not determine epileptogenesis in the developing rat. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Sepulveda, CA USA. RP Sankar, R (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Box 951752, Los Angeles, CA 90095 USA. FU NINDS NIH HHS [NS13515, NS01792] NR 20 TC 64 Z9 73 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2000 VL 41 SU 6 BP S53 EP S56 DI 10.1111/j.1528-1157.2000.tb01557.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 351KN UT WOS:000089156500011 PM 10999520 ER PT J AU Wasterlain, CG Liu, H Mazarati, AM Baldwin, RA Shirasaka, Y Katsumori, H Thompson, KW Sankar, R de Vasconselos, AP Nehlig, A AF Wasterlain, CG Liu, H Mazarati, AM Baldwin, RA Shirasaka, Y Katsumori, H Thompson, KW Sankar, R de Vasconselos, AP Nehlig, A TI Self-sustaining status epilepticus: A condition maintained by potentiation of glutamate receptors and by plastic changes in substance P and other peptide neuromodulators SO EPILEPSIA LA English DT Article; Proceedings Paper CT 5th Workshop on the Neurobiology of Epilepsy (WONOEP V) CY SEP 08-10, 1999 CL CESKY KRUMLOV, CZECH REPUBLIC SP Hoechst Marion Roussell, Parke Davis, Div Warner Lambert Co, Abbott Labs, Danippon Pharmaceut Co, Astra Charnwood, Daiichipharmaceut, Ortho McNeil Pharmaceut, UCB Pharma & Sanolfi DE epilepsy; status epilepticus; glutamate; NMDA receptors; substance P; tachykinins ID BRIEF ELECTRICAL-STIMULATION; PERFORANT PATH; MODEL; SEIZURES; 2-DEOXYGLUCOSE; MAINTENANCE; DRUGS; RATS AB We describe a model of self-sustaining status epilepticus (SSSE) induced by stimulation of the perforant path in free-running rats. In this model, seizures can be transiently suppressed by intrahippocampal injection of a blocker of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate synapses but return in the absence of further stimulation when the drug ceases to act. However, seizures are irreversibly abolished by blockers of N-methyl-D-aspartate receptors given locally or systemically. SSSE is enhanced by substance P and its agonists and blocked by its antagonists. SSSE induces novel expression of substance P-like immunoreactivity in hippocampal principal cells. These changes and those in other limbic peptides may contribute to the maintenance of SSSE and to the modulation of hippocampal excitability during epileptic seizures. C1 VA Greater Los Angeles Hlth Care 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. INSERM, U398, Strasbourg, France. RP Wasterlain, CG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [R01 NS 13515-21] NR 25 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2000 VL 41 SU 6 BP S134 EP S143 DI 10.1111/j.1528-1157.2000.tb01572.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 351KN UT WOS:000089156500026 PM 10999535 ER PT J AU Twomey, J AF Twomey, J TI Genetic knowledge, human values, and responsibility. SO ETHICS & BEHAVIOR LA English DT Book Review C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Twomey, J (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1050-8422 J9 ETHICS BEHAV JI Ethics Behav. PY 2000 VL 10 IS 4 BP 403 EP 406 DI 10.1207/S15327019EB1004_7 PG 4 WC Ethics; Psychology, Multidisciplinary SC Social Sciences - Other Topics; Psychology GA 362BG UT WOS:000089758300007 ER PT J AU Biederman, J Spencer, T AF Biederman, J Spencer, T TI Non-stimulant treatments for ADHD SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Review DE ADHD; non-stimulant treatments ID DEFICIT HYPERACTIVITY DISORDER; OPEN CLINICAL-TRIAL; DOUBLE-BLIND; TOURETTES-SYNDROME; TIC DISORDER; PSYCHIATRIC STATUS; RISK-FACTORS; NICOTINE EXPOSURE; CIGARETTE-SMOKING; FOLLOW-UP AB We reviewed the literature of medication trials in ADHD to evaluate the scope of the available non-stimulant treatments. A variety of compounds with a common noradrenergic/ dopaminergic activity have shown documented anti-ADHD activity. There is a substantial body of literature documenting the efficacy of tricyclic antidepressants on ADHD in over 1,000 subjects. In addition, the atypical antidepressant bupropion and the novel noradrenergic specific antidepressant tomoxetine have also been documented to be effective in the treatment of ADHD in controlled clinical trials. Despite wide use, the scientific base supporting the efficacy of alpha-2, noradrenergic agonists continues to be limited. Several lines of evidence provide preliminary support for the potential benefits of cholinergic cognitive enhancing drugs in such as anticholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). Despite these promising results, more research is needed on alternative pharmacologic treatments for the treatment of ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Univ, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Univ, ACC-725,Fruit St, Boston, MA 02114 USA. NR 118 TC 12 Z9 13 U1 7 U2 7 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PY 2000 VL 9 SU 1 BP 51 EP 59 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 382RQ UT WOS:000165836600007 ER PT J AU Philip, BK Pearman, MH Kovac, AL Chelly, JE Wetchler, BV McKenzie, R Monk, TG Dershwitz, M Mingus, M Sung, YF Hahne, WF Brown, RA AF Philip, BK Pearman, MH Kovac, AL Chelly, JE Wetchler, BV McKenzie, R Monk, TG Dershwitz, M Mingus, M Sung, YF Hahne, WF Brown, RA CA Dolasetron PONV Prevention Study G TI Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: a randomized, placebo-controlled study SO EUROPEAN JOURNAL OF ANAESTHESIOLOGY LA English DT Article DE anti-emetic; dolasetron; nausea; emesis; 5-HT3 antagonist; post-operative complications, postoperative nausea and vomiting; outpatient surgery ID INTRAVENOUS DOLASETRON; GYNECOLOGIC SURGERY; ONDANSETRON; BLIND; CISPLATIN; MESYLATE; EMESIS; WOMEN AB In a multicentre, randomized, double-blind, placebo-controlled dose-ranging study, 1030 patients undergoing outpatient surgery with general anaesthesia received i.v. dolasetron mesylate (12.5, 25, 50, or 100 mg) or placebo. The principal outcome measure was the proportion of patients who were free of emesis or rescue medication for the 24-h period after the study drug was given; the subsidiary outcome measure was survival time without rescue medication. Effects on nausea were quantified using a visual analogue scale. Compared with placebo, a complete response was significantly higher when all four dolasetron doses were combined (49% vs. 58%, P = 0.025). In females, dolasetron, 12.5-mg, dolasetron provided maximum clinical benefit (effectiveness compared with adverse events), with no additional benefit in complete response rates or nausea visual analogue scale scores at higher doses. No significant differences were observed in complete response for any dolasetron dose in males compared with placebo. The majority of adverse events reported were mild or moderate. Dolasetron provided well-tolerated, safe, and effective prophylaxis for post-operative nausea and vomiting with maximum effectiveness observed at a dose of 12.5 mg. C1 Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Baptist Med Ctr, Columbia, SC USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Texas, Houston, TX USA. Methodist Med Ctr Illinois, Peoria, IL USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Washington Univ Hosp, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Ctr, New York, NY USA. ASC Emory Clin, Atlanta, GA USA. Hoechst Marion Roussel, Kansas City, MO USA. RP Philip, BK (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0265-0215 J9 EUR J ANAESTH JI Eur. J. Anaesth. PD JAN PY 2000 VL 17 IS 1 BP 23 EP 32 DI 10.1046/j.1365-2346.2000.00594.x PG 10 WC Anesthesiology SC Anesthesiology GA 299GB UT WOS:000086189200005 PM 10758440 ER PT J AU Goodman, A Cagliero, E AF Goodman, A Cagliero, E TI Megestrol-induced clinical adrenal insufficiency SO EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY LA English DT Article DE megestrol; adrenal insufficiency; Cushingoid features ID ACETATE; AIDS AB Objective: To describe a case of megestrol-induced adrenal insufficiency. Methods: A patient who received megestrol and then developed pituitary-adrenal axis abnormalities is described. The literature is reviewed. Results: The patient developed megestrol-induced Cushingoid features. She developed adrenal insufficiency when megestrol was stopped. Conclusion: Megestrol call induce alterations of the pituitary-adrenal axis in some patients. It is important to consider a diagnosis of adrenal insufficiency in patients with symptoms of fatigue, hypotension, and asthenia who have been treated with megestrol. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, WACC 231, Boston, MA 02114 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU S O G CANADA INC PI MONTREAL PA 1 PLACE VILLE MARIE, MONTREAL, QB 3900, CANADA SN 0392-2936 J9 EUR J GYNAECOL ONCOL JI Eur. J. Gynaecol. Oncol. PY 2000 VL 21 IS 2 BP 117 EP 118 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 313PP UT WOS:000087008300003 PM 10843465 ER PT J AU Sakihama, T Hunsicker, ME Hussey, RE Reinherz, EL AF Sakihama, T Hunsicker, ME Hussey, RE Reinherz, EL TI Human CD4 residue Phe 43 is critical for repertoire development and maturation of MHC class II restricted CD4 single-positive T lineage cells in vivo SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4; T cell repertoire; MHC class II; coreceptor function; transgenic mouse ID IMMUNODEFICIENCY-VIRUS GP120; CD4-DEFICIENT MICE; DEFICIENT MICE; MOLECULES; BINDING; RECEPTOR; ANTIGEN; RECOGNITION; LYMPHOCYTES; ACTIVATION AB To determine the functional significance of structural alteration of CD4-MHC class II interaction in vivo, two human (h)CD4-transgenic (tg) mice were established on a murine (m)CD4(-/-) H-2(b) background. The MHC class II binding-competent hCD4 (R240AhCD4) rescues the number and helper activity of hCD4(+)CD8(-) single-positive (SP) mature T cells in mCD4(-/-) mice. In contrast, the MHC class II binding-deficient F431 hCD4 mutant cannot facilitate normal differentiation of double-positive thymocytes to CD4(+)CD8(-) SP thymocytes. Hence, only 20-25 % of CD4(+)CD8(-) SP T cells found in wild-type or R240A hCD4tg mice are generated, with resultant diminished helper responses. Differentiation of F431 hCD4 SP T cells is MHC class II but not class I dependent as demonstrated by crossing F431 hCD4tg mice onto MHC-deficient mice. These cells show a different pattern of TCR Vu and VP gene usage relative to comparable R240A hCD4 SP T cells from R240 AhCD4tg animals. Expression of activation markers including CD25 and CD69 on F431 hCD4 SP T cells suggests that autoreactive specificities may not have been eliminated intrathymically. Collectively, the results show that CD4-MHC class II interaction significantly influences intrathymic repertoire selection. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Lab Immunobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Lab Immunobiol, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI43649] NR 46 TC 5 Z9 5 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2000 VL 30 IS 1 BP 279 EP 290 PG 12 WC Immunology SC Immunology GA 271KM UT WOS:000084592800031 PM 10602051 ER PT J AU Reppert, SM AF Reppert, SM TI Molecular analysis of the mammalian circadian clock SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 2000 VL 12 SU S BP 1 EP 1 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236600002 ER PT J AU Bithell, A Alberta, JA Stiles, CD Williams, BP AF Bithell, A Alberta, JA Stiles, CD Williams, BP TI PDGF-regulated genes involved in neurogenesis SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 UCL, Windeyer Inst, London, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 2000 VL 12 SU S BP 261 EP 261 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601494 ER PT J AU Smith, CM Alberta, JA Liu, W Stiles, CD Williams, BP AF Smith, CM Alberta, JA Liu, W Stiles, CD Williams, BP TI PDGF-regulated genes involved in neuronal development SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 UCL, London, England. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 2000 VL 12 SU S BP 325 EP 325 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601853 ER PT J AU Berman, S Munakata, J Naliboff, BD Chang, L Mandelkern, M Silverman, D Kovalik, E Mayer, EA AF Berman, S Munakata, J Naliboff, BD Chang, L Mandelkern, M Silverman, D Kovalik, E Mayer, EA TI Gender differences in regional brain response to visceral pressure in IBS patients SO EUROPEAN JOURNAL OF PAIN-LONDON LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; POSITRON EMISSION TOMOGRAPHY; CHRONIC PAIN; MENSTRUAL-CYCLE; PERCEPTION; HUMANS; REPRESENTATION; STIMULATION; PATTERNS; CORTEX AB In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were: much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed. (C) 2000 European Federation of Chapters of the International Association for the Study of Pain. C1 W Los Angeles Vet Affairs Med Ctr, Div Nucl Med, PET Ctr, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, Div Digest Dis, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychol, Div Digest Dis, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90073 USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Nucl Med, PET Ctr, UCLA CURE Neuroenter Dis Program, Bldg 115,Rm 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK48351]; NINR NIH HHS [NR04881] NR 64 TC 110 Z9 114 U1 1 U2 6 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1090-3801 J9 EUR J PAIN-LONDON JI Eur. J. Pain-London PY 2000 VL 4 IS 2 BP 157 EP 172 DI 10.1053/eujp.2000.0167 PG 16 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 337GX UT WOS:000088350000006 PM 10957697 ER PT J AU Duerinckx, AJ Shaaban, A Lewis, A Perloff, J Laks, H AF Duerinckx, AJ Shaaban, A Lewis, A Perloff, J Laks, H TI 3D MR imaging of coronary arteriovenous fistulas SO EUROPEAN RADIOLOGY LA English DT Article DE coronary arteriovenous fistula; MRI; MR angiography; coronary artery; surgery; three-dimensional imaging ID MAGNETIC-RESONANCE ANGIOGRAPHY; ARTERY BYPASS GRAFTS; NONINVASIVE DIAGNOSIS; PATENCY; MANAGEMENT; FLOW AB Coronary arteriovenous fistula are uncommon if not rare, but represent the most prevalent hemodynamically significant congenital malformations the coronary arterial circulation. The goal of this report is to evaluate the use of 3D volume rendering from transaxial breathhold coronary MR angiograms to visualize coronary arteriovenous fistulas. Corollary MR angiography offers a new non-invasive technique that accurately defines the anatomy of these malformations, setting the stage for surgical intervention. C1 W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Radiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Adult Congenital Heart Dis Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Div Cardiothorac Surg, Los Angeles, CA 90095 USA. RP Duerinckx, AJ (reprint author), VA N Texas Healthcare Syst, Serv Radiol, 4500 S Lancaster Rd, Dallas, TX 75216 USA. NR 27 TC 10 Z9 11 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2000 VL 10 IS 9 BP 1459 EP 1463 DI 10.1007/s003309900273 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 352EG UT WOS:000089201100016 PM 10997437 ER PT J AU Saini, S Levine, LA Bramson, RT Jordan, PF Thrall, JH AF Saini, S Levine, LA Bramson, RT Jordan, PF Thrall, JH TI Cost of hospital-based radiological examinations: an update SO EUROPEAN RADIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Symposium on Strategic Studies in Radiology CY AUG 19-21, 1999 CL BERLIN, GERMANY C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Saini, S (reprint author), Harvard Univ, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2000 VL 10 SU 3 BP S368 EP S369 DI 10.1007/PL00014096 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 336GR UT WOS:000088294000011 PM 11001449 ER PT J AU Alper, CA Dubey, DP Yunis, EJ Awdeh, Z AF Alper, CA Dubey, DP Yunis, EJ Awdeh, Z TI A simple estimate of the general population frequency of the MHC susceptibility gene for autoimmune polygenic disease SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article DE polygenic disease; autoimmune disease; diabetes, type 1; multiple sclerosis; MHC ID DEPENDENT DIABETES-MELLITUS; AFFECTED SIB METHOD; HLA; HAPLOTYPES; TWINS; MODEL AB We wished to determine the frequencies of the MHC and non-MHC susceptibility genes for polygenic autoimmune diseases like type 1 diabetes (IDDM). We used Mendelian inheritance and the Hardy-Weinberg equilibrium to calculate the frequencies of mating pairs and susceptible offspring under classical recessive and dominant inheritance of the MHC susceptibility gene. We then analyzed the distribution of haplotype sharing by affected sib pairs of the 4 MHC haplotypes in each of the kinds of mating pairs in terms of the frequency of the disease susceptibility gene. For IDDM, the analysis was consistent with a recessive, but not a dominant, MHC susceptibility gene of frequency 0.525 at a distribution of 55, 38 and 7% of affected sib pairs who share 2, 1 and 0 MHC haplotypes, respectively. A simple relationship was obtained: if inheritance is recessive, the MHC susceptibility gene frequency is the square root of the fraction of affected sib pairs who share no MHC haplotypes multiplied by 4. For recessive inheritance, affected sib pairs who share no haplotypes are solely in families where both parents are homozygous MHC-susceptible. Although homozygous MHC susceptibles represent over 25% of the population, only 2-3% of them are IDDM-susceptible at non-MHC susceptibility loci, also required for disease expression. Predictions from our analysis fit all published observations of the familial occurrence of disease. The analysis is general, simple and provides a single estimate (not a range) of the MHC susceptibility gene frequency. This approach should be applicable to other MHC-determined polygenic diseases. Copyright (C) 2000 S. Karger AG,Basel. C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alper, CA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 29583]; NIADDK NIH HHS [AM 26844] NR 30 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 2000 VL 17 IS 3 BP 138 EP 147 DI 10.1159/000019133 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA 340LM UT WOS:000088534700003 PM 10899739 ER PT J AU Rao, VLR Dogan, A Bowen, KK Dempsey, RJ AF Rao, VLR Dogan, A Bowen, KK Dempsey, RJ TI Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus SO EXPERIMENTAL NEUROLOGY LA English DT Article DE astrocytes; microglia; mRNA; peripheral-type benzodiazepine receptor; PK11195; quantitative autoradiography; traumatic brain injury ID TUMOR-NECROSIS-FACTOR; GLOBAL FOREBRAIN ISCHEMIA; CORTICAL IMPACT INJURY; PROTEIN MESSENGER-RNA; LIGAND H-3 PK11195; BINDING-SITES; PORTACAVAL ANASTOMOSIS; QUANTITATIVE AUTORADIOGRAPHY; CULTURED ASTROCYTES; ENHANCED EXPRESSION AB In mammalian CNS, the peripheral-type benzodiazepine receptor (PTBR) is localized on the outer mitochondrial membrane within the astrocytes and microglia. PTBR transports cholesterol to the site of neurosteroid biosynthesis. Several neurodegenerative disorders were reported to be associated with increased densities of PTBR. In the present study, we evaluated the changes in the PTBR density and gene expression in the brains of rats as a function of time (6 h to 14 days) after traumatic brain injury (TBI). Sham-operated rats served as control. Between 3 and 14 days after TBI, there was a significant increased in the binding of PTBR antagonist [H-3]PK11195 (by 106 to 185%, P < 0.01, as assessed by quantitative autoradiography and in vitro filtration binding) and PTBR mRNA expression (by 2- to 3.4-fold, P < 0.01, as assessed by RT-PCR) in the ipsilateral thalamus. At 14 days after the injury, the neuronal number decreased significantly (by 85 to 90%, P < 0.01) in the ipsilateral thalamus. At the same time point, the ipsilateral thalamus also showed increased numbers of the glial fibrillary acidic protein positive cells (astrocytes, by similar to 3.5-fold) and the ED-1 positive cells (microglia/macrophages, by similar to 36-fold), the two cell types known to be associated with PTBR, Increased PTBR expression following TBI seems to be associated with microglia/macrophages than astrocytes as PTBR density at different periods after TBI correlated better with the number of ED-1 positive cells (r(2) = 0.95) than the GFAP positive cells (r(2) = 0.56). TBI-induced increased PTBR expression is possibly an adaptive response to cellular injury and may play a role in the pathophysiology of TBI. (C) 2000 Academic Press. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Rao, VLR (reprint author), Univ Wisconsin, Dept Neurol Surg, Madison, WI 53706 USA. NR 62 TC 87 Z9 87 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 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2000 VL 161 IS 1 BP 102 EP 114 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 290FU UT WOS:000085666300009 ER PT S AU Poorkaj, P D'Souza, I Bird, TD Schellenberg, GD AF Poorkaj, P D'Souza, I Bird, TD Schellenberg, GD BE Lee, VMY Trojanowski, JQ Buee, L Christen, Y TI Tau mutations: Genetics and pathogenetic mechanisms SO FATAL ATTRACTIONS: PROTEIN AGGREGATES IN NEURODEGENERATIVE DISORDERS SE RESEARCH AND PERSPECTIVES IN ALZHEIMERS DISEASE LA English DT Proceedings Paper CT Meeting on Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders CY APR 12, 1999 CL PARIS, FRANCE SP Fdn Ispen ID PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE-SYSTEM TAUOPATHY; AUTOSOMAL-DOMINANT PARKINSONISM; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; PROTEIN-TAU; PRESENILE-DEMENTIA; ANTISENSE OLIGONUCLEOTIDES; FUNCTIONAL IMPLICATIONS AB Frontotemporal dementia with parkinsonism-chromosome 17 type is caused by mutations in the gene that encodes tau. These mutations can either be missense mutations or mutations in intronic regions immediately adjacent to exon 10 (E10). Some missense mutations cause disease by altering the biochemical properties of the tau protein produced. Other missense mutations act by altering the regulation of inclusion of the alternatively spliced E10. Some of these gene regulatory missense mutations are in an exon splicing enhancer element. Another mutation is in an exon splicing silencer element. These mutations can either increase or decrease exon 10 inclusion in processed tau transcripts. E10 inclusion is also negatively regulated by a cis element spanning the E10-intron 10 boundary. Thus there are at least three different regulatory mechanisms that control whether E10 is included in tau transcripts. In some FTDP-17 families and in progressive supranuclear palsy subjects, genetic studies predict that tau mutations or alleles are responsible for disease, yet no mutations are present in the open reading frame of the gene or in intronic sequences immediately flanking tau exons. The nature and action of these mutations remain to be elucidated. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, Seattle, WA 98108 USA. RP Poorkaj, P (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, Seattle, WA 98108 USA. NR 61 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 3-540-67172-2 J9 RES PER ALZ PY 2000 BP 53 EP 64 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BQ75F UT WOS:000089402900005 ER PT J AU Smith, JJ AF Smith, JJ TI Physician modification of legally marketed medical devices: Regulatory implications under the Federal Food, Drug, and Cosmetic Act SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ctr Innovat Minimally Invas Therapy, Boston, MA USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 4 Z9 4 U1 0 U2 1 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 2000 VL 55 IS 2 BP 245 EP 254 PG 10 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 329QA UT WOS:000087917500005 PM 12269367 ER PT J AU Smith, JJ Shyjan, AM AF Smith, JJ Shyjan, AM TI Defining "least burdensome means" under the Food and Drug Administration Modernization Act of 1997 SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, JJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 10 TC 5 Z9 5 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 2000 VL 55 IS 3 BP 435 EP 447 PG 13 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 358PQ UT WOS:000089566800008 PM 11824468 ER PT J AU Sato, M Maulik, G Bagchi, D Das, DK AF Sato, M Maulik, G Bagchi, D Das, DK TI Myocardial protection by protykin, a novel extract of trans-resveratrol and emodin SO FREE RADICAL RESEARCH LA English DT Article DE protykin; resveratrol; emodin; grape; red wine; antioxidant; ischemia/reperfusion; peroxyl radical; hydroxyl radical; heart; flavonoids; cardioprotection ID FREE-RADICAL SCAVENGERS; ISCHEMIA-REPERFUSION; LIPID-PEROXIDATION; DENSITY-LIPOPROTEIN; HEART; INJURY; CELLS; WINE; FLAVONOIDS; INHIBITOR AB Protykin is an all-natural, high potency standardized extract of trans-resveratrol (20%) and emodin (10%) derived from the dried rhizome of Polygonum cuspidatum. Previous studies have demonstrated free radical scavenging and anti-inflammatory activities of resveratrol. Since free radicals play a crucial role in the pathogenesis of myocardial ischemia/reperfusion injury, we examined whether Protykin could preserve the heart during ischemic arrest. Sprague-Dawley rats were divided into two groups: experimental group was gavaged Protykin (100 mg/kg body wt) dissolved in corn oil for three weeks, while the control group was gavaged corn oil alone. After three weeks, rats were sacrificed, isolated hearts perfused via working mode, were made,globally ischemic for 30 min followed by 2 h of reperfusion. Left ventricular functions were continuously monitored and malonaldehyde (MDA) (presumptive marker for oxidative stress) formation were estimated. At the end of each experiment, myocardial infarct size was measured by TTC staining method. Peroxyl radical scavenging activity of Protykin was determined by examining its ability to remove peroxyl radical generated by 2,2'-azobis (2-amidinopropane) dihydrochloride, while hydroxy radical scavenging activity was tested with its ability to reduce 7-OH.-coumarin-3-carboxylic acid. The results of our study demonstrated that the Protykin group provided cardioprotection as evidenced by improved post-ischemic left ventricular functions (dy, dp/dt(max)) and aortic flow as compared to control group. This was further supported by the reduced infarct size in the Protykin group. Formation of MDA was also reduced by Protykin treatment. In vitro studies demonstrated that Protykin possessed potent peroxyl and hydroxyl radical scavenging activities. The results of this study indicate that Protykin can provide cardioprotection, presumably by virtue of its potent free radical scavenging activity. C1 Univ Connecticut, Sch Med, Dept Surg, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Creighton Univ, Sch Pharm & Allied Hlth Profess, Omaha, NE 68178 USA. RP Das, DK (reprint author), Univ Connecticut, Sch Med, Dept Surg, Farmington, CT 06030 USA. FU NHLBI NIH HHS [HL22559, HL33889, HL34360] NR 42 TC 65 Z9 79 U1 0 U2 3 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2000 VL 32 IS 2 BP 135 EP 144 DI 10.1080/10715760000300141 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276HG UT WOS:000084871500004 PM 10653484 ER PT S AU Irizarry, MC Gomez-Isla, T Gomez-Tortosa, E Hyman, BT AF Irizarry, MC Gomez-Isla, T Gomez-Tortosa, E Hyman, BT BE Kato, T TI Quantitative neuropathological assessment of Alzheimer disease and amyloid precursor protein transgenic mice SO FRONTIERS OF THE MECHANISMS OF MEMORY AND DEMENTIA SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 16th Yokohama 21st Century Forum on Brain Science in the Coming Century CY NOV 10-12, 1999 CL YOKOHAMA, JAPAN SP Yokohama City, Yokohama City Univ, Grad Sch Integrated Sci DE dementia; neurofibrillary tangle; amyloid plaque; Lewy body; stereology; neurodegeneration ID NEURONAL LOSS; ABNORMALITIES C1 Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Boston, MA 02114 USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 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 0-444-50382-X J9 INT CONGR SER PY 2000 IS 1200 BP 133 EP 136 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BP96Z UT WOS:000086779300045 ER PT B AU Rosowski, JJ AF Rosowski, JJ BE Rosowski, JJ Merchant, SN TI Mechanisms of sound conduction in normal and diseased ears SO FUNCTION AND MECHANICS OF NORMAL, DISEASED AND RECONSTRUCTED MIDDLE EARS LA English DT Proceedings Paper CT 2nd International Symposium on Middle Ear Mechanics in Research and Otosurgery CY OCT 21-24, 1999 CL BOSTON, MA SP Harvard Med Sch, Dept Continuing Educ, Massachusetts Eye & Ear Infirmary, Dept Otolaryngol DE external ear; middle ear; conductive hearing loss ID MIDDLE-EAR AB This paper reviews the four basic processes of sound conduction from the environment to the inner ear: 1. sound collection by the head, bully and external ear; 2. sound transformation by the tympanic membrane (TM) and ossicles of the middle ear; 3. direct-acoustic stimulation of the inner ear by sound in the middle ear cavity; and 4. stimulation of the inner ear by sound that is conducted by the whole body. These four processes are combined into three sound-conduction routes, where one route results from the combination of the external ear and TM and ossicular processes, the second route results from the combination of the external ear and the direct-acoustic processes, and the third route is the whole-body process that also depends on the normal operation of the external and middle ear structures. The contribution of the three routes to normal hearing is discussed, as well as how these routes are differentially affected by pathologies. It is concluded that, in the normal ear, sound conduction via the external ear and TM-ossicular system dominates sound conduction via the other routes. However, in cases of severe TM and ossicular pathology, the acoustic and whole-body routes can dominate sound conduction and thereby limit the magnitude of conductive hearing losses to generally less than 60 dB HL. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 2 Z9 2 U1 2 U2 3 PU KUGLER PUBLICATIONS BV PI THE HAGUE PA PO BOX 97747, 2509 GC THE HAGUE, NETHERLANDS BN 90-6299-181-5 PY 2000 BP 137 EP 145 PG 9 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS14B UT WOS:000168820700011 ER PT B AU Nadol, JB AF Nadol, JB BE Rosowski, JJ Merchant, SN TI Histopathological correlates of residual and recurrent conductive hearing loss following tympanoplasty and stapedectomy SO FUNCTION AND MECHANICS OF NORMAL, DISEASED AND RECONSTRUCTED MIDDLE EARS LA English DT Proceedings Paper CT 2nd International Symposium on Middle Ear Mechanics in Research and Otosurgery CY OCT 21-24, 1999 CL BOSTON, MA SP Harvard Med Sch, Dept Continuing Educ, Massachusetts Eye & Ear Infirmary, Dept Otolaryngol DE residual/recurrent conductive hearing loss; tympanoplasty; stapedectomy ID CHRONIC OTITIS-MEDIA; MIDDLE-EAR MECHANICS; STAGE TYMPANOPLASTY; RECONSTRUCTED EARS; TYMPANOSCLEROSIS AB Hearing results following tympanoplasty for chronic otitis media and following stapedectomy for otosclerosis commonly result in either residual or recurrent conductive hearing loss. The purpose of this study was to review the histopathology of human temporal bone specimens from patients who in life had undergone surgery for chronic otitis media or otosclerosis in order to identify probable causes of this hearing loss. In chronic otitis media, these pathological changes include tympanosclerosis, resorptive osteitis of the ossicles, fibrocystic sclerosis and sclerosing osteitis of the temporal bone, fibrous thickening or atrophic changes in the tympanic membrane. In addition, ossicular replacement grafts and prostheses are subject to an inflammatory response and resorption. Following stapedectomy, the most common causes of residual and recurrent conductive hearing loss include resorptive osteitis of the incus, obliteration of the round window by otosclerosis, unremoved footplate fragments in contact with the prosthesis, contact of the prosthesis with the bony margin of the oval window, adhesions in the middle ear, and new bone formation within the oval window. Better control of the inflammatory responses in chronic otitis media and following surgical manipulation of the middle ear, either for chronic otitis or for otosclerosis, may decrease the occurrence of residual and recurrent conductive hearing loss and must be considered in modification of procedures and prostheses for these surgeries. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU KUGLER PUBLICATIONS BV PI THE HAGUE PA PO BOX 97747, 2509 GC THE HAGUE, NETHERLANDS BN 90-6299-181-5 PY 2000 BP 189 EP 203 PG 15 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS14B UT WOS:000168820700016 ER PT B AU Merchant, SN Whittemore, KR Poon, B Lee, CY Rosowski, JJ AF Merchant, SN Whittemore, KR Poon, B Lee, CY Rosowski, JJ BE Rosowski, JJ Merchant, SN TI Clinical measurements of tympanic membrane velocity using Laser Doppler vibrometry - Preliminary results, methodological issues and potential applications SO FUNCTION AND MECHANICS OF NORMAL, DISEASED AND RECONSTRUCTED MIDDLE EARS LA English DT Proceedings Paper CT 2nd International Symposium on Middle Ear Mechanics in Research and Otosurgery CY OCT 21-24, 1999 CL BOSTON, MA SP Harvard Med Sch, Dept Continuing Educ, Massachusetts Eye & Ear Infirmary, Dept Otolaryngol DE middle ear; conductive hearing loss ID TIME-AVERAGED HOLOGRAPHY; HUMAN MIDDLE-EAR; VIBRATIONS; CAT AB Traditional methods of investigating the mechanics of middle ear function in patients with conductive hearing loss and middle ear disease include audiometry and tympanometry. These methods cannot reliably differentiate among ossicular pathologies, especially when the tympanic membrane is intact or when there has been previous middle ear surgery. Laser Doppler vibrometry has been proposed as a method to improve the diagnosis of middle car lesions. Recently-introduced laser Doppler vibrometry devices with improved demodulators make it possible to measure tympanic membrane velocity in a non-invasive manner in the span of a few minutes. In this paper, the authors present their preliminary measurements of tympanic membrane velocity using laser vibrometry and discuss the potential applications and some methodological issues related to clinical laser vibrometry measurements. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. MIT, Speech & Hearing Sci Program, Div Hlth Sci & Technol, Cambridge, MA USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 6 Z9 6 U1 0 U2 1 PU KUGLER PUBLICATIONS BV PI THE HAGUE PA PO BOX 97747, 2509 GC THE HAGUE, NETHERLANDS BN 90-6299-181-5 PY 2000 BP 367 EP 381 PG 15 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS14B UT WOS:000168820700033 ER PT J AU Reuter, U del Rio, MS Moskowitz, MA AF Reuter, U del Rio, MS Moskowitz, MA TI Experimental models of migraine SO FUNCTIONAL NEUROLOGY LA English DT Article; Proceedings Paper CT Conference on Migraine and Other Head Pain CY JUN 27-29, 1999 CL PAVIA, ITALY SP Minist Sanita, Minist Univ Ricerca Sci, Soc Italiana Studio Cafalee, Soc Italiana Neurol, European Headache Federat, Int Headache Soc DE aura; methods; migraine; pathophysiology; neurogenic inflammation; rCBF ID GENE-RELATED PEPTIDE; RAT DURA-MATER; PLASMA-PROTEIN EXTRAVASATION; TRIGEMINAL NUCLEUS CAUDALIS; SUPERIOR SAGITTAL SINUS; C-FOS EXPRESSION; SUBSTANCE-P; BLOOD-VESSELS; ELECTRICAL-STIMULATION; EXTRACEREBRAL CIRCULATION AB Experimental models have been developed to study various aspects of migraine. Here we describe the most commonly used models - mostly animal models which led to the development of a pathophysiological concept of migraine. We focus on activation studies of the trigeminovascular system, the sphenopalatine ganglion, the superior sagittal sinus, the dura mater as well as blood vessels. The most common consequences of activation are noted and include protein extravasation, neuropeptide release: rCBF and diameter changes, c-fos expression and electrical neuronal activity. In addition, we briefly summarize the results of cortical spreading depression studies, as they relate to the human migraine aura. These models will continue to be useful to elucidate migraine pathophysiology and explore drug mechanisms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 70 TC 16 Z9 16 U1 1 U2 2 PU C I C-EDIZIONI INT SRL PI ROME PA CORSO TRIESTE, 42, 00198 ROME, ITALY SN 0393-5264 EI 1971-3274 J9 FUNCT NEUROL JI Funct. Neurol. PY 2000 VL 15 IS 3 SU S BP 9 EP 18 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 395DK UT WOS:000166563300001 PM 11200808 ER PT J AU del Rio, MS Reuter, U Moskowitz, MA AF del Rio, MS Reuter, U Moskowitz, MA TI Central and peripheral mechanisms of migraine SO FUNCTIONAL NEUROLOGY LA English DT Article; Proceedings Paper CT Conference on Migraine and Other Head Pain CY JUN 27-29, 1999 CL PAVIA, ITALY SP Minist Sanita, Minist Univ Ricerca Sci, Soc Italiana Studio Cafalee, Soc Italiana Neurol, European Headache Federat, Int Headache Soc DE central mechanisms; migraine; peripheral mechanisms; trigeminovascular ID FAMILIAL HEMIPLEGIC MIGRAINE; TRANSCRANIAL MAGNETIC STIMULATION; STEM TRIGEMINAL NEURONS; EXTRACEREBRAL CIRCULATION; OCCIPITAL CORTEX; CLUSTER HEADACHE; BLOOD-VESSELS; CHANNEL GENE; SUBSTANCE-P; AURA AB Central (cortex and upper brainstem) and peripheral (trigeminovascular) mechanisms are involved in the pathophysiology of migraine. We propose that unknown migraine triggers initiate depolarization of cortical neurons followed concomitantly by a transient increase in blood flow. This transient hyperemia spreads at a rate of 3-6 mm/min followed by hypoperfusion which is more long-lasting. Through unknown mechanisms (probably chemical), we hypothesize that this wave activates or sensitizes trigeminovascular axons which is a consequence of neuropeptide release and neurogenic inflammation. Orthodromic conduction along trigeminovascular fibers transmits information centrally via the trigeminal caudalis and other brain stem nuclei to higher cortical structures for registration and modulation of nociceptive information. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Neurol, Charlestown, MA USA. RI Moskowitz, Michael/D-9916-2011 NR 37 TC 15 Z9 15 U1 0 U2 1 PU C I C-EDIZIONI INTERNAZIONALI SRL PI ROME PA VIA L SPALLANZANI 11, 00161 ROME, ITALY SN 0393-5264 J9 FUNCT NEUROL JI Funct. Neurol. PY 2000 VL 15 IS 3 SU S BP 157 EP 162 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 395DK UT WOS:000166563300019 ER PT J AU Wang, TC Dangler, CA Chen, D Goldenring, JR Koh, T Raychowdhury, R Coffey, RJ Ito, S Varro, A Dockray, GJ Fox, JG AF Wang, TC Dangler, CA Chen, D Goldenring, JR Koh, T Raychowdhury, R Coffey, RJ Ito, S Varro, A Dockray, GJ Fox, JG TI Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer SO GASTROENTEROLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; TRANSGENIC MICE; MENETRIERS DISEASE; PYLORI INFECTION; ACID-SECRETION; MUCOSA; DIFFERENTIATION; STOMACH; PROGASTRIN; OMEPRAZOLE AB Background & Aims: Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined. Methods: The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice. Results: INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria, Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor or. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (less than or equal to 8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P less than or equal to 0.05). Conclusions: These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Univ Lund, Dept Pharmacol, Lund, Sweden. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Vet Adm Med Ctr, Augusta, GA 30904 USA. Vanderbilt Univ, Med Ctr, Dept Med & Cell Biol, Nashville, TN USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 724,32 Fruit St, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NCI NIH HHS [R01 CA67529] NR 46 TC 362 Z9 377 U1 1 U2 17 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 2000 VL 118 IS 1 BP 36 EP 47 DI 10.1016/S0016-5085(00)70412-4 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 268GC UT WOS:000084405100011 PM 10611152 ER PT J AU Fink, DJ DeLuca, NA Yamada, M Wolfe, DP Glorioso, JC AF Fink, DJ DeLuca, NA Yamada, M Wolfe, DP Glorioso, JC TI Design and application of HSV vectors for neuroprotection SO GENE THERAPY LA English DT Review DE herpes simplex; gene transfer; neurodegenerative disease; nerve growth factor ID HERPES-SIMPLEX VIRUS; TRIGEMINAL GANGLIA; LATENT INFECTION; TYPE-1; EXPRESSION; CELLS; TRANSCRIPTS; RECEPTOR; MUTANTS; ENTRY AB Herpes simplex virus has been extensively genetically modified for gene transfer to nerve and other tissues, to create vectors that are devoid of viral gene expression and toxicity. Recombinant vectors have been engineered to express genes which protect neurons against toxic insults resulting in cell death, including nerve growth factor (NGF) and anti-apopiotic genes (eg bcl-2). This review describes experiments using HSV vectors expressing these gene products and their potential protective role in ameliorating neurodegenerative processes in animal model systems. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Glorioso, JC (reprint author), Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, E1240 Biomed Sci Tower, Pittsburgh, PA 15261 USA. FU NCI NIH HHS [2R01CA66141-10A2]; NEI NIH HHS [5R01EY11528-03]; NIAMS NIH HHS [5R01AR4552603] NR 20 TC 37 Z9 37 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2000 VL 7 IS 2 BP 115 EP 119 DI 10.1038/sj.gt.3301118 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 281DZ UT WOS:000085143800004 PM 10673716 ER PT J AU Reiter, RE Sato, I Thomas, G Qian, JQ Gu, ZN Watabe, T Loda, M Jenkins, RB AF Reiter, RE Sato, I Thomas, G Qian, JQ Gu, ZN Watabe, T Loda, M Jenkins, RB TI Coamplification of prostate stem cell antigen (PSCA) and MYC in locally advanced prostate cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; GENETIC ALTERATIONS; ALLELIC IMBALANCE; EXPRESSION; PROTOONCOGENE; AMPLIFICATION; CARCINOMAS; PROTEIN AB Gain of sequences on chromosome arm 8q is a common feature of prostate cancer that may correlate with metastatic and androgen-independent progression. The target gene(s) for this gain is not known, although MYC is amplified in a subset of advanced tumors and is one potential candidate. Prostate stem cell antigen (PSCA) is a prostate-specific cell surface protein that maps to chromosome region 8q24.2 and is overexpressed in prostate cancer. Our aim in this study was to test the hypothesis that PSCA overexpression may result from overrepresentation of chromosome arm 8q. Twenty locally advanced prostate cancers were analyzed by dual-probe fluorescence in situ hybridization (FISH) for alterations of MYC and PSCA. Extra copies of MYC were found in 12/20 (60%) tumors, including 5 (25%) with simple gain (no increase in MYC copy number relative to the chromosome 8 centromere) and 7 (35%) with an additional increase (AI or overrepresentation) in MYC copy number relative to the centromere. In the five cases with simple gain of MYC, there was a concomitant gain of PSCA, PSCA was overrepresented in 5/7 (71%) cases with AI of MYC. Immunohistochemical staining of the 20 tumors with monoclonal antibodies specific for PSCA showed a high degree of correlation between PSCA gene overrepresentation and protein overexpression. Four of 5 tumors with Al of PSCA overexpressed PSCA protein, compared with only 2/15 tumors with a normal PSCA copy number or simple gain of PSCA (P = 0.0 14). These results demonstrate that PSCA is co-overrepresented with MYC in a majority of cases, but may not be a necessary part of the 8q amplicon. PSCA protein overexpression can result from AI of PSCA and might be useful as a cell surface marker on prostate cancer cells with 8q overrepresentation. Genes Chromosomes Cancer 27:95-103, 2000. (C) 2000 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci 66 134, Los Angeles, CA 90095 USA. Mayo Clin, Rochester, MN USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Univ Calif Los Angeles, Dept Microbiol & Mol Genet, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Reiter, RE (reprint author), Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci 66 134, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 24 TC 71 Z9 78 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 2000 VL 27 IS 1 BP 95 EP 103 DI 10.1002/(SICI)1098-2264(200001)27:1<95::AID-GCC12>3.0.CO;2-3 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 260PV UT WOS:000083959800012 PM 10564591 ER PT J AU Hong, SL O'Hagan, RC Hou, H Horner, JW Lee, HW DePinho, RA AF Hong, SL O'Hagan, RC Hou, H Horner, JW Lee, HW DePinho, RA TI Essential role for Max in early embryonic growth and development SO GENES & DEVELOPMENT LA English DT Article DE Max; mammalian development; Myc function ID C-MYC PROTEIN; N-MYC; TARGETED DISRUPTION; ONCOGENIC ACTIVITY; DNA-BINDING; MAMMALIAN DEVELOPMENT; RAS COTRANSFORMATION; MOUSE DEVELOPMENT; ANTAGONIST MAD1; REPRESSOR SIN3 AB Loss of Max function in the mouse resulted in generalized developmental arrest of both embryonic and extraembryonic tissues at early postimplantation (similar to E5.5-6.5), coincident with loss or dilution of maternal Max stores in the expanding embryo in vivo and in blastocyst outgrowths in vitro. Developmentally arrested embryos were reduced in size and exhibited widespread cytological degeneration and feeble BrdU incorporation. Max and, by extension, the Myc superfamily, serve essential roles in early mammalian development and a maternal reservoir of Max exists in sufficient amount to sustain Myc superfamily function through preimplantation stages of development. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 39 TC 4 Z9 4 U1 1 U2 1 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 2000 VL 14 IS 1 BP 17 EP 22 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 276GC UT WOS:000084866400003 ER PT J AU Rinkenberger, JL Horning, S Klocke, B Roth, K Korsmeyer, SJ AF Rinkenberger, JL Horning, S Klocke, B Roth, K Korsmeyer, SJ TI Mcl-1 deficiency results in peri-implantation embryonic lethality SO GENES & DEVELOPMENT LA English DT Article DE Mcl-1; apoptosis implantation; embryo; blastocyst; Bcl-2 family ID HAMSTER OVARY CELLS; BCL-2 FAMILY; IMMUNOHISTOCHEMICAL ANALYSIS; PREIMPLANTATION DEVELOPMENT; MDM2-DEFICIENT MICE; HEMATOPOIETIC-CELLS; MOUSE BLASTOCYST; GENE-EXPRESSION; DEATH; APOPTOSIS AB We disrupted the Mcl-1 locus in murine ES cells to determine the developmental roles of this Bcl-2 family member. Deletion of Mcl-1 resulted in peri-implantation embryonic lethality. Mcl-1(-/-) embryos do not implant in utero, but could be recovered at E3.5-4.0. Null blastocysts failed to hatch or attach in vitro, indicating a trophectoderm defect, although the inner cell mass could grow in culture. Of note, Mcl-1(-/-) blastocysts showed no evidence of increased apoptosis, but exhibited a delay in maturation beyond the precompaction stage. This model indicates that Mcl-1 is essential for preimplantation development and implantation, and suggests that it has a function beyond regulating apoptosis. C1 Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Med, St Louis, MO 63110 USA. OI Roth, Kevin/0000-0002-0643-995X FU NCI NIH HHS [CA49712-10] NR 38 TC 217 Z9 222 U1 0 U2 6 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 2000 VL 14 IS 1 BP 23 EP 27 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 276GC UT WOS:000084866400004 PM 10640272 ER PT J AU Faraone, SV Biederman, J Monuteaux, MC AF Faraone, SV Biederman, J Monuteaux, MC TI Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder SO GENETIC EPIDEMIOLOGY LA English DT Review DE ADHD; conduct disorder; power; linkage analysis; ascertainment ID 4-YEAR FOLLOW-UP; CONDUCT DISORDER; DSM-III; GENERAL-POPULATION; ADHD CHILDREN; FAMILIAL SUBTYPES; BIPOLAR DISORDER; RECEPTOR POLYMORPHISM; DOPAMINE-D4 RECEPTOR; SEGREGATION ANALYSIS AB Converging evidence from family, twin, and adoption studies points to a substantial genetic component of the etiology of attention deficit hyperactivity disorder (ADHD). These data about ADHD have motivated molecular genetic studies of the disorder, which have produced intriguing but somewhat conflicting results. Some studies have reported associations with candidate genes and others not. Our review of the literature shows that one problem facing molecular genetic studies of ADHD is that its recurrence risk to first-degree relatives is only about five times higher than the population prevalence. This suggests that, to produce consistently replicated results, molecular genetic studies should either use much larger samples or should select those families in which genes exert the largest effect. Risch [(1990a) Am J Hum Genet 46:222-228; (1990b) Am J Hum Genet 46:229-241] proved that the statistical power of a linkage study increases with the magnitude of risk ratios (lambda's) computed by dividing the affection rate among each relative type to the rate of affection in the population. Our prior work suggests two dimensions of genetic heterogeneity that might be useful for selecting ADHD subjects for molecular genetic studies: comorbidity with conduct disorder and persistence of ADHD into adolescence. This paper shows that these sub-phenotypes are useful for molecular genetic studies because (1) they have much higher empirical lambda values and (2) they affect a substantial minority of ADHD patients. Genet. Epidemiol. 18:1-16, 2000. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R01MH57934, R13MH59126] NR 116 TC 121 Z9 127 U1 8 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2000 VL 18 IS 1 BP 1 EP 16 PG 16 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 270RR UT WOS:000084550400001 PM 10603455 ER PT J AU Wildermuth, MC AF Wildermuth, Mary C. TI Metabolic control analysis: biological applications and insights SO GENOME BIOLOGY LA English DT Review AB Metabolic control analysis provides a robust mathematical and theoretical framework for describing metabolic and signaling pathways and networks, and for quantifying the controls over these processes. Its application has already shed light on some of the principles underlying the regulation of metabolic pathways, and it is well suited to the analysis of the types of data emerging from genomic studies. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Wildermuth, MC (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. EM wildermu@genetics.mgh.harvard.edu NR 30 TC 4 Z9 4 U1 0 U2 1 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 2000 VL 1 IS 6 AR 1031.1 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EV UT WOS:000207583400005 ER PT J AU Reizis, B Lee, JT Leder, P AF Reizis, B Lee, JT Leder, P TI Homologous genomic fragments in the mouse pre-T cell receptor alpha (pTa) and Xist loci SO GENOMICS LA English DT Article ID X-CHROMOSOME INACTIVATION; GENE AB We recently characterized a genomic region located upstream of the mouse pre-T cell receptor alpha (pTa) gene, which controls pTa expression in pre-T cells. We now report an unexpected homology between this region and a region in the mouse X chromosome inactivation center between the 3' end of the Xist gene and the start of an, antisense transcript Tsix, The homology is extended over 4 kb of genomic sequence split by an expanded repeat region and is observed only in the mouse, not in the rat. Despite high sequence similarity to the pTa transcriptional enhancer, the homologous X chromosome fragment appears to have lost its enhancer activity. These data underscore the complex organization of the mouse genome and, in particular, of the X chromosome inactivation center. (C) 2000 Academic Press. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Leder, P (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. OI Reizis, Boris/0000-0003-1140-7853 NR 11 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 2000 VL 63 IS 1 BP 149 EP 152 DI 10.1006/geno.1999.6068 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286FC UT WOS:000085432100020 PM 10662556 ER PT J AU Cutrer, FM AF Cutrer, FM TI What does "fast" mean in migraine management? SO HEADACHE QUARTERLY-CURRENT TREATMENT AND RESEARCH LA English DT Article; Proceedings Paper CT Roundtable Meeting on Managing Migraine CY JUL 18-22, 1999 CL LAKE BUENA VISTA, FLORIDA C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Headache Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU DIAMOND HEADACHE CLINIC RESEARCH & EDUC FOUNDATION PI CHICAGO PA 467 WEST DEMING PLACE, CHICAGO, IL 60614 USA SN 1059-7565 J9 HEADACHE Q-CURR TREA JI Headache Q.-Curr. Treat. Res. PY 2000 VL 11 SU 1 BP 17 EP 19 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 371KD UT WOS:000165177400006 ER PT J AU Ockene, JK Emmons, KM Mermelstein, RJ Perkins, KA Bonollo, DS Voorhees, CC Hollis, JF AF Ockene, JK Emmons, KM Mermelstein, RJ Perkins, KA Bonollo, DS Voorhees, CC Hollis, JF TI Relapse and maintenance issues for smoking cessation SO HEALTH PSYCHOLOGY LA English DT Review DE smoking cessation; smoking treatment; adherence; smoking intervention ID SELF-HELP MATERIALS; WEIGHT-GAIN; RANDOMIZED TRIAL; CIGARETTE-SMOKING; UNITED-STATES; QUIT SMOKING; LONGITUDINAL ANALYSIS; NICOTINE DEPENDENCE; INTERVENTION TRIAL; TOBACCO SMOKING AB This article reviews short-term (6 months) and longer term (12-24 months) maintenance of cessation and relapse in adult smokers and the factors and treatments that affect these outcomes. MedLine and PsycLIT searches were done for research published in English between 1988 and 1998 meeting a defined set of criteria. Intensive intervention, telephone counseling, and use of pharmacotherapy were found to improve outcomes; however, compared with public health approaches, they reach relatively few smokers. Brief interventions during medical visits are cost-effective and could potentially reach most smokers but are not consistently delivered. Predictors of relapse include slips, younger age, nicotine dependence, low self-efficacy, weight concerns, and previous quit attempts. Potential areas for research, recommendations for longer follow-up assessments, and standard definitions for slip, relapse, and long-term maintenance are discussed. C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Ockene, JK (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. RI Perkins, Kenneth/E-4085-2010 NR 127 TC 185 Z9 189 U1 3 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2000 VL 19 IS 1 SU S BP 17 EP 31 DI 10.1037//0278-6133.19.Suppl1.17 PG 15 WC Psychology, Clinical; Psychology SC Psychology GA 290RW UT WOS:000085692500003 PM 10709945 ER PT J AU White, JK Titus, JS Tanabe, H Aretz, T Torchiana, DF AF White, JK Titus, JS Tanabe, H Aretz, T Torchiana, DF TI The use of a novel tissue sealant as a hemostatic adjunct in cardiac surgery SO HEART SURGERY FORUM LA English DT Article; Proceedings Paper CT 3rd Annual NewEra Cardiac Care Conference CY JAN 13-16, 2000 CL SAN DIEGO, CA ID FIBRIN SEALANT; ADHESION PREVENTION; AORTIC DISSECTION; AIR LEAKS; HYDROGEL; GLUE; BIOCOMPATIBILITY; OPERATIONS; COPOLYMERS; EFFICACY AB Background: In spite of advances in the management of bleeding associated with cardiac surgery, hemorrhage remains a troublesome problem, particularly in complex cases and high risk patients. In minimally invasive cardiac surgery, limited exposure and tight quarters may make accurate suturing difficult, and increase the risk of surgical bleeding. A surgical sealant that effectively prevents suture line bleeding would be a valuable resource for cardiac surgeons and might help to facilitate minimal access cases. Methods: We undertook acute canine studies with a new polyethylene glycol-based tissue sealant (FocalSeal(TM), Focal, Inc., Lexington, MA) to determine its effectiveness in controlling bleeding from graduated needle punctures sites in the arteries of heparinized animals. For chronic canine studies, the sealant was applied to the suture line of a left internal mammary artery (LIMA) to left anterior descending (LAD) anastomoses. The anastomoses were then evaluated for patency and tissue reaction after a three-month recovery period. Results: The sealant prevented bleeding from arterial puncture wounds up to 2.5 mm in diameter. Three months following the application of sealant to coronary anastomoses, no adverse tissue reaction was found on histologic examination. All anastomoses treated with the sealant remained patent. Conclusions: When applied as a hemostatic adjunct to sutures at a coronary anastomosis, the sealant appears to be an effective means of preventing bleeding without adverse tissue reaction or scarring. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Bullfinch 119, Boston, MA 02114 USA. EM DTORCHIANA@PARTNERS.ORG NR 34 TC 14 Z9 16 U1 1 U2 4 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PY 2000 VL 3 IS 1 BP 56 EP 61 AR 2000-8999 PG 6 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 334WV UT WOS:000088209400010 PM 11064548 ER PT J AU Sturm, E Zimmerman, TL Crawford, AR Svetlov, SI Sundaram, P Ferrara, JLM Karpen, SJ Crawford, JM AF Sturm, E Zimmerman, TL Crawford, AR Svetlov, SI Sundaram, P Ferrara, JLM Karpen, SJ Crawford, JM TI Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line SO HEPATOLOGY LA English DT Article ID PLASMA-MEMBRANE VESICLES; INFLAMMATORY CYTOKINES; UP-REGULATION; SALT UPTAKE; LIVER; HEPATOCYTES; CHOLESTASIS; EXPRESSION; TRANSPORT; INDUCE AB Endotoxemia leads to cytokine-mediated alterations of the hepatocellular sodium-taurocholate-cotransporting polypeptide (ntcp). We hypothesized that stimulated macrophages are essential transducers for down-regulating hepatocellular bile salt uptake in response to endotoxin (lipopolysaccharide [LPS]) exposure, Using an in vitro model, we exposed mouse macrophages (IC-21 cell line) to LPS for 24 hours. Concentrations of cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 increased 10.6-fold, 12.5-fold, and 444-fold, respectively, in LPS-conditioned IC-21 medium (CM) versus unconditioned IC-21 medium (UM), WIF-B rat hepatoma hybrid cells were incubated with either CM or UM or treated directly with medium containing recombinant TNF-alpha, IL-1 beta, and IL-6. [H-3]Taurocholate ([H-3]TC) uptake decreased in WIF-B cells exposed to either TNF-alpha (54% of control), IL-1 beta (78%), IL-6 (55%) as single additives, or in triple combination (TCC) (43%), A virtually identical decrease was observed after exposing WIF-B cells to CM (52%, P <.001). LPS had no direct effect on [H-3]TC uptake. CM treatment did not decrease L-alanine transport in WIF-B cells. Blocking antibodies against TNF-alpha, IL-1 beta, and IL-6 restored the diminished [H-3]TC uptake in cells exposed to TCC and CM to 87% and 107% of controls, respectively. Northern blotting revealed that ntcp messenger RNA (mRNA) expression was significantly reduced in WIF-B cells after exposure to CM, and in primary rat hepatocytes exposed to CM or TNF-alpha (68%, 14%, and 29% of control, respectively). We conclude that macrophages and their ability to secrete the cytokines TNF-alpha, IL-1 beta, and IL-6 may be essential in mediating the endotoxin-induced cholestatic effect of decreased hepatocellular bile salt uptake. C1 Yale Univ, Sch Med, Program Gastrointestinal Pathol, New Haven, CT USA. Yale Univ, Sch Med, Sect Digest Dis, New Haven, CT USA. Yale Univ, Sch Med, Yale Liver Ctr, Dept Pediat, New Haven, CT USA. Dana Farber Canc Ctr, Boston, MA USA. RP Crawford, JM (reprint author), Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, POB 100275, Gainesville, FL 32610 USA. FU NIDDK NIH HHS [R01 DK056239, DK53512, DK39512, R01 DK056239-01] NR 35 TC 18 Z9 19 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2000 VL 31 IS 1 BP 124 EP 130 DI 10.1002/hep.510310120 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270RV UT WOS:000084550700020 PM 10613737 ER PT J AU Hui, KKS Liu, J Makris, N Gollub, RL Chen, AJW Moore, CI Kennedy, DN Rosen, BR Kwong, KK AF Hui, KKS Liu, J Makris, N Gollub, RL Chen, AJW Moore, CI Kennedy, DN Rosen, BR Kwong, KK TI Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects SO HUMAN BRAIN MAPPING LA English DT Article DE neuroimaging; complementary medicine; pain; acupuncture ID HUMAN CEREBRAL-CORTEX; SENSORY STIMULATION; CINGULATE CORTEX; FUNCTIONAL MRI; UNITED-STATES; BLOOD-FLOW; PAIN; PARCELLATION; LOCALIZATION; ACTIVATION AB Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modem medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, MHG NMR CTR, Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. EW Immune Inst, Waltham, MA USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hui, KKS (reprint author), Massachusetts Gen Hosp, MHG NMR CTR, Dept Radiol, CNY 2,149 13th St, Boston, MA 02129 USA. RI Moore, Christopher/C-5588-2009; Kennedy, David/H-3627-2012; OI Gollub, Randy L./0000-0002-9434-4044 NR 62 TC 360 Z9 423 U1 8 U2 57 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. PY 2000 VL 9 IS 1 BP 13 EP 25 DI 10.1002/(SICI)1097-0193(2000)9:1<13::AID-HBM2>3.0.CO;2-F PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 272JG UT WOS:000084646300002 PM 10643726 ER PT J AU Badgaiyan, RD AF Badgaiyan, RD TI Executive control, willed actions, and nonconscious processing SO HUMAN BRAIN MAPPING LA English DT Article DE implicit memory; working memory; explicit memory; prefrontal cortex; cingulate cortex ID WORKING-MEMORY; CINGULATE CORTEX; STROOP; TASK; INTERFERENCE; PERFORMANCE; RECOGNITION; SELECTION; RETRIEVAL; ATTENTION AB Neuroimaging studies have identified a number of cortical areas involved in the executive control of conscious actions. The areas most frequently implicated are prefrontal and cingulate cortices. Evidence suggests that both of these areas may be essential for executive control of willed action. Prefrontal cortex, however may be responsible for the initial processing. Executive control is usually discussed with reference to willed actions and is assumed to regulate complex cognitive responses. Although many implicit processes involve complex responses, it is not known whether these actions are also controlled by executive processes. Significantly some implicit tasks like those involving motor sequence learning and cross-modality priming activate the same areas of prefrontal cortex that are implicated in the executive control of willed actions. It is, however, not clear whether a single executive process controls both implicit and explicit processes, or the implicit processes are regulated by a separate set of executive control having distinct neuroanatomical location and processing properties. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Badgaiyan, RD (reprint author), Harvard Univ, William James Hall,Rm 875,33 Kirkland St, Cambridge, MA 02138 USA. FU NIMH NIH HHS [MH57915-02] NR 27 TC 37 Z9 37 U1 3 U2 8 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. PY 2000 VL 9 IS 1 BP 38 EP 41 DI 10.1002/(SICI)1097-0193(2000)9:1<38::AID-HBM4>3.0.CO;2-T PG 4 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 272JG UT WOS:000084646300004 PM 10643728 ER PT J AU Hadjikhani, N Tootell, RBH AF Hadjikhani, N Tootell, RBH TI Projection of rods and cones within human visual cortex SO HUMAN BRAIN MAPPING LA English DT Article DE fmri; visual cortex; retinotopy; V8; rods; cones; fovea ID MACAQUE MONKEY; FUNCTIONAL-ANALYSIS; PROCESSING STREAMS; COLOR-BLINDNESS; GANGLION-CELLS; AREA V2; SEGREGATION; TOPOGRAPHY; PATHWAYS; STIMULATION AB There are two basic types of photoreceptors in the retina: rods and cones. Using a single stimulus viewed at two different light levels, we tested whether input from rods and input from cones are topographically segregated at subsequent levels of human visual cortex. Here we show that rod-mediated visual input produces robust activation in area MT+, and in the peripheral representations of multiple retinotopic areas. However, such activation was selectively absent in: (1) a cortical area selectively activated by colored stimuli (V8) and (2) the foveal representations of lower tier retinotopic areas. These cortical differences reflect corresponding differences in perception between scotopic and photopic conditions. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Hadjikhani, N (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 NR 37 TC 28 Z9 28 U1 2 U2 10 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. PY 2000 VL 9 IS 1 BP 55 EP 63 DI 10.1002/(SICI)1097-0193(2000)9:1<55::AID-HBM6>3.0.CO;2-U PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 272JG UT WOS:000084646300006 PM 10643730 ER PT J AU Miller, PW Sharma, S Stolina, M Butterfield, LH Luo, J Lin, Y Dohadwala, M Batra, RK Wu, L Economou, JS Dubinett, SM AF Miller, PW Sharma, S Stolina, M Butterfield, LH Luo, J Lin, Y Dohadwala, M Batra, RK Wu, L Economou, JS Dubinett, SM TI Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication SO HUMAN GENE THERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; IN-VIVO; LUNG-CANCER; RECOMBINANT ADENOVIRUSES; AUTOLOGOUS TUMOR; DOWN-REGULATION; MURINE TUMORS; GROWTH-FACTOR; THERAPY AB In two murine lung cancer models adenoviral interleukin 7-transdnced dendritic cells (DC-AdIL-7) were administered intratumorally, resulting in complete tumor regression. Intratumoral DC-AdIL-7 therapy was as effective as DCs pulsed with specific tumor peptide antigens, Comparison with other intratumoral therapies including recombinant IL-7, AdIL-7 vector alone, unmodified DCs, IL-7-transduced fibroblasts, or DCs pulsed with tumor lysates revealed DC-AdIL-7 therapy to be superior in achieving antitumor responses and augmenting immunogenicity, Mice with complete tumor eradication as a result of either DC-AdIL-7 or AdIL-7 therapy were rechallenged with parental tumor cells 30 days or more after complete tumor eradication, All the DC-AdIL-7-treated mice completely rejected a secondary rechallenge, whereas the AdIL-7-treated mice had sustained antitumor effects in only 20-25% of the mice, DC-AdIL-7 therapy was more effective than AdIL-7 in achieving systemic antitumor responses and enhancing immunogenicity. After complete tumor eradication, those mice treated with DC-AdIL-7 evidenced significantly greater release of splenocyte GM-CSF and IFN-gamma than did controls or AdIL-7-treated mice, After intratumoral injection, gene-modified DCs trafficked from the tumor to lymph node sites and spleen, DCs were detected in nodal tissues for up to 7 days after intratumoral injection, We report that intratumoral DC-AdIL-7 leads to significant systemic immune responses and potent antitumor effects in murine lung cancer models. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Ctr Hlth Sci 37 131,Dept Med,Wadsworth Pulm Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Ctr Hlth Sci 37 131,Dept Med,Wadsworth Pulm Lab, 10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R01 CA79976, P01 CA5926, R01 CA71818] NR 47 TC 82 Z9 88 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 1 PY 2000 VL 11 IS 1 BP 53 EP 65 DI 10.1089/10430340050016157 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 274PY UT WOS:000084775300006 PM 10646639 ER PT J AU Mokliatchouk, O Blacker, D Rabinowitz, D AF Mokliatchouk, O Blacker, D Rabinowitz, D TI Association tests for traits with variable age at onset SO HUMAN HEREDITY LA English DT Article DE admixture; ascertainment; conditional likelihood; efficient score; logistic regression; population stratification; proportional hazards; transmission/disequilibrium ID TRANSMISSION DISEQUILIBRIUM TEST; ALZHEIMER-DISEASE; TRANSMISSION/DISEQUILIBRIUM TEST; BIPOLAR DISORDER; LINKAGE ANALYSIS; APOLIPOPROTEIN-E; OF-ONSET; MARKERS; CHROMOSOME-12; ALLELES AB This paper is concerned with testing association between marker genotypes and traits with variable age at onset. Two methods are proposed, one which makes use of both age-at-ascertainment and age-at-onset information, and one which may be applied when only age-at-ascertainment information is available. (Here, by age-at ascertainment, is meant the subject's age when presence of onset and age at onset are determined; for subjects who have died or are otherwise censored before ascertainment, the censoring time should be used instead). Adjustment for confounding due to population stratification is carried out by conditioning an observed traits and parental genotypes, or, if complete parental genotypes are not available, by conditioning on observed traits and the minimal sufficient statistics under the null hypothesis for the parental genotypes. Proportional hazards regression models and logistic regression models are used to motivate the methods, but correct type I error rates result even if the models are not correct. An illustrative example is described. Copyright (C) 2000 S. Karger AG, Basel. C1 Columbia Univ, Dept Stat, New York, NY 10027 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Rabinowitz, D (reprint author), Columbia Univ, Dept Stat, Mail Code 4403,Broadway & 120th St, New York, NY 10027 USA. NR 35 TC 8 Z9 8 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2000 VL 51 IS 1-2 BP 46 EP 53 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 374EK UT WOS:000165331300008 ER PT J AU Takeda, K Takemoto, C Kobayashi, I Watanabe, A Nobukuni, Y Fisher, DE Tachibana, M AF Takeda, K Takemoto, C Kobayashi, I Watanabe, A Nobukuni, Y Fisher, DE Tachibana, M TI Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance SO HUMAN MOLECULAR GENETICS LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR; DNA-BINDING; MICROPHTHALMIA GENE; HUMAN HOMOLOG; PROTEIN; ACTIVATION; EXPRESSION; IDENTIFICATION; DOMAINS AB MITF (microphthalmia-associated transcription factor) is a basic-helix-loop-helix-leucine zipper (bHLHZip) factor which regulates expression of tyrosinase and other melanocytic genes via a CATGTG promoter sequence, and is involved in melanocyte differentiation. Mutations of MITF in mice or humans with Waardenburg syndrome type 2 (WS2) often severely disrupt the bHLHZip domain, suggesting the importance of this structure. Here, we show that Ser298, which locates downstream of the bHLHZip and was previously found to be mutated in individuals with WS2, plays an important role in MITF function. Glycogen synthase kinase 3 (GSK3) was found to phosphorylate Ser298 in vitro, thereby enhancing the binding of MITF to the tyrosinase promoter. The same serine was found to be phosphorylated in vivo, and expression of dominant-negative GSK3 beta selectively suppressed the ability of MITF to transactivate the tyrosinase promoter. Moreover, mutation of Ser298, as found in a WS2 family, disabled phosphorylation of MITF by GSK3 beta and impaired MITF function. These findings suggest that the Ser298 is important for MITF function and is phosphorylated probably by GSK3 beta. C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Sendai, Miyagi 9808575, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIMH, Bethesda, MD 20892 USA. Saitama Canc Ctr, Res Inst, Ina, Saitama 3620806, Japan. RP Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. EM mtachiba@cancer-c.pref.saitama.jp RI Kobayashi, Ichiro/G-8638-2012 FU NHLBI NIH HHS [KO8 HL3700]; NIAMS NIH HHS [AR43369] NR 36 TC 96 Z9 99 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2000 VL 9 IS 1 BP 125 EP 132 DI 10.1093/hmg/9.1.125 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 274VJ UT WOS:000084785500015 PM 10587587 ER PT J AU North, PE Waner, M Mizeracki, A Mihm, MC AF North, PE Waner, M Mizeracki, A Mihm, MC TI GLUT1: A newly discovered immunohistochemical marker for juvenile hemangiomas SO HUMAN PATHOLOGY LA English DT Article DE GLUT1; juvenile hemangioma; vascular malformation; pyogenic granuloma; hemangioendothelioma; angiosarcoma ID BLOOD-BRAIN-BARRIER; GLUCOSE-TRANSPORTER ISOFORMS; ENDOTHELIAL-CELLS; CAPILLARY HEMANGIOMA; EXPRESSION; OVEREXPRESSION; MICROVESSELS; HEXOKINASE; ASTROCYTES; ONCOGENES AB Juvenile hemangiomas are common, benign vascular tumors of infancy. These lesions enlarge rapidly through cellular hyperplasia during the first year of life and then involute over several years. Distinctive histopathologic features of hemangiomas diminish during this evolution, and differentiation from vascular malformations becomes increasingly difficult. This distinction has important therapeutic implications, as juvenile hemangiomas differ from malformations in natural history and in potential for recurrence. We report here that high endothelial immunoreactivity for the erythrocyte-type glucose transporter protein GLUT1 is a specific feature of juvenile hemangiomas during all phases of these lesions. In a retrospective study, we found intense endothelial GLUT1 immunoreactivity, involving more than 50% of lesional microvessels, in 91% (139 of 143) of juvenile hemangiomas from patients aged 1 month to 11 years. No endothelial GLUT1 immunoreactivity was found in any of 66 vascular malformations (17 arteriovenous, 33 venous, 11 lymphatic, and 5 port-wine) from patients aged 5 days to 75 years, or in any of 20 pyogenic granulomas or 7 granulation tissue specimens. Abundant Ki-67 positivity in these latter lesions established that GLUT1 expression does not simply reflect mitotically active endothelium. Focal GLUT1 immunoreactivity was found in 3 of 12 angiosarcomas, but not in any of 5 hemangioendotheliomas (epithelioid or infantile kaposiform). These findings establish GLUT1 immunoreactivity as a highly selective and diagnostically useful marker for juvenile hemangiomas. Because high levels of endothelial GLUT1 expression in normal tissue are restricted to microvessels with blood-tissue barrier function, these findings also have implications for the molecular and developmental pathogenic mechanisms of juvenile hemangiomas. HUM PATHOL 31:11-22. Copyright (C) 2000 by WB, Saunders Company. C1 Arkansas Childrens Hosp, Dept Pediat Pathol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP North, PE (reprint author), Arkansas Childrens Hosp, Dept Pediat Pathol, 800 Marshall St, Little Rock, AR 72202 USA. NR 52 TC 382 Z9 407 U1 0 U2 21 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 2000 VL 31 IS 1 BP 11 EP 22 DI 10.1016/S0046-8177(00)80192-6 PG 12 WC Pathology SC Pathology GA 277BB UT WOS:000084911900003 PM 10665907 ER PT J AU Cooper, RA Widman, LM Jones, DK Robertson, RN Ster, JF AF Cooper, RA Widman, LM Jones, DK Robertson, RN Ster, JF TI Force sensing control for electric powered wheelchairs SO IEEE TRANSACTIONS ON CONTROL SYSTEMS TECHNOLOGY LA English DT Article DE electric powered wheelchair; force sensing control; human-machine control; people with disabilities; tremor AB People with many types of disabilities use electric powered wheelchairs (EPW's) for mobility. Excessive intention tremor, limited range of motion, athetoid motions, and spastic rigidity can reduce or prohibit the control over an EPW. This study focused on the design and testing of a newly developed isometric joystick (IJ) for EPW control. The IJ was tested against existing performance standards and compared to a commercial position sensing joystick (PSJ), When averaged across all subjects (both controls and impaired subjects) the root-mean-square tracking error and time to complete the driving course were not significantly different when using the rule (p < 0.05), Results within a subject, however, did show significance. Across all subjects, nevertheless, the IJ was superior to the PSJ for two tasks: driving straight and driving in a circle. Further development of control algorithms, especially the implementation of digital control, could lead to greater improvement in performance with the IJ. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. Calif State Univ Sacramento, Sch Engn & Comp Sci, Biomed Engn Program, Sacramento, CA 95819 USA. Cent Michigan Univ, Dept Ind & Engn Technol, Mt Pleasant, MI 48859 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Calif State Univ Sacramento, Sch Engn Comp Sci, Sacramento, CA 95819 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. NR 16 TC 37 Z9 37 U1 0 U2 2 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 2000 VL 8 IS 1 BP 112 EP 117 DI 10.1109/87.817696 PG 6 WC Automation & Control Systems; Engineering, Electrical & Electronic SC Automation & Control Systems; Engineering GA 275FT UT WOS:000084809300011 ER PT J AU Jacquot, S AF Jacquot, S TI CD27/CD70 interactions regulate T dependent B cell differentiation SO IMMUNOLOGIC RESEARCH LA English DT Article DE CD27; CD70; TNF receptor family; T dependent B cell responses; T-B interactions; plasma cell differentiation ID TUMOR-NECROSIS-FACTOR; FACTOR RECEPTOR FAMILY; N-TERMINAL KINASE; FACTOR LIGAND; PLASMA-CELLS; GENE FAMILY; CD27; ANTIGEN; ACTIVATION; MEMBER AB CD27 is a tumor necrosis factor (TNF) receptor family member whose expression is limited to cells of the lymphoid lineage. Constitutively expressed on T lymphocytes, it is a costimulatory molecule for a regulatory subset. Induced on B lymphocytes after antigenic challenge, it is a marker of memory cells. CD70, CD27 ligand, is a TNF related trans-membrane protein induced upon activation on T and B cells. In complement of ligation of CD40, another TNF receptor family member expressed by B cells, CD27/CD70 interaction plays a key role in T dependent B cell responses and is responsible for plasma cell differentiation. B lymphocyte responses appear thus controlled by different T cell subsets expressing CD154 (CD40 ligand), CD27, or CD70 (CD27 ligand). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol,Dept Med, Boston, MA 02115 USA. RP Jacquot, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol,Dept Med, 44 Binney St, Boston, MA 02115 USA. NR 51 TC 28 Z9 28 U1 0 U2 0 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 2000 VL 21 IS 1 BP 23 EP 30 DI 10.1385/IR:21:1:23 PG 8 WC Immunology SC Immunology GA 303ZH UT WOS:000086457700003 PM 10803880 ER PT J AU Mentzer, SJ AF Mentzer, SJ TI Dendritic cells in the pathophysiology of sarcoidal reactions SO IN VIVO LA English DT Review DE dentritic cells; sarcoidal reactions; immune response ID PERIPHERAL LYMPHOID ORGANS; COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; LANGERHANS CELLS; EOSINOPHILIC GRANULOMA; MIGRATION PATTERNS; CONDUCTING AIRWAYS; GM-CSF; LUNG; EPITHELIUM AB Dendritic cells play an important role in regulating both normal and pathophysiologic immune responses. Complicating the interpretation of dendritic cell function has been the observation that dendritic cells are not only rare, but can demonstrate multiple maturation/differentiation states. Despite these experimental limitations, the accumulating evidence suggests that dendritic cell are a dynamic migratory population that can be recruited into areas of peripheral inflammation. In the peripheral site of inflammation, dendritic cell function appears to involve the processing of antigen and its subsequent presentation to T lymphocytes. Dendritic cells also appeal to be capable of transporting antigen to the regional lymph node through the afferent lymphatics. Dendritic cells can be found in the paracortex where they appear to be interacting with T lymphocytes to provide both membrane-bound and soluble activation signals. The central,regulatory role of the dendritic cell in immune responses suggests that sarcoidal reactions, and other mononuclear inflammatory processes, are likely to be clinical entities that reflect perturbed dentritic cell function. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Immunophysiol Lab, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL47078] NR 45 TC 5 Z9 5 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JAN-FEB PY 2000 VL 14 IS 1 BP 209 EP 212 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 298YD UT WOS:000086167600027 PM 10757079 ER PT J AU Young, VB Knox, KA Schauer, DB AF Young, VB Knox, KA Schauer, DB TI Cytolethal distending toxin sequence and activity in the enterohepatic pathogen Helicobacter hepaticus SO INFECTION AND IMMUNITY LA English DT Article ID CAMPYLOBACTER-JEJUNI; ESCHERICHIA-COLI; CELL-CYCLE; SHIGELLA-DYSENTERIAE; BACTERIAL-INFECTION; BOWEL-DISEASE; SP-NOV; MICE; PYLORI; PULLORUM AB Little is known about the molecular pathogenesis of hepatitis and enteroculitis caused by enterohepatic Helicobacter species. Sonicates of the murine pathogen Helicobacter hepaticus were found to cause progressive cell distension, accumulation of filamentous actin, and G(2)/M cell cycle arrest in HeLa cell monolayers. The genes encoding this cytotoxic activity were cloned from H. hepaticus. Three open reading frames with closest homology to cdtA, cdtB, and cdtC from Campylobacter jejuni were identified. Sonicates of a laboratory strain of Escherichia coli carrying the cloned cdtABC gene cluster from H. hepaticus reproduced the cytotoxic activities seen with sonicates of H. hepaticus. Cytolethal distending toxin activity is a potential virulence determinant of H. hepaticus that may play a role in the pathogenesis of Helicobacter-associated hepatitis and enterocolitis. C1 MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Schauer, DB (reprint author), MIT, Div Bioengn & Environm Hlth, Rm 56-787, Cambridge, MA 02139 USA. RI Young, Vincent/B-3179-2009 OI Young, Vincent/0000-0003-3687-2364 FU NIAID NIH HHS [AI01398]; NIDDK NIH HHS [DK52413, R01 DK052413, R56 DK052413] NR 39 TC 101 Z9 107 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2000 VL 68 IS 1 BP 184 EP 191 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800027 PM 10603386 ER PT J AU Ryan, ET Crean, TI Kochi, SK John, M Luciano, AA Killeen, KP Klose, KE Calderwood, SB AF Ryan, ET Crean, TI Kochi, SK John, M Luciano, AA Killeen, KP Klose, KE Calderwood, SB TI Development of a Delta glnA balanced lethal plasmid system for expression of heterologous antigens by attenuated vaccine vector strains of Vibrio cholerae SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; VIRULENCE DETERMINANTS; ANTIBODY-RESPONSES; ORAL IMMUNIZATION; SUICIDE VECTOR; B-SUBUNIT; LIVE; CONSTRUCTION; MUTAGENESIS; INFECTION AB We have previously shown that more prominent immune responses are induced to antigens expressed from multicopy plasmids in live attenuated vaccine vector strains of Vibrio cholerae than to antigens expressed from single-copy genes on the V. cholerae chromosome. Here, we report the construction of a Delta glnA derivative of V. cholerae vaccine strain Peru2, This mutant strain, Peru2 Delta glnA, is unable to grow on medium that does not contain glutamine; this growth deficiency is complemented by pKEK71-NotI, a plasmid containing a complete copy of the Salmonella typhimurium glnA gene, or by pTIC5, a derivative of pKEK71-NotI containing a 1.8-kbp fragment that directs expression of CtxB with a 12-amino-acid epitope of the serine-rich Entamoeba histolytica protein fused to the amino terminus. Strain Peru2 Delta glnA(pTIC5) produced 10-fold more SREHP-12-CtxB in supernatants than did ETR3, a Peru2-derivative strain containing the same fragment inserted on the chromosome. To assess immune responses to antigens expressed by this balanced lethal system in vivo, we inoculated germfree mice on days 0, 14, 28, and 42 with Peru2 Delta glnA, Peru2 Delta glnA(pKEK71-NotI), Peru2(pTIC5), Peru2 Delta glnA (pTIC5), or ETR3, All V. cholerae strains were recoverable from stool for 8 to 12 days after primary inoculation, including Peru2 Delta glnA; strains containing plasmids continued to harbor pKEK71-NotI or pTIC5 for 8 to 10 days after primary inoculation. Animals were sacrificed on day 56, and serum, stool and biliary samples were analyzed for immune responses. Vibriocidal antibody responses, reflective of in vivo colonization, were equivalent in all groups of animals. However, specific anti-CtxB immune responses in serum (P less than or equal to 0.05) and bile (P less than or equal to 0.001) were significantly higher in animals that received Peru2 Delta glnA(pTIC5) than in those that received ETR3, confirming the advantage of higher-level antigen expression in vivo. The development of this balanced lethal system thus permits construction and maintenance of vaccine and vector strains of V. cholerae that express high levels of immunogenic antigens from plasmid vectors without the need for antibiotic selection pressure. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. AVANT Immunotherapeut Inc, Needham, MA 02494 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [KO8 AI01332, AI40725, R01 AI040725] NR 28 TC 36 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2000 VL 68 IS 1 BP 221 EP 226 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800032 PM 10603391 ER PT J AU Chen, TT Dong, H Tang, YXP Dallas, MM Malamy, MH Duncan, MJ AF Chen, TT Dong, H Tang, YXP Dallas, MM Malamy, MH Duncan, MJ TI Identification and cloning of genes from Porphyromonas gingivalis after mutagenesis with a modified Tn4400 transposon from Bacteroides fragilis SO INFECTION AND IMMUNITY LA English DT Article ID CYSTEINE PROTEINASE; ESCHERICHIA-COLI; RESISTANCE AB Porphyromonas gingivalis is a gram-negative, black-pigmented, oral anaerobe strongly associated with adult periodontitis. Previous transposon mutagenesis studies with this organism were based on the Bacteroides transposon Tn4351. characterization of Tn4351-disrupted genes by cloning has not been an efficient way to analyze large numbers of mutants and is further complicated by the high rate of cointegration of the suicide delivery vector containing Tn4351, In this study, we mutagenized P. gingivalis with a modified version of the Bacteroides fragilis transposon Tn4400. Plasmid pYT646B carrying the transposon was mobilized from Escherichia coli to P. gingivalis ATCC 33277 by conjugation. Both normal and inverse transposition frequencies were similar (3 x 10(-8)). However, the inverse transposon (Tn4400') contains a pBR322 replicon and a beta-lactamase gene; thus, the cloning of disrupted genomic DNAs from inverse transposition mutants was easily accomplished after ligation of genomic fragments and transformation into E. coli. Thousands of transconjugants could be obtained in a single mating experiment, and inverse transposition was random as demonstrated by Southern hybridization. By this procedure the disrupted genes from P. gingivalis pleiotropic mutants were quickly cloned, sequenced, and identified. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 The Fenway, Boston, MA 02115 USA. FU NIAID NIH HHS [R01AI19497, R01 AI019497]; NIDCR NIH HHS [R01 DE 10510, R01 DE010510] NR 14 TC 15 Z9 16 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2000 VL 68 IS 1 BP 420 EP 423 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800062 PM 10603421 ER PT B AU Gu, L Tseng, SC Rollins, BJ AF Gu, L Tseng, SC Rollins, BJ BE Letts, LG Morgan, DW TI The role of MCP-1 in disease SO INFLAMMATORY PROCESSES: MOLECULAR MECHANISMS AND THERAPEUTIC OPP ORTUNITIES SE PROGRESS IN INFLAMMATION RESEARCH LA English DT Proceedings Paper CT 9th International Conference of the Inflammation-Research-Association CY NOV 01-05, 1998 CL HERSHEY, PA SP Chrysalis Preclin Serv Corp, Glaxo Wellcome Inc, Novartis Pharmaceut Corp, Pfizer Inc, Cent Res Div, Inflammat Res Assoc ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR-2; MOLECULAR-CLONING; TRANSGENIC MICE; CELL-LINE; EXPRESSION; PURIFICATION; RECRUITMENT; CHEMOTAXIS; GLOMERULONEPHRITIS C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. RP Gu, L (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-6025-9 J9 PROG INFLAM RES JI Prog. Inflamm. Res. PY 2000 BP 99 EP 107 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA BQ83U UT WOS:000089786700010 ER PT J AU Zusman, RM AF Zusman, RM TI The role of alpha(1)-blockers in combination therapy for hypertension SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Review ID BENIGN PROSTATIC HYPERPLASIA; BLOOD-PRESSURE; DOUBLE-BLIND; ANTIHYPERTENSIVE AGENTS; RESISTANT HYPERTENSION; INSULIN SENSITIVITY; TREATMENT REGIMEN; CROSS-OVER; DOXAZOSIN; TERAZOSIN AB Antihypertensive monotherapy provides adequate blood pressure control in less than 50% of patients with hypertension (BP>140/90 mmHg), especially those with stage 2-3 disease. This article reviews clinical studies that demonstrate that add-on therapy with an alpha(1)-blocker (doxazosin, terazosin or prazosin) is an effective and well-tolerated regimen for improving blood pressure control in patients with inadequately controlled hypertension. Furthermore, alpha(1)-blockers have therapeutic benefits that go beyond blood pressure management. They have a small but positive effect on the serum lipid profile and they have favourable or benign effects on conditions that frequently coexist with hypertension, such as type 2 diabetes mellitus and benign prostatic hyperplasia. C1 Massachusetts Gen Hosp, Div Hypertens & Vasc Med, Boston, MA 02114 USA. RP Zusman, RM (reprint author), Massachusetts Gen Hosp, Div Hypertens & Vasc Med, 15 Parkman St,WACC 482, Boston, MA 02114 USA. NR 48 TC 9 Z9 10 U1 0 U2 3 PU MEDICOM INTERNATIONAL PI SURREY PA CHURSTON HOUSE, PORTSMOUTH RD, ESHER, SURREY KT10 9AD, ENGLAND SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD JAN-FEB PY 2000 VL 54 IS 1 BP 36 EP 41 PG 6 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 281LW UT WOS:000085162800010 PM 10750258 ER PT J AU Gans, JS Counselman, EF AF Gans, JS Counselman, EF TI Silence in group psychotherapy: A powerful communication SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article AB Silence in a psychotherapy group, including leader, member, subgroup, and whole-group silence, is a common phenomenon with many possible forms, uses, and meanings. Five common sources of silence in group psychotherapy are described: situational factors, individual dynamics, member-to-member interactions, group dynamics, and leader-related dynamics. Silence cart reflect defenses or indicate conditions favorable to intensified group work. Silence, sometimes mistaken for psychological inactivity, should be viewed as significant communication. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02181 USA. NR 25 TC 9 Z9 10 U1 1 U2 2 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 2000 VL 50 IS 1 BP 71 EP 86 PG 16 WC Psychology, Clinical SC Psychology GA 271VA UT WOS:000084613300008 PM 10646293 ER PT J AU Goodman, A Chaudhuri, PM Tobin-Enos, NJ Hutchinson, ML AF Goodman, A Chaudhuri, PM Tobin-Enos, NJ Hutchinson, ML TI The false negative rate of cervical smears in high risk HIV seropositive and seronegative women SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE ASCUS; HIV; Pap smear ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; PAPANICOLAOU SMEARS; CYTOLOGY; COLPOSCOPY; CANCER; PREVALENCE; FREQUENCY; ACCURACY AB We undertook a prospective study of cytology and concurrent colposcopically directed biopsies of both Human Immunodeficiencey Virus seronegative (HIV-) and seropositive (HIV +) women at high risk for cervical intraepithelial neoplasia (CIN) to determine the accuracy of Pap smears in this population. Women were recruited from a sexually transmitted disease clinic and a women's prison in eastern Massachusetts. All were interviewed, blood was tested for HIV with CD4 counts done in 101 of the 102 HIV + women, and all received a pelvic exam that included a conventional Pap smear, a Thinprep test, and colposcopy with directed biopsies and endocervical curettage. A total of 184 women volunteered. 82 were HIV- and 102 were HIV+. The prevalence of CIN in HIV+ women was 37%, more than twice the 17% prevalence of CIN in HIV-women (P = 0.002). When Atypical Squamous Cells of Undetermined Significance (ASCUS) findings were included with "negative" cytology, the conventional Pap smear false negative rates for HIV- and HIV+ women were 21% and 37%, respectively. When ASCUS was included with "positive" cytology, the false negative rates dropped to 14.3% for HIV- women and 10.5% for HIV+ women. We conclude that ASCUS diagnoses comprised the majority of false negatives in HIV+ women. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Tufts Univ Hlth, Medford, MA USA. Parkland Med Ctr, Dept Obstet & Gynecol, Derry, NH USA. Brown Univ, Women & Infants Hosp, Dept Cytol, Providence, RI USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Wang Ambulatory Care Ctr Suite 231, Boston, MA 02114 USA. NR 33 TC 4 Z9 5 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JAN-FEB PY 2000 VL 10 IS 1 BP 27 EP 32 DI 10.1046/j.1525-1438.2000.00001.x PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 300DB UT WOS:000086236600005 ER PT J AU Penson, RT Kronish, K Duan, Z Feller, AJ Stark, P Cook, SE Duska, LR Fuller, AF Goodman, AK Nikrui, N MacNeill, KM Matulonis, UA Preffer, FI Seiden, MV AF Penson, RT Kronish, K Duan, Z Feller, AJ Stark, P Cook, SE Duska, LR Fuller, AF Goodman, AK Nikrui, N MacNeill, KM Matulonis, UA Preffer, FI Seiden, MV TI Cytokines IL-1 beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNF alpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE cytokines; immunotherapy; ovarian cancer; paclitaxel; prognosis ID ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; CELL-LINE; INTERLEUKIN-6; SERUM; TAXOL; IDENTIFICATION; ANGIOGENESIS; RESISTANCE AB In vitro work suggests that cytokines may be important modulators of the cytotoxic effects of paclitaxel and subsequent drug resistance. This has been investigated in vivo in patients with ovarian cancer by ELISA. There was consistently elevated expression of IL-6 and IL-8 but not MCP-1, IL-1 beta, IL-2, GM-CSF or TNF alpha. Peritoneal fluid concentrations of IL-6, IL-8 and MCP-1 were two to three logs greater than serum concentrations. Elevated concentrations of IL-6 correlated with a poor final outcome (P = 0.039), and increased IL-6 and IL-8 correlated with a poor initial response to chemotherapy (P = 0.041 and P = 0.041, respectively). There was a relatively clear pattern of change in all three cytokines. In serum, IL-6, IL-8 and MCP-1 decreased with the administration of steroids prior to paclitaxel, and increased in the 24 h after paclitaxel. Postoperative drainage fluid was relatively acellular, preventing flow-cytometric analysis of epithelial cells for apoptosis, but suggested activation of T cells by paclitaxel. IL-6 and IL-8 appear to be of prognostic importance in epithelial ovarian cancer. Treatment with paclitaxel is associated with an increase in expression of a limited number of cytokines in patients with ovarian cancer, notably IL-6, IL-8 and MCP-1. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Jackson 1021,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 98 Z9 118 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JAN-FEB PY 2000 VL 10 IS 1 BP 33 EP 41 DI 10.1046/j.1525-1438.2000.00003.x PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 300DB UT WOS:000086236600006 ER PT J AU Salazar, H Scully, RE AF Salazar, H Scully, RE TI The International Society of Gynecological Pathologists - Its founding and early years SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE International Society of Gynecological Pathologists; medical history; gynecological pathology; WHO tumor classification AB The International Society of Gynecological Pathologists was founded in 1976 to facilitate an exchange of knowledge about gynecological disease throughout the world. The Society moved quickly to schedule companion meetings with established international and regional pathology and gynecology societies, including the International Academy of Pathology, its United States-Canadian Division, and the International Federation of Gynecology and Obstetrics, and to sponsor smaller meetings within individual countries. In 1981 the Society founded this journal, and in 1983, at the invitation of the World Health Organization, it assumed the responsibility of revising the WHO classifications of tumors of the female genital tract. The foundation of the Society appears to have been solid in view of its present robust health. C1 Reading Hosp & Med Ctr, Dept Pathol, Reading, PA 19612 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Salazar, H (reprint author), Reading Hosp & Med Ctr, Dept Pathol, POB 16052, Reading, PA 19612 USA. NR 3 TC 3 Z9 3 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 2000 VL 19 IS 1 BP 3 EP 6 DI 10.1097/00004347-200001000-00002 PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 268CF UT WOS:000084396200002 PM 10638448 ER PT J AU Dickersin, GR AF Dickersin, GR TI The role of electron microscopy in gynecological pathology SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE electron microscopy; ultrastructure; gynecological pathology; female genital tract; neoplasm; embryology ID SMALL-CELL-CARCINOMA; PROBABLE WOLFFIAN ORIGIN; PEUTZ-JEGHERS SYNDROME; FEMALE ADNEXAL TUMOR; YOLK-SAC TUMOR; OVARY; DIFFERENTIATION; NEOPLASMS; ULTRASTRUCTURE; HYPERCALCEMIA AB Electron microscopy, as a diagnostic method, has been available to pathologists for about half a century. Its use in studying normal and abnormal gynecological tissues has been applied during the second half of that period, and many works on specific female genital topics have been published. Several of those subjects are worthy of citing in a review of the present type. Clear cell carcinoma has been revealed to be a mullerian, rather than a wolffian, derivative. Small cell carcinoma of the ovary with hypercalcemia is comprised of cells shown ultrastructurally to be epithelial, but unlike surface epithelial cells, germ cells, sex-cord cells, or neuroendocrine cells. Further electron microscopic studies provided evidence that these small cell tumors are not adult diffuse granulosa cell tumors, endometrioid stromal tumors, primitive neuroectodermal tumors, or numerous other primary and metastatic small cell tumors. Electron microscopy has also been useful in determining that not all signer-ring cell tumors of the ovary are stromal, and that there are multiple types of signet-ring (vacuolated) cells in ovarian tumors. Smooth muscle tumors are well known to have multiple light microscopic phenotypes, and electron microscopy has proven to be diagnostic in many of these cases, especially in epithelioid smooth muscle tumors. A number of other gynecological neoplasms that have been better defined by electron microscopic studies are described. Embryology and histogenesis are other areas of study in which electron microscopy has been a major contributor of new information at the subcellular level. Electron microscopy, solely or in harmony with clinical information, light microscopy, and immunohistochemistry, has been and is a valuable tool for the pathologist in the study of histogenesis and accurate diagnosis of gynecological lesions. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Dickersin, GR (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 100 Blossom St,Cox 5, Boston, MA 02114 USA. NR 37 TC 4 Z9 5 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 2000 VL 19 IS 1 BP 56 EP 66 DI 10.1097/00004347-200001000-00007 PG 11 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 268CF UT WOS:000084396200007 PM 10638453 ER PT J AU Young, RH AF Young, RH TI Dusting off old books: Comments on classic gynecologic pathology books of yesteryear SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE old books; gynecologic pathology; Thomas S-Cullen; Howard A-Kelly; Cuthbert Lockyer; C-Frederic Fluhmann; Samuel H-Geist; Gemma Barzilai; John McLean Morris; Robert E-Scully; John H-Teacher; Emil Novak AB Selected outstanding books from the older literature on gynecological pathology are reviewed with emphasis on drawing attention to the abundant helpful information and outstanding illustrations that are worthy of review by present-day pathologists. The first three works are Cancer of the Uterus, Myomata of the Uterus, and Adenomyoma of the Uterus by Thomas S. Cullen. The senior author of the second book is Howard A. Kelly even though he did not have any role in the preparation of the text; he was given senior authorship by Dr. Cullen as a token of appreciation to his mentor. The next book, Fibroids and Allied Tumors by Cuthbert Lockyer, is particularly noteworthy for the quality of the numerous color illustrations. The final book on the uterus is The Cervix Uteri and Its Diseases by C. Frederic Fluhmann. It provides detailed coverage of the normal and pathologic aspects of the cervix, including the endocervical clefts (glands) and their abnormalities. The next three books are on the ovary: Ovarian Tumors by Samuel H. Geist, Atlas of Ovarian Tumors by Gemma Barzilai, and Endocrine Pathology of the Ovary by John McLean Morris acid Robert E. Scully. The first is notable for the quality of the coverage of clinical and gross aspects of ovarian tumors and the second for the quality of the description of the microscopic features. The third book expanded the range of functioning ovarian tumors by showing that this could be a feature of tumors not usually considered hormonally active and also discussed in detail the endocrine function of non-neoplastic lesions. The final two books cover general gynecological pathology: Manual of Obstetrical and Gynaecological Pathology by John H. Teacher and Gynecological and Obstetrical Pathology by Emil Novak. Both have particularly outstanding coverage of normal histology and non-neoplastic lesions. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. NR 33 TC 13 Z9 15 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 2000 VL 19 IS 1 BP 67 EP 84 DI 10.1097/00004347-200001000-00008 PG 18 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 268CF UT WOS:000084396200008 PM 10638454 ER PT J AU Nakamura, S Gelber, RD Blattner, S Sallan, SE Chanock, SJ AF Nakamura, S Gelber, RD Blattner, S Sallan, SE Chanock, SJ TI Long-term follow-up and infectious complications of therapy for acute lymphoblastic leukemia in children SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article DE infection; neutropenia; antibiotics; cancer ID COLONY-STIMULATING FACTOR; PATIENTS RECEIVING CIPROFLOXACIN; PNEUMOCYSTIS-CARINII PNEUMONIA; CANCER-PATIENTS; NEUTROPENIC PATIENTS; PRIMARY IMMUNODEFICIENCIES; INTENSIVE CHEMOTHERAPY; RISK-FACTORS; FEVER; STREPTOCOCCI AB Infection is a major complication of therapy for acute lymphoblastic leukemia (ALL) in children. Recent advances in supportive care have contributed to improvements in long-term survivorship following treatment for ALL. Of 220 children treated for ALL on Dana-Farber Cancer Institute (DFCI) Consortium Protocol 85-001, a retrospective study of all 72 children at the DFCI and Maine Children's Cancer Program was conducted to determine the incidence and impact of infection in pediatric patients not on hematopoietic growth factor support. There were two deaths on therapy, both of which were associated with infection. Our results show that severe infection, requiring hospitalization is far more likely to occur during induction therapy. The risk for hospitalization decreased during therapy, after remission was achieved with fewer children hospitalized during the continuation phase of therapy than during the intensification phase. Fever and neutropenia was the most common reason for hospitalization and in less than 30% of instances an etiology was determined. At a median follow-up of 9 years, the event-free survival (EFS) of the 220 patients enrolled on Protocol 85-001 was 78%. The 9 years EFS by risk groups (standard, high and very high risk) was 89%, 75% and 58%, respectively (p = 0.0005). In conclusion, serious infectious complications were more likely to occur during induction and intensification. Thus, strategies to prevent infection should be targeted to induction and intensification phases of therapy for childhood ALL. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Maine Childrens Canc Program, Portland, ME USA. RP Chanock, SJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, 10-13N240, Bethesda, MD 20892 USA. NR 38 TC 4 Z9 4 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 2000 VL 6 IS 5 BP 321 EP 330 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 287TQ UT WOS:000085522900002 ER PT J AU Mulsant, BH Harman, JS Kelleher, KJ Schulberg, HC Kupfer, DJ Reynolds, CF AF Mulsant, BH Harman, JS Kelleher, KJ Schulberg, HC Kupfer, DJ Reynolds, CF TI Treatment of depression in vulnerable populations: Narrowing the gap SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Intervent Res Ctr Study Late Life Mood Disorders, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2000 VL 30 IS 4 BP 399 EP 400 PG 2 WC Psychiatry SC Psychiatry GA 413LU UT WOS:000167614300010 ER PT J AU Hetelekidis, S Schnitt, SJ Silver, B Manola, J Bornstein, BA Nixon, AJ Recht, A Gelman, R Harris, JR Connolly, JL AF Hetelekidis, S Schnitt, SJ Silver, B Manola, J Bornstein, BA Nixon, AJ Recht, A Gelman, R Harris, JR Connolly, JL TI The significance of extracapsular extension of axillary lymph node metastases in early-stage breast cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Therapeutic-Radiology-and-Oncology CY OCT 30, 1996 CL LOS ANGELES, CALIFORNIA SP Soc Therapeut Radiol & Oncol DE breast neoplasms; axillary dissection; extracapsular extension; regional nodal failure; radiotherapy ID RADIATION-THERAPY; RADIOTHERAPY; PROGNOSIS AB Purpose: To investigate if extracapsular extension (ECE) of axillary lymph node metastases predicts for a decreased rate of disease-free survival or an increased rate of regional recurrence of breast carcinoma. Methods: The study population consisted of 368 patients with T1 or T2 breast cancer and pathologically-positive lymph nodes treated with breast-conserving therapy between 1968 and 1986, The median number of sampled lymph nodes was 10, Median follow-up time for the surviving patients was 139 months (range 70-244), Twenty percent of the patients were treated with supraclavicular RT, and 64% received both axillary and supraclavicular RT, with a median dose to the nodes of 45 Gy, The following factors were evaluated: presence of ECE, number of sampled lymph nodes (LN), number of involved LN, size of primary tumor, histologic grade of tumor, presence of lymphatic vessel invasion (LVI), presence of an extensive intraductal component (EIC), radiation dose, use of adjuvant chemotherapy, and age of patient. Recurrences were reported as the 5-year crude sites of first failure, and were divided into breast recurrences (LR), regional nodal failure (RNF, defined as isolated axillary, supraclavicular, or internal mammary recurrence), and distant metastases (DM), Results: One hundred twenty-two patients (33%) had FCE and 246 patients did not. The median number of LN with ECE was 1 (range 1-10) and 20% of patients had ECE in greater than or equal to 4 LN, Patients with ECE tended to be older (median age 51 vs. 47, p = 0.01), and had a higher number of involved LN (median 3 vs. 2, p = 0.005) than patients without ECE, Forty-three percent of patients with ECE had 2:4 involved LN compared to 15% of patients without ECE (p < 0.0001). Models of ECE and the above factors revealed no significant correlation between ECE and either disease-free or overall survival. There was no statistically significant increase in local, regional nodal, or distant failures in patients with FCE as compared to patients without ECE, Conclusion: In this population of patients with nodal involvement, the presence of ECE correlates with the number of involved LN but does not appear to add predictive power to models of local, regional, or distant recurrence when the number of positive LN is included. (C) 2000 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Silver, B (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 41 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2000 VL 46 IS 1 BP 31 EP 34 DI 10.1016/S0360-3016(99)00424-1 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 275XD UT WOS:000084844700007 PM 10656369 ER PT J AU Datta, MW Young, RH AF Datta, MW Young, RH TI Malignant melanoma metastatic to the testis: A report of three cases with clinically significant manifestations SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; metastasis; malignant melanoma ID CLINICOPATHOLOGICAL ANALYSIS; TESTICULAR METASTASIS; CELL TUMOR; CARCINOMA; MELANURIA; SEMINOMA; OVARY AB Three cases of malignant melanoma metastatic to the testis, each of which was a challenge in pathologic interpretation, are reported. The patients were 43, 55, and 80 years of age, respectively. A history of malignant melanoma was not known to the initial examining pathologist in two of the cases. The testicular tumors were all uni lateral. One rook the form of multiple nodules, but the others were discrete solitary masses. On microscopic examination diffuse, nested, follicular, and fascicular pat terns, usually in combination, were seen. The tumor cells had moderate to abundant eosinophilic cytoplasm in two cases, but scanty cytoplasm in a third. In one case there was also a component of cells with copious foamy cytoplasm. Rare areas of melanin pigment were identified in two tumors. Immunohistochemistry for S-100 and HMB-45 was positive in the two cases in which it was performed. In the third case electron microscopy revealed aberrant melanosomes within the tumor cells. The differential diagnosis in these and rare other cases of malignant melanoma involving the testis during life is broad and includes seminoma, malignant lymphoma, and Leydig cell tumor. When the diagnosis is entertained, a search for melanin pigment, immunohistochemical stains for S-100 protein and HMB 45, and further inquiry into the clinical history are often crucial. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Datta, MW (reprint author), Med Coll Wisconsin, Dept Pathol, POB 26509, Milwaukee, WI 53226 USA. NR 30 TC 15 Z9 15 U1 1 U2 1 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 2000 VL 8 IS 1 BP 49 EP 57 DI 10.1177/106689690000800110 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 288ZE UT WOS:000085594200008 PM 11493964 ER PT J AU Sultzer, DL AF Sultzer, DL TI Selective serotonin reuptake inhibitors and trazodone for treatment of depression, psychosis, and behavioral symptoms in patients with dementia SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article; Proceedings Paper CT Meeting of the International-Psychogeriatric-Association on Behavioral and Psychological Symptoms of Dementia CY 1999 CL LANSDOWNE, VIRGINIA SP Int Psychogeriatr Assoc ID DOUBLE-BLIND; ALZHEIMERS-DISEASE; PLACEBO; CITALOPRAM; DISTURBANCES; HALOPERIDOL; MULTICENTER; FLUOXETINE; AGITATION; EFFICACY C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Mental Hlth Serv, Los Angeles, CA USA. RP Sultzer, DL (reprint author), W Los Angeles VA Med Ctr, Mental Hlth Serv, 3 South,116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 16 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2000 VL 12 SU 1 BP 245 EP 251 DI 10.1017/S1041610200007109 PG 7 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 410HL UT WOS:000167434500042 ER PT J AU Pettinati, HM Volpicelli, JR Pierce, JD O'Brien, CP AF Pettinati, HM Volpicelli, JR Pierce, JD O'Brien, CP TI Improving naltrexone response: An intervention for medical practitioners to enhance medication compliance in alcohol dependent patients SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Research-Society-of-Alcoholism CY JUN, 1996 CL WASHINGTON, D.C. SP Res Soc Alcoholism DE medication compliance; naltrexone; alcohol dependence; pharmacotherapy; compliance enhancement ID PLACEBO-CONTROLLED TRIAL; DEPRESSION; DRUG AB The effectiveness of naltrexoale, a FDA-approved medication for alcohol dependence, can be improved if we support and help patients to consistently take their medication. We illustrate how patient noncompliance with treatment negatively affects outcome, and, we describe a new intervention to enhance medication compliance. Outcome was evaluated for 196 alcohol dependent outpatients who were treated with 50 mg/day naltrexone or placebo for 12 weeks. For patients who adhered to the prescribed treatment, relapse rates were lower with naltrexone than placebo (10% vs. 38.6%, p < 0.001). I;or noncompliant patients, relapse rates were high and comparable between naltrexone-and placebo-treated patients (42.9% vs. 40%). In a second study of 100 alcohol dependent outpatients, we introduced an intervention that resulted in better medication compliance rates compared to a previous naltrexone study of patients who did not receive the intervention (77.0% vs, 60.8%, p < 0.01). This provided some support for the use of an intervention that targets medication compliance when prescribing naltrexone. [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: getinfo@haworthpressinc.com < Website:http://www.hwaorthpressinc.com>]. C1 Univ Penn, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia Med Ctr Vet Affairs, Philadelphia, PA USA. RP Pettinati, HM (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [AA-07517, AA-09544]; NIDA NIH HHS [DA-05186] NR 33 TC 83 Z9 86 U1 1 U2 2 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 2000 VL 19 IS 1 BP 71 EP 83 DI 10.1300/J069v19n01_06 PG 13 WC Substance Abuse SC Substance Abuse GA 302YD UT WOS:000086393300006 PM 10772604 ER PT J AU Sharon, E Rubin, A Turner, W Gastfriend, DR AF Sharon, E Rubin, A Turner, W Gastfriend, DR TI Challenges to engaging patients in ASAM Criteria placements SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Maine, Orono, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2000 VL 19 IS 2 MA 20A BP 150 EP 150 PG 1 WC Substance Abuse SC Substance Abuse GA 306NA UT WOS:000086601700034 ER PT J AU Newman, JR Ewing, SE McColl, RD Borus, JS Nierenberg, AA Pava, J Fava, M AF Newman, JR Ewing, SE McColl, RD Borus, JS Nierenberg, AA Pava, J Fava, M TI Tridimensional personality questionnaire and treatment response in major depressive disorder: a negative study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE depression; fluoxetine; tridimensional personality questionnaire; treatment response ID ANTIDEPRESSANT RESPONSE; TEMPERAMENT; STATES; MOOD; DESIPRAMINE; FLUOXETINE; DIMENSIONS; TRAITS AB Background: Recent studies have found that the Tridimensional Personality Questionnaire can be used to help predict antidepressant treatment response in depressed outpatients. As this finding could be of great clinical importance, we attempted to replicate these findings. Methods: Our study included 199 outpatients with major depressive disorder in an 8-week open trial with fluoxetine 20 mg/day. The Tridimensional Personality Questionnaire (TPQ) was administered to all patients before treatment. Results: There was a significant correlation between pre-treatment scores on the TPQ subscale of harm avoidance and severity of depression at baseline as determined by Hamilton Depression Rating Scale-17 (HAM-D-17) scores. There was no correlation of harm avoidance scores and percent improvement of HAM-D-17 after treatment with fluoxetine, Then was also no correlation of baseline HAM-D-17 scores or percent improvement with the subscales of reward dependence and novelty seeking. Limitations: Our study's limitations include a possible selection bias, lack of controls and fixed dosing of fluoxetine. Conclusions: In contrast to previous studies, we failed to find a relationship between temperament type as defined by the TPQ and antidepressant response. Our failure to replicate the findings of other studies may in large par? be related to the use of different classes of antidepressants. Further studies using similar antidepressants may be helpful to clarify this discrepancy. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. RP Newman, JR (reprint author), Childrens Hosp, 300 Longwood Ave,Fegan 8, Boston, MA 02115 USA. NR 22 TC 33 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN-MAR PY 2000 VL 57 IS 1-3 BP 241 EP 247 DI 10.1016/S0165-0327(99)00046-4 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299AA UT WOS:000086172600028 PM 10708838 ER PT J AU Gibbon, G Szeftel, A Klaustermeyer, W AF Gibbon, G Szeftel, A Klaustermeyer, W TI Toxic epidermal necrolysis due to itraconazole SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 1000 BP S339 EP S339 DI 10.1016/S0091-6749(00)91426-X PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100994 ER PT J AU Sanchez, H Guadalupe, J Bush, RK AF Sanchez, H Guadalupe, J Bush, RK TI Humoral immunologic response of brown Norway rats to rAlt a2 sensitization and DNA vaccination SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 854 BP S291 EP S291 DI 10.1016/S0091-6749(00)91282-X PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100850 ER PT J AU Sauty, A Wagner, L Mach, F Yang, OO Neote, K Libby, P Spertini, F Luster, AD AF Sauty, A Wagner, L Mach, F Yang, OO Neote, K Libby, P Spertini, F Luster, AD TI Internalization of CXCR3 on activated T cells following contact with IFNg-Activated human endothelial cells: Differential effects of I-TAC, Mig, and I-TAG SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ Lausanne Hosp, Div Allergy Immunol, Lausanne, Switzerland. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Pfizer Inc, Div Cent Res, Groton, CT 06340 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 2000 VL 105 IS 1 SU S MA 819 BP S278 EP S279 DI 10.1016/S0091-6749(00)91247-8 PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100815 ER PT J AU Waytes, AT Peake, B Engl, W Wappler, N Rosen, FS AF Waytes, AT Peake, B Engl, W Wappler, N Rosen, FS TI Pharmacokinetic evaluation of a vapor-heated C1-inhibitor concentrate SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Bayer AG, Vienna, Austria. Ctr Blood Res, Boston, MA 02115 USA. Baxter Hyland Immuno, Rochester, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 672 BP S226 EP S226 DI 10.1016/S0091-6749(00)91100-X PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100668 ER PT J AU Kradin, R AF Kradin, R TI Response to Richard Kradin's 'Generosity: a psychological and interpersonal factor of therapeutic relevance' and his 'Reply to Ann Casement' (JAP 1999, 44, 2, pp. 221-36 & 245-8) - Reply to Anderson SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Cox 5 Bldg, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD JAN PY 2000 VL 45 IS 1 BP 131 EP 134 DI 10.1111/1465-5922.00142 PG 4 WC Psychology, Psychoanalysis SC Psychology GA 281ZC UT WOS:000085190500012 ER PT J AU Gill, TJ Sledge, JB Muller, ME AF Gill, TJ Sledge, JB Muller, ME TI The management of severe acetabular bone loss using structural allograft and acetabular reinforcement devices SO JOURNAL OF ARTHROPLASTY LA English DT Article DE allograft; revision; arthroplasty; hip; reinforcement; bone loss ID TOTAL HIP-ARTHROPLASTY; FEMORAL-HEAD ALLOGRAFTS; CONGENITAL DISLOCATION; REVISION ARTHROPLASTY; RECONSTRUCTION; DEFICIENCY; SOCKET; RING; REPLACEMENT AB The cases of 37 acetabular reconstructions in 35 patients with major structural pelvic bone loss were reviewed. At an average follow-up of 7.1 years, patients rated their results as excellent in 12 cases (32.4%), good in 22 (59.5%), fair in 2 (5.4%), and poor in 1 (2.7%). Thirty-four cases (91.9%) were classified as a clinical success. Thirty-six allografts (97.3%) had radiographic evidence of full incorporation. Of the unrevised hips, 1 (2.7%) was classified as definitely loose, 2 (5.4%) as probably loose, and 4 (10.8%) as possibly loose. One revision of an acetabular component was required because of late sepsis. This is the first reported series on the use of acetabular reinforcement devices with solid bulk allograft covering more than 50% of the socket. The allograft is protected in the early postoperative period, superior migration of the cup is virtually eliminated as a complication and the incidence of aseptic loosening is greatly diminished. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gill, TJ (reprint author), Massachusetts Gen Hosp, WACC-514,15 Parkman St, Boston, MA 02114 USA. NR 49 TC 65 Z9 72 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2000 VL 15 IS 1 BP 1 EP 7 DI 10.1016/S0883-5403(00)90973-2 PG 7 WC Orthopedics SC Orthopedics GA 274PX UT WOS:000084775200001 PM 10654455 ER PT J AU Dearborn, JT Harris, WH AF Dearborn, JT Harris, WH TI Acetabular revision arthroplasty using so-called jumbo cementless components - An average 7-year follow-up study SO JOURNAL OF ARTHROPLASTY LA English DT Article DE acetabular revision; cementless jumbo cups ID REINFORCEMENT RING; HIP-ARTHROPLASTY; DEFICIENCY AB The optimal technique for acetabular revision surgery in the face of major bone stock deficiency remains controversial. One subset of these problem cases consists of hips that are amenable to reconstruction using a large, hemispherical cementless acetabular component, the so-called jumbo acetabular component. We report the intermediate-term experience of 24 hips in 24 patients who underwent an uncemented acetabular revision using a hemispherical acetabular component of greater than or equal to 66 mm diameter. In 16 hips, the femoral component was replaced as well. Of the 18 hips in patients alive after 5 years, 15 were assessed at a mean follow-up of 7.0 years (range, 5.0-10.3 years). The mean final Harris Hip Score was 86 points (range, 45-100 points). No acetabular component had been revised, and none were loose radiographically. In this difficult group, a bimodal distribution resulted. The complication rate was high. In those without infection, the results were excellent. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126, Boston, MA 02114 USA. NR 36 TC 65 Z9 78 U1 2 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2000 VL 15 IS 1 BP 8 EP 15 DI 10.1016/S0883-5403(00)90999-9 PG 8 WC Orthopedics SC Orthopedics GA 274PX UT WOS:000084775200002 PM 10654456 ER PT J AU Kumar, R Gaerlan, MSM Burgess, T AF Kumar, R Gaerlan, MSM Burgess, T TI Carpal tunnel syndrome in the presence of wrist flexion and absence of repetitive movements SO JOURNAL OF BACK AND MUSCULOSKELETAL REHABILITATION LA English DT Article DE carpal tunnel syndrome; wrist flexion; intracarpal pressure ID PRESSURES AB One of the mechanical factors associated with carpal tunnel syndrome is repeated movement of flexion and extension at the wrist. The objective of this study was to determine whether prolonged positioning of flexion at the wrist, in the absence of repetitive movement, could cause carpal tunnel syndrome. The study was performed in a group of stroke patients with prolonged flexion but poor volitional movement at the wrist. Forty-right patients who suffered stroke at least 6 months before the study were included. Patients with severe spasticity (Ashworth scale > 3) and motor strength of > 2/5 were excluded. Tinels Phalen's, Semmes-Weinstein monofilament tests, median and ulnar nerve conduction studies were performed on all patients, if both nerves showed abnormal latencies or conduction, contralateral median and ulnar nerves and peroneal nerve in one extremity were also studied, to rule out peripheral neuropathy. Patients with peripheral neuropathy were subsequently excluded from the study. Carpal tunnel syndrome was diagnosed if distal motor latency was > 4.2 m sec and/or if distal sensory latency was > 3.5 m sec. Twenty-one patients met the inclusion criteria. None of them were wearing resting hand splint. Mean age of the patients was 61.2 +/- 9.9 yr. Resting position of the wrist was flexion in all patients. Seven of the 21 hands showed cat-pal tunnel syndrome (30%). There was no significant difference in the degree of wrist flexion between those who had and those who did not have carpal tunnel syndrome, demonstrating that carpal tunnel syndrome can occur in the presence of flexion of the wrist even in the absence of repetitive movements. C1 VA Greater Los Angeles Hlth Care Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Multicampus Phys Med & Rehabil Residency Program, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Occupat Therapy Dept, Los Angeles, CA USA. RP Kumar, R (reprint author), VA Greater Los Angeles Hlth Care Syst, Dept Phys Med & Rehabil, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 19 TC 0 Z9 0 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8127 J9 J BACK MUSCULOSKELET JI J. Back Musculoskelet. Rehabil. PY 2000 VL 14 IS 3 BP 127 EP 131 PG 5 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 455FF UT WOS:000170016300008 ER PT J AU Lewandrowski, KU Gresser, JD Wise, DL Trantolo, DJ Hasirci, V AF Lewandrowski, KU Gresser, JD Wise, DL Trantolo, DJ Hasirci, V TI Tissue responses to molecularly reinforced polylactide-co-glycolide implants SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE polylactide-co-glycolide; dimensional stability; polypropylene fumarate ID BONE-CEMENT; FRACTURES; FIXATION; OSTEOTOMY; SCREWS; DEGRADATION; SKULL; PLATE AB Plates for internal fixation fabricated from biodegradable polymers degrade via an autocatalytic route. When they are used in bone implants of significant size and thickness, hollowing of the implant may occur while the overall dimensions appear unchanged. We hypothesized that incorporation of a cross-linked polypropylene fumarate matrix into polylactide-co-glycolide bone plates may provide an internal molecular network which prevents implant collapse. Cross-linking reagents of varying hydrophilicity including N-vinylpyrrolidone (VP), hydroxyethylmethacrylate (HEMA), and ethyleneglycol dimethacrylate (EGDMA) were employed. With the objective of determining the most biocompatible and structurally sound composition for molecular reinforcement, we investigated tissue responses in both subcutaneous and orthotopic rodent implantation models in relation to maintenance of implant integrity by histologic, histomorphometric, and stereomicroscopic analysis. Results showed that tissue responses were correlated with dimensional stability of the implants. The most favorable results were seen with the hydrophobic cross-linker EGDMA; this may have been related to the initial reduction of the water uptake by the implant. Cross-linking of polypropylene fumarate with EGDMA within a polylactide-co-glycolide bone plate may offer a means to maintain excellent biocompatibility while improving dimensional stability of biodegradable bone plates. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [1 R43 AR 44450-01A1, AR 45062] NR 32 TC 8 Z9 8 U1 1 U2 4 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 2000 VL 11 IS 4 BP 401 EP 414 DI 10.1163/156856200743788 PG 14 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 331AB UT WOS:000087993600006 PM 10903038 ER PT J AU Lewandrowski, KU Gresser, JD Bondre, SP Silva, AE Wise, DL Trantolo, DJ AF Lewandrowski, KU Gresser, JD Bondre, SP Silva, AE Wise, DL Trantolo, DJ TI Developing porosity of poly(propylene glycol-co-fumaric acid) bone graft substitutes and the effect on osteointegration: A preliminary histology study in rats SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE bioresorbable; bone graft substitute; porosity; poly(propylene fumarate) ID CEMENT; FOAMS AB Bioresorbable bone graft substitutes could eliminate disadvantages associated with the use of autografts, allografts: and other synthetic materials. We investigated a bioresorbable bone graft substitute made from the unsaturated polyester poly(propylene fumarate) which is crosslinked in the presence of soluble and insoluble calcium filler salts. This compact bone graft substitute material develops porosity in vivo by leaching of the soluble filler salts. In attempt to develop materials whose in live porosity can be designed such that implant degradation would occur at a rate that remains supportive of the overall structural integrity of the repairing defect site, we studied the early tissue response upon implantation in a bony defect. Three grout formulations of varying solubilities using slightly soluble hydroxyapatite (HA) and soluble calcium acetate (CA) were evaluated in 3 mm holes made in the anteromedial tibial metaphysis of 200 g Sprague Dawley rats (n = 16 per formulation for a total of 48 animals). Grout formulations cured in situ. Animals from each formulation were sacrificed in groups of 8 at 4 days and 3 weeks postoperatively. Histologic analysis of the healing process revealed improved in vivo osteointegration of bone graft substitutes when a higher loading of calcium acetate was employed. All formulations maintained implant integrity and did not provoke sustained inflammatory responses. This study suggested that the presence of a soluble salt permits in vivo development of porosity of a poly(propylene fumarate) based bone graft substitute material. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062, R44 AR 44317-03] NR 14 TC 23 Z9 24 U1 0 U2 7 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 2000 VL 11 IS 8 BP 879 EP 889 DI 10.1163/156856200744075 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 393VL UT WOS:000166490300007 PM 11211098 ER PT J AU Atlas, SJ Chang, YC Kammann, E Keller, RB Deyo, RA Singer, DE AF Atlas, SJ Chang, YC Kammann, E Keller, RB Deyo, RA Singer, DE TI Long-term disability and return to work among patients who have a herniated lumbar disc: The effect of disability compensation SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID LOW-BACK-PAIN; OUTCOMES RESEARCH; SCIATICA; HEALTH; PREDICTORS; SPINE; REHABILITATION; RECOVERY; SURGERY; PROGRAM AB Background Low-back problems are one of the most frequent reasons for disability compensation claims by workers. However, the effect of Workers' Compensation status on the long-term outcome for workers with sciatica has not been studied in detail, to our knowledge. Therefore, we believe that it is important to describe the long-term outcomes for patients who have herniation of a lumbar disc and sciatica according to the Workers' Compensation status at the time of the preoperative consultation, Methods: We conducted a prospective, observational study of patients who had sciatica and were seeking care from specialist physicians in community-based practices throughout Maine. Among 440 eligible patients, 199,were receiving Workers' Compensation at the time of entry into the study (baseline) and 241,were not, Three hundred and twenty-six patients (74 percent) completed questionnaires at the time of a four-year follow-up. The outcomes that we assessed included disability compensation and work status as well as relief from symptoms, functional status, and quality of life. Results: Patients who were receiving Workers' Compensation at baseline were more likely to be young, male, and employed as laborers, They reported worse functional status; however, the clinical findings for these patients were similar to those for patients who,were not receiving Workers' Compensation, Patients who had been receiving Workers' Compensation at baseline,were more likely to be receiving disability benefits at the time of the four-year follow-up compared,vith those,who had not (27 percent of 133 compared with 7 percent of 189; p < 0.001); however, they were only slightly less likely to be,working at the time of the four-year followup (80 percent of 133 compared,vith 87 percent of 190; p = 0.09), Operative management did not influence these comparisons, but it decreased symptoms and improved functional status, Patients who had been receiving Workers' Compensation at baseline also had significantly less relief from symptoms and improvement in quality of life than patients who had not been receiving Workers' Compensation (all p < 0.001), In multivariate models, Workers' Compensation status at baseline was an independent predictor of wether the patient would be receiving disability benefits after four years (odds ratio, 3.5; 95 percent confidence interval, 1.7 to 7.6) but was not an independent predictor of whether the patient,would be working on a job for pay at the time of the four-year follow-up (odds ratio, 0.6; 95 percent confidence interval, 0.3 to 1.2), Conclusions: Even after adjustment for the initial treatment of the sciatica and for other clinical factors, patients who had been receiving Workers' Compensation at baseline were more likely to be receiving disability benefits and were less likely to report relief from symptoms and improvement in quality of life at the time of the four-year follow up than patients who had not been receiving Workers' Compensation at baseline, Nonetheless, most patients returned to work regardless of their initial disability status, and those who had been receiving Workers' Compensation at baseline were only slightly less likely to be working after four years. Whether or not they had been receiving Workers' Compensation at baseline, patients who had been managed,vith an operation reported greater relief from symptoms and improvement in functional status at the time of the four-year follow-up compared,with patients who had been managed nonoperatively, even though the outcomes,vith regard to disability and work status in these two groups were comparable. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Maine Med Assessment Fdn, Manchester, NH 04351 USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98103 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98103 USA. Univ Washington, Dept Med, Seattle, WA 98103 USA. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. FU AHRQ HHS [HS-08194, HS-06344, HS-09804] NR 36 TC 84 Z9 85 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN PY 2000 VL 82A IS 1 BP 4 EP 15 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 274HC UT WOS:000084759400002 PM 10653079 ER PT J AU Daltroy, LH Liang, MH Phillips, CB Daugherty, MB Hinson, M Jenkins, M McCauley, R Meyer, W Munster, A Pidcock, F Reilly, D Tunell, W Warden, G Wood, D Tompkins, R AF Daltroy, LH Liang, MH Phillips, CB Daugherty, MB Hinson, M Jenkins, M McCauley, R Meyer, W Munster, A Pidcock, F Reilly, D Tunell, W Warden, G Wood, D Tompkins, R TI American burn association/shriners hospitals for children burn outcomes questionnaire: Construction and psychometric properties SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID PROMPT ESCHAR EXCISION; HEALTH-STATUS; RELIABILITY; ARTHRITIS; MORTALITY; INJURIES; SCALE AB To develop a standardized, practical, self-administered questionnaire to monitor pediatric patients with burns and to evaluate the effectiveness of comprehensive pediatric burn management treatments, a group of experts generated a set of items to measure relevant burn outcomes. Children between the ages of 5 and 18 pears were assessed in a cross-sectional study. Both parent and adolescent responses were obtained from children 11 to 18 years old. The internal reliability of final scales ranged from 0.82 to 0.93 among parents and from 0.75 to 0.92 among adolescents. Mean differences between parent and adolescent were small; the greatest difference occurred in the appearance subscale. Parental scales showed evidence of validity and potential for sensitivity to change. In an effort to support the construct validity of the new scales, they were compared with the Child Health Questionnaire and related to each other in clinically sensible ways. These burn outcomes scales reliably and validly assess function in patients with burns, and the scales have been developed in such a way that they are likely to be sensitive to change over time. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, RBB Multipurpose Arthritis & Musculoskeletal Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Shriners Hosp Crippled Children, Cincinnati, OH USA. Shriners Hosp Crippled Children, Boston, MA USA. Shriners Hosp Crippled Children, Galveston, TX USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Baltimore Reg Burn Ctr, Baltimore, MD USA. Kennedy Krieger Inst, Baltimore, MD USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Univ Oklahoma, Childrens Hosp, Oklahoma City, OK USA. Shriners Hosp Crippled Children, Tampa, FL USA. RP Tompkins, R (reprint author), Massachusetts Gen Hosp, GRB 1302,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 51 Z9 51 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JAN-FEB PY 2000 VL 21 IS 1 BP 29 EP 39 DI 10.1097/00004630-200021010-00007 PN 1 PG 11 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 277NN UT WOS:000084939800006 PM 10661536 ER PT J AU Baciu, PC Saoncella, S Lee, SH Denhez, F Leuthardt, D Goetinck, PF AF Baciu, PC Saoncella, S Lee, SH Denhez, F Leuthardt, D Goetinck, PF TI Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization SO JOURNAL OF CELL SCIENCE LA English DT Article DE syndecan-4; signaling; cytoskeleton; focal adhesion ID HEPARAN-SULFATE PROTEOGLYCANS; KINASE-C; EXTRACELLULAR-MATRIX; ADHESION; FAMILY; SPECIFICITY; CASK/LIN-2; MOLECULES; RECEPTORS; BIOLOGY AB Syndecan-4 is a cell surface heparan sulfate proteoglycan which, in cooperation with integrins, transduces signals for the assembly of focal adhesions and actin stress fibers in cells plated on fibronectin. The regulation of these cellular events is proposed to occur, in part, through the interaction of the cytoplasmic domains of these transmembrane receptors with intracellular proteins. To identify potential intracellular proteins that interact with the cytoplasmic domain of syndecan-4, we carried out a yeast two-hybrid screen in which the cytoplasmic domain of syndecan-4 was used as bait. As a result of this screen, we have identified a novel cellular protein that interacts with the cytoplasmic domain of syndecan-4 but not with those of the other three syndecan family members. The interaction involves both the membrane proximal and variable central regions of the cytoplasmic domain. We have named this cDNA and encoded protein syndesmos, Syndesmos is ubiquitously expressed and can be myristylated. Consistent with its myristylation and syndecan-4 association, syndesmos colocalizes with syndecan-4 in the ventral plasma membranes of cells plated on fibronectin. When overexpressed in NIH 3T3 cells, syndesmos enhances cell spreading, actin stress fiber and focal contact formation in a serum-independent manner. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Goetinck, PF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD22016, HD37490] NR 44 TC 51 Z9 54 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2000 VL 113 IS 2 BP 315 EP 324 PG 10 WC Cell Biology SC Cell Biology GA 283DC UT WOS:000085260000014 PM 10633082 ER PT J AU Kearns, AE Demay, MB AF Kearns, AE Demay, MB TI BMP-2 induces the expression of activin beta A and follistatin in vitro SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bone morphogenetic protein; BMP; activin; follistatin; bone ID BONE MORPHOGENETIC PROTEIN-7; INDIAN HEDGEHOG; LEG BUD; CARTILAGE; RAT; BINDING; SUPERFAMILY; RECEPTORS; NOGGIN; CELLS AB Activins are members of the transforming growth factor beta (TGF-beta) superfamily and have been shown to be multifunctional regulators of development and cell differentiation. Increasing evidence suggests activin beta A is involved in skeletal development. Using differential display PCR we have identified activin beta A as a gene associated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induced differentiation of a mouse limb bud cell line, MLB13MYC clone 17, from a prechondroblastic to an osteoblastic phenotype. The expression of activin beta A peaks at 24 h of rhBMP-2 treatment before detection of osteocalcin mRNA expression. Cycloheximide treatment inhibits induction of activin beta A, indicating a requirement for new protein synthesis. The induction of the mRNA encoding follistatin, an activin binding protein, was a Iso examined. Follistatin mRNA increases within 18 h of rhBMP-2 treatment, as activin beta A mRNA increases but before it peaks. Treatment of MLB13MYC clone 17 cells with purified activin beta A concomitant with rhBMP-2 does not affect markers of chondrocyte or osteoblast differentiation, nor does treatment With purified activin beta A alone. This suggests that activin beta A exerts its effect via a paracrine mechanism. In situ hybridization analysis demonstrates that activin beta A expression is localized to cells in the developing interphalangeal joints of embryonic mouse limbs. This is consistent with in vivo induction by BMP-2 which is also expressed in the developing joints. Activin beta A, therefore, is downstream from BMP-2 in the cascade of events that result in skeletal development. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR45011]; NIDDK NIH HHS [DK36597] NR 38 TC 15 Z9 16 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 2000 VL 79 IS 1 BP 80 EP 88 DI 10.1002/1097-4644(2000)79:1<80::AID-JCB80>3.0.CO;2-K PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 344ZV UT WOS:000088791700007 PM 10906757 ER PT J AU Zeng, WL Remold-O'Donnell, E AF Zeng, WL Remold-O'Donnell, E TI Human monocyte/neutrophil elastase inhibitor (MNEI) is regulated by PU.1/Spi-1, Sp1, and NF-kappa B SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE monocytes; neutrophils; promoter; regulation of gene transcription; protease; protease inhibitor ID LEUKEMIA-CELL-LINE; TRANSCRIPTION FACTOR SPI-1/PU.1; DNA-BINDING PROTEINS; NEUTROPHIL ELASTASE; MYELOID CELLS; PROMOTER ACTIVITY; HUMAN-MONOCYTES; CD11B PROMOTER; CATHEPSIN-G; GENE AB Human monocyte/neutrophil elastase inhibitor (MNEI) is a specific inhibitor of the neutrophil azurophil granule proteases including elastase. To understand the physiological mechanisms that regulate expression of MNEI, we dissected a 1.0 kb region upstream of exon 1. On transient transfection, promoter activity of MNEI-luciferase constructs was highest in U937 myeloid cells, followed by K562 hematopoietic cells, followed by HeLa cervical carcinoma cells, indicating that the MNEI promoter is most active in myeloid cells and is also active in non-myeloid cells. Three transcription factor binding elements, which confer the majority of activity, are located within the first 180 base pairs of the promoter, one of which, located at -128, was active in U937 and K562 cells but inactive in non-myeloid HeLa cells. The three proximal elements were identified by transient transfection, mutation, gel shift and competition assays as Sp1 at -170, PU.1/Spi-1 at -128, and Sp1 at -66. The trans-acting factors that bind and control these elements were detected, and their identity confirmed by antibody supershift assays. Further upstream at -821, an additional regulatory element was identified controlled by NF-kappa B, which supports the highest levels of MNEI transcriptional activity. In U937 cells, reporter gene expression by the MNEI-luciferase construct that included the NF-kappa B element was two- to three-fold greater than the construct without the element. In addition, treatment of myeloid cells with lipopolysaccharide, a complex glycolipid of gram-negative bacteria, activated NF-kappa B to bind the -821 element, together suggesting that enhancement of expression of the anti-inflammatory MNEI gene is linked to innate immune responses to bacterial infection. J. Cell. Biochem. 78.519-532, 2000. (C) 2000 Wiley-Liss. Inc. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL041579, HL41579] NR 52 TC 12 Z9 12 U1 0 U2 4 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 2000 VL 78 IS 4 BP 519 EP 532 DI 10.1002/1097-4644(20000915)78:4<519::AID-JCB1>3.0.CO;2-V PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 339DJ UT WOS:000088462100001 PM 10861849 ER PT J AU Schatten, H Ripple, M Balczon, R Weindruch, R Chakrabarti, A Taylor, M Hueser, CN AF Schatten, H Ripple, M Balczon, R Weindruch, R Chakrabarti, A Taylor, M Hueser, CN TI Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cytoskeleton; mitosis; cell proliferation; cell culture; centrosomes ID SEA-URCHIN EGGS; MONOCLONAL-ANTIBODY; CARCINOMA-CELLS; NUCLEAR MATRIX; GAMMA-TUBULIN; PROTEIN; FERTILIZATION; CYCLE; MICROTUBULES; DIVISION AB We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibit-ed cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. (C) 2000 Wiley-Liss, inc. C1 Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Ctr Canc Res, Columbia, MO 65211 USA. Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Hosp, GRECC, Madison, WI 53792 USA. Univ S Alabama, Dept Cellular & Struct Biol, Mobile, AL 36688 USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Med, Madison, WI 53706 USA. RP Schatten, H (reprint author), Univ Missouri, Dept Vet Pathobiol, 1600 E Rollins St, Columbia, MO 65211 USA. FU NIA NIH HHS [T32AG0002/3-06] NR 73 TC 16 Z9 16 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2000 VL 76 IS 3 BP 463 EP 477 DI 10.1002/(SICI)1097-4644(20000301)76:3<463::AID-JCB13>3.0.CO;2-S PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 281WM UT WOS:000085184500013 PM 10649443 ER PT J AU Syngal, S Clarke, G Bandipalliam, P AF Syngal, S Clarke, G Bandipalliam, P TI Potential roles of genetic biomarkers in colorectal cancer chemoprevention SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Translational Chemoprevention - Breast and Colon Cancer CY JUN 21-24, 1998 CL HAIFA, ISRAEL SP Chemoprevent Branch, Div Canc Prevent, Control Natl Canc Inst, Israel Canc Assoc, Univ Michigan DE chemoprevention; genetic biomarkers; colorectal cancer; mutations; hereditary nonpolyposis colorectal cancer; familial adenomatous polyposis ID COLON-CANCER; POLYPOSIS; MUTATIONS; LOCALIZATION; PROGRESS; HOMOLOG; HMSH2; RISK AB Colorectal cancer is a significant cause of morbidity and mortality in industrialized societies and the second most frequent cause of cancer death in the United States. Surrogate endpoint biomarkers are gaining wide acceptance in early diagnosis and short-term cancer chemoprevention trials in place of cancer endpoints. Molecular genetic biomarkers can be useful tools in identifying subjects at risk of developing cancer and screening for early cancers amenable to complete cure. They may be useful both in predicting and assessing response to a given therapy and in determining prognosis after an initial diagnosis has been made. Ideally, biomarkers should fulfill some, if not all, of the following criteria: variability of expression between phases of carcinogenesis, association with cancer risk, ability to undergo modification in response to a chemopreventive agent, and finally, permit ease of measurement. In consideration of colorectal cancer chemoprevention, several genetic biomarkers seem to meet many of these criteria, as they do exhibit distinct variability of expression at different phases of carcinogenesis, are often strongly associated with increased cancer risk (especially the hereditary/familial syndromes), are generally able to be measured relatively easily through peripheral blood sampling (germline mutations) or by colonic mucosal sampling by endoscopic techniques (somatic mutations). In some cases, genetic biomarkers have also been demonstrated to undergo modification in response to a chemopreventive agent. With further understanding of the genetic and molecular changes involved in sporadic and familial colorectal carcinogenesis, genetic biomarkers appear to hold great potential for the identification of subjects at high risk of developing colorectal cancer, as well as the development of novel chemopreventive approaches and form a promising area for further research. (C) 2000 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. NR 38 TC 2 Z9 2 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 2000 SU 34 BP 28 EP 34 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 298YV UT WOS:000086169600007 ER PT J AU Dietrich, WD Truettner, J Prado, R Stagliano, NE Zhao, WZ Busto, R Ginsberg, MD Watson, BD AF Dietrich, WD Truettner, J Prado, R Stagliano, NE Zhao, WZ Busto, R Ginsberg, MD Watson, BD TI Thromboembolic events lead to cortical spreading depression and expression of c-fos, brain-derived neurotrophic factor, glial fibrillary acidic protein, and heat shock protein 70 mRNA in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE in situ hybridization; embolic events; platelets; thrombosis; genes; stroke ID CAROTID-ARTERY THROMBOSIS; MIDDLE CEREBRAL-ARTERY; NERVE GROWTH-FACTOR; MESSENGER-RNAS; BLOOD-FLOW; ISCHEMIA; OCCLUSION; MK-801; CONSEQUENCES; PLATELET AB The hypotheses that cerebral embolic events lead to repetitive episodes of cortical spreading depression (CSD) and that these propagating waves trigger the expression of c-fos, brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and heat shock protein 70 (HSP70) mRNA were tested. Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) (n = 18) or sham (n = 8) procedures. In a subgroup of rats (n = 5), laser-Doppler flowmetry probes were placed overlying the right parietal cortex to record CSD-Like changes in cortical blood flow during the initial 2-hour postinjury period. Rats were killed by decapitation at 2 or 24 hours after CCAT, and brains were processed for in situ localization of the gene expression. Two to five intermittent transient hyperemic episodes lasting 1 to 2 minutes were recorded ipsilaterally after CCAT. At 2 hours after CCAT, the widespread expression of c-fos and BDNF mRNAs was observed throughout the ipsilateral cerebral cortex. Pretreatment with the N-methyl-D-aspartate receptor blocker MK-801 (2 mg/kg) 1 hour before CCAT reduced the expression of BDNF mRNA expression at 2 hours. At 24 hours after CCAT, increased expression of GFAP mRNA was present in cortical and subcortical regions. In contrast, multifocal regions of HSP70 expression scattered throughout the thrombosed hemisphere were apparent at both 2 and 24 hours after injury. These data indicate that thromboembolic events lead to episodes of CSD and time-dependent alterations in gene expression. The ability of embolic processes to induce widespread molecular responses in neurons and glia may be important in the pathogenesis of transient ischemic attacks and may influence the susceptibility of the postembolic brain to subsequent insults including stroke. C1 Univ Miami, Sch Med, Dept Neurol Surg R48, Miami, FL 33101 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33101 USA. Univ Miami, Sch Med, Cerebral Vasc Dis Res Ctr, Miami, FL 33101 USA. Harvard Univ, Massachusetts Gen Hosp, Charlestown, MA USA. RP Dietrich, WD (reprint author), Univ Miami, Sch Med, Dept Neurol Surg R48, POB 016960, Miami, FL 33101 USA. FU NINDS NIH HHS [NS-23244, NS-05820, NS-27127] NR 42 TC 26 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2000 VL 20 IS 1 BP 103 EP 111 DI 10.1097/00004647-200001000-00014 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 281PJ UT WOS:000085169600014 PM 10616798 ER PT J AU Endres, M Fan, GP Hirt, L Fujii, M Matsushita, K Liu, X Jaenisch, R Moskowitz, MA AF Endres, M Fan, GP Hirt, L Fujii, M Matsushita, K Liu, X Jaenisch, R Moskowitz, MA TI Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE neurotrophins; cerebral ischemia; BDNF; NT4 ID NERVE GROWTH-FACTOR; TRANSIENT FOREBRAIN ISCHEMIA; CEREBRAL-ARTERY OCCLUSION; TYROSINE KINASE RECEPTOR; REDUCES INFARCT SIZE; NEUROTROPHIC FACTOR; RAT-BRAIN; MESSENGER-RNAS; MOLECULAR-CLONING; TRKB RECEPTORS AB The neurotrophins and the tyrosine kinase (Trk) B receptor may play a protective role in the pathophysiology of cerebral ischemia. In this study, the authors investigated whether reducing endogenous expression of TrkB-binding neurotrophins modifies the susceptibility to ischemic injury after 1-hour middle cerebral artery occlusion followed by 23 hours of reperfusion in a filament middle cerebral artery occlusion model. Mice lacking both alleles for neurotrophin-4 (nt4(-/-)) or deficient in a single allele for brain-derived neurotrophic factor (bdnf(+/-)) exhibited larger cerebral infarcts compared to wildtype inbred 129/SVjae mice (68% and 91%, respectively, compared to controls). Moreover, lesions were larger (21%) in nt4(-/-) mice after permanent middle cerebral artery occlusion. Hence, expression of both NT4 and BDNF, and by inference the TrkB receptor, confers resistance to ischemic injury. C1 Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Hirt, Lorenz/G-3553-2010; OI Hirt, Lorenz/0000-0002-2921-5000; Fan, Guoping/0000-0001-5235-6410 FU NINDS NIH HHS [NS10828] NR 40 TC 44 Z9 67 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2000 VL 20 IS 1 BP 139 EP 144 DI 10.1097/00004647-200001000-00018 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 281PJ UT WOS:000085169600018 PM 10616802 ER PT J AU Deckersbach, T Savage, CR Henin, A Mataix-Cols, D Otto, MW Wilhelm, S Rauch, SL Baer, L Jenike, MA AF Deckersbach, T Savage, CR Henin, A Mataix-Cols, D Otto, MW Wilhelm, S Rauch, SL Baer, L Jenike, MA TI Reliability and validity of a scoring system for measuring organizational approach in the Complex Figure Test SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; GLUCOSE METABOLIC RATES; EXPLICIT MEMORY; PRODUCTIONS; STRATEGIES; IMPLICIT AB The Rey-Osterrieth Complex Figure Test (RCFT) is a widely-used measure of visuospatial construction and nonverbal memory. One of the critical aspects of this test is that organizing the figure into meaningful perceptual units during copy enhances its subsequent free recall from memory. This study examined the psychometric properties of a new system for quantifying the organizational approach to the RCFT figure and compared it to another compatible scoring system. We investigated interrater reliability of both systems and explored the influences of copy organization and copy accuracy on immediate recall. Seventy-one participants meeting DSM-IV criteria for obsessive-compulsive disorder and 55 healthy control participants completed the copy and immediate free recall condition of the RCFT. Interrater reliability was evaluated by Kappa coefficients and Pearson correlations. The effects of copy organization and copy accuracy on immediate recall were evaluated using multiple regression analyses. Results indicated that the organizational approach could be assessed with high reliability using both scoring systems. Organization during copy was a strong predictor for subsequent free recall from memory using both approaches. Multiple regression analysis indicated that all organizational elements were not equally predictive of memory performance. This new system represents a very simple and reliable approach to scoring organization on the RCFT, since it requires the identification of only 5 figure components. These characteristics should contribute to its clinical utility. C1 Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Barcelona, Dept Psychiat & Clin Psychobiol, Catalunya, Spain. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, 149-9102,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Mataix-Cols, David/G-3843-2010 OI Mataix-Cols, David/0000-0002-4545-0924 NR 36 TC 42 Z9 44 U1 3 U2 11 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2000 VL 22 IS 5 BP 640 EP 648 DI 10.1076/1380-3395(200010)22:5;1-9;FT640 PG 9 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 370ZD UT WOS:000165152400010 PM 11094399 ER PT J AU Hadigan, C Corcoran, C Stanley, T Piecuch, S Klibanski, A Grinspoon, S AF Hadigan, C Corcoran, C Stanley, T Piecuch, S Klibanski, A Grinspoon, S TI Fasting hyperinsulinemia in human immunodeficiency virus-infected men: Relationship to body composition, gonadal function, and protease inhibitor use SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE; TESTOSTERONE LEVELS; DIABETES-MELLITUS; FAT ACCUMULATION; WASTING SYNDROME; HYPOGONADAL MEN; GLUCOSE; LIPIDS; HYPERLIPIDEMIA; LIPODYSTROPHY AB Fat redistribution in the setting of protease inhibitor use is increasingly common and is associated with insulin resistance in human immunodeficiency virus (HIV)-infected patients. However, little is known regarding the factors that may contribute to abnormal insulin regulation in this population. We assessed fasting insulin levels in HIV-infected men and determined the relationship among insulin, body composition, endogenous gonadal steroid concentrations, and antiviral therapy in this population. We also determined the effects of exogenous testosterone administration using the homeostatic model for insulin resistance (HOMA IR) in hypogonadal HIV-infected men with the acquired immunodeficiency syndrome wasting syndrome. Fifty HIV-infected men with acquired immunodeficiency syndrome wasting were com;pared with 20 age- and body mass index (BMI)-matched healthy control subjects. Insulin concentrations were significantly increased in HIV-infected patients compared to those in control patients (16.6 +/- 1.8 vs. 10.4 +/- 0.8 mu U/mL; P < 0.05) and were increased in nucleoside reverse transcriptase (NRTI)-treated patients who did not receive a protease inhibitor (PI; 21.7 +/- 4.3 us. 10.4 +/- 0.8 mu U/mL; P < 0.05). Insulin concentrations and HOMA IR were inversely correlated with the serum free testosterone concentration (r = -0.36; P = 0.01 for insulin level; r = -0.30; P = 0.03 for HOMA), but not to body composition parameters, age, or BMI. In a multivariate regression analysis, free testosterone (P = 0.05), BMI(P < 0.01), and lean body mass (P = 0.04) were significant. Lower lean body mass and higher BMI predicted increased insulin resistance. The HIV-infected patients demonstrated an increased trunk fat to total fat ratio (0.49 +/- 0.02 vs. 0.45 +/- 0.02; P < 0.05) and an increased trunk fat to extremity fat ratio (1.27 +/- 0.09 us. 0.95 +/- 0.06, P = 0.01), but a reduced extremity fat to total fat ratio (0.44 +/- 0.01 us. 0.49 +/- 0.01; P = 0.02) and reduced overall total body fat (13.8 +/- 0.7 us. 17.2 +/- 0.9 kg; P < 0.01) compared to the control subjects. Increased truncal fat and reduced extremity fat were seen among NRTI-treated patients, but this pattern was most severe among patients receiving combined NRTI and PI therapy [trunk fat to extremity ratio, 1.47 +/- 0.15 vs. 0.95 +/- 0.06 (P < 0.01); extremity fat to total fat ratio, 0.40 +/- 0.02 us. 0.49 +/- 0.01(P < 0.05)]. Insulin responses to testosterone administration were investigated among 52 HIV-infected men with hypogonadism and wasting (weight <90% ideal body weight and/or weight loss >10%) randomized to either testosterone (300 mg, im, every 3 weeks) or placebo for 6 months. Testosterone administration reduced HOMA IR in the HIV-infected men(-0.6 +/- 0.7 vs. + 1.41 +/- 0.8, testosterone vs, placebo, P = 0.05) in association with increased lean body mass (P = 0.02). These data demonstrate significant hyperinsulinemia in HIV-infected patients, which can occur in the absence of PI use. In NRTI-treated patients not receiving PI, a precursor phenotype is apparent, with increased truncal fat, reduced extremity fat, and increased insulin concentrations. This phenotype is exaggerated in patients receiving PI therapy, with further increased truncal fat and reduced extremity fat, although hyperinsulinemia per se is not worse. Endogenous gonadal steroid levels are inversely related to hyperinsulinemia in HIV-infected men, but reduced lean body mass and increased weight are the primary independent predictors of hyperinsulinemia. Indexes of insulin sensitivity improve in response to physiological androgen administration among hypogonadal HIV-infected patients, and this change is again related primarily to increased lean body mass in response to testosterone administration. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [F32-DK-09218, R01-DK-49302] NR 26 TC 96 Z9 98 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2000 VL 85 IS 1 BP 35 EP 41 DI 10.1210/jc.85.1.35 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200007 PM 10634360 ER PT J AU Grinspoon, S Corcoran, C Stanley, T Baaj, A Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Stanley, T Baaj, A Basgoz, N Klibanski, A TI Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; REPLACEMENT THERAPY; MOOD AB Hypogonadism is prevalent among human immunodeficiency virus-infected men, in whom significantly reduced quality of life and mood disturbances have been reported. Previous studies have not investigated the relationship between depression score and gonadal function among such patients. We first compared depression scores in hypogonadal (n = 52) and eugonadal (n = 10) patients with acquired immunodeficiency syndrome (AIDS) wasting, matched for weight and disease status, and then investigated the effects of testosterone administration on depression score in a randomized, double-blind, placebo-controlled study among the group of hypogonadal men with AIDS wasting. The primary end point in all comparisons was the Beck Depression Inventory. Hypogonadal patients demonstrated significantly increased scores on the Beck inventory compared with eugonadal-, age-, weight-, and disease status-matched subjects (15.5 +/- 1.1 vs. 10.6 +/- 1.4 mean +/- SEM, P = 0.02). Among the combined hypogonadal and eugonadal subjects, a significant inverse correlation was seen between the Beck score and both free (r = -0.41, P < 0.01) and total serum testosterone levels (r = -0.43, P < 0.001). The relationship between the Beck score and testosterone levels remained highly significant, controlling for weight, viral load, CD4 count, and anti-depressant use (P < 0.01 for free testosterone, P < 0.001 for total testosterone). Furthermore, when subjects were divided into two groups, based on a Beck score greater than 18 or less than or equal to 18, serum total and free testosterone levels were significantly lower in the subjects with a Beck score greater than 18, whereas there were no differences in weight, viral load, CD4 count, or Karnofsky status. End of study data were available in 39 patients who completed the randomized, placebo-controlled study. Beck score decreased significantly only in the subjects receiving testosterone (-5.8 +/- 1.3, P < 0.001), but not in subjects randomized to placebo (-2.7 +/- 1.3, P > 0.05). In a regression analysis, the change in Beck score was related significantly to change in weight (P < 0.01). These data demonstrate increased depression score in association with hypogonadism in men with AIDS wasting, independent of weight, virologic status, and other disease factors. In such patients, administration of testosterone results in a significant improvement in depression inventory score. This effect may be a direct effect of testosterone or related to positive effects of testosterone on weight and/or other anthropometric indices. Additional studies are needed to assess the effects of testosterone on clinical depression indices in human immunodeficiency virus-infected patients. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR01066]; NIDDK NIH HHS [F32-DK09218, R01-DK49302] NR 16 TC 87 Z9 89 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2000 VL 85 IS 1 BP 60 EP 65 DI 10.1210/jc.85.1.60 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200011 PM 10634364 ER PT J AU Makrigiannakis, A Amin, K Coukos, G Tilly, JL Coutifaris, C AF Makrigiannakis, A Amin, K Coukos, G Tilly, JL Coutifaris, C TI Regulated expression and potential roles of p53 and Wilms' tumor suppressor gene (WT1) during follicular development in the human ovary SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; GRANULOSA-CELL APOPTOSIS; P53-INDUCED APOPTOSIS; TRANSCRIPTION FACTOR; RAT OVARY; IN-VIVO; PROTEIN; BCL-2; REPRESSION; BAX AB It has been previously demonstrated that the gonadotropin-mediated inhibition of apoptosis in rat ovarian granulosa cells is associated with changes in the expression of several cell death-regulatory genes, including p53. In addition, it has been shown that the actions of p53 may be amplified through a cooperative interaction with the Wilms' tumor suppressor gene product (WT1). Based on these findings, the present studies were conducted to determine whether p53 and WT1 are expressed and gonadotropin regulated in the human ovary and to study the relationship between tumor suppressor gene expression and apoptosis in human granulosa/lutein cells (GCs). Analysis of total RNA prepared from human GCs using the RT-PCR demonstrated the presence of p53 messenger RNA (mRNA) and four WT1 mRNA splice variants. These observations were supported by Northern blot analysis of total RNA prepared from human GCs, which revealed the presence of a single (similar to 2.8 kb) p53 mRNA transcript and two primary (similar to 1.8 and similar to 3.5 kb) WT1 mRNA transcripts. Western blot analysis of nuclear protein extracts from human GCs yielded one immunoreactive protein of the expected size (similar to 53 kDa) recognized by a p53 antibody and one immunoreactive protein of the expected size (similar to 52-54 kDa)recognized by the WT1 antibody. Immunohistochemical staining showed that both molecules were localized to nuclei of human GCs and were coordinately regulated during follicular development. Immunofluorescence analysis showed that p53 protein was localized exclusively to nuclei of GCs undergoing apoptosis during in vitro culture and was similarly localized to nuclei and cytoplasm of apoptotic granulosa cells in atretic follicles in vivo. To further evaluate whether human GC apoptosis is linked to increased expression of tumor suppressor genes, we analyzed levels of p53 and WT1 mRNA and protein in GCs induced to undergo apoptosis in vitro. Healthy (nonapoptotic) GCs snap-frozen immediately after isolation from patients undergoing in vitro fertilization-embryo transfer possessed relatively low, but detectable, levels of p53 and WT1 mRNA and protein. However, following serum-free culture to induce apoptosis, p53 mRNA and protein levels increased significantly after 24 h, paralleling the increase in the number of apoptotic GCs. The induction of both p53 mRNA and protein in GCs was inhibited by the addition of human CG to the culture medium. In contrast, WT1 mRNA and protein levels remained constitutive in GCs incubated for 24 h compared with GCs snap-frozen immediately after isolation. We conclude that the p53 and WT1 genes are expressed at the mRNA and protein levels in human GCs and that expression of p53 is regulated during follicular maturation. Nuclear accumulation of p53 protein occurs in human GCs during apoptosis in vitro and in vivo, and p53 mRNA and protein are up-regulated in GCs starved of hormonal support but down-regulated by the presence of human CG. We propose that the products of these two principal tumor suppressor genes serve as important regulators of human follicular development and corpus luteum function. C1 Univ Penn, Med Ctr, Dept Obstet & Gynecol, Div Human Reprod, Philadelphia, PA 19104 USA. Univ Penn, Ctr Med, Ctr Res Reprod & Womens Hlth, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Med, Div Pulm, Dept Med, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Coutifaris, C (reprint author), Univ Penn, Med Ctr, Dept Obstet & Gynecol, Div Human Reprod, 106 Dulles,3400 Spruce St, Philadelphia, PA 19104 USA. EM ccoutifaris@obgyn.upenn.edu FU NICHD NIH HHS [R01-HD31903, R01-HD34226] NR 51 TC 34 Z9 35 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2000 VL 85 IS 1 BP 449 EP 459 DI 10.1210/jc.85.1.449 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200073 PM 10634423 ER PT J AU Huang, CA Fuchimoto, Y Scheier-Dolberg, R Murphy, MC Neville, DM Sachs, DH AF Huang, CA Fuchimoto, Y Scheier-Dolberg, R Murphy, MC Neville, DM Sachs, DH TI Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELL DEPLETION; MAJOR HISTOCOMPATIBILITY COMPLEX; TOTAL-BODY IRRADIATION; VS-HOST DISEASE; MINIATURE SWINE; ALLOGENEIC CHIMERAS; ANKYLOSING-SPONDYLITIS; MONOCLONAL-ANTIBODIES; RADIATION CHIMAERAS AB Bone marrow transplantation (BMT) has considerable potential for the treatment of malignancies, hemoglobinopathies, and autoimmune diseases, as well as the induction of transplantation allograft tolerance. Toxicities associated with standard preparative regimens for bone marrow transplantation, however make this approach unacceptable for all but the most severe of these clinical situations. Here, we demonstrate that stable mixed hematopoietic cell chimerism and donor-specific tolerance can be established in miniature swine, using a relatively mild, non-myeloablative preparative regimen. We conditioned recipient swine with whole-body and thymic irradiation, and we depleted their T-cells by CD3 immunotoxin-treatment. Infusion of either bone marrow cells or cytokine-mobilized peripheral blood stem cells from leukocyte antigen-matched animals resulted in stable mixed chimerism, as detected by flow cytometry in the peripheral blood, thymus, and bone marrow, without any clinical evidence of graft-versus-host disease (GvHD). Long-term acceptance of donor skin and consistent rejection of third-party skin indicated that the recipients had developed donor-specific tolerance. C1 Massachusetts Gen Hosp, Tranplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Tranplantat Biol Res Ctr, MGH East,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [1RO1 HL-63430, 5RO1 HL-46532] NR 37 TC 152 Z9 159 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2000 VL 105 IS 2 BP 173 EP 181 DI 10.1172/JCI7913 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 275HX UT WOS:000084815700006 PM 10642595 ER PT J AU Kido, Y Burks, DJ Withers, D Bruning, JC Kahn, CR White, MF Accili, D AF Kido, Y Burks, DJ Withers, D Bruning, JC Kahn, CR White, MF Accili, D TI Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GROWTH-FACTOR-I; PHOSPHOTYROSINE PROTEIN; GLUCOSE-TOLERANCE; SUBSTRATE FAMILY; NIDDM; DISRUPTION; MUSCLE; TRAITS; MEMBER AB Type 2 diabetes is characterized by abnormalities of insulin action in muscle, adipose tissue, and Liver and by altered beta-cell function. To analyze the role of the insulin signaling pathway in these processes, we have generated mice with combined heterozygous null mutations in insulin receptor (ir), insulin receptor substrate (irs-1), and/or irs-2. Diabetes developed in 40% of ir/irs-1/irs-2(+/-), 20% of ir/irs-1(+/-), 17% of ir/irs-2(+/-), and 5% of ir(+/-) mice. Although combined heterozygosity for ir/irs-1(+/-) and ir/irs-2(+/-) results in a similar number of diabetic mice, there are significant differences in the underlying metabolic abnormalities. ir/irs-1(+/-) mice develop severe insulin resistance in skeletal muscle and liver, with compensatory beta-cell hyperplasia, In contrast, ir/irs-2(+/-) mice develop severe insulin resistance in liver, mild insulin resistance in skeletal muscle, and modest beta-cell hyperplasia. Triple heterozygotes develop severe insulin resistance in skeletal muscle and liver and marked beta-cell hyperplasia. These data indicate tissue-specific differences in the roles of IRSs to mediate insulin action, with irs-1 playing a prominent role in skeletal muscle and irs-2 in Liver. They also provide a practical demonstration of the polygenic and genetically heterogeneous interactions underlying the inheritance of type 2 diabetes. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20842 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Howard Hughes Med Inst, Boston, MA 02215 USA. RP Accili, D (reprint author), Berrie Res Pavil,1150 St Nicholas Ave,Room 238A, New York, NY 10032 USA. RI Withers, Dominic/D-7671-2014 OI Withers, Dominic/0000-0002-8009-7521 NR 39 TC 324 Z9 343 U1 2 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2000 VL 105 IS 2 BP 199 EP 205 DI 10.1172/JCI7917 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 275HX UT WOS:000084815700009 PM 10642598 ER PT J AU Witt, DJ Kemper, M Stead, A Ginocchio, CC Caliendo, AM AF Witt, DJ Kemper, M Stead, A Ginocchio, CC Caliendo, AM TI Relationship of incremental specimen volumes and enhanced detection of human immunodeficiency virus type 1 RNA with nucleic acid amplification technology SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PLASMA; QUANTITATION AB The relationship between specimen input volume and the frequency of reported human immunodeficiency virus type 1 (HIV-1) RNA copy numbers by nucleic acid amplification technology (the NASBA HIV-1 RNA QT system) was investigated. Results obtained with both clinical specimens and dilution panels indicated that both the absolute number of reported results and the reported HIV-1 RNA copy number were directly proportional to the specimen input volumes evaluated (0.1, 0.5, and 1.0 mi), Conversion of the reported HIV-I RNA copy numbers to a constant 1.0-ml volume indicated that the numerical relationship among the specimen input volumes and the HIV-1 RNA copy numbers was multiplicative. The HIV-I RNA copy numbers reported for the 0.5-ml input volume were approximately 5-fold increased over those reported for the 0.1-ml input volume, and those reported for the 1.0 ml input volume were 10-fold increased over those reported for the 0.1-ml input volume. For the specimen input volumes investigated, a common linear range of 264 to 5,400,000 HIV-I RNA copies was observed. The use of increased specimen input volumes did not result in a loss of assay specificity, as the results reported for specimens from 50 seronegative blood donors were negative at all three specimen input volumes. In conclusion, an increase in the input volume of specimens analyzed by nucleic acid amplification technology can be useful for the enhanced detection of HIV-1 RNA. C1 Organon Teknika Corp, Durham, NC 27712 USA. Sacramento Med Fdn, Sacramento, CA USA. NYU, N Shore Univ Hosp, Sch Med, Manhasset, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Witt, DJ (reprint author), Organon Teknika Corp, 100 Akzo Ave, Durham, NC 27712 USA. NR 11 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2000 VL 38 IS 1 BP 85 EP 89 PG 5 WC Microbiology SC Microbiology GA 273CN UT WOS:000084689800016 PM 10618068 ER PT J AU Iwen, PC Sigler, L Tarantolo, S Sutton, DA Rinaldi, MG Lackner, RP McCarthy, DI Hinrichs, SH AF Iwen, PC Sigler, L Tarantolo, S Sutton, DA Rinaldi, MG Lackner, RP McCarthy, DI Hinrichs, SH TI Pulmonary infection caused by Gymnascella hyalinospora in a patient with acute myelogenous leukemia SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BLASTOMYCES-DERMATITIDIS; INVASIVE ASPERGILLOSIS; IMMUNOCOMPROMISED PATIENTS; AJELLOMYCES-DERMATITIDIS; COCCIDIOIDES-IMMITIS; SP-NOV; TAXONOMY; IDENTIFICATION; EXPERIENCE AB We report the first case of invasive pulmonary infection caused by the thermotolerant ascomycetous fungus Gymnascella hyalinospora in a 43-year-old female from the rural midwestern United States. The patient was diagnosed with acute myelogenous leukemia and treated with induction chemotherapy. She was discharged in stable condition with an absolute neutrophil count of 100 cells per pi. Four days after discharge, she presented to the Cancer Clinic with fever and pancytopenia. A solitary pulmonary nodule was found in the right middle lobe which was resected by video-assisted thoracoscopy (VATHS). Histopathological examination revealed septate branching hyphae, suggesting a diagnosis of invasive aspergillosis; however, occasional yeast-like cells were also present. The culture grew a mold that appeared dull white with a slight brownish tint that failed to sporulate on standard media. The mold was found to be positive by the AccuProbe Blastomyces dermatitidis Culture ID Test (Gen-Probe Inc., San Diego, Calif.), but this result appeared to be incompatible with the morphology of the structures in tissue. The patient was removed from consideration for stem cell transplant and,ias treated for 6 weeks with amphotericin B (AmB), followed by itraconazole (Itr). A VATHS with biopsy performed 6 months later showed no evidence of mold infection. In vitro, the isolate appeared to be susceptible to AmB and resistant to fluconazole and -5-fluorocytosine. Results for Itr could not be obtained for the case isolate due to its failure to grow in polyethylene glycol used to solubilize the drug; however, MICs for a second isolate appeared to be elevated. The case isolate was subsequently identified as G. hyalinospora based on its formation of oblate, smooth-walled ascospores within yellow or yellow-green tufts of aerial hyphae on sporulation media. Repeat testing with the Blastomyces probe demonstrated false-positive results with the case isolate and a reference isolate of G. hyalinospora. This case demonstrates that both histopathologic and cultural features should be considered for the proper interpretation of this molecular test and extends the list of fungi recognized as a cause of human mycosis in immunocompromised patients. C1 Univ Nebraska, Nebraska Med Ctr 986495, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. Univ Alberta, Devonian Bot Garden, Microfungus Collect & Herbarium, Edmonton, AB, Canada. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Long Isl Jewish Med Ctr, Dept Surg, Long Isl, NY USA. RP Iwen, PC (reprint author), Univ Nebraska, Nebraska Med Ctr 986495, Dept Pathol & Microbiol, Omaha, NE 68198 USA. NR 37 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2000 VL 38 IS 1 BP 375 EP 381 PG 7 WC Microbiology SC Microbiology GA 273CN UT WOS:000084689800067 PM 10618119 ER PT J AU Schwid, HA Rooke, GA AF Schwid, HA Rooke, GA TI Systolic blood pressure at end-expiration measured by the automated systolic pressure variation monitor is equivalent to systolic blood pressure during apnea SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE blood pressure; mechanical ventilation; heart function; cardiovascular function; circulatory physiology; hemodynamics ID SEPSIS-INDUCED HYPOTENSION; VENTILATED PATIENTS; HEMODYNAMIC-CHANGES; GRADED HEMORRHAGE; FLUID THERAPY; INDICATOR; VOLUME; GUIDE; DOGS AB Objective. It is necessary to define a reference systolic arterial blood pressure (RP) to calculate delta-Up (dUp) and delta-Down (dDown) for systolic pressure variation. Most studies define the reference pressure as the average systolic blood pressure during a short period of apnea. We describe an automated systolic pressure variation monitor that measures airway pressure and defines the reference pressure as the systolic blood pressure at end-expiration. The present study compares the reference systolic blood pressure measured at end-expiration by the automated systolic pressure variation monitor and the reference systolic blood pressure measured during apnea to test whether the end-expiration value is an adequate substitute for the value during apnea. Methods. After obtaining informed consent, 108 sets of measurements of systolic pressure variation (SPV) were made in 20 intubated, mechanically-ventilated, anesthetized patients by the automated SPV monitor and during apnea. Measurements were taken during periods of hemodynamic stability defined as three consecutive end-expiratory systolic blood pressures within four mmHg of each other. The three systolic pressures at end-expiration were averaged (RPmonitor). Immediately following these measurements, the ventilator was turned off and the systolic blood pressure was measured at 6, 8, 10 and 12 seconds of apnea. The reference pressure during apnea (RPapnea) was defined as the average of the systolic blood pressure at 8, 10 and 12 seconds of apnea. For each measurement set, RPmonitor and the systolic blood pressure at 6 seconds of apnea (SBP6) were compared to RPapnea using Bland-Altman analysis. Results. Bland-Altman analysis for the difference between SBP6 and RPapnea yielded a small bias of -0.3 mmHg with standard deviation of 1.3, indicating that the systolic pressure tends to continue to increase slightly after 6 seconds of apnea. Results were similar for the difference between RPmonitor and RPapnea (-0.2 +/- 3.1 mmHg). Conclusions. dUp and dDown are calculated using the reference pressure. RPmonitor is an average of 0.2 mm Hg less than RPapnea, thus dUp calculated by the automated SPV monitor is an average of 0.2 mm Hg greater than dUp measured by the reference pressure during apnea and dDown is 0.2 mm Hg less. Since the bias of -0.2 mmHg is clinically insignificant, there is acceptable agreement between the reference pressure obtained during apnea and that obtained by the automated SPV monitor at end-expiration. The mean difference between RPmonitor and RPapnea is explained by the continued rise in systolic pressure during the period of apnea as demonstrated by the difference between SBP6 and RPapnea. C1 Univ Washington, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Anesthesia Serv 112A, Seattle, WA 98108 USA. RP Schwid, HA (reprint author), Univ Washington, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Anesthesia Serv 112A, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Rooke, Alec/F-8909-2013 NR 12 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1387-1307 J9 J CLIN MONITOR COMP JI J. Clin. Monitor. Comp. PY 2000 VL 16 IS 2 BP 115 EP 120 DI 10.1023/A:1009933029279 PG 6 WC Anesthesiology SC Anesthesiology GA 355ZW UT WOS:000089419300005 PM 12578068 ER PT J AU Souders, JE AF Souders, JE TI Pulmonary air embolism SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE venous air embolism; surgical positioning; precordial Doppler ultrasound; end-tidal carbon dioxide ID TRANS-ESOPHAGEAL ECHOCARDIOGRAPHY; CATHETER INTRODUCER SHEATH; END-EXPIRATORY PRESSURE; DECOMPRESSION-SICKNESS; DOPPLER ULTRASOUND; CUTANEOUS O-2; GAS EMBOLISM; LUNG TRAUMA; BLOOD-FLOW; DOGS AB Pulmonary air embolism is a well-known consequence of surgery, trauma, diving, and aviation. This article reviews the physiological effects, means of detection and methods of prevention and treatment of pulmonary air embolism. The primary physiological effects are elevated pulmonary artery pressures, increased ventilation-perfusion inhomogeneity, and right ventricular failure. The degree of physiological impairment depends on the volume of gas entrained, the rate of entrainment, the type of gas entrained, and the position of the patient when the embolism occurs. Transesophageal echocardiography is the most sensitive method of detection, but it is invasive. Precordial Doppler ultrasound is almost as sensitive and poses no risk to the patient. End-tidal carbon dioxide monitoring is used on all patients and is a moderately sensitive method of detection, which is useful during surgeries that have a low incidence of air embolism. For high-risk procedures, precordial Doppler ultrasound and a multi-orifice right heart catheter should be used to detect and treat pulmonary air embolism. Prevention measures include volume expansion, careful positioning, positive end-expiratory pressure, military anti-shock trousers, and jugular venous compression. Treatment of pulmonary air embolism includes flooding the surgical site with saline, controlling sites of air entry, repositioning the patient with the surgical site below the right atrium, aspiration of air from a central venous catheter, cessation of inhaled nitrous oxide, and resuscitation with oxygen, intravenous fluids, and inotropic agents. Some hypotheses on the effects of air in the pulmonary vasculature and investigational treatment options are discussed. C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Souders, JE (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Box 358280,S-112-Anes,1660 S Columbian Way, Seattle, WA 98108 USA. NR 59 TC 35 Z9 37 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1387-1307 J9 J CLIN MONITOR COMP JI J. Clin. Monitor. Comp. PY 2000 VL 16 IS 5-6 BP 375 EP 383 DI 10.1023/A:1011455701892 PG 9 WC Anesthesiology SC Anesthesiology GA 429UJ UT WOS:000168535300006 PM 12580220 ER PT J AU Feinstein, DM Raemer, DB AF Feinstein, DM Raemer, DB TI Arterial-line monitoring system simulation SO JOURNAL OF CLINICAL MONITORING AND COMPUTING LA English DT Article DE simulation; monitoring ID PRESSURE AB Objective. We sought to improve the realism of our patient simulation environment by developing a simulation of the arterial-line monitoring system. Properties of the system we wished to depict were: electro-mechanical delay between ECG and radial artery pressure, beat to beat amplitude variability and respiratory variation, realistic looking pulse pressure in hypertensive and hypotensive states, a functional link to the stopcock and transducer flush, and filtering characteristics of the measurement system. Methods. A standard clinical pressure transducer and stopcock were modified to provide data about their state to a personal computer. A software program was written to modify the arterial pressure waveform from a patient simulator according to the pressure transducer and stopcock state as well as user settings to produce a new waveform. Results. All of the desired improvements in the realism of the arterial waveform were implemented. Conclusions. The realism of scenarios using the patient simulator is enhanced by having the arterial-line monitoring system more accurately simulated. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Anesthesia, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Raemer, DB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1387-1307 J9 J CLIN MONITOR COMP JI J. Clin. Monitor. Comp. PY 2000 VL 16 IS 7 BP 547 EP 552 DI 10.1023/A:1011434028338 PG 6 WC Anesthesiology SC Anesthesiology GA 450KH UT WOS:000169741400012 PM 12580215 ER PT J AU Schomer, DL Bonmassar, G Lazeyras, F Seeck, M Blum, A Anami, K Schwartz, D Belliveau, JW Ives, J AF Schomer, DL Bonmassar, G Lazeyras, F Seeck, M Blum, A Anami, K Schwartz, D Belliveau, JW Ives, J TI EEG-linked functional magnetic-resonance imaging in epilepsy and cognitive neurophysiology SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE functional MRI; partial epilepsy; evoked potentials; cognitive neurophysiology ID HUMAN VISUAL-CORTEX; TRANSVERSE RELAXATION; SENSORY STIMULATION; STATUS EPILEPTICUS; BRAIN-FUNCTION; MRI; OXYGENATION; PERFUSION; CONTRAST; BLOOD AB The ability to trigger functional magnetic resonance imaging (fMRI) acquisitions related to the occurrence of LEG-based physiologic transients has changed the field of fMRI into a more dynamically based technique. By knowing the temporal relationship between focal increases in neuronal firing rates and the provoked focal increase in blood flow, investigators are able to maximize the fMR-linked images that show where the activity originates. Our mastery of recording EEG inside the bore of a MR scanner has also allowed us to develop cognitive paradigms that record not only the fMR BOLD images, but also the evoked potentials (EPs). The EPs can subsequently be subjected to localization paradigms that can be compared to the localization seen on the BOLD images. These two techniques will most probably be complimentary. BOLD responses are dependent on a focal increase in metabolic demand while the EPs may or may not be related to energy demand increases. Additionally, recording EPs require that the source or sources of that potential come from an area that is able to generate far-field potentials. These potentials are related to the laminar organization of the neuronal population generating that potential. As best we know the BOLD response does not depend on any inherent laminar neuronal organization. Therefore, by merging these two recording methods, it is likely that we will gain a more detailed understanding of not only the areas involved in certain physiologic events, e,g, focal epilepsy or cognitive processing, but also on the sequencing of the activation of the various participating regions. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02114 USA. Univ Hosp Geneva, Dept Neurol, Geneva, Switzerland. Univ Hosp Geneva, Dept Radiol, Geneva, Switzerland. RP Schomer, DL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, GZ-522,330 Brookline Ave, Boston, MA 02215 USA. NR 62 TC 42 Z9 43 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JAN PY 2000 VL 17 IS 1 BP 43 EP 58 DI 10.1097/00004691-200001000-00005 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 286YZ UT WOS:000085477600005 PM 10709810 ER PT J AU Alexanian, R Anderson, K Barlogie, B Berenson, J Dalton, WS Kyle, RA AF Alexanian, R Anderson, K Barlogie, B Berenson, J Dalton, WS Kyle, RA TI Sydney E. Salmon, MD - In Memoriam SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Biographical-Item C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Calif Los Angeles, Los Angeles, CA USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Mayo Clin, Rochester, MN USA. RP Alexanian, R (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 1 BP 1 EP 2 PG 2 WC Oncology SC Oncology GA 271EP UT WOS:000084581500001 ER PT J AU Lee, SJ Klar, N Weeks, JC Antin, JH AF Lee, SJ Klar, N Weeks, JC Antin, JH TI Predicting costs of stem-cell transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; BLOOD PROGENITOR CELLS; NON-HODGKINS-LYMPHOMA; VERSUS-HOST DISEASE; DIFFUSE ALVEOLAR HEMORRHAGE; G-CSF; AUTOLOGOUS TRANSPLANTATION; MYELOGENOUS LEUKEMIA; ECONOMIC-EVALUATION; MYELOID-LEUKEMIA AB Purpose: Few studies have formally evaluated the relationship between costs, baseline patient characteristics, and major complications of stem-cell transplantation. We sought (1) to determine whether obtaining baseline information enabled identification of patients whose treatments would be the most costly and (2) to estimate inpatient costs for managing specific transplantation complications. Patients and Methods: We collected inpatient costs and clinical information for 236 consecutive patients undergoing transplantation at a single institution between July 1, 1994, and February 20, 1997. Multivariable linear regression was used to evaluate the associations between baseline patient characteristics and costs of hospitalization for initial transplantation and between clinical events and such costs. Results: The median initial inpatient cost in 1997 dollars was $55,500 for autologous transplantation (range, $28,200 to $148,200) and $105,300 for allogeneic transplantation (range, $32,500 to $338,000), When only baseline variables were considered, use of a mismatched allogeneic donor and year of transplantation were significant predictors of costs. No characteristics predicted which patients would incur the highest 10% of costs. When clinical events were considered, infection and in-hospital death were associated with higher costs in autologous transplant recipients ($18,400 and $20,500, respectively), whereas infection, veno-occlusive disease, acute graft-versus-host disease, and death were predicted to add between $15,300 and $28,100 each to allogeneic transplantation costs. Conclusion: We were not able to identify before transplantation the patients whose treatments would be the most costly. However, the association between clinical complications and higher costs suggests that prevention may have significant economic benefits. Interventions that decrease these complications may have favorable cost-benefit ratios even if they do not affect overall survival. (C) 2000 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75267-01] NR 37 TC 56 Z9 57 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 1 BP 64 EP 71 PG 8 WC Oncology SC Oncology GA 271EP UT WOS:000084581500010 PM 10623694 ER PT J AU Hillner, BE Weeks, JC Desch, CE Smith, TJ AF Hillner, BE Weeks, JC Desch, CE Smith, TJ TI Pamidronate in prevention of bone complications in metastatic breast cancer: A cost-effectiveness analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SKELETAL COMPLICATIONS; EFFICACY AB Purpose: Pamidronate is effective in reducing bony complications in patients with metastatic breast cancer who have known osteolytic lesions. However, pamidronate does not increase survival and is associated with additional financial costs and inconvenience. We conducted a post-hoc evaluation of the cost-effectiveness of pamidronate using the results of two randomized trials that evaluated pamidronate 90 mg administered intravenously every month versus placebo. Patients and Methods: The trials differed only in the initial systemic therapy administered (hormonal or chemotherapy), Total skeletal related events (SREs), including surgery for pathologic fracture, radiation for fracture or pain control, conservatively treated pathologic fracture, spinal cord compression, or hypercalcemia, were taken directly from the trials. Using ct societal perspective, direct health care costs were assigned to each SRE, Each group's monthly survival was equal and was projected to decline using observed median survivals. The cost of pamidronate reflected the average wholesale price of the drug plus infusion. The value or disutility of an adverse event per month was evaluated using a zero value (events avoided) or an assigned one (range, 0.2 to 0.8). Results: The cost of pamidronate therapy exceeded the cost savings from prevented adverse events. The difference between the treated and placebo groups was larger with hormonal systemic therapy than with chemotherapy (additional $7,685 compared with $3,968 per woman), The projected net cost per SRE avoided wets $3,940 with chemotherapy and $9,390 with hormonal therapy. The cost-effectiveness ratios were $108,200 with chemotherapy and $305,300 with hormonal therapy per quality-adjusted year. Conclusion: Although pamidronate is effective in preventing a feared, common adverse outcome in metastatic breast cancer, its use is associated with high incremental costs per adverse event avoided. The analysis is most sensitive to the costs of pamidronate and pathologic fractures that were asymptomatic or treated conservatively. (C) 2000 by American Society of Clinical Oncology. C1 Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Hillner, BE (reprint author), Virginia Commonwealth Univ, Dept Internal Med, Box 980170, Richmond, VA 23298 USA. RI Hillner, Bruce/A-6852-2009 NR 17 TC 89 Z9 91 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 1 BP 72 EP 79 PG 8 WC Oncology SC Oncology GA 271EP UT WOS:000084581500011 PM 10623695 ER PT J AU Harris, JE Ryan, L Hoover, HC Stuart, RK Oken, MM Benson, AB Mansour, E Haller, DG Manola, J Hanna, MG AF Harris, JE Ryan, L Hoover, HC Stuart, RK Oken, MM Benson, AB Mansour, E Haller, DG Manola, J Hanna, MG TI Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group study E5283 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROSPECTIVELY RANDOMIZED TRIAL; HUMAN COLORECTAL-CANCER; METASTATIC MELANOMA; SURVIVAL AB Purpose: A randomized phase III clinical trial of adjuvant active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guerin (BCG) vaccine wets conducted to determine whether surgical resection plus ASI was more beneficial than resection alone in stage II and III colon cancer patients. Patients and Methods: Patients(n = 412) with colon cancer (297 with stage II disease, 115 with stage III disease) were randomly allocated to an observation arm or to a treatment arm in which they received three weekly intradermal vaccine injections of 10(7) irradiated autologous tumor cells beginning approximately 4 weeks after surgery. The first two weekly injections also contained 10(7) BCG organisms. Patients were observed for determination of time to recurrence and disease-free and overall survival. Results: This was a negative study in that after a 7.6-year median follow-up period, there were no statistically significant differences in clinical outcomes between the treatment arms. However, there were disease-free survival (P = .078) and overall survival (P = .12) trends in fervor of ASI when treatment compliance was evaluated, ie, patients who received the intended treatment had a delayed cutaneous hypersensitivity (DCH) response to the third vaccination (induration greater than or equal to 5 mm). Also, the magnitude of the DCH response correlated with improved prognosis. The 5-year survival proportion was 84.6% for those with indurations greater than 10 mm, compared with 45.0% for those with indurations less than 5 mm. Conclusions: When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits. (C) 2000 by American Society of Clinical Oncology. C1 Rush Presbyterian St Lukes Med Ctr, Sect Med Oncol, Chicago, IL 60612 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Lehigh Valley Hosp Ctr, Allentown, PA 18102 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH 44106 USA. Univ Penn, Philadelphia, PA 19104 USA. Intracel Corp, Rockville, MD USA. RP Harris, JE (reprint author), Rush Presbyterian St Lukes Med Ctr, Sect Med Oncol, 1725 W Harrison St, Chicago, IL 60612 USA. OI Stuart, Robert/0000-0001-7549-8008 FU NCI NIH HHS [CA20365, CA23318, CA25988] NR 22 TC 141 Z9 152 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 1 BP 148 EP 157 PG 10 WC Oncology SC Oncology GA 271EP UT WOS:000084581500021 PM 10623705 ER PT J AU Galsky, M Darling, M Hecht, J Salgia, R AF Galsky, M Darling, M Hecht, J Salgia, R TI Unusual presentations of lung cancer - Case 1. Small bowel obstruction due to metastatic lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARCINOMA C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Galsky, M (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 1 BP 227 EP 228 PG 2 WC Oncology SC Oncology GA 271EP UT WOS:000084581500029 PM 10623713 ER PT J AU Sledge, GW Hu, P Falkson, G Tormey, D Abeloff, M AF Sledge, GW Hu, P Falkson, G Tormey, D Abeloff, M CA Eastern Cooperative Oncology Grp TI Comparison of chemotherapy with chemohormonal therapy as first-line therapy-for metastatic, hormone-sensitive breast cancer: An Eastern Cooperative Oncology Group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOCRINE THERAPY; TAMOXIFEN; TRIAL AB Purpose: Although hormonal therapy represents standard therapy for metastatic hormone-sensitive disease, many patients receive initial chemotherapy because of the location, bulk, or aggressiveness of their disease. It is uncertain whether simultaneous hormonal therapy provides additional benefit compared with chemotherapy alone. Eastern Cooperative Oncology Group trial E3186 was initiated to explore this question. Patients and Methods: Between January 1988 and December 1992, 231 patients with estrogen receptor (ER)-positive or ER-unknown metastatic breast cancer were randomized to receive either chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil [CAF]) or chemohormonal therapy (CAF plus tamoxifen and Halotestin [fluoxymesterone; Pharmacia-Upjohn, Kalamazoo, MI] [CAFTH]) as front-line therapy for metastatic breast cancer. patients who experienced a complete response to induction therapy either received or did not receive maintenance cyclophosphamide, methotrexate, fluorouracil, prednisone, and TH as a secondary randomization, Results: The response rates (complete response and partial response) of patients who received CAF and CAFTH were similar (69.2% v 68.9%, respectively; P = .99). Time to treatment failure (TTF) was slightly longer for patients who received chemohormonal therapy compared with chemotherapy alone patients (13.4 months v 10.3 months, respectively; P = .087), and TTF was significantly longer in ER-positive compared with ER-negative patients (17.4 months v 10.3 months, respectively; P = .048). However, ER status had no effect on overall survival (30.0 months For CAF v 29.3 months for CAFTH). Conclusion: In patients with potentially hormone-sensitive metastatic breast cancer, chemohormonal therapy prolongs TTF for ER-positive patients without improving overall survival. (C) 2000 by American Society of Clinical Oncology. C1 Indiana Canc Pavil, Indianapolis, IN 46260 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Sledge, GW (reprint author), Indiana Canc Pavil, RT-473,535 Barnhill Dr, Indianapolis, IN 46260 USA. NR 15 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 2 BP 262 EP 266 PG 5 WC Oncology SC Oncology GA 275TK UT WOS:000084836100004 PM 10637238 ER PT J AU Hayman, JA Hillner, BE Harris, JR Pierce, LJ Weeks, JC AF Hayman, JA Hillner, BE Harris, JR Pierce, LJ Weeks, JC TI Cost-effectiveness of adding an electron-beam boost to tangential radiation therapy in patients with negative margins after conservative surgery for early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 14-19, 1998 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol ID RANDOMIZED CLINICAL-TRIAL; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; CONSERVING THERAPY; RADICAL-MASTECTOMY; TRADE-OFF; IRRADIATION; RECURRENCE; CHEMOTHERAPY; RESECTION AB Purpose: Electron-beam boosts (EBB) are routinely added after conservative surgery and tangential radiation therapy (TRT) for early-stage breast cancer, We performed an incremental cost-utility analysis to evaluate their cost-effectiveness. Methods: A Markov model examined the impact of adding an EBB to TRT from a societal perspective. Outcomes were measured in quality-adjusted life years (QALYs), On the basis of the Lyon trial, the EBB was assumed to reduce local recurrences by approximately 2% at 10 years but to have no impact on survival. patients' utilities were used to adjust for quality of life. Given the small absolute benefit of the EBB, baseline utilities were assumed to be the same with or without it, an assumption evaluated by Monte Carlo simulation. Direct medical, time, and travel casts were considered. Results: Adding the EBB led to an additional cost of $2,008, an increase of 0.0065 QALYs and, therefore, an incremental cost-effectiveness ratio of over $300,000/QALY. In a sensitivity analysis, the ratio was moderately sensitive to the efficacy and cost of the EBB and highly sensitive to patients' utilities for treatment without it, Even if patients do value a small risk reduction, the mean cost-effectiveness ratio estimated by the Monte Carlo simulation remains high, at $70,859/QALY (95% confidence interval, $53,141 to $105,182/QALY), Conclusion: On the basis of currently available data, the cost-effectiveness ratio for the EBB is well above the commonly cited threshold for cost-effective care ($50,000/QALY). The EBB becomes cost-effective only if patients place an unexpectedly high value on the small absolute reduction in local recurrences achievable with it. (C) 2000 by American Society of Clinical Oncology. C1 Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. RP Hayman, JA (reprint author), Univ Michigan, Med Ctr, Dept Radiat Oncol, UH B2C490,Box 0010,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Hillner, Bruce/A-6852-2009 NR 37 TC 29 Z9 29 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 2 BP 287 EP 295 PG 9 WC Oncology SC Oncology GA 275TK UT WOS:000084836100008 PM 10637242 ER PT J AU Cugini, MA Haffajee, AD Smith, C Kent, RL Socransky, SS AF Cugini, MA Haffajee, AD Smith, C Kent, RL Socransky, SS TI The effect of scaling and root planing on the clinical and microbiological parameters of periodontal diseases: 12-month results SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases; periodontitis; treatment; SRP; microbiology; maintenance ID RELEASE TETRACYCLINE FIBERS; NON-SURGICAL TREATMENT; SUBGINGIVAL MICROBIOTA; ADULT PERIODONTITIS; THERAPY; PATHOGENS; POCKETS AB Background/aims: Previously, we reported that SRP resulted in a decrease in mean pocket depth and attachment level and reduced prevalence and levels of Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola at 3 and 6 months post-SRP in 57 subjects with adult periodontitis. 32 of the 57 subjects were monitored at 9 and 12 months. Thus, the purpose of the present investigation was to evaluate the microbial and clinical effects of SRP in 32 (mean age 48+/-11) subjects over a 12-month period. Method: Clinical assessments of plaque, gingival redness, suppuration, bleeding on probing, pocket depth and attachment level were made prior to SRP and at 3, 6, 9, and 12 months post-therapy. Subgingival plaque samples were taken at each visit and analyzed using the checkerboard DNA-DNA hybridization technique for the presence and levels of 40 subgingival species. Each subject also received maintenance scaling at each of the subsequent monitoring visits. Differences in clinical parameters and prevalence and levels of bacterial species were analyzed pre- and post-therapy using the Wilcoxon signed ranks test. The Quade test for related samples was used for analysis of multiple visits. Results: Mean pocket depth (mm+/-SEM) decreased from 3.2+/-0.3 at baseline to 2.9+/-0.3 at 12 months (p<0.01). Mean attachment level showed significant reduction at 6 months, but did not diminish further. Bleeding on probing and plaque were significantly reduced at 12 months (p<0.001, p<0.05, respectively). P. gingivalis, B. forsythus and T. denticola decreased in prevalence and levels up to the 6-month visit and remained at these lower levels at 9 and 12 months. Significant increases in levels and prevalence were noted at 12 months for Actinomyces naeslundii genospecies 2, Actinomyces odontolyticus, Fusobacterium nucleatum as polymorphum, Streptococcus mitis, Capnocytophaga sp, and Veillonella parvula. Conclusions: The data suggest that the maintenance phase of therapy may be essential in consolidating clinical and microbiological improvements achieved as a result of initial therapy. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. Forsyth Inst, Dept Biostat, Boston, MA USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04881] NR 24 TC 121 Z9 127 U1 1 U2 8 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JAN PY 2000 VL 27 IS 1 BP 30 EP 36 DI 10.1034/j.1600-051x.2000.027001030.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 271CP UT WOS:000084576700005 PM 10674959 ER PT J AU Sakellari, D Goodson, JM Socransky, SS Kolokotronis, A Konstantinidis, A AF Sakellari, D Goodson, JM Socransky, SS Kolokotronis, A Konstantinidis, A TI Concentration of 3 tetracyclines in plasma, gingival crevice fluid and saliva SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE tetracycline; minocycline; doxycycline; tetracyclines/analysis; blood; antibiotics/therapeutic use; gingival crevicular fluid/analysis ID MINOCYCLINE; DOXYCYCLINE AB Background: Systemically-administered tetracyclines have been used widely for treatment of periodontal diseases with little understanding of their delivery characteristics to periodontal tissues. This study was designed to measure concentrations of 3 tetracyclines in gingival crevice fluid (GCF), plasma and saliva of following systemic administration. Method: The concentration of tetracycline (TC), minocycline (MN) and doxycycline (DX) was measured in gingival crevice fluid (GCF), plasma and saliva of 20 subjects following single sequential standard oral systemic doses. Gingival crevice fluid concentration was measured at 4 sites (2 shallow and 2 deep) before administration, and at 1 h and 2 h following administration. Plasma and saliva concentrations were measured from in samples at the same time points. No antibacterial activity was detected before administration. The highest concentrations were measured 2 h after administration. Results: The average concentrations at 2 h were highest in plasma (TC=1.02, MN=2.18, DX=2.35 mu g/ml). Intermediate concentrations were measured in GCF (TC=0.61, MN=1.49, DX=1.65 mu g/ml). Saliva concentrations (TC=0.09 MN=0.31, DX=0.47 mu g/ml) were the lowest of the 3 fluids monitored. Data are presented indicating that the average GCF concentration of systemically administered terracyclines is less than the that of plasma concentration. The concentration of tetracyclines in GCF was strongly associated with plasma concentration, indicating a primary role of drug absorption in the delivery of these systemically administered antibiotics to the site of action in periodontal therapy The average GCF concentration in individuals varied widely (between 0 and 8 mu g/ml) with approximately 50% of samples not achieving levels of 1 mu g/ml. Conclusions: These observations suggest that poor absorption of orally-administered tetracyclines in many individuals may account for much of the variability in clinical response to antibiotics observed in practice. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. Aristotelian Univ Salonika, Sch Dent, Dept Periodontol, Salonika, Greece. RP Goodson, JM (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. RI SAKELLARI, DIMITRA/F-3299-2011 FU NIDCR NIH HHS [DE-11814, DE-04881] NR 14 TC 54 Z9 65 U1 4 U2 7 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JAN PY 2000 VL 27 IS 1 BP 53 EP 60 DI 10.1034/j.1600-051x.2000.027001053.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 271CP UT WOS:000084576700008 PM 10674962 ER PT J AU Sarid-Segal, O Knapp, CM Ciraulo, AM Greenblatt, DJ Shader, RI Ciraulo, DA AF Sarid-Segal, O Knapp, CM Ciraulo, AM Greenblatt, DJ Shader, RI Ciraulo, DA TI Decreased EEG sensitivity to alprazolam in subjects with a parental history of alcoholism SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID INTRAVENOUS DIAZEPAM; ABUSE LIABILITY; ETHANOL; RISK; SONS; MEN; ELECTROENCEPHALOGRAM; PHARMACOKINETICS; PHARMACODYNAMICS; PLASMA AB Altered benzodiazepine sensitivity in subjects with a history of parental alcoholism (PHP) compared to control subjects (NC) has been reported for regional brain blood volume, eye movement tasks, and subjective effects. This study tests the hypothesis that PHP subjects are less sensitive to benzodiazepine effects on EEG activity than are NC subjects. total ;EEG activity was recorded in PHP and NC subjects after administration of the benzodiazepine, alprazolam (1 mg), or placebo. PHP subjects had decreased sensitivity to the EEG effects of alprazolam compared to NC subjects. Significant differences were detected for change in percent relative beta activity and alpha and theta band power. Pharmacokinetic parameters did not differ significantly between groups. These results suggest that PHP subjects are less sensitive to the effects of alprazolam on central electrophysiological activity than are NC subjects. (C) 2000 the American College of Clinical Pharmacology. C1 Boston Univ, Sch Med, Dept Psychiat, Div Psychiat, Boston, MA 02118 USA. VA Boston Hlth Care Syst, Boston, MA USA. Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. RP Ciraulo, DA (reprint author), Boston Univ, Sch Med, Dept Psychiat, Div Psychiat, Suite 914,720 Harrison Ave, Boston, MA 02118 USA. OI Shader, Richard/0000-0002-1888-7565 FU NIAAA NIH HHS [AA-11715]; NIDA NIH HHS [DA-50038]; NIMH NIH HHS [MH-34223] NR 28 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2000 VL 40 IS 1 BP 84 EP 90 DI 10.1177/00912700022008603 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 269FH UT WOS:000084465700011 PM 10631626 ER PT J AU Cohen, LS AF Cohen, LS TI Introduction - New trends in treating premenstrual dysphoric disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2000 VL 61 SU 12 BP 3 EP 4 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 364CG UT WOS:000089874000001 ER PT J AU Arana, GW AF Arana, GW TI An overview of side effects caused by typical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Planning Roundtable on Side Effects of Antipsychotic Medications: Physician's Choice of Medication and Patient Compliance CY JAN 22, 1999 CL DALLAS, TEXAS ID LONG-TERM; SCHIZOPHRENIC-PATIENTS; TARDIVE-DYSKINESIA; HYPERPROLACTINEMIA; NEUROLEPTICS; MANAGEMENT; HALOPERIDOL; MEDICATIONS; AKATHISIA; DRUGS AB Typical antipsychotics often combine efficacy in treating antipsychotic illnesses with a side effect profile that can affect every system of the body and range from the annoying-photosensitivity and jaundice, for example-to the disabling-seizures and blindness, among others-to the potentially fatal-agranulocytosis and neuroleptic malignant syndrome. The side effects of conventional antipsychotics are associated with effects at CNS transmission and receptor sites and appear in relation to dose levels and potency of the drug. Characteristics of patients-including gender, age, and comorbid medical illness-can make them more or less susceptible to particular antipsychotic side effects. Side effects influence patient quality of life and affect patient compliance with medications. This article will consider the physiologic systems affected by conventional neuroleptics, the sexual and reproductive side effects of typical antipsychotics, and the central nervous side effects of the conventional neuroleptics in the light of these concerns. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Psychiat, Mental Hlth Serv, Charleston, SC 29401 USA. RP Arana, GW (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Psychiat, Mental Hlth Serv, 109 Bee St, Charleston, SC 29401 USA. NR 27 TC 71 Z9 76 U1 2 U2 8 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 2000 VL 61 SU 8 BP 5 EP 11 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 311ZE UT WOS:000086916500002 PM 10811237 ER PT J AU Fava, M AF Fava, M TI Management of nonresponse and intolerance: Switching strategies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Optimizing Treatment Outcome in Depression held in conjunction with the 152nd Annual Meeting of the American-Psychiatric-Association CY MAY 16, 1999 CL WASHINGTON, D.C. SP Amer Psychiat Assoc ID MAJOR DEPRESSION; RESISTANT; BUPROPION; DISCONTINUATION; VENLAFAXINE; SERTRALINE; EFFICACY; TRIAL AB Approximately 29% to 46% of depressed patients show only partial or no response to treatment with antidepressants, with intolerance a frequent cause of treatment Failure or discontinuation. Clinicians frequently switch to other antidepressants patients who have failed to tolerate or to respond to antidepressant treatment. The switching strategy involves substitution of another agent for the agent that has either caused intolerable side effects or has failed to induce a response. Fredman and colleagues have recently surveyed 402 psychiatrists from various parts of the country and asked them what steps they would take for patients who fail to respond ro 8 weeks or more of an adequate dose of a selective serotonin reuptake inhibitor (SSRI). interestingly, switching to a non-SSRI agent was the most popular choice indicated by psychiatrists (44% of respondents), with dual-acting agents and bupropion bring the next most commonly chosen agents. Even though there are no controlled trials of switching strategies in the literature to dare, clinicians often choose this course of action. This article will review some of the currently available studies on switching strategics. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 21 TC 78 Z9 79 U1 1 U2 2 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 2000 VL 61 SU 2 BP 10 EP 12 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 290QF UT WOS:000085686600003 PM 10714618 ER PT J AU Glazer, WM AF Glazer, WM TI Review of incidence studies of tardive dyskinesia associated with typical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Update on Tardive Dyskinesia CY MAR 23, 1999 CL DALLAS, TEXAS ID RISK-FACTORS; OLDER PATIENTS; NEUROLEPTIC MEDICATIONS; FOLLOW-UP; OUTPATIENTS; SCHIZOPHRENIA; PREVALENCE AB Unless researchers make an organized effort, patients with tardive dyskinesia are difficult to study and easily lost to follow up. Because there is no treatment for tardive dyskinesia, investigators are obliged to study the natural history of the disorder and identify risk and prognostic factors to further understand pathophysiologic mechanisms and to guide prevention and treatment efforts. Abundant variability exists among incidence studies of tardive dyskinesia, depending to some extent on design issues. In this article, the design concepts of incidence and prevalence studies are described, along with results, methodological problems, and identified risk factors in Various tardive dyskinesia incidence studies involving the use of typical antipsychotic medications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Glazer, WM (reprint author), POB 121, Menemsha, MA 02552 USA. NR 24 TC 71 Z9 76 U1 2 U2 2 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 2000 VL 61 SU 4 BP 15 EP 20 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 295WP UT WOS:000085991100004 PM 10739326 ER PT J AU Glazer, WM AF Glazer, WM TI Extrapyramidal side effects, tardive dyskinesia, and the concept of atypicality SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium on Antipsychotic Standard of Care - Redefining the Defition of Atypical Antipsychotics CY NOV 18, 1998 CL SAN FRANCISCO, CALIFORNIA ID NEUROLEPTIC MEDICATIONS; SCHIZOPHRENIC-PATIENTS; RECEPTOR OCCUPANCY; HALOPERIDOL; OLANZAPINE; RISPERIDONE; OUTPATIENTS; PLACEBO; RISK; PREVALENCE AB The most frequent problems associated with the older generation of antipsychotic agents are extrapyramidal side effects (EPS) and tardive dyskinesia. Neuroleptic-induced EPS are thought to be caused by blockade of nigrostriatal dopamine tracts resulting in a relative increase in cholinergic activity; tardive dyskinesia is less well understood but is thought to be a supersensitivity response to chronic dopamine blockade. The leading hypothesis for the mechanism of action of the newer generation of atypical antipsychotics is the presence of a high serotonin-to-dopamine receptor blockade ratio in the brain. When serotonergic activity is blocked-as is the case with atypical antipsychotics-dopamine release increases and balances out the dopamine blockade effect at postsynaptic receptor sites, which results in few or no EPS. Prospective data indicate that the risk of tardive dyskinesia in patients taking atypical antipsychotics is less than that for those taking typical antipsychotics. This article reviews the mechanisms of neuroleptic-induced EPS and tardive dyskinesia and discusses the relationship between these movement disorders and atypical antipsychotic agents. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Glazer, WM (reprint author), POB 121, Menemsha, MA 02552 USA. NR 28 TC 101 Z9 103 U1 2 U2 2 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 2000 VL 61 SU 3 BP 16 EP 21 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 293UB UT WOS:000085870800004 PM 10724129 ER PT J AU Glazer, WM AF Glazer, WM TI Expected incidence of tardive dyskinesia associated with atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Update on Tardive Dyskinesia CY MAR 23, 1999 CL DALLAS, TEXAS ID BLIND OLANZAPINE TRIAL; LONG-TERM; RISPERIDONE; HALOPERIDOL; CLOZAPINE; PLACEBO; SCHIZOPHRENIA; PREVALENCE; DISORDERS AB Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Glazer, WM (reprint author), POB 121, Menemsha, MA 02552 USA. NR 31 TC 73 Z9 77 U1 0 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 2000 VL 61 SU 4 BP 21 EP 26 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 295WP UT WOS:000085991100005 PM 10739327 ER PT J AU Frazer, A AF Frazer, A TI Norepinephrine involvement in antidepressant action SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Norepinephrine: Neurotransmitter for the Millennium held in Conjunction with the 152nd Annual Meeting of the American-Psychiatric-Association CY MAY 15, 1999 CL WASHINGTON, D.C. SP Amer Psychiat Assoc ID LOCUS-COERULEUS; NORADRENERGIC MODULATION; MASSETERIC REFLEX; RAT-BRAIN; DEPRESSION; BUPROPION; SEROTONIN; METABOLITES; SYSTEM; PROJECTIONS AB Because of the introduction and popularity of the selective serotonin reuptake inhibitor (SSRI) antidepressants, much attention was centered on the indolealkylamine 5-hydroxytryptamine, or serotonin. To some extent, this focus on serotonin occurred at the expense of the catecholamine neurotransmitter norepinephrine. Nevertheless, it has been apparent for almost 40 years that selective blockers of norepinephrine reuptake may be antidepressants (e.g., desipramine). This brief review covers the acute pharmacologic effects that may be responsible for the efficacy of currently marketed antidepressants as well as that of reboxetine, a newly developed selective norepinephrine reuptake inhibitor. Also discussed is the fact that the acute pharmacologic profile of selective reuptake inhibitors often predicts effects they produce when given long term. For example, the long-term administration of SSRIs produces certain effects on serotonergic systems, but not noradrenergic ones. By contrast, selective norepinephrine reuptake inhibitors, when given long term, modify certain noradrenergic parameters, but not serotonergic indices. Finally, it is speculated how drugs that enhance central noradrenergic transmission might ameliorate the symptoms of depression. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. RP Frazer, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Mail Code 7764,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIMH NIH HHS [MH57001, MH29094] NR 44 TC 69 Z9 71 U1 0 U2 0 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 2000 VL 61 SU 10 BP 25 EP 30 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 335NU UT WOS:000088250200004 PM 10910014 ER PT J AU Fava, M AF Fava, M TI New approaches to the treatment of refractory depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Spectrum of Depression - New Treatment Approaches CY MAY 19, 1999 CL WASHINGTON, D.C. ID SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; TREATMENT-RESISTANT DEPRESSION; DOUBLE-BLIND; MAJOR DEPRESSION; ANTIDEPRESSANT RESPONSE; BUSPIRONE AUGMENTATION; COMBINATION TREATMENT; LITHIUM AUGMENTATION; SEXUAL DYSFUNCTION AB Although the majority of patients with depression respond well to their initial pharmacologic treatment. as many as 30% to 45% fail to achieve an adequate response. Tn addition to the more traditional lithium and thyroid hormone augmentation strategies. a number of new pharmacotherapeutic approaches are currently bring used to help manage refractory depression, including the addition of another agent or a switch to another antidepressant. Augmentation and switching strategies are often sc selected in order to obtain a different neurochemical effect (e.g., adding a relatively noradrenergic agent to a relatively serotonergic antidepressant). In particular, several studies have suggested that depressed patients refractory to treatment with selective serotonin reuptake inhibitors (SSRIs) may show a good response to newer agents that have a pharmacologic profile distinct from the SSRIs. Furthermore, preliminary studies have shown that the addition of SSRIs to either noradrenergic drugs such as the tricyclic antidepressants (TCAs) or dopaminergic agents may be efficacious, even though concerns about drug-drug interactions and tricyclic cardiac toxicity have limited the use of TCA-SSRI combinations. The introduction of reboxetine, a relatively selective norepinephrine reuptake inhibitor, may increase the use of the latter therapeutic approach because of its improved safety profile compared with the TCAs. The review of treatment options fur refractory depression that follows will outline the advantages, disadvantages, and level of support Tor a number of new treatment strategies. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 76 TC 76 Z9 80 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 2000 VL 61 SU 1 BP 26 EP 32 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 289MH UT WOS:000085625200005 PM 10703760 ER PT J AU Fava, M AF Fava, M TI Weight gain and antidepressants SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Conference on New Strategies for Improving the Treatment of Depression CY OCT 15, 1999 CL SAN FRANCISCO, CALIFORNIA ID MAJOR DEPRESSIVE DISORDER; LONG-TERM TREATMENT; DOUBLE-BLIND; BODY-WEIGHT; RECURRENT DEPRESSION; IMIPRAMINE TREATMENT; PSYCHOTROPIC-DRUGS; AMITRIPTYLINE; BUPROPION; PLACEBO AB Weight gain during antidepressant treatment can be either a sign of improvement in patients who have weight loss as a symptom of depression or a residual symptom in patients who overeat when depressed. However, significant weight gain during the acute phase of treatment or weight gain that continues despite achieving full remission of depressive symptoms is likely to be a side effect of antidepressant treatment. Weight gain is a relatively common problem during both acute and long-term treatment with antidepressants, and it is an important contributing factor to noncompliance. This article will review the literature with regard to the relative risk for weight gain of antidepressants. It appears that tricyclic antidepressants (TCAs) and perhaps monoamine oxidase inhibitors (MAOIs) may be more likely to cause weight gain than the selective serotonin reuptake inhibitors (SSRIs) or the newer antidepressants, with the exception of mirtazapine, which may be placed between the SSRIs and the TCAs in terms of relative risk for weight gain. Paroxetine may be more likely to cause weight gain than the other SSRIs during long-term treatment, and bupropion and nefazodone may be less likely to cause weight gain than the SSRIs in the long term, although more studies are necessary to confirm these impressions. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,ACC 812, Boston, MA 02114 USA. NR 44 TC 185 Z9 190 U1 1 U2 15 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 2000 VL 61 SU 11 BP 37 EP 41 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 338RJ UT WOS:000088432800006 PM 10926053 ER PT J AU Simpson, GM AF Simpson, GM TI The treatment of tardive dyskinesia and tardive dystonia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Update on Tardive Dyskinesia CY MAR 23, 1999 CL DALLAS, TEXAS ID BLIND OLANZAPINE TRIAL; LONG-TERM; CLOZAPINE WITHDRAWAL; VITAMIN-E; HALOPERIDOL; PLACEBO AB The enthusiasm produced by the introduction of antipsychotic medication in the 1950s gave way to a certain frustration in the 1970s and 1980s. Despite the development of a large number of new drugs, little progress was made in treatment because these new agents were, in essence, therapeutically equivalent. This lack of progress was perhaps also related to an emphasis on tardive dyskinesia in the 1970s, i.e., the preoccupation with a negative effect of treatment. The reverse is taking place today. Clozapine and the other atypical antipsychotics are associated in people's minds with fewer or absent extrapyramidal symptoms and less tardive dyskinesia than the older typical agents. As a result, a certain amount of complacency exists. Tardive dyskinesia not only may be painful and disfiguring, but it also predicts poor outcome in patients with schizophrenia. Although many treatments have been tried, none have proven completely efficacious. The best treatment for tardive dyskinesia and dystonia is prevention, which is a function of medication choice. pharmacologic interventions for tardive dyskinesia include clozapine and the other atypical antipsychotics. If typical antipsychotics must be used, they should be started at the lowest possible levels. Studies of risperidone suggest that it, too, should be used at very low doses to minimize the risk of tardive dyskinesia. It is also possible that schizophrenic patients taking atypical antipsychotics may experience fewer spontaneous dyskinesias, although further study is warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Simpson, GM (reprint author), Univ So Calif, Sch Med, 1937 Hosp Pl,GRH 240, Los Angeles, CA 90033 USA. NR 28 TC 38 Z9 38 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 2000 VL 61 SU 4 BP 39 EP 44 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 295WP UT WOS:000085991100008 PM 10739330 ER PT J AU Glick, RL Ghaemi, SN AF Glick, RL Ghaemi, SN TI The emergency treatment of depression complicated by psychosis or agitation SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Conference on Treatment of Acute Psychosis CY NOV 17-18, 1999 CL DALLAS, TEXAS ID CLINICAL PREDICTORS; MAJOR DEPRESSION; MOOD DISORDERS; RISPERIDONE; SCHIZOPHRENIA; HALOPERIDOL; FLUOXETINE; OLANZAPINE; INHIBITOR; TRIAL AB With the availability of newer, safer antidepressants in the past decade, initiation of definitive treatment for depression in the emergency setting has become an accepted practice. However, the use of newer antidepressants and atypical antipsychotics in depression complicated by psychosis or agitation has not yet been well studied. This article will review relevant data and make recommendations for the emergency management of psychotic and agitated depressive syndromes. C1 Univ Michigan Hlth Syst, Dept Psychiat, Ann Arbor, MI USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Glick, RL (reprint author), Univ Michigan, Sch Med, C5124 Med Sci 1,1301 Catherine St, Ann Arbor, MI 48109 USA. NR 36 TC 6 Z9 6 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 2000 VL 61 SU 14 BP 43 EP 48 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 389RY UT WOS:000166252600007 PM 11154016 ER PT J AU Tondo, L Baldessarini, RJ AF Tondo, L Baldessarini, RJ TI Reduced suicide risk during lithium maintenance treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT International Conference Commemorating the 50th anniversary of the Gold Standard for Bipolar Disorder Treatment: Lithium CY SEP, 1999 CL ATLANTA, GEORGIA SP Emory Univ, Sch Med ID MANIC-DEPRESSIVE PATIENTS; RECURRENT MOOD DISORDERS; BIPOLAR DISORDER; MAJOR DEPRESSION; FLUOXETINE TREATMENT; MORTALITY; PREVENTION; BEHAVIOR; ANTIDEPRESSANTS; DISCONTINUATION AB Background: About 20% of deaths of bipolar disorder patients are suicides associated with depressive or mixed episodes. Long-term lithium treatment may be associated with reduction of suicidal risk. Method: We reviewed studies and our previously reported data to quantify relationships of presence versus absence of lithium maintenance and suicides or suicide attempts in bipolar disorder patients. Results: Results from 22 studies (1974-1998) yielded 7-fold lower suicidal rates for patients during long-term lithium treatment than for these patients when they were not receiving such treatment, patients lacking such treatment, or for patients after lithium discontinuation. Conclusions: Protection against suicide with lithium is incomplete, but rates of suicides plus attempts during lithium treatment may approach general population base rates. Better protection against bipolar depression is essential for limiting suicidal risk; alternatives to lithium require further study for effects on suicidal behavior. C1 Harvard Univ, Sch Med, Int Consortium Res Bipolar Disorders, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Bipolar Psychot Disorders Program, Belmont, MA USA. Univ Cagliari, Dept Psychol, I-09124 Cagliari, Italy. Stanley Fdn Int Res Ctr, Lucio Bini Psychiat Ctr, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 105 TC 71 Z9 73 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2000 VL 61 SU 9 BP 97 EP 104 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 314YQ UT WOS:000087085500014 PM 10826667 ER PT J AU Pollack, MH Rapaport, MH Clary, CM Mardekian, J Wolkow, R AF Pollack, MH Rapaport, MH Clary, CM Mardekian, J Wolkow, R TI Sertraline treatment of panic disorder: Response in patients at risk for poor outcome SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 21st Biannual Meeting of the Collegium Internationale-Neuro-Psychopharmacologicum CY JUL 22-25, 1998 CL GLASGOW, SCOTLAND SP Int NeuroPsychopharmacol ID PROSPECTIVE FOLLOW-UP; DOUBLE-BLIND; DRUG-TREATMENT; SHORT-TERM; AGORAPHOBIA; PREDICTORS; DEPRESSION; MULTICENTER; PLACEBO; COMORBIDITY AB Background: More than one third of panic disorder patients have a chronic and/or recurrent form of the disorder, accounting fur much of the individual and societal cost associated with the illness. Six clinical variables have been most consistently identified as high-risk predictors of Door outcome: (1) panic severity, (2) presence of agoraphobia, (3) comorbid depression, (4) comorbid personality disorder, (5) duration of illness, and (6) female sex. No published research has systematically examined the differential antipanic efficacy of selective serotonin reuptake inhibitors in patients at high risk for poor outcome. Method: Data were pooled (N = 664) from 4 double-blind, placebo-controlled studies of the efficacy of sertra-line: for the treatment of DSM-III-R panic disorder. Two of the studies were 12-week; fixed-dose studies with starting daily doses of sertraline, 50 mg, and 2 were 10-week flexible-dose studies with starting daily doses of sertra-line, 3,5 mg. All other study design features were the same, except for the exclusion of women of childbearing potential in the 2 fixed-dose studies. Exclusion of patients with marked personality disorders and depression meant that only 3 of the poor-outcome variables could be evaluated. Results: Clinical improvement was similar for patients treated with sertraline whether or not they carried an agoraphobia diagnosis, had a duration of illness > 2 years, or wen female. Patients with high baseline panic severity had significantly (p = .01) less improvement on the endpoint Clinical Global Impressions-Improvement (CGI-I) scale than patients with moderate severity, although the Clinical Global Impressions-Severity of Illness scale change score was higher in the patients with high severity (-2,00 vs. -1.31). For patients with 3 or more high-risk variables, there was a modest, but statistically significant, tendency For reduced global improvement (endpoint CGI-I score of 2.7 for the high-risk vs. 2.4 for the non-high-risk group; p = .017), although the high-risk group actually had a similar endpoint reduction in frequency of panic attacks (82%) compared with the non-high-risk group (78%). Conclusion: Treatment of panic disorder with sertraline was generally effective, even in the presence of baseline clinical variables that have been associated with poor treatment response. The main limitations of the analysis were the reliance on pooled data from 4 studies (even if the designs were similar) and our inability to examine the impact of depression and personality disorders on response to treatment because of the exclusion criteria of the clinical trials. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. San Diego Vet Affairs Healthcare Syst, San Diego, CA USA. Pfizer Inc, New York, NY USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC812, Boston, MA 02114 USA. NR 37 TC 22 Z9 23 U1 2 U2 2 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 2000 VL 61 IS 12 BP 922 EP 927 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 394QG UT WOS:000166534300006 PM 11206597 ER PT J AU Suri, RA Altshuler, LL Rasgon, NL Calcagno, JL Frye, MA Gitlin, MJ Hwang, S Zuckerbrow-Miller, J AF Suri, RA Altshuler, LL Rasgon, NL Calcagno, JL Frye, MA Gitlin, MJ Hwang, S Zuckerbrow-Miller, J TI Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 153rd Annual Meeting of the American-Psychiatric-Association CY MAY 13-18, 2000 CL CHICAGO, ILLINOIS SP Amer Psychiat Assoc ID DOUBLE-BLIND AB Background: Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine. Method: A randomized, single-blind, parallel group study of 10 weeks' duration comparing the efficacy of sertraline, 50 mg/day; sertraline, 100 mg/day; and fluoxetine, 20 mg/day, was conducted in 44 psychiatric outpatients with DSM-IV unipolar major depressive disorder. Anti-depressant dosages were doubled at 6 weeks for subjects who had not achieved remission. Primary outcome measurements included the 71-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions-Improvement scale (CGI-I), with scores of less than or equal to 7 on the HAM-D and less than or equal to 2 on the CGI-I representing a positive treatment response, i.e., remission. Results: At 4 weeks, significant differences in rate of positive treatment response were noted, with 0% for sertraline, 50 mg; 46% for sertraline, 100 mg; and 31% for fluoxetine, 20 mg (p = .023). At 6 weeks, positive treatment response rates were 21%, 43%, and 31% for subjects taking 50 mg of sertraline, those taking 100 mg of sertraline, and those taking 20 mg of fluoxetine, respectively, with treatment groups no longer differing significantly from each other. In subjects for whom antidepressant dose was doubled at week 6, response rates at week 10 (4 weeks on increased dose) were 40% for sertraline, 100 mg; 43% for sertraline, 200 mg; and 55% for fluoxetine, 40 mg. Conclusion: Subjects taking sertraline, 100 mg, and fluoxetine, 20 mg, demonstrated an earlier treatment response compared with subjects taking sertraline, 50 mg. For patients without a positive response at 6 weeks, an increased antidepressant dose resulted in remission for a substantial proportion of patients when assessed 4 weeks later. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Suri, RA (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. NR 15 TC 27 Z9 27 U1 3 U2 6 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 2000 VL 61 IS 12 BP 942 EP 946 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 394QG UT WOS:000166534300009 PM 11206600 ER PT J AU Klein, I Paradis, AL Poline, JB Kosslyn, SM Le Bihan, D AF Klein, I Paradis, AL Poline, JB Kosslyn, SM Le Bihan, D TI Transient activity in the human calcarine cortex during visual-mental imagery: An event-related fMRI study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL-ANATOMY; ACTIVATION; ATTENTION; PET; PERCEPTION; MODULATION; MEMORY; AREAS; TIME AB Although it is largely accepted that visual-mental imagery and perception draw on many of the same neural structures, the existence and nature of neural processing in the primary visual cortex (or area V1) during Visual imagery remains controversial. We tested two general hypotheses: The first Nas chat V1 is activated only when images with many details are formed and used, and the second was that V1 is activated whenever images are formed, even if they are not necessarily used to perform a task. We used event-related functional magnetic resonance imaging (ER-fMRI) to detect and characterize the activity in the calcarine sulcus (which contains the primary visual cortex) during single instances of mental imagery. The results revealed reproducible transient activity in this area whenever participants generated or evaluated a mental image. This transient activity was strongly enhanced when participants evaluated characteristics of objects; whether or not details actually needed to be extracted from the image to perform the task. These results show that visual imagery processing commonly involves the earliest stages of the visual system. C1 CEA, DSV, DRM, Serv Hosp Frederic Joliot, F-91401 Orsay, France. Coll France, LPAA, CNRS, Paris, France. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Le Bihan, D (reprint author), CEA, DSV, DRM, Serv Hosp Frederic Joliot, 4 Pl Gen Leclerc, F-91401 Orsay, France. RI Paradis, Anne-Lise/F-2109-2013 OI Paradis, Anne-Lise/0000-0002-5933-0448 NR 35 TC 91 Z9 93 U1 1 U2 6 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 VL 12 SU 2 BP 15 EP 23 DI 10.1162/089892900564037 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 388QX UT WOS:000166194100003 PM 11506644 ER PT J AU Wagner, AD Maril, A Schacter, DL AF Wagner, AD Maril, A Schacter, DL TI Interactions between forms of memory: When priming hinders new episodic learning SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID INFERIOR PREFRONTAL CORTEX; MEDIAL TEMPORAL-LOBE; EVENT-RELATED FMRI; FUNCTIONAL MRI; HUMAN BRAIN; RETRIEVAL; REPETITION; MODEL; PET; RECOGNITION AB Human memory consists of multiple forms, including priming and explicit memory. Although considerable evidence indicates that priming and explicit memory are functionally and neuroanatomically distinct, little is know about when and how these different forms of memory interact. Here, behavioral and functional magnetic resonance imaging (fMRI) methods were used to examine a novel and counterintuitive hypothesis: Priming during episodic encoding may be negatively associated with subsequent explicit memory. Using an experimental design that exploited known properties of spacing or lag effects, the magnitudes of behavioral and neural priming during a second study episode were varied and the relation between these magnitudes of priming during re-encoding and performance on a subsequent explicit memory test was examined. Results revealed that greater behavioral priming (reduced reaction times) and neural priming (reduced left inferior prefrontal brain activation) during re-encoding were associated with lower levels of subsequent explicit memory. Moreover, those subjects who demonstrated greater behavioral and neural priming effects during re-encoding following a long lag tended to demonstrate the least benefit in subsequent explicit memory due to this second study episode. These findings suggest that priming for past experiences can hinder new episodic encoding. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Wagner, AD (reprint author), MIT, Dept Brain & Cognit Sci, NE20-436, Cambridge, MA 02139 USA. FU NIA NIH HHS [AG05778]; NIMH NIH HHS [MH60941] NR 44 TC 80 Z9 80 U1 4 U2 10 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 VL 12 SU 2 BP 52 EP 60 DI 10.1162/089892900564064 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 388QX UT WOS:000166194100006 PM 11506647 ER PT J AU Hinrichs, H Scholz, M Tempelmann, C Woldorff, MG Dale, AM Heinze, HJ AF Hinrichs, H Scholz, M Tempelmann, C Woldorff, MG Dale, AM Heinze, HJ TI Deconvolution of event-related fMRI responses in fast-rate experimental designs: Tracking amplitude variations SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID FUNCTIONAL MRI; ATTENTION AB Recent developments towards event-related functional magnetic resonance imaging has greatly err-ended the range of experimental designs. If the events occur in rapid succession, the corresponding time-locked responses overlap significantly and need to be deconvolved in order to separate the contributions of different events. Here we present a deconvolution approach, which is especially aimed at the analysis of fMRI data where sequence- or context-related responses are expected. For this purpose, we make the assumption of a hemodynamic response function (HDR) with constant yet not predefined shape but with possibly variable amplitudes. This approach reduces the number of variables to be estimated but still keeps the solutions flexible with respect to the shape. Consequently, statistical efficiency is improved. Temporal variations of the HDR strength are directly indicated by the amplitudes derived by the algorithm. Both the estimation efficiency and statistical inference are further supported by an improved estimation of the noise covariance. Using synthesized data sets, both differently shaped HDRs and varying amplitude factors were correctly identified. The gain in statistical sensitivity led to improved ratios of false- and true-positive detection rates for synthetic activations in these data. In an event-related fMRI experiment with a human subject, different HDR amplitudes could be derived corresponding to stimulation at different visual stimulus contrasts. Finally, in a visual spatial attention experiment we obtained different fMRI response amplitudes depending on the sequences of attention conditions. C1 Univ Magdeburg, Dept Neurol 2, D-39120 Magdeburg, Germany. Duke Univ, Durham, NC 27706 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. RP Hinrichs, H (reprint author), Univ Magdeburg, Dept Neurol 2, Leipziger Str 44, D-39120 Magdeburg, Germany. RI Dale, Anders/A-5180-2010 NR 23 TC 73 Z9 74 U1 0 U2 4 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 VL 12 SU 2 BP 76 EP 89 DI 10.1162/089892900564082 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 388QX UT WOS:000166194100008 PM 11506649 ER PT J AU Pennington, BF Filipek, PA Lefly, D Chhabildas, R Kennedy, DN Simon, JH Filley, CM Galaburda, A DeFries, JC AF Pennington, BF Filipek, PA Lefly, D Chhabildas, R Kennedy, DN Simon, JH Filley, CM Galaburda, A DeFries, JC TI A twin MRI study of size variations in the human brain SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID INTELLIGENCE; EEG; ABILITIES AB Although it is well known that there is considerable variation among individuals in the size of the human brain, the etiology of less extreme individual differences in brain size is largely unknown. We present here data from the first large twin sample (N = 132 individuals) in which the size of brain structures has been measured. As part of an ongoing project examining the brain correlates of reading disability (RD), whole brain morphometric analyses of structural magnetic response image (MRI) scans were performed on a sample of adolescent twins. Specifically, there were 25 monozygotic (MZ) and 23 dizygotic (DZ) pairs in which at least one member of each pair had RD and 9 MZ and 9 DZ pairs in which neither member had RD. We first factor-analyzed volume data for 13 individual brain structures, comprising all of the neocortex and most of the subcortex. This analysis yielded two factors ("cortical" and "subcortical") that account for 64% of the variance. We next tested whether genetic and environmental influences on brain size variations varied for these two factors or by hemisphere. We computed intraclass correlations within MZ and DZ pairs in each sample for the cortical and subcortical factor scores, for left and right neocortex, and for the total cerebral volume. All five MZ correlations were substantial (r's = .78 to .98) and significant in both samples, as well as being larger than the corresponding DZ correlations, (r's = 0.32 to 0.65) in both samples. The MZ-DZ differences was significant for 3 variables in the RD sample and for one variable in the smaller control sample. These results indicate significant genetic influences on these variables. The magnitude of genetic influence did not vary markedly either for the 2 factors or the 2 hemispheres. There was also a positive correlation between brain size and full-scale IQ, consistent with the results of earlier studies. The total cerebral volume was moderately correlated (r = .42, p < .01, two-tailed) with full-scale IQ in the RD sample; there was a similar trend in the smaller control sample (r = .31, p < .07, two-tailed). Corrections of similar magnitude were found between the subcortical factor and full-scale IQ, whereas the results for the cortical factor (r = .16 and .13) were smaller and not significant. In sum, these results provide evidence for the heritability of individual differences in brain size which do not vary markedly by hemisphere or for neocortex relative to subcortex. Since there are also correlations between brain size and full-scale IQ in this sample, it is possible that genetic influences on brain size partly contribute to individual differences in IQ. C1 Univ Denver, Dept Psychol, Denver, CO 80208 USA. Univ Calif Irvine, Irvine, CA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Colorado, Boulder, CO 80309 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Pennington, BF (reprint author), Univ Denver, Dept Psychol, 2155 S Race St, Denver, CO 80208 USA. RI Kennedy, David/H-3627-2012 FU NICHD NIH HHS [P30 HD04024, P50 HD27802]; NIMH NIH HHS [K02 MH00419] NR 39 TC 134 Z9 136 U1 0 U2 3 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JAN PY 2000 VL 12 IS 1 BP 223 EP 232 DI 10.1162/089892900561850 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 298MV UT WOS:000086144200015 PM 10769318 ER PT J AU Badgaiyan, RD Schacter, DL Alpert, NM AF Badgaiyan, RD Schacter, DL Alpert, NM TI Characterization of the nature of cerebral blood flow changes in within and cross-modality priming SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, PET Imaging Lab, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 2A BP 20 EP 20 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800031 ER PT J AU Parsons, LM Schmahmann, JD Bower, JM AF Parsons, LM Schmahmann, JD Bower, JM TI Neurological evidence implicating the cerebellum in fine auditory discriminations. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 75A BP 33 EP 33 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800104 ER PT J AU Kuperberg, G Dale, A Greve, D Sitnikova, T Waters, G Holcomb, P Caplan, D AF Kuperberg, G Dale, A Greve, D Sitnikova, T Waters, G Holcomb, P Caplan, D TI Neural activity during pragmatic and syntactic processing of sentences: Evidence from event-related fMRI and brain potentials SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Boston, MA 02111 USA. Boston Univ, Boston, MA 02215 USA. Inst Psychiat, London, England. RI Dale, Anders/A-5180-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 21B BP 46 EP 47 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800168 ER PT J AU Vincent, DJ Horner, MD Roberts, DR Bloomer, CW Dubno, JR Horwitz, AR AF Vincent, DJ Horner, MD Roberts, DR Bloomer, CW Dubno, JR Horwitz, AR TI Refining an fMRI language paradigm using a nonlinguistic task. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 37B BP 49 EP 50 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800184 ER PT J AU Wraga, M Kosslyn, SM Thompson, WL Alpert, NM AF Wraga, M Kosslyn, SM Thompson, WL Alpert, NM TI Motor and nonmotor strategies for mental rotation of objects: A pet study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 51C BP 75 EP 75 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800313 ER PT J AU Mitchell, KJ Raye, CL Johnson, MK Wagner, AD AF Mitchell, KJ Raye, CL Johnson, MK Wagner, AD TI An fMRI examination of the role of left and right prefrontal cortex in episodic memory SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 14F BP 132 EP 132 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800616 ER PT J AU Sperling, R Cocchiarella, A Bates, J Rentz, D Schacter, D Rosen, B Albert, M AF Sperling, R Cocchiarella, A Bates, J Rentz, D Schacter, D Rosen, B Albert, M TI Face-name association fMRI studies SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 41F BP 137 EP 137 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800643 ER PT J AU Salat, DH Kaye, JA Janowsky, JS AF Salat, DH Kaye, JA Janowsky, JS TI Relationship between age, regional prefrontal volumes, and performance on working memory tasks with healthy aging: Is working memory necessarily working memory? SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 103F BP 148 EP 148 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800705 ER PT J AU Balto, K Muller, R Carrington, DC Dobeck, J Stashenko, P AF Balto, K Muller, R Carrington, DC Dobeck, J Stashenko, P TI Quantification of periapical bone destruction in mice by micro-computed tomography SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE micro-computed tomography; bone resorption; periapical lesion ID MAXILLOMANDIBULAR REGION; ENDODONTIC INFECTIONS; DIGITAL SUBTRACTION; CANCELLOUS BONE; IN-VIVO; LESIONS; ARCHITECTURE; RESOLUTION; SECTIONS; BIOPSIES AB Bacterial infections of the dental pulp result in tissue destruction and periapical bone resorption. The availability of genetically engineered mouse strains is a major advantage in the use of this model system for studies of periapical pathogenesis. The main limitation of the mouse model is its small size, and the necessity for laborious histologic analyses to quantify periapical bone destruction. In the present study, we evaluated the use of a new technology, high-resolution micro-computed tomography (micro-CT), for the rapid and non-invasive quantification of periapical bone destruction. Periapical lesions were induced in the lower first molars of mice by exposing the pulp to the oral environment. Mandibles were harvested on day 21 after pulp exposure, and were subjected to micro-CT analysis, with 17-mu m-thick radiographic sections. Samples were then decalcified, embedded, and sectioned for histolology. The cross-sectional area of periapical lesions was determined by image analysis of corresponding micro-CT and histologic sections. The results showed a highly significant correlation between micro-CT and histology (p < 0.0001), with mean differences of 4.1% (range, 0.9 to 7.2%) between the two methods. The mean error associated with image analysis was 4.9% for images obtained by both micro-CT and histology. The variability of replicate (n = 5) independent micro-CT determinations was 3.4%, less than that associated with the image analysis error. These results demonstrate that micro-CT imaging is a rapid, reproducible, and non-invasive method, that gives results that an closely comparable with those obtained by histology. Micro-CT appears to have utility for the accurate quantification of changes in bone architecture in small biological specimens. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02215 USA. Forsyth Inst, Dept Histol, Boston, MA 02215 USA. Harvard Univ, Sch Dent Med, Dept Endodont, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02215 USA. EM Pstashenko@forsyth.org RI Muller, Ralph/A-1198-2008 OI Muller, Ralph/0000-0002-5811-7725 FU NIA NIH HHS [AG-13333]; NIDCR NIH HHS [DE-09018, DE-11664] NR 31 TC 82 Z9 84 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2000 VL 79 IS 1 BP 35 EP 40 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277XV UT WOS:000084959600008 PM 10690658 ER PT J AU Hu, JCC Ryu, OH Chen, JJ Uchida, T Wakida, K Murakami, C Jiang, H Qian, Q Zhang, C Ottmers, V Bartlett, JD Simmer, JP AF Hu, JCC Ryu, OH Chen, JJ Uchida, T Wakida, K Murakami, C Jiang, H Qian, Q Zhang, C Ottmers, V Bartlett, JD Simmer, JP TI Localization of EMSP1 expression during tooth formation and cloning of mouse cDNA SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel; serine proteinase; EMSP1; mouse ID MATRIX SERINE PROTEINASE-1; ENAMEL MATURATION; AMELOGENESIS; RAT; AMELOBLASTS; SECRETION; GROWTH; TEETH; STAGE; PIG AB Enamel Matrix Serine Proteinase 1 (EMSP1) is a proteolytic enzyme that has been isolated from the developing enamel of pig teeth. Its apparent function is to degrade the organic matrix in preparation for enamel maturation. The expression of EMSP1 has never been investigated in another organism besides the pig, and EMSP1 expression in the enamel organ has never been specifically demonstrated in ameloblasts. Here we report the expression of recombinant pig EMSP1 (rpEMSP1), the generation of rabbit polyclonal antibodies against rpEMSP1, the characterization of the antibodies and EMSP1 expression by Western blot and immunohistochemical analyses, the cloning and characterization of a full-length cDNA encoding mouse EMSP1, and the localization of EMSP1 expression in ameloblasts in mouse day 14 first and second molars by in situ hybridization. The full-length mouse EMSP1 cDNA clone has 1237 nucleotides, excluding the poly(A+) tail, and encodes a preproprotein of 255 amino acids. Mouse EMSP1 shares 75% amino acid identity with pig EMSP1 and has three potential N-linked glycosylation sites, two of which are conserved in the pig homologue. Western blot analysis shows that the polyclonal antibodies are specific for EMSP1 and do not cross-react with trypsin. Immunohistochemistry of pig incisors shows discrete staining in the surface enamel at the earliest part of the maturation stage. In mouse molars, in situ hybridization gives a distinct and specific signal in maturation-stage ameloblasts, and in the junctional epithelium following tooth eruption. We conclude that EMSP1 is expressed by pig and mouse ameloblasts during the early maturation stage of amelogenesis. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, San Antonio, TX 78284 USA. Hiroshima Univ, Sch Dent, Dept Oral Anat, Minami Ku, Hiroshima 7348553, Japan. Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. RP Simmer, JP (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE10721, DE11301, R29 DE012098] NR 29 TC 38 Z9 40 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2000 VL 79 IS 1 BP 70 EP 76 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277XV UT WOS:000084959600013 PM 10690663 ER PT J AU Dibart, S Warbington, M Bouhmadouche, M Van Dyke, TE Dobeck, JM Skobe, Z AF Dibart, S Warbington, M Bouhmadouche, M Van Dyke, TE Dobeck, JM Skobe, Z TI Bacterial invasion of dental tissues in chronic adult periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Boston Univ, Sch Dent Med, Boston, MA 02215 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 83 BP 154 EP 154 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000082 ER PT J AU Hou, L Sasaki, H Stashenko, P AF Hou, L Sasaki, H Stashenko, P TI TLR4-deficient mice exhibit reduced bone destruction following endodontic infection. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 108 BP 157 EP 157 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000110 ER PT J AU Soukos, NS Hamblin, HR Deutsch, TF Fabian, RL Keel, S Hasan, T AF Soukos, NS Hamblin, HR Deutsch, TF Fabian, RL Keel, S Hasan, T TI Epidermal growth factor receptor targeted immunophotodiagnosis of oral precancer. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 170 BP 165 EP 165 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000173 ER PT J AU Socransky, SS Smith, CM Haffajee, AD AF Socransky, SS Smith, CM Haffajee, AD TI Detection of "refractory microbial profiles" in periodontitis and healthy subjects. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 216 BP 170 EP 170 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000216 ER PT J AU Goodson, JM Palys, MD Socransky, SS AF Goodson, JM Palys, MD Socransky, SS TI Gingival bleeding accentuated by plaque in healthy IL-1(+) genotype subjects. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 221 BP 171 EP 171 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000219 ER PT J AU Levine, M Rondalapolla, S Owen, WL Socransky, SS AF Levine, M Rondalapolla, S Owen, WL Socransky, SS TI Antibody-based diagnostic for refractory periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 218 BP 171 EP 171 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000221 ER PT J AU Sasaki, H Stashenko, P AF Sasaki, H Stashenko, P TI Functional role of IL-10 and IL-12 in murine periapical lesions. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 264 BP 176 EP 176 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000264 ER PT J AU Johnson, DA Yeh, CK Saunders, MJ Dodds, MWJ AF Johnson, DA Yeh, CK Saunders, MJ Dodds, MWJ TI Salivary function in full denture wearers SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, ALMD, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 627 BP 222 EP 222 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000625 ER PT J AU Jin, S Duncan, MJ Taubman, MA Smith, DJ AF Jin, S Duncan, MJ Taubman, MA Smith, DJ TI Cloning of the gbpB gene from Streptococcus mutans. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 643 BP 224 EP 224 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000641 ER PT J AU Dillon, KC Maiden, MFJ AF Dillon, KC Maiden, MFJ TI Fluorogenic substrate screening of a Bacteroides forsythus genomic expression library. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 660 BP 226 EP 226 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000661 ER PT J AU Dong, H Belliveau, L Chen, T Duncan, MJ AF Dong, H Belliveau, L Chen, T Duncan, MJ TI Sialidase activity of Porphyromonas gingivalis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 711 BP 232 EP 232 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000707 ER PT J AU Yong, R Chen, T Dewhirst, F Duncan, MJ AF Yong, R Chen, T Dewhirst, F Duncan, MJ TI Identification of a putative internalin-like gene in Porphyromonas gingivalis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 712 BP 232 EP 232 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000711 ER PT J AU Thomas, BD Murray, LL Kent, RL Tanner, ACR AF Thomas, BD Murray, LL Kent, RL Tanner, ACR TI Microbiota of early periodontitis in adults by DNA probe assay. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 718 BP 233 EP 233 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000718 ER PT J AU Levanos, VA Galvin, JL Boches, SK Dewhirst, FE Paster, BJ AF Levanos, VA Galvin, JL Boches, SK Dewhirst, FE Paster, BJ TI Predominant cultivable and uncultivable bacterial species an adult periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 723 BP 234 EP 234 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000721 ER PT J AU Tanner, ACR Galvin, JL Boches, SK Dewhirst, FE Paster, BJ AF Tanner, ACR Galvin, JL Boches, SK Dewhirst, FE Paster, BJ TI Cultivable and uncultivable treponemes in early periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 724 BP 234 EP 234 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000725 ER PT J AU Ohyama, H Todd, R Kohno, Y Zhang, X Alevizo, I Mahadev, M Bradbury, L Leung, SM Posner, M Kent, R Donoff, B Warrington, J Wong, DT AF Ohyama, H Todd, R Kohno, Y Zhang, X Alevizo, I Mahadev, M Bradbury, L Leung, SM Posner, M Kent, R Donoff, B Warrington, J Wong, DT TI Molecular profiling of the oral cancer cell using high-throughout analysis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Boston, MA USA. Forsyth Inst, Boston, MA USA. Affymetrix Inc, Santa Clara, CA USA. Ciphergen Biosyst Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 761 BP 239 EP 239 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000760 ER PT J AU Mark, LL Haffajee, AD Socransky, SS Kent, RL Guerrero, D Kornman, K Newman, MG Stashenko, P AF Mark, LL Haffajee, AD Socransky, SS Kent, RL Guerrero, D Kornman, K Newman, MG Stashenko, P TI Interleukin-1 genotype and monocyte IL-1 beta expression in adult periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Interleukin Genet Inc, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 915 BP 258 EP 258 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000912 ER PT J AU Cruz, GD Halpert, N Xue, X Galvis, DL Tavares, M Legeros, RZ AF Cruz, GD Halpert, N Xue, X Galvis, DL Tavares, M Legeros, RZ TI The dental health status of Haitian Americans in New York city. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NYU, Coll Dent, New York, NY USA. Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1175 BP 290 EP 290 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001167 ER PT J AU Smith, DJ King, WF Houstis, O Gusek, E Trantolo, DJ Wise, DL Taubman, MA AF Smith, DJ King, WF Houstis, O Gusek, E Trantolo, DJ Wise, DL Taubman, MA TI Anamnesis of mucosal immunity after intranasal immunization with bioadhesive PLGA-GTF microparticles. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Cambridge Sci Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1311 BP 307 EP 307 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001303 ER PT J AU Taubman, MA Smith, DJ Holmberg, CJ Lees, A AF Taubman, MA Smith, DJ Holmberg, CJ Lees, A TI Effect of immunization route on isotype of antibody to glucosyltransferrase-polysaccharide conjugate. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Dept Immunol, Boston, MA USA. Vir Syst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1309 BP 307 EP 307 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001302 ER PT J AU King, WF Godiska, R Smith, DJ Taubman, MA AF King, WF Godiska, R Smith, DJ Taubman, MA TI Passive immunization with IgY antibody to GBP-B interferes with Streptococcus mutans infection in rats. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Ophidian Pharmaceut, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1317 BP 308 EP 308 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001310 ER PT J AU Kawai, T Kawashima, N Eastcott, JW Taubman, MA AF Kawai, T Kawashima, N Eastcott, JW Taubman, MA TI Antigen specific T cell intervention for periodontal bone resorption in BALC/c mice colonized with A-actinomycetemcomitans. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Dept Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1364 BP 314 EP 314 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001361 ER PT J AU Blaeser, BF Dodson, TB August, MA AF Blaeser, BF Dodson, TB August, MA TI Panoramic findings as predictors for inferior alveolar nerve injury. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1575 BP 340 EP 340 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001567 ER PT J AU Tjaderhane, L Palosaari, H Sulkala, M Wahlgren, J Larmas, M Bartlett, JD Sorsa, T Salo, T AF Tjaderhane, L Palosaari, H Sulkala, M Wahlgren, J Larmas, M Bartlett, JD Sorsa, T Salo, T TI Caries induces the expression of MMP-20 mRNA in human teeth. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Helsinki, Helsinki, Finland. Oulu Univ, SF-90220 Oulu, Finland. Forsyth Dent Ctr, Boston, MA 02115 USA. RI Tjaderhane, Leo/J-5017-2015 OI Tjaderhane, Leo/0000-0002-5018-478X NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1605 BP 344 EP 344 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001598 ER PT J AU Sorkin, BC Jonsson, M Poveromo, J Khalil, NM Shaulov, A Esch, TR AF Sorkin, BC Jonsson, M Poveromo, J Khalil, NM Shaulov, A Esch, TR TI Leukocytes express E-cadherin in a mouse model for Sjogren's syndrome. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1619 BP 346 EP 346 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001613 ER PT J AU Nara, Y Mori, N Nakayama, K Nagakura, Y Tanaka, H Dogon, IL AF Nara, Y Mori, N Nakayama, K Nagakura, Y Tanaka, H Dogon, IL TI Bond strength of resin adhesive system to minute area of caries-affected dentin SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Forsyth Dent Ctr, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1834 BP 373 EP 373 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001832 ER PT J AU Boches, SK Mitchell, PM Galvin, JL Loesche, WJ Kazor, CE Dewhirst, FE Paster, BJ AF Boches, SK Mitchell, PM Galvin, JL Loesche, WJ Kazor, CE Dewhirst, FE Paster, BJ TI Cultivable and uncultivable bacteria on the healthy tongue dorsum. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 2 Z9 3 U1 1 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2018 BP 396 EP 396 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002015 ER PT J AU Loo, CY Corliss, DA Ganeshkumar, N AF Loo, CY Corliss, DA Ganeshkumar, N TI Identification of genes associated with biofilm formation of Streptococcus gordonii. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2223 BP 421 EP 421 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002214 ER PT J AU Bartlett, JD Caterina, JJ Xue, J AF Bartlett, JD Caterina, JJ Xue, J TI Enamelysin (MMP-20) promoter characterization SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2241 BP 424 EP 424 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002235 ER PT J AU Haffajee, AD Torresyap, G Thompson, M Guerrero, DM Socransky, SS AF Haffajee, AD Torresyap, G Thompson, M Guerrero, DM Socransky, SS TI Effect of manual and powered toothbrushes on clinical parameters. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2274 BP 428 EP 428 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002271 ER PT J AU Maseki, T Shirota, A Oshita, S Kimishima, T Nara, Y Tanaka, H Dogon, LL AF Maseki, T Shirota, A Oshita, S Kimishima, T Nara, Y Tanaka, H Dogon, LL TI Dentin bonding of a new adhesive resin cement system. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Forsyth Dent Ctr, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2489 BP 455 EP 455 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002483 ER PT J AU Gemmel, A Tavares, M Crawford, S Alperin, S Bellinger, D Soncini, J Braveman, N AF Gemmel, A Tavares, M Crawford, S Alperin, S Bellinger, D Soncini, J Braveman, N TI Serum lead levels and number of caries in the children's amalgam trial. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Forsyth Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2543 BP 461 EP 461 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002534 ER PT J AU Crawford, S Tavares, M Alpen, S Gemmel, A Soncini, J Braveman, N AF Crawford, S Tavares, M Alpen, S Gemmel, A Soncini, J Braveman, N TI Comparison of baseline variables for subjects in the children's amalgam trial. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Forsyth Inst, Boston, MA USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2545 BP 462 EP 462 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002539 ER PT J AU Tavares, M Crawford, S Alperin, S Soncini, J Gemmell, A Braveman, N AF Tavares, M Crawford, S Alperin, S Soncini, J Gemmell, A Braveman, N TI Caries prevalence and treatment needs in the children's amalgam TnaI SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2546 BP 462 EP 462 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002543 ER PT J AU Kenyon, SG Mitchell, PM Margolis, HC Dewhirst, FE Paster, BJ AF Kenyon, SG Mitchell, PM Margolis, HC Dewhirst, FE Paster, BJ TI Bacterial population distribution of caries-active vs caries-free subjects. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2566 BP 464 EP 464 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002561 ER PT J AU Russell, MK Maiden, MFJ Lopman, J Boches, SK Galvin, JL Dewhirst, FE Paster, BJ AF Russell, MK Maiden, MFJ Lopman, J Boches, SK Galvin, JL Dewhirst, FE Paster, BJ TI Low pH bacterial species associated with root surfaces. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2571 BP 465 EP 465 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002564 ER PT J AU Hirose, M Yahata, S Matsumoto, D Igarashi, S Margolis, HC AF Hirose, M Yahata, S Matsumoto, D Igarashi, S Margolis, HC TI Site-specificity of mineral ions in dental plaque SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Hokkaido Univ, Dept Pediat Dent, Sapporo, Hokkaido 060, Japan. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2578 BP 466 EP 466 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002575 ER PT J AU Maiden, MFJ AF Maiden, MFJ TI DNA sequence of the N-acetylhexosaminidase (nahA) gene from Bacteroides forsythus. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2666 BP 477 EP 477 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002663 ER PT J AU Dayan, S Stashenko, P Niederman, R Kupper, T AF Dayan, S Stashenko, P Niederman, R Kupper, T TI Effect of IL-1 alpha over-expression by keratinocytes an periodontal bone loss. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2740 BP 486 EP 486 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002735 ER PT J AU Caron, C Xue, J Bartlett, JD AF Caron, C Xue, J Bartlett, JD TI Expression, localization, and functional characterisation of Gelatinase A in developing teeth. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Laval, Fac Dent, Quebec City, PQ, Canada. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2962 BP 514 EP 514 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002958 ER PT J AU Yue, I Shastri, P Sinisterra, RD Stashenko, P Niederman, R Langer, R AF Yue, I Shastri, P Sinisterra, RD Stashenko, P Niederman, R Langer, R TI Treatment of periodontal disease by a polymeric chlorhexidine delivery device SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, MIT, Sch Dent Med, Forsyth Dent Ctr, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2993 BP 518 EP 518 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002987 ER PT J AU Kamolmatyakul, S Chen, W Li, YP AF Kamolmatyakul, S Chen, W Li, YP TI IL-1 alpha up-regulate cathepsin K expression in osteoclasts via tyrosine kinase-NF-kappa B pathway SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3056 BP 525 EP 525 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003048 ER PT J AU Lin, AL Biggs, WS Stephan, KT Carlson, KA Johnson, DA Yeh, CK AF Lin, AL Biggs, WS Stephan, KT Carlson, KA Johnson, DA Yeh, CK TI Salivary anticandidal activities in an early HIV(+) corhort. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. STVHCS, GRECC, Audie L Murphy Vet Hosp, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3383 BP 566 EP 566 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003372 ER PT J AU Lin, AL Guo, ZM Dang, H Wu, Y Johnson, DA Yeh, CK AF Lin, AL Guo, ZM Dang, H Wu, Y Johnson, DA Yeh, CK TI Gamma radiation-induced DNA damage in mouse salivary glands SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, Audie L Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3381 BP 566 EP 566 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003371 ER PT J AU Yeh, CK Sims, CA Wu, Y Carlson, KA Stephan, KT Johnson, DA AF Yeh, CK Sims, CA Wu, Y Carlson, KA Stephan, KT Johnson, DA TI Evaluation of salivary gland function in HIV disease SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, GRECC, Audie L Murphy Vet Hosp,STVHCS, San Antonio, TX USA. Wilford Hall AFB Med Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3382 BP 566 EP 566 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003375 ER PT J AU Rovaldi, CR Chen, T Duncan, MJ Rothstein, DM AF Rovaldi, CR Chen, T Duncan, MJ Rothstein, DM TI Porphyromonas gingivalis mutants resistant to photodynamic therapy SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Periodonix Inc, Watertown, MA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3424 BP 571 EP 571 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003416 ER PT J AU Davies, GM Krali, E Lee, A Chandler, JM Garcia, R AF Davies, GM Krali, E Lee, A Chandler, JM Garcia, R TI Alveolar bone height and tooth loss in the VA longitudinal study. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Merck Res Labs, W Point, PA USA. Boston Univ, Va Boston Healthcare Syst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3487 BP 579 EP 579 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003476 ER PT J AU Stack, KM Papas, A Singh, M Altman, K Al Quaraini, W Depoala, P AF Stack, KM Papas, A Singh, M Altman, K Al Quaraini, W Depoala, P TI Patterns in food consumption in head and neck radiation patients. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Tufts Univ, Sch Dent Med, Forsyth Res Inst, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3699 BP 606 EP 606 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003690 ER PT J AU Feres, M Haffajee, AD Allard, K Som, S Socransky, SS AF Feres, M Haffajee, AD Allard, K Som, S Socransky, SS TI Effect of systemically administered amoxicillin on subgingival plaque composition. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. RI Feres, Magda/H-7964-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3720 BP 608 EP 608 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003712 ER PT J AU Allard, K Feres, M Haffajee, AD Goodson, JM Socransky, SS AF Allard, K Feres, M Haffajee, AD Goodson, JM Socransky, SS TI Antibiotic resistance of subgingival species during and after antibiotic therapy. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. RI Feres, Magda/H-7964-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3721 BP 609 EP 609 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003713 ER PT J AU Becker, MR Griffen, AL Leys, EJ Kenyon, SG Dewirst, FE Paster, BJ AF Becker, MR Griffen, AL Leys, EJ Kenyon, SG Dewirst, FE Paster, BJ TI Checkerboard analysis of bacterial species associated with early childhood caries. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3816 BP 620 EP 620 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003808 ER PT J AU Ahroni, JH Boyko, EJ AF Ahroni, JH Boyko, EJ TI Responsiveness of the SF-36 among veterans with diabetes mellitus SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE health status; diabetes mellitus complications; reproducibility of results; quality of life ID QUALITY-OF-LIFE; HEALTH-STATUS; FUNCTIONAL STATUS; GLYCEMIC CONTROL AB To examine the responsiveness of the Medical Outcomes Study 36-Item Short Form (SF-36) to the development of diabetes complications over time. We studied a cohort of 331 diabetic veterans participating in a prospective study of risk factors for foot complications. Eight SF-36 scales [general health (GH), physical functioning (PF), social functioning (SF), mental health (MH), physical role (RP), emotional role (RE), bodily pain (BP), and vitality VT)] and 25 diabetes complications characteristics (DCC) from history and symptom questionnaires and physical exam findings were compared over a mean interval of 3.1 years. The subjects were mostly married, white males with a mean age of 63.5 years, with primarily type 2 diabetes (91%) and a mean diabetes duration of 9.7 years at baseline. There was a statistically significant interval decrease in the GH scale of 6.1 points (effect size [ES] 0.24), PF decreased 9.7 (ES 0.38), SF decreased 5.8 (ES 0.19), PR decreased 14.7 (ES 0.38), BP decreased 4.0 (ES 0.14), VT decreased 4.5 (ES 0.16), total DCC increased by 1.8 (ES 0.53), and hemoglobin Al, declined 1.3% (ES 0.48). An increase of > 1 DCC was associated with an average loss of 7.2 to 11.8 points on six SF 36 scales (GH, PF, SF, RP, BP, VT). The development of any renal complication was related to decrements in five SF-36 scales (GH, PF, SE RP, VT) while the appearance of any neuropathy complication was associated with a decline in four SF-36 scales (GH, PF, PR, VT). These results imply that six of the SF-36 scales are responsive to the development of diabetes complications over time among elderly veterans, supporting their use in longitudinal research. Renal and neuropathy complications have the greatest effects on the SF-36. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. RP Ahroni, JH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. NR 19 TC 50 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2000 VL 14 IS 1 BP 31 EP 39 DI 10.1016/S1056-8727(00)00066-0 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340ED UT WOS:000088519400006 PM 10925064 ER PT J AU Sagarin, MJ Brown, DFM Nadel, ES AF Sagarin, MJ Brown, DFM Nadel, ES TI Respiratory distress and leg pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID ACUTE PULMONARY-EMBOLISM; PATENT FORAMEN OVALE; HELICAL CT; SPIRAL CT; NONINVASIVE VENTILATION; PARADOXICAL EMBOLISM; DIAGNOSIS; ANGIOGRAPHY; ECHOCARDIOGRAPHY; STREPTOKINASE C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JAN PY 2000 VL 18 IS 1 BP 95 EP 100 DI 10.1016/S0736-4679(99)00167-5 PG 6 WC Emergency Medicine SC Emergency Medicine GA 274BN UT WOS:000084744000020 PM 10645846 ER PT J AU Brown, D Breton, S AF Brown, D Breton, S TI H+V-ATPase-dependent luminal acidification in the kidney collecting duct and the epididymis/vas deferens: Vesicle recycling and transcytotic pathways SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE intercalated cell; H+V-ATPase; proton pump; anion exchanger; carbonic anhydrase; LGP120; kidney; epididymis ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; SECRETING EPITHELIAL-CELLS; PLASMA-MEMBRANE DOMAINS; MALE REPRODUCTIVE-TRACT; INTERCALATED CELLS; RAT-KIDNEY; BICARBONATE TRANSPORT; CARBONIC-ANHYDRASE; ANION-EXCHANGER; ALKALI LOADS AB Many vertebrate transporting epithelia contain characteristic 'mitochondria-rich' cells that express high levels of a vacuolar proton-pumping ATPase (H+V-ATPase) on their plasma membrane and on intracellular vesicles. In the kidney cortex, A-cells and B-cells are involved in proton secretion and bicarbonate secretion, respectively, in the distal nephron and collecting duct. A-cells have an H+V-ATPase on their apical plasma membrane and on intracellular vesicles, whereas the cellular location of the H+V-ATPase can be apical, basolateral, bipolar or diffuse in B-cells. The rat epididymis and vas deferens also contain a distinct population of H+V-ATPase-rich epithelial cells. These cells are involved in generating a low luminal pH, which is involved in sperm maturation and in maintaining sperm in an immotile state during their passage through the epididymis and vas deferens, In both kidney and reproductive tract, H+V-ATPase-rich cells have a high rate of apical membrane recycling, H+V-ATPase molecules are transported between the cell surface and the cytoplasm in vesicles that have a well-defined 'coat' structure formed of the peripheral V-1 subunits of the H+V-ATPase. In addition, we propose that B-type intercalated cells have a transcytotic pathway that enables them to shuttle H+V-ATPase molecules from apical to basolateral plasma membrane domains. This hypothesis is supported by data showing that A-cells and B-cells have different intracellular trafficking pathways for LGP120, a lysosomal glycoprotein. LGP120 was found both on the basolateral plasma membrane and in lysosomes in B-cells, whereas no LGP120 was detectable in the plasma membrane of A-cells. We propose that the 'polarity reversal' of the H+V-ATPase in B-intercalated cells is mediated by a physiologically regulated transcytotic pathway that may be similar to that existing in some other cell types. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. FU NIDDK NIH HHS [DK 42956, DK 38452] NR 63 TC 123 Z9 126 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JAN PY 2000 VL 203 IS 1 BP 137 EP 145 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 277ZG UT WOS:000084963000016 PM 10600682 ER PT J AU Doukas, AG Bamberg, M Gillies, R Evans, R Kollias, N AF Doukas, AG Bamberg, M Gillies, R Evans, R Kollias, N TI Spectroscopic determination of skin viability. A predictor of postmortem interval SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; postmortem interval; time of death; skin viability; fluorescence spectroscopy; fluorescein diacetate; ethidium bromide ID PERCUTANEOUS-ABSORPTION; CELL-GROWTH; TIME; CARCINOMA; DEATH; ASSAY; RATS AB We have demonstrated that skin viability decreases at a measurable rate following death in an animal model. The decreased skin viability was measured by fluorescein diacetate and ethidium bromide using fluorescence emission spectroscopy. There is significant decrease of the fluorescence intensity of the fluorescein diacetate assay between the 1-4 h, the 6-24 h, and the >40 h time points postmortem. For times between 6-24 h and >40 h postmortem the ethidium bromide assay showed consistent and significant increases in signal. The fluorescence measurements in this study showed that under the experimental conditions the time of death could be determined for <4, 6-24 and >40 h potmotrem. The application of these assays in the field will require further study of the environmental factors. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Off Chief Med Examiner, Boston, MA USA. RP Kollias, N (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, BHX 630, Boston, MA 02114 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 2000 VL 45 IS 1 BP 36 EP 41 PG 6 WC Medicine, Legal SC Legal Medicine GA 293BB UT WOS:000085830700007 PM 10641917 ER PT J AU Silva, JA Leong, GB Weinstock, R Gonzales, CL AF Silva, JA Leong, GB Weinstock, R Gonzales, CL TI A case of Cotard's syndrome associated with self-starvation SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; Cotard's syndrome; major depressive disorder; self-destructive behavior; self-starvation; mental disorder; forensic psychiatry ID DELUSIONAL MISIDENTIFICATION; CAPGRAS SYNDROME AB Cotard's syndrome is a psychotic condition often associated with nihilistic delusions. This syndrome can be associated with destructive behaviors directed at the self and/or others. In this report we highlight the psychiatric-legal issues involving a case of Cotard's syndrome associated with self-starvation. C1 Palo Alto Vet Hlth Care Syst, Menlo Pk Div, Palo Alto, CA USA. Western State Hosp, Tacoma, WA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Silva, JA (reprint author), POB 20928, San Jose, CA 95160 USA. NR 24 TC 8 Z9 8 U1 0 U2 5 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 2000 VL 45 IS 1 BP 188 EP 190 PG 3 WC Medicine, Legal SC Legal Medicine GA 293BB UT WOS:000085830700027 PM 10641937 ER PT J AU Abdel-Fattah, G Yoffe, B Krishnan, B Khaoustov, V Itani, K AF Abdel-Fattah, G Yoffe, B Krishnan, B Khaoustov, V Itani, K TI MDM2/p53 protein expression in the development of colorectal adenocarcinoma SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE mdm2 oncogene; p53; colorectal cancer ID TUMOR-SUPPRESSOR GENE; SOFT-TISSUE TUMORS; WILD-TYPE P53; IMMUNOHISTOCHEMICAL EXPRESSION; HUMAN SARCOMAS; AMPLIFICATION; CANCER; PRODUCT; TRANSACTIVATION; PROGRESSION AB The murine double minutes 2 (MDM2) oncoprotein inhibits p53-mediated tumor suppression. MDM2 has been shown. to be overexpressed in sarcomas and more recently was implicated in the pathogenesis of carcinomas. The purpose of this study was to determine the expression pattern of MDM2 in adenomas and colorectal adenocarcinomas and decide whether there is a correlation between MDM2 and p53 protein status. Paraffin-embedded tissues from 52 colorectal cancer (CRC) specimens and their adjacent normal tissue (N-CRC) were studied. In addition, 56 sporadic adenomas were investigated for the im munohistochemical expression of MDM2 and p53 proteins. Immunoreactivity of p53 indicating p53 gene mutation (p53 +) was significantly higher in CRC (44 %) compared to adenomas (23.2 %) (P <0.01). None of the N-CRC specimens expressed the immunoreactive p53 protein. MDM2 overexpression (MDM2 +) was similar in adenomas (30.3 %) and CRC (25 %), but only 2 (3.8 %) of 52 N-CRC specimens showed overexpression of MDM2. In most cases MDM2 expression was associated with negative p53 expression (wild-type p53) in both adenomas (r = 0.59, P <0.001) and CRC (r = 0.69, P <0.0001). No correlation was found between MDM2, p53 expression, and either the histologic grade, nodal stage or morphology of the tumors. There is greater p53 mutation in CRC compared to adenomas and N-CRC. The data indicate that MDM2 is overexpressed in CRC and is significantly associated with wild-type p53 compared to N-CRC specimens from the same patient. The MDM2 expression pattern is similar in adenomas and CRC, which may suggest that MDM2 overexpression is an early event in the progression of CRC. C1 Houston VA Med Ctr, DeBakey Dept Surg, Houston, TX USA. Houston VA Med Ctr, Dept Med, Houston, TX USA. Houston VA Med Ctr, Dept Pathol, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Itani, K (reprint author), VAMC, Dept Surg, 112A, Houston, TX 77030 USA. NR 32 TC 21 Z9 22 U1 0 U2 1 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN-FEB PY 2000 VL 4 IS 1 BP 109 EP 114 DI 10.1016/S1091-255X(00)80041-4 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 278NR UT WOS:000084996300020 PM 10631371 ER PT J AU Hermida, R Vesely, D Kanabrocki, E Bremner, F Third, J Ryan, M AF Hermida, R Vesely, D Kanabrocki, E Bremner, F Third, J Ryan, M TI Circadian pattern in serum atrial natriuretic prohormones in aging male subjects SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract C1 Univ Vigo, Bioengn & Chronobiol Labs, Vigo, Spain. Univ S Florida, Hlth Sci Ctr, Tampa, FL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. MacNeal Card Grp, Berwyn, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PY 2000 VL 18 SU 4 BP S64 EP S64 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 366HW UT WOS:000090000800334 ER PT J AU Siri, F Dolgilevich, S Atlas, S AF Siri, F Dolgilevich, S Atlas, S TI Use of microdialysis to assess interstitial fluid angiotensin II concentration in the rat heart SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract C1 Bronx Vet Affairs Med Ctr, Hypertens Res Lab, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PY 2000 VL 18 SU 4 BP S21 EP S21 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 366HW UT WOS:000090000800104 ER PT J AU Kol, A Lichtman, AH Finberg, RW Libby, P Kurt-Jones, EA AF Kol, A Lichtman, AH Finberg, RW Libby, P Kurt-Jones, EA TI Cutting edge: Heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; HUMAN-MONOCYTES; INTERLEUKIN-1 SECRETION; INFECTIOUS AGENTS; DROSOPHILA TOLL; MESSENGER-RNA; LIPOPOLYSACCHARIDE; LPS; RECOGNITION; EXPRESSION AB Heat shock proteins (HSP), highly conserved across species, are generally viewed as intracellular proteins thought to serve protective functions against infection and cellular stress. Recently, we have reported the surprising finding that human and chlamydial HSP60, both present in human atheroma, can activate vascular cells and macrophages, However, the transmembrane signaling pathways by which extracellular HSP60 may activate cells remains unclear. CD14, the monocyte receptor for LPS, binds numerous microbial products and can mediate activation of monocytes/macrophages and endothelial cells, thus promoting the innate immune response. We show here that human HSP60 activates human PBMC and monocyte derived macrophages through CD14 signaling and p38 mitogen-activated protein kinase, sharing this pathway with bacterial LPS, These findings provide further insight into the molecular mechanisms by which extracellular HSP may participate in atherosclerosis and other inflammatory disorders by activating the innate immune system. C1 Harvard Univ, Program Infect Dis D1440, Sch Med,Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Cardiovasc Div, Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. RP Kurt-Jones, EA (reprint author), Harvard Univ, Program Infect Dis D1440, Sch Med,Dept Adult Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NHLBI NIH HHS [P01HL48743, P50-HL56985]; NIAID NIH HHS [R01AI31628] NR 43 TC 371 Z9 389 U1 1 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 13 EP 17 PG 5 WC Immunology SC Immunology GA 266VP UT WOS:000084321200004 PM 10604986 ER PT J AU Appleman, LJ Berezovskaya, A Grass, I Boussiotis, VA AF Appleman, LJ Berezovskaya, A Grass, I Boussiotis, VA TI CD28 costimulation mediates T cell expansion via IL-2-independent and IL-2-dependent regulation of cell cycle progression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; MULTIORGAN TISSUE DESTRUCTION; B-CELLS; POSTTRANSCRIPTIONAL REGULATION; RETINOBLASTOMA PROTEIN; DNA-REPLICATION; LYMPHOCYTES-T; P27(KIP1); ACTIVATION; MICE AB In the presence of TCR ligation by Ag, CD28 pathway mediates the most potent costimulatory signal for T cell activation, cytokine secretion, and T cell expansion, Although CD28 costimulation promotes T cell expansion due to IL-2 secretion and subsequent signaling via the IL-2 receptor, recent studies indicate that the dramatic T cell expansion mediated through the unopposed CD28 stimulation in CTLA4-deficient mice is IL-2 independent. Therefore, we sought to dissect the effects of CD28 and IL-2 receptor pathways on cell cycle progression and determine the molecular mechanisms by which the CD28 pathway regulates T cell expansion, Here we show that CD28 costimulation directly regulates T cell cycle entry and progression through the G(1) phase in an IL-2-independent manner resulting in activation of cyclin D2-associated cdk4/cdk6 and cyclin E-associated cdk2. Subsequent progression into the S phase is mediated via both IL-2-dependent and IL-2-independent mechanisms and, although in the absence of IL-2 the majority of T cells are arrested at the G(1)/S transition, a significant fraction of them progresses into the S phase. The key regulatory mechanism for the activation of cyclin-cdk complexes and cell cycle progression is the down-regulation of p27(kip1) cdk inhibitor, which is mediated at the posttranscriptional level by its ubiquitin-dependent degradation in the proteasome pathway Therefore, CD28 costimulation mediates T cell expansion in an IL-2-independent and IL-2 dependent manner and regulates cell cycle progression at two distinct points: at the early G(1) phase and at the G(1)/S transition. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Med Oncol, Smith 852,44 Binney St, Boston, MA 02115 USA. OI Appleman, Leonard/0000-0003-4951-7388 FU NHLBI NIH HHS [HL 54785]; NIAID NIH HHS [AI 41584, AI 43552] NR 77 TC 126 Z9 133 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 144 EP 151 PG 8 WC Immunology SC Immunology GA 266VP UT WOS:000084321200023 PM 10605005 ER PT J AU Stolina, M Sharma, S Lin, Y Dohadwala, M Gardner, B Luo, J Zhu, L Kronenberg, M Miller, PW Portanova, J Lee, JC Dubinett, SM AF Stolina, M Sharma, S Lin, Y Dohadwala, M Gardner, B Luo, J Zhu, L Kronenberg, M Miller, PW Portanova, J Lee, JC Dubinett, SM TI Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL LUNG-CANCER; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ESTABLISHED MURINE TUMORS; IFN-GAMMA PRODUCTION; HUMAN COLON-CANCER; CLASS-I EXPRESSION; GENE-THERAPY; EFFECTIVE ERADICATION; PROSTAGLANDIN E(2); DENDRITIC CELLS AB Cyclooxygenase-2 (COX-2), the enzyme at the rate-limiting step of prostanoid production, has been found to be overexpressed in human lung cancer. To evaluate lung tumor COX-2 modulation of antitumor immunity, we studied the antitumor effect of specific genetic or pharmacological inhibition of COX-2 in a murine Lewis lung carcinoma (3LL) model. Inhibition of COX-2 led to marked lymphocytic infiltration of the tumor and reduced tumor growth. Treatment of mice with anti-PGE(2) mAb replicated the growth reduction seen in tumor-bearing mice treated with COX-2 inhibitors. COX-2 inhibition was accompanied by a significant decrement in IL-10 and a concomitant restoration of IL-12 production by APCs, Because the COX-2 metabolite PGE2 is a potent inducer of IL-10, it was hypothesized that COX-2 inhibition led to antitumor responses by down-regulating production of this potent immunosuppressive cytokine. In support of this concept, transfer of IL-10 transgenic T lymphocytes that overexpress IL-10 under control of the IL-2 promoter reversed the COX-2 inhibitor-induced antitumor response. We conclude that abrogation of COX-2 expression promotes antitumor reactivity by restoring the balance of IL-10 and IL-12 in vivo. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Dept Med,Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Wadsworth Pulm Lab, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. GD Searle & Co, St Louis, MO 63167 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Dept Med,Jonsson Comprehens Canc Ctr, W111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA71818] NR 70 TC 352 Z9 374 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 361 EP 370 PG 10 WC Immunology SC Immunology GA 266VP UT WOS:000084321200049 PM 10605031 ER PT J AU van den Brink, MRM Moore, E Horndasch, KJ Crawford, JM Hoffman, J Murphy, GF Burakoff, SJ AF van den Brink, MRM Moore, E Horndasch, KJ Crawford, JM Hoffman, J Murphy, GF Burakoff, SJ TI Fas-deficient lpr mice are more susceptible to graft-versus-host disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; MRL-LPR/LPR MICE; CELL-MEDIATED CYTOTOXICITY; COLONY-STIMULATING FACTOR; INDUCED APOPTOSIS; IFN-GAMMA; T-CELLS; DIFFERENTIAL EXPRESSION; LIGAND INTERACTIONS AB The Fas/Fas ligand (FasL) pathway is involved in a variety of regulatory mechanisms that could be important for the development of graft-vs-host disease (GVHD) after bone marrow transplantation (BR IT), such as cytolysis of target cells by cytotoxic T cells, regulation of inflammatory responses, peripheral deletion of autoimmune cells, costimulation of T cells, and activation-induced cell death. To further evaluate the role of Fas/FasL in the complex pathophysiology of GVHD, we used Fas-deficient B6.lpr mice as recipients in a MHC-matched minor histocompatibility Ag-mismatched murine model for GVHD after allogeneic BMT (C3H.SW --> B6), We found a significantly higher morbidity and mortality from GVHD compared with control B6 recipients. In contrast, B6.lpr recipients had very little hepatic GVHD, although all other specific GVHD target organs (skin, intestines, and thymus) were more severely affected than in the control B6 recipients. B6,lpr recipients with GVHD demonstrated intact donor lymphoid engraftment and an increase in expansion of donor T cells and monocytes/macrophages compared with control B6 recipients. Serum levels of IFN-gamma and TNF-alpha were higher in B6,lpr recipients than in control B6 recipients, and monocytes/macrophages in B6.lpr recipients appeared more sensitized. B6,lpr recipients had more residual peritoneal macrophages after BMT, and peritoneal macrophages from B6.lpr mice could induce a greater proliferative response from C3H.SW splenocytes, This study demonstrates that the expression of Fas in the recipient is required for GVHD of the liver, but show's unexpected consequences when host tissues lack the expression of Fas for the development of GVHD in other organs and systemic GVHD. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Thomas Jefferson Med Ctr, Dept Pathol, Philadelphia, PA 19107 USA. RP van den Brink, MRM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Box 111,1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [5PO1 CA39542, R01 CA40358] NR 76 TC 45 Z9 45 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 469 EP 480 PG 12 WC Immunology SC Immunology GA 266VP UT WOS:000084321200062 PM 10605044 ER PT J AU Siegel, R AF Siegel, R TI How short can courses be in lower respiratory tract infections? SO JOURNAL OF INTERNATIONAL MEDICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Congress on Infectious Diseases (ICID) CY APR 10-13, 2000 CL BUENOS AIRES, ARGENTINA DE community-acquired pneumonia; antibiotics; short-course therapy; cefuroxime; cefuroxime axetil; switch therapy; sequential therapy; step-down therapy ID COMMUNITY-ACQUIRED PNEUMONIA; CEFUROXIME AXETIL; EARLY SWITCH; THERAPY; ANTIBIOTICS; MANAGEMENT; PENICILLIN; DISCHARGE; OUTCOMES AB Prospective clinical studies conducted over the last 10 years provide data on which to base decisions regarding the treatment of community-acquired pneumonia (CAP), including the need for hospitalization, optimal timing of the switch from intravenous to oral antibiotic therapy and the discharge of patients. Validated treatment algorithms, such as the classification of community-acquired pneumonia, now enable decisions to be made on which patients with CAP require hospitalization, as well as identifying those who will benefit from early switch therapy Generally, unstable CAP patients are suitable candidates for early switch therapy, which consists of rapid initiation of 1 - 2 days' intravenous therapy followed by 5 days' oral therapy, with early discharge from hospital after the receipt of one or two doses of oral antibiotic. Studies with intravenous cefuroxime and followed by oral cefuroxime axetil suggest this regimen is both effective and well tolerated as rapid switch therapy and has the potential to reduce overall healthcare costs and improve patient satisfaction. C1 Med ICU, Bronx Vet Affairs Med Ctr, Dept Pulm & Crit Care Med, Bronx, NY 10468 USA. RP Siegel, R (reprint author), Med ICU, Bronx Vet Affairs Med Ctr, Dept Pulm & Crit Care Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 26 TC 2 Z9 3 U1 0 U2 0 PU CAMBRIDGE MED PUBL PI WORTHING PA WICKER HOUSE, HIGH ST, WORTHING BN11 1DJ, W SUSSEX, ENGLAND SN 0300-0605 J9 J INT MED RES JI J. Int. Med. Res. PY 2000 VL 28 SU 1 BP 37A EP 47A PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 371KB UT WOS:000165177200005 PM 11092228 ER PT J AU Lerner, LH Qureshi, AA Reddy, BV Lerner, EA AF Lerner, LH Qureshi, AA Reddy, BV Lerner, EA TI Nitric oxide synthase in toxic epidermal necrolysis and Stevens-Johnson syndrome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE apoptosis; immunoenzyme techniques; nitric oxide synthase; nitric oxide; polymerase chain reaction; reverse transcriptase; Stevens-Johnson syndrome; toxic epidermal necrolysis ID VERSUS-HOST DISEASE; LANGERHANS CELLS; LYELL SYNDROME; APOPTOSIS; INHIBITION AB Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe cutaneous drug reactions of unknown mechanism. Nitric oxide can cause apoptosis and necrosis. The inducible form of nitric oxide synthase generates large amounts of nitric oxide and has been described in human skin. We propose that a large burst of nitric oxide in toxic epidermal necrolysis and Stevens-Johnson syndrome may cause the epidermal apoptosis and necrosis. Skin biopsies were taken from seven patients with actively progressing Stevens-Johnson syndrome or toxic epidermal necrolysis. Expression of inducible nitric oxide synthase was examined by reverse transcription-polymerase chain reaction and by immunoperoxidase staining for inducible nitric oxide synthase protein. Messenger RNA for inducible nitric oxide synthase was detected by reverse transcription-polymerase chain reaction and confirmed by the sequencing of polymerase chain reaction products. Strong staining for inducible nitric oxide synthase was observed in inflammatory cells in the lower epidermis and upper dermis. Diffuse, weaker staining was observed in keratinocytes. Expression of inducible nitric oxide synthase is consistent with the hypothesis that nitric oxide mediates the epidermal necrosis in toxic epidermal necrolysis and provides a potential target for therapeutic intervention. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Lerner, LH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 820,Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R0I-AR42005, R0I-AR44510-01] NR 27 TC 45 Z9 49 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 196 EP 199 DI 10.1046/j.1523-1747.2000.00816.x PG 4 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700032 PM 10620138 ER PT J AU Carven, GJ Sato, AK Santambrogio, L Strominger, JL Stern, LJ AF Carven, GJ Sato, AK Santambrogio, L Strominger, JL Stern, LJ TI Dendritic cells secrete a protease activity capable of processing intact antigen into antigenic peptides for presentation to T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 211 EP 211 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700062 ER PT J AU Santambrogio, L Sato, AK Carven, GJ Dorf, ME Strominger, JL Stern, LJ AF Santambrogio, L Sato, AK Carven, GJ Dorf, ME Strominger, JL Stern, LJ TI Extracellular antigen processing and presentation by dendritic cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 214 EP 214 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700080 ER PT J AU Myatkowskj, P Seeley, RJ Havel, PJ Baskin, DG Matsumoto, AM Wilkinson, CW Schwartz, MW AF Myatkowskj, P Seeley, RJ Havel, PJ Baskin, DG Matsumoto, AM Wilkinson, CW Schwartz, MW TI Hypothalamic melanin concentrating hormone is a target for the anorexic effect of estrogen. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Cincinnati, Cincinnati, OH USA. Univ Calif Davis, Davis, CA 95616 USA. RI Schwartz, Michael/H-9950-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 65 BP 12A EP 12A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600075 ER PT J AU Kletke, ML Barsness, S Drolet, G Moe, KE Schwartz, RS Vitiello, MV Merriam, GR AF Kletke, ML Barsness, S Drolet, G Moe, KE Schwartz, RS Vitiello, MV Merriam, GR TI Effects of gender and estrogen replacement status on responses to GH-releasing hormone treatment in normal aging. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound HCS, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 337 BP 62A EP 62A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600344 ER PT J AU Sohn, EH Wolden-Hanson, T Marck, BT Matsumoto, AM AF Sohn, EH Wolden-Hanson, T Marck, BT Matsumoto, AM TI Testosterone (T)-induced increase in neuropeptide-Y (NPY) gene expression is attenuated in old compared to young male Brown Norway rats: Contribution of T to age-related decline in NPY gene expression. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 336 BP 62A EP 62A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600343 ER PT J AU Ericksen, SE Craft, S Leverenz, JB Roth, RA Cook, DG AF Ericksen, SE Craft, S Leverenz, JB Roth, RA Cook, DG TI Insulin degrading enzyme levels in Alzheimer's disease. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 422 BP 77A EP 77A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600426 ER PT J AU Nowbar, S Burkart, KM Zwillich, CW AF Nowbar, S Burkart, KM Zwillich, CW TI Hypoventilation among obese inpatients: A common and under-diagnosed problem. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 445 BP 81A EP 81A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600449 ER PT J AU Smolik, S Rodriquez, A Burns, S AF Smolik, S Rodriquez, A Burns, S TI A cross-sectional study of non-radicular, mecanical neck pain and cervical strength. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Rehabil Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 451 BP 83A EP 83A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600455 ER PT J AU Clark, RA AF Clark, RA TI Neutrophil respiratory burst oxidase in hose defenses. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 747 BP 138A EP 138A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600747 ER PT J AU deAndrade, JA Young, KR McGiffin, D Zorn, G Alexander, CB Christie, JD Jackson, R AF deAndrade, JA Young, KR McGiffin, D Zorn, G Alexander, CB Christie, JD Jackson, R TI Reactive nitrogen species correlate with airway inflammation in lung transplants. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Alabama, Birmingham VAMC, Birmingham, AL USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 936 BP 174A EP 174A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600936 ER PT J AU Kurent, JE Pennypacker, L AF Kurent, JE Pennypacker, L TI Enhancement of physician education in palliative and end-of-life care. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Med Univ S Carolina, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 964 BP 179A EP 179A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600964 ER PT J AU Pearson, AM Baksa, KA Harikrishnan, A Dearolf, CR Ezekowitz, RAB AF Pearson, AM Baksa, KA Harikrishnan, A Dearolf, CR Ezekowitz, RAB TI Identification and characterization of phagocytosis genes in Drosophila melanogaster SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pediat, Immunol Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 24 BP 14 EP 14 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200027 ER PT J AU Tager, AM Dufour, JH Goodarzi, K Bercury, SD von Andrian, UH Luster, AD AF Tager, AM Dufour, JH Goodarzi, K Bercury, SD von Andrian, UH Luster, AD TI BLTR mediates leukotriene B-4-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 70 BP 21 EP 21 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200071 ER PT J AU Takahashi, K Gordon, JS Ming, H Sastry, K Motwana, M Epstein, JE Thiel, S Jensenius, JC Ezekowitz, RAB AF Takahashi, K Gordon, JS Ming, H Sastry, K Motwana, M Epstein, JE Thiel, S Jensenius, JC Ezekowitz, RAB TI Mannose binding protein A null mice display enhanced survival in an acute septic peritonitis model SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 121 BP 30 EP 30 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200121 ER PT J AU Exley, M Bigley, N Cheng, O Tahir, S Koezuka, Y Taniguchi, M Bubley, G Alt, F Snapper, S Balk, S AF Exley, M Bigley, N Cheng, O Tahir, S Koezuka, Y Taniguchi, M Bubley, G Alt, F Snapper, S Balk, S TI Role of CD1-reactive T cells in Th1-like responses. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Wright State Univ, Dayton, OH 45435 USA. Harvard Univ, Childrens Hosp, Ctr Blood Res, HHMI, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02116 USA. Kirin Brewery Co Ltd, Gunma, Japan. Chiba Univ, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 134 BP 32 EP 32 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200136 ER PT J AU Hou, R Cheng, O Tahir, SMA Gausling, R Greenfield, E Rache, F Strominger, JL Balk, SP Wilson, SB Exley, MA AF Hou, R Cheng, O Tahir, SMA Gausling, R Greenfield, E Rache, F Strominger, JL Balk, SP Wilson, SB Exley, MA TI Characterization of a monoclonal antibody which recognizes CD1d reactive NK T cell SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 136 BP 32 EP 32 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200137 ER PT J AU Weber, GF Ashkar, S AF Weber, GF Ashkar, S TI Stress response genes: the genes that make cancer metastasize SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE cancer; metastasis; stress response; posttranslational modification; knockout mouse ID INTERCELLULAR-ADHESION MOLECULE-1; SELECTIN-DEFICIENT MICE; PLASMINOGEN-ACTIVATOR RECEPTOR; CYTOTOXIC T-LYMPHOCYTES; HUMAN BREAST-CANCER; CELL-ADHESION; TUMOR-CELLS; P-SELECTIN; MATRIX METALLOPROTEINASES; IMMUNE-RESPONSES AB Cancer is characterized by dysregulated growth control, overcoming of replicative senescence, and metastasis formation. The topology of cancer spread is mediated by a set of developmentally nonessential genes which are physiologically involved in stress responses, inflammation, wound healing, and neovascularization. The function of these gene products is extensively modified posttranscriptionally. In cancer, metastasis genes are dysregulated at the levels of expression or splicing. These genes constitute a unique group of cancer-related biomolecules. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Orthoped Surg,Lab Skeletal Disorders & Rehab, Boston, MA 02115 USA. RP Weber, GF (reprint author), New England Med Ctr, Dept Radiat Oncol, 750 Washington St,NEMC 824, Boston, MA 02111 USA. FU NCI NIH HHS [CA76176] NR 48 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PY 2000 VL 78 IS 8 BP 404 EP 408 DI 10.1007/s001090000138 PG 5 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 369YM UT WOS:000165095400004 PM 11097109 ER PT J AU Klein, L Kyewski, B AF Klein, L Kyewski, B TI "Promiscuous" expression of tissue antigens in the thymus: a key to T-cell tolerance and autoimmunity? SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE T cell tolerance; thymus; promiscuous gene expression ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS; SELF-ANTIGENS; INTRATHYMIC EXPRESSION; EXTRATHYMIC TOLERANCE; PERIPHERAL TOLERANCE; PROTEOLIPID PROTEIN; CLONAL ELIMINATION; CROSS-PRESENTATION; MYASTHENIA-GRAVIS C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. German Canc Res Ctr, Tumor Immunol Program, D-69120 Heidelberg, Germany. RP Klein, L (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 1 Jimmy Fund Way, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011 NR 99 TC 73 Z9 73 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PY 2000 VL 78 IS 9 BP 483 EP 494 DI 10.1007/s001090000146 PG 12 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 381CQ UT WOS:000165745100004 PM 11140374 ER PT J AU Henderson, DC AF Henderson, DC TI Competence and character through life. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2000 VL 188 IS 1 BP 56 EP 57 DI 10.1097/00005053-200001000-00013 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 273WL UT WOS:000084732300012 ER PT J AU Sandhu, FA Martuza, RL AF Sandhu, FA Martuza, RL TI Craniofacial hemangiopericytoma associated with oncogenic osteomalacia: case report SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE hemangiopericytoma; oncogenic osteomalacia; octreotide scan ID TERM FOLLOW-UP; MENINGEAL HEMANGIOPERICYTOMA; TUMORS; MENINGIOMA AB A craniofacial hemangiopericytoma associated with oncogenic osteomalacia is described and the literature is reviewed. A 46 year-old male with multiple fractures and hypophosphatemia was found to have a craniofacial mass extending from the right ethmoid sinus into the right frontal lobe. Initial detection of the tumor was made with an (111)Indium-pentreotide scan (Octreoscan). Gross total resection of the tumor was achieved and the patient received postoperative radiation therapy. One year after surgery, the patient remains free of tumor with significant increase in bone density and normal phosphate levels. This is the first report of a hemangiopericytoma invading the brain that was associated with paraneoplastic hypophosphatemia and osteomalacia. Also, this is the first reported detection of a hemangiopericytoma by an Octreoscan. Primary detection and secondary surveillance of hemangiopericytomas may be possible with serial Octreoscans. C1 Georgetown Univ, Med Ctr, Dept Neurosurg, Washington, DC 20007 USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, WHT502,55 Fruit St, Boston, MA 02114 USA. RI huang, hongqi/N-1473-2014 NR 23 TC 19 Z9 22 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PY 2000 VL 46 IS 3 BP 241 EP 247 DI 10.1023/A:1006352106762 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 331UB UT WOS:000088036100005 PM 10902855 ER PT J AU Salim, H Ferre, S Dalal, A Peterfreund, RA Fuxe, K Vincent, JD Lledo, PM AF Salim, H Ferre, S Dalal, A Peterfreund, RA Fuxe, K Vincent, JD Lledo, PM TI Activation of adenosine A(1) and A(2A) receptors modulates dopamine D-2 receptor-induced responses in stably transfected human neuroblastoma cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE intracellular calcium; adenosine receptors; dopamine receptors; stable transfection; basal ganglia; adenosine deaminase ID BASAL GANGLIA; INTEGRATIVE MECHANISM; CALCIUM CHANNELS; OPPOSING ACTIONS; SH-SY5Y CELLS; RAT; CURRENTS; STIMULATION; MEMBRANES; BINDING AB Adenosine can influence dopaminergic neurotransmission in the basal ganglia via postsynaptic interaction between adenosine A(2A) and dopamine D-2 receptors, We have used a human neuroblastoma cell line (SH-SY5Y) that was found to express constitutively moderate levels of adenosine A(1) and A(2A) receptors (similar to 100 fmol/mg of protein) to investigate the interactions of A(2A)/D-2 receptors, at a cellular level. After transfection with human D-2L receptor cDNA, SH-SY5Y cells expressed between 500 and 1,100 fmol of D-2 receptors/mg of protein. In membrane preparations, stimulation of adenosine A(2A) receptors decreased the affinity of dopamine D-2 receptors for dopamine. In intact cells, the calcium concentration elevation induced by KCI treatment was moderate, and dopamine had no effect on either resting intracellular free Ca2+ concentration ([Ca2+](i)) or KCl-induced responses. In contrast, pretreatment with adenosine deaminase for 2 days dramatically increased the elevation of [Ca2+](i) evoked by KCl, which then was totally reversed by dopamine. The effects induced by 48-h adenosine inactivation were mimicked by application of adenosine A(1) antagonists and could not be further reversed by acute activation of either A(1) or A(2A) receptors, Acute application of the selective A(1) receptor agonist CGS-21680 counteracted the D-2 receptor-induced [Ca2+](i) responses. The present study shows that SH-SY5Y cells are endowed with functional adenosine A(2A) and A(1) receptors and that A(2A) receptors exert an antagonistic acute effect on dopamine D-2 receptor-mediated functions. In contrast, A(1) receptors induce a tonic modulatory role on these dopamine functions. C1 Inst Alfred Fessard, CNRS, F-91198 Gif Sur Yvette, France. Univ Cadi Ayyad, Fac Sci, Dept Biol, Marrakech, Morocco. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, Stockholm, Sweden. CSIC, IIBB, Dept Neurochem, Barcelona, Spain. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Crit Care Clin 3, Boston, MA 02114 USA. RP Lledo, PM (reprint author), Inst Alfred Fessard, CNRS, Ave Terrasse, F-91198 Gif Sur Yvette, France. RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 NR 33 TC 55 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2000 VL 74 IS 1 BP 432 EP 439 DI 10.1046/j.1471-4159.2000.0740432.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 266HM UT WOS:000084294600049 PM 10617149 ER PT J AU Yao, JK Reddy, RD van Kammen, DP AF Yao, JK Reddy, RD van Kammen, DP TI Abnormal age-related changes of plasma antioxidant proteins in patients with schizophrenia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S78 EP S78 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200312 ER PT J AU Yao, JK Stanley, JA Reddy, R Keshavan, M Pettegrew, JW AF Yao, JK Stanley, JA Reddy, R Keshavan, M Pettegrew, JW TI Correlations of membrane phospholipids between peripheral and central measures SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S78 EP S78 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200311 ER PT J AU Klivenyi, P Andreassen, OA Ferrante, RJ Dedeoglu, A Mueller, G Lancelot, E Bogdanov, M Andersen, JK Jiang, DM Beal, MF AF Klivenyi, P Andreassen, OA Ferrante, RJ Dedeoglu, A Mueller, G Lancelot, E Bogdanov, M Andersen, JK Jiang, DM Beal, MF TI Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MPTP; 3-nitropropionic acid; malonate; oxidative damage; free radicals; glutathione; Parkinson's; Huntington's ID NEURONAL NITRIC-OXIDE; EXCITOTOXICITY IN-VIVO; HUNTINGTONS-DISEASE; OXIDATIVE STRESS; BUTHIONINE SULFOXIMINE; PARKINSONS-DISEASE; HYDROGEN-PEROXIDE; RAT-BRAIN; NEURODEGENERATIVE DISEASES; SUPEROXIDE-DISMUTASE AB Glutathione peroxidase (GSHPx) is a critical intracellular enzyme involved in detoxification of hydrogen peroxide (H2O2)to water. In the present study we examined the susceptibility of mice with a disruption of the glutathione peroxidase gene to the neurotoxic effects of malonate, 3-nitropropionic acid (3-NP), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Glutathione peroxidase knock-out mice showed no evidence of neuropathological or behavioral abnormalities at 2-3 months of age. Intrastriatal injections of malonate resulted in a significant twofold increase in lesion volume in homozygote GSHPx knock-out mice as compared to both heterozygote GSHPx knock-out and wild-type control mice. Malonate-induced increases in conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid, an index of hydroxyl radical generation, were greater in homozygote GSHPx knock-out mice as compared with both heterozygote GSHPx knock-out and wild-type control mice. Administration of MPTP resulted in significantly greater depletions of dopamine, 3,4-dihydroxybenzoic acid, and homovanillic acid in GSHPx knock-out mice than those seen in wild-type control mice. Striatal 3-nitrotyrosine (3-NT) concentrations after MPTP were significantly increased in GSHPx knock-out mice as compared with wild-type control mice. Systemic 3-NP administration resulted in significantly greater striatal damage and increases in 3-NT in GSHPx knockout mice as compared to wild-type control mice. The present results indicate that a knock-out of GSHPx may be adequately compensated under nonstressed conditions, but that after administration of mitochondrial toxins GSHPx plays an important role in detoxifying increases in oxygen radicals. C1 Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA USA. Univ So Calif, Dept Gerontol, Los Angeles, CA USA. Cornell Univ, Weill Med Med, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, WRN 408,32 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS10828, NS16367, NS31579] NR 58 TC 161 Z9 165 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2000 VL 20 IS 1 BP 1 EP 7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 271ET UT WOS:000084581800006 PM 10627575 ER PT J AU Nehring, RB Wischmeyer, E Doring, F Veh, RW Sheng, M Karschin, A AF Nehring, RB Wischmeyer, E Doring, F Veh, RW Sheng, M Karschin, A TI Neuronal inwardly rectifying K+ channels differentially couple to PDZ proteins of the PSD-95/SAP90 family SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inwardly rectifying; Kir channel; GIRK; postsynaptic density; chapsyns; MAGUK; yeast two-hybrid ID RECTIFIER POTASSIUM CHANNEL; NMDA RECEPTOR SUBUNITS; POSTSYNAPTIC DENSITY; FUNCTIONAL EXPRESSION; RAT-BRAIN; GUANYLATE KINASES; HUMAN HIPPOCAMPUS; MOLECULAR-BASIS; FASCICLIN-II; DOMAIN AB Several signaling proteins clustered at the postsynaptic density specialization in neurons harbor a conserved C-terminal PDZ domain recognition sequence (X-S/T-X-V/I) that mediates binding to members of the PSD-95/SAP90 protein family. This motif is also present in the C termini of some inwardly rectifying K+ (Kir) channels. Constitutively active Kir2 channels as well as G protein-gated Kir3 channels, which are fundamental for neuronal excitability, were analyzed as candidates for binding to PSD-95/SAP90 family members. Therefore C termini of Kir2.1(+), Kir2.3(+), Kir2.4(-), Kir3.1(-), Kir3.2(-), Kir3.3(-) and Kir3.4(-) subunits (+, motif present; -, motif absent) were used as baits in the yeast two-hybrid assay to screen for in vivo interaction with PDZ domains 1-3 of PSD-95/SAP90. In contrast to Kir2.1 and Kir2.3, all Kir3 fragments failed to bind PSD-95 in this assay, which was supported by the lack of coimmunoprecipitation and colocalization of the entire proteins in mammalian cells. A detailed analysis of interaction domains demonstrated that the C-terminal motif in Kir3 channels is insufficient for binding PDZ domains. Kir2.1 and Kir2.3 subunits on the other hand coprecipitate with PSD-95. When coexpressed in a bicistronic internal ribosome entry site expression vector in HEK-293 cells macroscopic and elementary current analysis revealed that PSD-95 suppressed the activity of Kir2.3 channels by >50%. This inhibitory action of PSD-95, which predominantly affects the single-channel conductance, is likely attributable to a molecular association with additional internal interaction sites in the Kir2.3 protein. C1 Max Planck Inst Biophys Chem, D-37070 Gottingen, Germany. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Karschin, A (reprint author), Max Planck Inst Biophys Chem, Fassberg 11, D-37070 Gottingen, Germany. NR 59 TC 90 Z9 95 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2000 VL 20 IS 1 BP 156 EP 162 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 271ET UT WOS:000084581800023 PM 10627592 ER PT J AU Braun, C Schweizer, R Elbert, T Birbaumer, N Taub, E AF Braun, C Schweizer, R Elbert, T Birbaumer, N Taub, E TI Differential activation in somatosensory cortex for different discrimination tasks SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortical reorganization; plasticity; learning; somatosensory evoked potentials; dipole source analysis; tactile sensation threshold; human ID ADULT OWL MONKEYS; CORTICAL REPRESENTATION; BRAILLE READERS; AREA 3B; REORGANIZATION; PLASTICITY; AMPUTATION; HUMANS; HAND; EEG AB Maps of the body surface in somatosensory cortex have been shown to be highly plastic, altering their configuration in response to changes in use of body parts. The current study investigated alterations in the functional organization of the human somatosensory cortex resulting from massed practice. Over a period of 4 weeks, subjects were given synchronous tactile stimulation of thumb (D1) and little finger (D5) for 1 hr/d. They had to identify the orientation of the stimuli. Neuroelectric source localization based on high-resolution EEG revealed that, when subjects received passive tactile stimulation of D1 or D5, the representations of the fingers in primary somatosensory cortex were closer together after training than before. There was also an apparently correlative tendency to anomalously mislocalize near-threshold tactile stimuli equally to the distant finger costimulated during training rather than preferentially to the finger nearest to the finger stimulated in a post-training test. However, when the stimulus discrimination had to be made, neuroelectric source imaging revealed that the digital representations of D1 and D5 were further apart after training than before. Thus, the same series of prolonged repetitive stimulations produced two different opposite effects on the spatial relationship of the cortical representations of the digits, suggesting that differential activation in the same region of somatosensory cortex is specific to different tasks. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Univ Konstanz, Dept Psychol, D-78457 Constance, Germany. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Braun, C (reprint author), MEG Ctr, Otfried Muller Str 7, D-72076 Tubingen, Germany. RI Elbert, Thomas/C-8556-2009; Braun, Christoph/E-4561-2010; Braun, Christoph/J-4160-2014 OI Braun, Christoph/0000-0002-7836-4010; Braun, Christoph/0000-0002-7836-4010 NR 23 TC 91 Z9 92 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 2000 VL 20 IS 1 BP 446 EP 450 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 271ET UT WOS:000084581800051 PM 10627620 ER PT J AU Spinner, RJ O'Driscoll, SW Jupiter, JB Goldner, RD AF Spinner, RJ O'Driscoll, SW Jupiter, JB Goldner, RD TI Unrecognized dislocation of the medial portion of the triceps: another cause of failed ulnar nerve transposition SO JOURNAL OF NEUROSURGERY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Society-for-Surgery-of-the-Hand CY SEP 03, 1999 CL BOSTON, MASSACHUSETTS SP Amer Soc Surg Hand DE failed ulnar nerve surgery; ulnar nerve transposition; snapping triceps; ulnar nerve dislocation ID CUBITAL TUNNEL-SYNDROME; SNAPPING TRICEPS; BRACHII MUSCLE; COMPLICATIONS; SURGERY; HEAD AB Object. Failed surgical treatment for ulnar neuropathy or neuritis due to dislocation of the ulnar nerve presents diagnostic and therapeutic challenges. The authors of this paper will establish unrecognized dislocation (snapping) of the medial portion of the triceps as a preventable cause of failed ulnar nerve transposition. Methods. Fifteen patients had persistent. painful snapping at the medial elbow after ulnar nerve transposition, which had been performed for documented ulnar nerve dislocation with or without ulnar neuropathy. The snapping was caused by a previously unrecognized dislocation of the medial portion of triceps over the medial epicondyle. Seven of the 15 patients also had persistent ulnar nerve symptoms. The comet diagnosis of snapping triceps was delayed for an average of 22 months after the initial ulnar nerve transposition. An additional surgical procedure was performed in nine of the 15 cases and, in part, consisted of lateral transposition or excision of the offending snapping medial portion of the triceps. Of the four patients in this group who had persistent neurological symptoms, submuscular transposition was performed in the two with more severe symptoms and treatment of the triceps alone was performed in the two with milder neurological symptoms. Excellent results were achieved in all surgically treated patients. Six patients declined additional surgery and experienced persistent snapping and/or ulnar nerve symptoms. Conclusions. Failure to recognize that dislocation of both the medial portion of the triceps and the ulnar nerve can exist concurrently may result in persistent snapping, elbow pain, and even ulnar nerve symptoms after a technically successful ulnar nerve transposition. C1 Mayo Clin, Dept Neurol Surg, Rochester, MN USA. Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. Duke Univ, Med Ctr, Div Orthopaed Surg, Durham, NC USA. RP Spinner, RJ (reprint author), St Marys Hosp, Mayo Clin, Dept Neurol Surg, Joseph 1-229E, Rochester, MN 55905 USA. OI O'Driscoll, Shawn/0000-0002-8225-3372 NR 26 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2000 VL 92 IS 1 BP 52 EP 57 DI 10.3171/jns.2000.92.1.0052 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 268ZP UT WOS:000084451500008 PM 10616082 ER PT J AU Quinones-Hinojosa, A Friedlander, RM Boyer, PJ Batchelor, TT Chiocca, EA AF Quinones-Hinojosa, A Friedlander, RM Boyer, PJ Batchelor, TT Chiocca, EA TI Solitary sciatic nerve lymphoma as an initial manifestation of diffuse neurolymphomatosis - Case report and review of the literature SO JOURNAL OF NEUROSURGERY LA English DT Article DE Burkittlike lymphoma; extranodal lymphoma; neurolymphomatosis; non-Hodgkin's lymphoma; sciatic nerve ID MALIGNANT-LYMPHOMAS; SYSTEM AB Solitary peripheral nerve lymphomas are exceedingly rare primary manifestations of diffuse peripheral nervous system or central nervous system (CNS) lymphomatosis. A 52-pear-old man presented with progressive weakness in gastrocnemius and anterior tibial muscle function, which was associated with radiating pain in the right leg. Magnetic resonance imaging studies revealed a solitary fusiform tumor, extending from the sciatic nerve, at the level of the lesser trochanter of the femur, into the posterior tibial nerve below the popliteal fossa. Intraoperative gross examination found that the tumor diffusely expanded the nerve, but did not extend from or into surrounding muscle or tendons. The final histological diagnosis was a solitary extranodal lymphoma (Burkittlike high-grade B-cen lymphoma). Postoperative staging did not reveal evidence of lymphomatous involvement of other organs, but additional chemo- and radiotherapies were administered. Four months after the surgical biopsy, the patient presented with a right facial nerve palsy. The results of cytological examination of cerebrospinal fluid were positive for the presence of atypical lymphocytes, which was consistent with apparently progressive neurolymphomatosis; however, the results of radiological studies were negative for systemic progression. The patient underwent intrathecal chemotherapy followed by systemic myelosuppressive chemotherapy with bone marrow rescue, but died of respiratory failure while still receiving treatment. Postmortem examination revealed extensive lymphomatosis in the peripheral nerves and spinal nerve roots without evidence of cranial nerve, CNS, or other organ system involvement. The aggressive biological characteristics of these tumors, their management, and pertinent literature are reviewed. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Cox Bldg Room 315, Boston, MA 02114 USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 20 TC 39 Z9 39 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 2000 VL 92 IS 1 BP 165 EP 169 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 268ZP UT WOS:000084451500023 PM 10616097 ER PT J AU Lee, KH Hajjar, RJ Matsui, T Choukroun, G Force, TL Rosenzweig, A AF Lee, KH Hajjar, RJ Matsui, T Choukroun, G Force, TL Rosenzweig, A TI Cardiac signal transduction SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASES; GROWTH-FACTOR-I; STAGE HEART-FAILURE; PHOSPHATIDYLINOSITOL 3-KINASE; MYOCARDIAL-INFARCTION; GENE-TRANSFER; MAP KINASES; CALCIUM; APOPTOSIS; STRESS C1 Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Sungkyunkwan Univ, Sch Med, Dept Nucl Med, Samsung Med Ctr, Seoul, South Korea. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp East, Cardiovasc Res Ctr, 149 13th St,4th Floor,Rm 4214, Boston, MA 02129 USA. EM rosenzweig@helix.mgh.harvard.edu RI Lee, Kyun Han/C-9648-2011; OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL59521, HL50361, HL57623] NR 50 TC 2 Z9 3 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JAN-FEB PY 2000 VL 7 IS 1 BP 63 EP 71 DI 10.1067/mnc.2000.103724 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 286DP UT WOS:000085428600009 PM 10698236 ER PT J AU Scrivani, SJ Moses, M Donoff, RB Kaban, LB AF Scrivani, SJ Moses, M Donoff, RB Kaban, LB TI Taste perception after lingual nerve repair SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 19, 1997 CL SEATTLE, WASHINGTON SP Amer Assoc Oral & Maxillofacial Surgeons ID INJURY AB Purpose: This retrospective study evaluates patients' perception of taste after lingual nerve injury and repair. It is hypothesized that return of taste is a distinct neurophysiologic phenomenon related to specialized taste physiology and it does not correlate with specific, objective sensory return. Patients and Methods: During 1995 to 1996, 30 patients underwent microsurgical repair of lingual nerve injuries. Of these, 22 patients met the inclusion criteria for this study. Chart review documented the date and cause of injury, sensory examination, injury classification, procedures, operative findings, and postoperative sensory examination. A telephone questionnaire addressed whole mouth taste perception with normal daily eating. The questions asked were: 1) Was your sense of taste changed or abnormal after your nerve injury? and 2) Did your sense of taste recover after nerve repair:, Results: All patients had a postinjury, prerepair sensory deficit on levels A, B, and C testing: neurotmesis (n = 14); and axonotmesis (n = 8). The mean time from injury to repair was 16 weeks (range, 3 to 41 weeks). Operative findings confirmed 12 Sunderland Class TV (partial transection) injuries and 10 Class V (complete transection) injuries. All patients had primary microsurgical repair without a nerve graft or entubulization. Postoperatively, 18 patients showed marked improvement in sensory testing at levels A, B and C, and 4 patients showed no significant change. A telephone interview regarding whole mouth taste perception indicated that 20 of 22 patients perceived changed, abnormal taste postinjury and pre-repair. Two patients reported normal taste perception. Postrepair, only 7 of 20 patients reported an increase or return of taste perception to a more normal level. The mean follow-up time was 80 weeks. Conclusion: Most patients (20 of 22) with lingual nerve injuries in this study perceived whole mouth taste as abnormal. After nerve repair, although 82% (18 of 22) of patients had improvement in somatosensory function, whole mouth taste was perceived as improved by only 35% (7 of 20). It is proposed that the perception of whole mouth taste may not be related to the ability to perceive multiple sensory modalities, but rather to special sensory (taste) modality perception. Also, central changes may occur in the special sensory fibers that impact on the brainstem nucleus for taste (nucleus solitarius) and therefore the patient's perception of taste. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA. NR 16 TC 18 Z9 18 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2000 VL 58 IS 1 BP 3 EP 5 DI 10.1016/S0278-2391(00)80003-8 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 270FC UT WOS:000084523900002 PM 10632158 ER PT J AU Louis, PJ Fugler, RC August, M AF Louis, PJ Fugler, RC August, M TI Mixed radiolucent/radiopaque lesion of the maxilla SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID DESMOPLASTIC VARIANT; AMELOBLASTOMA C1 Univ Alabama, Sch Dent, Dept Oral & Maxillofacial Surg, Birmingham, AL 35294 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA USA. RP Louis, PJ (reprint author), Univ Alabama, Sch Dent, Dept Oral & Maxillofacial Surg, 1919 7th Ave S, Birmingham, AL 35294 USA. NR 10 TC 6 Z9 6 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2000 VL 58 IS 1 BP 86 EP 90 DI 10.1016/S0278-2391(00)80022-1 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 270FC UT WOS:000084523900021 PM 10632170 ER PT J AU Sang, CN AF Sang, CN TI NMDA-Receptor antagonists in neuropathic pain: Experimental methods to clinical trials SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE NMDA-receptor antagonists; dextromethorphan; ketamine; analgesia; hyperalgesia; allodynia; capsaicin ID DOUBLE-BLIND; POSTHERPETIC NEURALGIA; KETAMINE; DEXTROMETHORPHAN; CAPSAICIN; PLACEBO; HYPERALGESIA; SENSITIZATION; ALFENTANIL; ALLODYNIA AB Recent clinical data suggest that chronic pain due to ne,ve or soft tissue injury may result in the sensitization of the central nervous system, mediated in part by the excitatory amino acids, glutamate and aspartate. Only a handful of N-methyl-D-aspartate antagonists are clinically available. These include ketamine, dextromethorphan, memantine, and amantadine, as well as three clinically used opioids (methadone, dextropropoxyphene, and ketobemidone). This review summarizes the single-dose efficacy of the first two compounds in the treatment of experimental and neuropathic pain. In all examples presented here, NMDA-receptor antagonists with affinity at the phencyclidine site have been shown to modulate pain and hyperalgesia but are limited by dose-limiting side effects. Thus, provided their therapeutic ratio is favorable, NMDA-receptor antagonists may be effective in the treatment of some types of chronic pain. J Pain Symptom Manage 2000;19:S21-S25. (C) U.S. Cancer Pain Relief Committee, 2000. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. RP Sang, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, 55 Fruit St, Boston, MA 02114 USA. NR 18 TC 72 Z9 73 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2000 VL 19 IS 1 SU S BP S21 EP S25 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 279XU UT WOS:000085071000006 PM 10687335 ER PT J AU Rapaport, R AF Rapaport, R TI Congenital hypothyroidism: Expanding the spectrum SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID INFANTS; ANTIBODIES; THYROXINE; CHILDREN C1 St Barnabas Med Ctr, Joslin Ctr Diabet & Endocrinol, Div Pediat Endocrinol, Livingston, NJ 07039 USA. RP Rapaport, R (reprint author), St Barnabas Med Ctr, Joslin Ctr Diabet & Endocrinol, Div Pediat Endocrinol, Livingston, NJ 07039 USA. NR 30 TC 13 Z9 15 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2000 VL 136 IS 1 BP 10 EP 12 DI 10.1016/S0022-3476(00)90041-6 PG 3 WC Pediatrics SC Pediatrics GA 277AF UT WOS:000084910000005 PM 10636966 ER PT J AU Pollack, MH Marzol, PC AF Pollack, MH Marzol, PC TI Panic: course, complications and treatment of panic disorder SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 9th Congress of the Association-of-European-Psychiatrists CY SEP 20-23, 1998 CL COPENHAGEN, DENMARK SP Assoc European Psychiatrists DE panic disorder; SSRIs; sertraline; treatment ID QUALITY-OF-LIFE; DOUBLE-BLIND; MULTICENTER TRIAL; PHOBIC ANXIETY; TERM TREATMENT; CHEST PAIN; PLACEBO; SERTRALINE; CLOMIPRAMINE; AGORAPHOBIA AB Panic disorder is a chronic condition typically associated with significant distress and disability. In addition to the acute distress associated with the panic attack itself, the disorder often leads to distressing anticipatory anxiety and phobic avoidance. Affected individuals experience significant impairment in social and vocational functioning, high utilization of medical resources, constriction of function, premature mortality and diminution in overall quality of life. Panic disorder is frequently comorbid with other conditions, particularly depression, as well as alcohol and other substance abuse, and other anxiety disorders including social phobia, generalized anxiety disorder, obsessive-compulsive disorder and posttraumatic stress disorder. A number of pharmacological agents and cognitive-behavioural treatments have been shown to be effective in the treatment of panic disorder, with the selective serotonin reuptake inhibitors (SSRIs) becoming first-line pharmacotherapy for this condition. Among these, the SSRI sertraline appears effective not only in improving symptoms of panic, but also in reducing anticipatory anxiety and improving multiple aspects of quality of life. For patients who remain partly or fully symptomatic despite adequate first-line treatment, a variety of strategies are emerging for the management of refractory conditions. We provide an overview of the prevalence, presentation and associated complications of panic disorder, review the therapeutic options and discuss the management of refractory patients. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Behav Therapy Unit, Boston, MA 02114 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Behav Therapy Unit, 15 Parkman St,WACC 815, Boston, MA 02114 USA. NR 53 TC 23 Z9 24 U1 3 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PY 2000 VL 14 IS 2 SU 1 BP S25 EP S30 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 328QR UT WOS:000087862000004 PM 10888028 ER PT J AU Sherwood, AM Graves, DE Priebe, MM AF Sherwood, AM Graves, DE Priebe, MM TI Altered motor control and spasticity after spinal cord injury: Subjective and objective assessment SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE classification; computer-assisted; electromyography; muscle spasticity; signal processing; spinal cord injuries ID MODIFIED ASHWORTH SCALE; INTRATHECAL BACLOFEN; SURFACE EMG; RELIABILITY; HYPERTONIA; CLASSIFICATION; RECORDINGS; STANDARDS; PLACEBO; SCI AB This study of measures of spasticity, or altered motor control, compares the clinically used Ashworth scale with a method based on surface electromyographic (sEMG) recordings called brain motor control assessment (BMCA) in a group of 97 subjects with spinal cord injury (SCI) and varying levels of motor dysfunction. In this paper, we describe how sEMG-derived scores relate to the severity of spasticity as judged clinically. When sEMG data from passive movements from the BMCA were analyzed by Ashworth category, we found that when the sEMG data were averaged for a limb, there was a significant difference between scores for those with Ashworth 0 vs. 2 and 3, and 1 vs. 2 and 3 (p<0.001), but not between 0 and 1. Analysis of the individual muscle scores improved the discrimination between Ashworth categories. Superiority of sEMG data over Ashworth category as an objective quantification of altered motor control ("spasticity") is argued. C1 VA Rehabil Res & Dev Ctr Excellence Hlth Aging Di, Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Dept Vet Affairs N Texas Hlth Care Syst, Dallas, TX 75216 USA. Univ Texas, SW Med Sch, Dept Phys Med & Rehabil, Dallas, TX 75235 USA. RP Sherwood, AM (reprint author), VA Rehabil Res & Dev Ctr Excellence Hlth Aging Di, Dept Vet Affairs Med Ctr, 2002 Holcombe Blvd,153, Houston, TX 77030 USA. OI Sherwood, Arthur/0000-0002-0110-4317 NR 61 TC 30 Z9 32 U1 0 U2 3 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 2000 VL 37 IS 1 BP 41 EP 52 PG 12 WC Rehabilitation SC Rehabilitation GA 380YM UT WOS:000165733300010 PM 10847571 ER PT J AU Shekelle, PG Morton, SC AF Shekelle, PG Morton, SC TI Principles of metaanalysis SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT OMERACT Imaging Task Force Workshop on Heterogeneity in Rheumatoid Arthritis Radiographics Trials - Issues to Consider in a Metaanalysis CY NOV 07, 1998 CL SAN DIEGO, CALIFORNIA SP Connet Corp DE metaanalysis ID SYSTEMATIC REVIEWS; TRIALS; HETEROGENEITY; QUALITY AB Metaanalysis is a relatively new tool to help make evidence based decisions. This technique involves the systematic examination of available evidence on a given clinical topic, and the summary of that evidence using statistical techniques that pool data from multiple studies to yield a single result. We briefly discuss the principal steps in a metaanalysis: identifying all the studies; assessing the studies for quality; organizing the studies into subgroups: and summarizing the results. C1 W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, Los Angeles, CA 90073 USA. Rand Hlth Program & Stat Grp, Santa Monica, CA USA. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 11 TC 9 Z9 9 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2000 VL 27 IS 1 BP 251 EP 252 PG 2 WC Rheumatology SC Rheumatology GA 274RC UT WOS:000084778000043 PM 10648049 ER PT J AU Nakagawa, A Marks, IM Park, JM Bachofen, M Baer, L Dottl, SL Greist, JH AF Nakagawa, A Marks, IM Park, JM Bachofen, M Baer, L Dottl, SL Greist, JH TI Self-treatment of obsessive-compulsive disorder guided by manual and computer conducted telephone interview SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID SCALE AB While on a waiting list for treatment by therapist-guided exposure and ritual prevention (ERP), patients with obsessive-compulsive disorder (OCD) did self-treatment at home guided by a manual plus a computer-driven telephone interview system (BT STEPS). Of 21 patients who used the system for at least three weeks while on the waiting list, one improved so much that subsequent therapist-guided ERP was unnecessary. Progress of the rest with the system predicted later progress with therapist-guided ERP. Improvement after using the system was similar to that of 20 matched historical controls who had had therapist-guided ERP without the prior use of BT STEPS. Outpatient users of BT STEPS needed less subsequent clinician-guided time than did their matched controls. in this pilot study, patients with OCD improved nearly as much with home self-treatment guided by a manual plus computer, as with treatment guided by a behaviour therapist. C1 Inst Psychiat, London SE5 8AF, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Healthcare Technol Syst, Madison, WI USA. RP Marks, IM (reprint author), Inst Psychiat, De Crespigny Pk, London SE5 8AF, England. NR 8 TC 26 Z9 27 U1 1 U2 7 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2000 VL 6 IS 1 BP 22 EP 26 DI 10.1258/1357633001933899 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 276TP UT WOS:000084893700004 PM 10824386 ER PT J AU DiFiglia, M AF DiFiglia, M TI Genetics of childhood disorders: X. Huntington disease SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp East, Dept Neurol & Immunol, Lab Cellular Neurobiol, Charlestown, MA USA. RP DiFiglia, M (reprint author), Yale Univ, Sch Med, Ctr Child Study, 230 S Frontage Rd, New Haven, CT 06520 USA. NR 6 TC 1 Z9 1 U1 0 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 2000 VL 39 IS 1 BP 120 EP 122 DI 10.1097/00004583-200001000-00025 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 270CT UT WOS:000084518400025 PM 10638076 ER PT J AU Ross, EV Naseef, GS McKinlay, JR Barnette, DJ Skrobal, M Grevelink, J Anderson, RR AF Ross, EV Naseef, GS McKinlay, JR Barnette, DJ Skrobal, M Grevelink, J Anderson, RR TI Comparison of carbon dioxide laser, erbium : YAG laser, dermabrasion, and dermatome - A study of thermal damage, wound contraction, and wound healing in a live pig model: Implications for skin resurfacing SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PORCINE SKIN; CO2-LASER; RHYTIDES; INCISION AB Background: Advances in laser technology allow for precise tissue removal and minimal thermal damage. However, mechanisms for cosmetic improvement have not been determined. Investigators have suggested that ablation, collagen shrinkage, and new collagen deposition all contribute to the clinical outcome. Objective: In a live farm pig, we examined gross and microscopic effects of thermal and mechanical ablation devices to characterize immediate and long-term mechanisms in skin rejuvenation. Methods: Two CO2 lasers, an erbium:YAG laser, a dermabrader, and a dermatome were used to treat Bank skin in a farm pig. There were 14 different treatment groups based on device type and working parameters. One to five sites were treated for each group. Wound surface areas were measured before treatment, immediately after treatment, and 7, 17, 23, 30, and 60 days thereafter. Biopsies were performed immediately after irradiation and 2, 7, 17, and 60 days after treatment. Results: For the CO2 laser-induced wounds, surface area measurements showed that immediate and final wound contraction tended to increase with initial residual thermal damage (RTD) for a range of values, above which immediate contraction remained relatively constant. Although there nas no immediate wound contraction with mechanical ablation devices, long-term wound contraction in the dermatome and dermabrasion sites increased with depth of ablation. The erbium:YAG laser sites healed in a manner similar to that of mechanically induced wounds. Wound contraction profiles over time were dependent on depth of RTD and depth of ablation. Sixty days postoperatively, histologic examination showed varying degrees of fibroplasia. Overall, there was greater compaction and horizontal orientation of collagen fibers in those wounds with more than 70 mu m of dermal RTD. Grossly, all wounds were similar after 60 days, with the exception of the deep dermabrasion sites, at which clinical scarring was observed. Conclusion: Our results show that CO2 laser resurfacing produces short- and long-term wound contraction that is greater than that induced by purely ablative methods for the same total depth of injury. The erbium laser produced Round contraction profiles similar to these produced by mechanical wounding. The data suggest that initial collagen contraction and thermal damage modulate wound healing. C1 USN Hosp, Dept Dermatol, San Diego, CA 92134 USA. Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. RP Ross, EV (reprint author), USN Hosp, Dept Dermatol, Box 324,34800 Bob Wilson Dr, San Diego, CA 92134 USA. NR 28 TC 66 Z9 66 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2000 VL 42 IS 1 BP 92 EP 105 DI 10.1016/S0190-9622(00)90016-1 PN 1 PG 14 WC Dermatology SC Dermatology GA 272VQ UT WOS:000084672000013 PM 10607327 ER PT J AU Albert, MR Mackool, BT AF Albert, MR Mackool, BT TI A dermatology ward at the beginning of the 20th century SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Consultat & Inpatient Serv, Boston, MA USA. RP Albert, MR (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,12N262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2000 VL 42 IS 1 BP 113 EP 123 DI 10.1016/S0190-9622(00)90018-5 PN 1 PG 11 WC Dermatology SC Dermatology GA 272VQ UT WOS:000084672000015 PM 10607329 ER PT J AU Kirkish, P Sreenivasan, S Welsh, R Van Gorp, W Eth, S Shoptaw, S Ling, W AF Kirkish, P Sreenivasan, S Welsh, R Van Gorp, W Eth, S Shoptaw, S Ling, W TI The future of criminal violence: Juveniles tried as adults SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID SEXUAL HOMICIDE; OFFENDERS; DELINQUENTS; PSYCHOPATHY; CHILDREN AB Juveniles tried as adults (JTA) represent a select and small subsample of juvenile offenders. This study seeks to provide a profile of habitually violent JTAs transferred to the adult penal system and to compare them with their adult counterparts. Twenty-nine incarcerated violent male juveniles tried as adults were compared with a sample of 27 incarcerated violent male offenders across demographic, neuropsychological, criminal history, psychopathy, and substance abuse variables. The JTAs were characterized by a high rate of gang membership (96%), substance abuse (alcohol, marijuana, and phenylcyclidene), and use of guns. In the juvenile sample, 65 percent used guns in violence not leading to arrest, and 93 percent used guns in a violent crime leading to arrest. Juvenile offenders were similar to their adult counterparts in patterns of criminality, although adult offenders had higher psychopathy scores. Both groups revealed generally intact neuropsychological functioning with the exception of a higher rate of perseverative responses in the adult sample. The results are discussed in terms of the implication of the degree of violence in a young offender population. C1 Loma Linda Univ, Loma Linda, CA 92350 USA. W Los Angeles Vet Adm Med Ctr, Forens Outreach Serv, VAMC, Los Angeles, CA USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Los Angeles Addict Treatment Res Consortium, Los Angeles, CA USA. Patton State Hosp, Patton, CA 92369 USA. Cornell Univ, Sch Med, Neuropsychol Lab, Ithaca, NY 14853 USA. New York Med Coll, Valhalla, NY 10595 USA. Los Angeles Addiction Treatment Res Ctr, Los Angeles, CA USA. Friends Res Inst Inc, Baltimore, MD 21285 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Loma Linda Univ, Loma Linda, CA 92350 USA. RP Kirkish, P (reprint author), DMH Forens Serv, POB 70673, Pasadena, CA 91117 USA. FU NIDA NIH HHS [5 P501 DA-09260] NR 57 TC 3 Z9 4 U1 1 U2 8 PU AMER ACAD PSYCHIATRY LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2000 VL 28 IS 1 BP 38 EP 46 PG 9 WC Law; Psychiatry SC Government & Law; Psychiatry GA 299TL UT WOS:000086213900009 PM 10774840 ER PT J AU Leong, GB Silva, JA Weinstock, R Ganzini, L AF Leong, GB Silva, JA Weinstock, R Ganzini, L TI Survey of forensic psychiatrists on evaluation and treatment of prisoners on death row SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article AB Psychiatrists have debated their role in evaluating prisoners accused of capital crimes and in treating prisoners on death row when restoration of competence would result in execution. Despite debate, there are no previous surveys of psychiatrists' opinions on this issue. We sent an anonymous questionnaire to all board-certified forensic psychiatrists in the United States. Of the 456 forensic psychiatrists identified, 290 (64%) returned the survey. Most respondents supported a role, in at least some cases, for psychiatric evaluation of prisoners accused of capital crimes. Respondents were divided on whether or nor psychiatrists should treat incompetent death row prisoners if restoration of competence would result in execution. Attitudes about the ethical acceptability of capital punishment were associated with views about the psychiatrists' role but were not determinative in every case. C1 Western State Hosp, Ctr Forens Serv, Tacoma, WA 98498 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA USA. Palo Alto Vet Affairs Healthcare Syst, Palo Alto, CA USA. Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Div Mental Hlth, Portland, OR USA. RP Leong, GB (reprint author), Western State Hosp, Ctr Forens Serv, MS 07-550,9601 Steilacoom Blvd, Tacoma, WA 98498 USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU AMER ACAD PSYCHIATRY LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2000 VL 28 IS 4 BP 427 EP 432 PG 6 WC Law; Psychiatry SC Government & Law; Psychiatry GA 392LB UT WOS:000166411600006 PM 11196252 ER PT J AU Sreenivasan, S Kirkish, P Garrick, T Weinberger, LE Phenix, A AF Sreenivasan, S Kirkish, P Garrick, T Weinberger, LE Phenix, A TI Actuarial risk assessment models: A review of critical issues related to violence and sex-offender recidivism assessments SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID PSYCHIATRIC-PATIENTS; PREDICTION; METAANALYSIS AB Risk assessment in the area of identification of violence has been dichotomized by several prominent researchers as the "clinical approach" versus the "actuarial method". The proponents of the actuarial approach argue for actuarially derived decisions to replace existing clinical practice. The actuarial method requires no clinical input, just a translation of the relevant material from the records to calculate the risk score. A risk appraisal approach based upon a sole actuarial method raises several questions: those of public safety, peer-accepted standards of practice, liability issues, and concordance with evidence-based medicine practice. We conclude that the sole actuarial approach fails to satisfy these critical issues. C1 Los Angeles Vet Adm, VA Med Ctr, Forens Outreach Serv, Los Angeles, CA 90073 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Calif Dept Mental Hlth, Mentally Disordered Offender Program, Sacramento, CA USA. W Los Angeles Vet Affairs Med Ctr, Consultat & Liaison Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ So Calif, Inst Psychiat Law & Behav Sci, Los Angeles, CA USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Calif Dept Mental Hlth, Sexually Violent Predator Program, San Luis Obispo, CA USA. RP Sreenivasan, S (reprint author), W Los Angeles Vet Affairs Med Ctr, 691-B116,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 39 TC 20 Z9 20 U1 0 U2 2 PU AMER ACAD PSYCHIATRY LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2000 VL 28 IS 4 BP 438 EP 448 PG 11 WC Law; Psychiatry SC Government & Law; Psychiatry GA 392LB UT WOS:000166411600008 PM 11196254 ER PT J AU Muder, RR AF Muder, RR TI Management of nursing home-acquired pneumonia: Unresolved issues and priorities for future investigation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID TERM-CARE FACILITY; RESIDENTS; HOSPITALIZATION; VALIDATION; INFECTIONS; MORTALITY; EMERGENCY; OUTCOMES; INDEX C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 23 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2000 VL 48 IS 1 BP 95 EP 96 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 273ET UT WOS:000084695500017 PM 10642029 ER PT J AU Dubey, AK Chueh, HC AF Dubey, AK Chueh, HC TI An XML-based format for guideline interchange and execution SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID CARE AB In building a general purpose guideline system based on GLIF -- the GuideLine Interchange Format, we encountered limitations in the GLIF specification. These limitations, while not so apparent in the static version of guideline content, became readily so in the context of real world implementation, and pertain not only to. GLIF-based systems, but generally as well. These limitations can be described as being in one of five categories. In this paper, we describe each of these categories in detail, and show how an execution environment based on XML data structures addresses these concerns. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Dubey, AK (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 205 EP 209 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500043 ER PT J AU Kim, CY Etemad, B Glenn, TF Mackey, HA Viator, GE Wallace, MB Mokhashi, MS Cotton, PB Hawes, RH AF Kim, CY Etemad, B Glenn, TF Mackey, HA Viator, GE Wallace, MB Mokhashi, MS Cotton, PB Hawes, RH TI Remote clinical assessment of gastrointestinal endoscopy (tele-endoscopy): An initial experience SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc AB Background: Gastrointestinal (GI) endoscopy is an effective tool to screen for cancers of the digestive tract. However, access to endoscopy is limited in many parts of South Carolina. This trial is a part of a prospective mufti part study for remote cancer screening in coastal South Carolina. This pilot study was to evaluate the quality of tele-endoscopy for cancer screening. Methods: 10 patients scheduled for endoscopic procedures were observed simultaneously by the endoscopist and a remote observer connected over a 512kbps ISDN line. Findings by both were compared for concordance on malignant or premalignant lesions: Results: The image quality was adequate to support remote diagnosis of GI cancer and abnormal lesions by an experienced observer. However, assessment of the esophagogastric junction for Barren's esophagus was equivocal. Conclusions: Overall, our tele-endoscopy setup shows great promise for remote supervision or observation of endoscopic procedures done by nurse endoscopists. Tele-endoscopy is both adequate and feasible for diagnosis of most gastrointestinal lesions. Subtle lesions still may be missed in our current setup. However, improvements are being made in our setup to address the problem with resolution prior to further evaluation. C1 Ralph H Johnson VA Med Ctr, Coastal Canc Control Program, Charleston, SC USA. Med Univ S Carolina, Ctr Digest Dis, Charleston, SC 29425 USA. RP Kim, CY (reprint author), Ralph H Johnson VA Med Ctr, Coastal Canc Control Program, Charleston, SC USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 423 EP 427 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500087 ER PT J AU Lovis, C Payne, TH AF Lovis, C Payne, TH TI Extending the VA CPRS electronic patient record order entry system using natural language processing techniques SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID LEGIBILITY AB An automated practitioner order entry system was recently implemented at the YA Puget Sound Health Care System. Since the introduction of this system, we have experienced various problems, among them an increase in time required for practitioners to enter orders. In order to improve usability and acceptance of the order entry, an alternate pathway was built within CPRS that allows direct natural language based order entry. Implementation of the extension in CPRS has been made possible because of the three layers CPRS architecture and its strong object oriented models. This paper discusses the advantages and needs for a natural language based order entry system and its implementation within an existing order entry system. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lovis, C (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Lovis, Christian/D-2634-2012 OI Lovis, Christian/0000-0002-2681-8076 NR 17 TC 1 Z9 1 U1 2 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 517 EP 521 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500106 ER PT J AU Payne, TH Savarino, J Marshall, R Hoey, CT AF Payne, TH Savarino, J Marshall, R Hoey, CT TI Use of a clinical event monitor to prevent and detect medication errors SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID ADVERSE DRUG EVENTS AB Errors in health care facilities are common and often unrecognized. We have used our clinical event monitor to prevent and detect medication errors by scrutinizing electronic messages sent to it when any medication order is written in our facility. fl growing collection of medication safety rules covering dose limit errors, laboratory monitoring, and other topics may be applied to each medication order message to provide an additional Layer of protection beyond existing order checks; reminders, and alerts available within our computer-based record system. During a typical day the event monitor receives 4802 messages, of which 4719 pertain to medication orders. We have found the clinical event monitor to be a valuable tool for clinicians and quality management groups charged with improving medication safety. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Payne, TH (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 640 EP 644 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500131 ER PT J AU Reilly, CA Zielstorff, RD Fox, RL O'Connell, EM Carroll, DL Conley, KA Fitzgerald, P Eng, TK Martin, A Zidik, CM Segal, M AF Reilly, CA Zielstorff, RD Fox, RL O'Connell, EM Carroll, DL Conley, KA Fitzgerald, P Eng, TK Martin, A Zidik, CM Segal, M TI A knowledge-based patient assessment system: Conceptual and technical design SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID NURSING ASSESSMENT AB dThis paper describes the design of an inpatient patient assessment application that captures nursing assessment data using a wireless laptop computer. The primary aim of this system is to capture structured information for facilitating decision support and quality monitoring. The system also aims to improve efficiency of recording patient assessments, reduce costs, and improve discharge planning and early identification of patient learning needs. Object-oriented methods were used to elicit functional requirements and to model the proposed system. A tools-based development approach is being used to facilitate rapid development and easy modification of assessment items and rules for decision support. Criteria for evaluation include perceived utitlity by clinician users, validity of decision support rules, time spent recording assessments, and perceived utility of aggregate reports for quality monitoring. C1 Massachusetts Gen Hosp, Patient Care Serv, Dept Nursing, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 680 EP 684 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500139 ER PT J AU Hill, E Hammond, KW AF Hill, E Hammond, KW TI The usability of multimedia automated psychological tests to screen for Alzheimer's disease SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1030 EP 1030 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500282 ER PT J AU Kreis, C Chueh, H AF Kreis, C Chueh, H TI NetNote: Multiple motives for a web based structured data entry interface. SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1054 EP 1054 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500305 ER PT J AU Mar, CM Chabal, C Jacobson, L Mariano, AJ Vore, A AF Mar, CM Chabal, C Jacobson, L Mariano, AJ Vore, A TI Interactive computerized chronic pain education program SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Talaria Inc, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1077 EP 1077 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500328 ER PT J AU McAlduff, J Berkowicz, D Barnett, GO Chueh, H AF McAlduff, J Berkowicz, D Barnett, GO Chueh, H TI An integrated, mobile web-based billing and diagnosis program SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1085 EP 1085 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500336 ER PT J AU Rothschild, JM Underwood, HR Weeks, J Earle, CC Fiskio, J Bates, DW AF Rothschild, JM Underwood, HR Weeks, J Earle, CC Fiskio, J Bates, DW TI A severity adjustment system using electronic data sources for predicting financial outcomes for oncology SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Avandel Inc, Seattle, WA USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Partners HealthCare Syst, Informat Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1126 EP 1126 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500377 ER PT J AU Murphy, SN Barnett, GO Chueh, HC AF Murphy, SN Barnett, GO Chueh, HC TI Visual query tool for finding patent cohorts from a clinical data warehouse of the Partners HealthCare System SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1174 EP 1174 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500424 ER PT J AU Clayton, D Campbell, MJ Longford, NT Armstrong, B Richardson, S Rushton, L Raab, GM Quinn, M Nelder, JA Bland, M Macfarlane, A Dryden, IL Smith, RI Berhane, K Thomas, DC Cotton, JW Coull, BA Mezzetti, M Ryan, LM Cowles, K Cox, C Cox, LH Gupta, S Hosmane, BS Gurrin, LC Pettitt, AN Saez, M Sheppard, L Lumley, T AF Clayton, D Campbell, MJ Longford, NT Armstrong, B Richardson, S Rushton, L Raab, GM Quinn, M Nelder, JA Bland, M Macfarlane, A Dryden, IL Smith, RI Berhane, K Thomas, DC Cotton, JW Coull, BA Mezzetti, M Ryan, LM Cowles, K Cox, C Cox, LH Gupta, S Hosmane, BS Gurrin, LC Pettitt, AN Saez, M Sheppard, L Lumley, T TI Combining evidence on air pollution and daily mortality from the 20 largest US cities: a hierarchical modelling strategy - Discussion SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Editorial Material ID LONDON WINTERS; APHEA PROJECT; LIKELIHOOD; EXPOSURE; ERRORS C1 MRC, Biostat Unit, Cambridge, England. Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. De Montfort Univ, Leicester LE1 9BH, Leics, England. London Sch Hyg & Trop Med, London, England. Inst Natl Sante & Rech Med, Villejuif, France. Napier Univ, Edinburgh EH14 1DJ, Midlothian, Scotland. Off Natl Stat, London, England. Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. Univ London St Georges Hosp, Sch Med, London, England. Radcliffe Infirm, Natl Perinatal Epidemiol Unit, Oxford OX2 6HE, England. Univ Nottingham, Nottingham NG7 2RD, England. Inst Terr Ecol, Penicuik EH26 0QB, Midlothian, Scotland. Univ So Calif, Los Angeles, CA USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. Univ Sains Malaysia, Pulan Pinang, Malaysia. Harvard Sch Publ Hlth, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. US EPA, Res Triangle Pk, NC 27711 USA. No Illinois Univ, De Kalb, IL 60115 USA. King Edward Mem Hosp, Perth, WA, Australia. Queensland Univ Technol, Brisbane, Qld, Australia. Univ Girona, Girona, Spain. Univ Washington, Seattle, WA 98195 USA. RP Clayton, D (reprint author), MRC, Biostat Unit, Cambridge, England. RI Ryan, Louise/A-4562-2009; Dryden, Ian/F-2790-2011; Smith, Rognvald/A-1890-2013; Dryden, Ian/C-8742-2017 OI Ryan, Louise/0000-0001-5957-2490; Smith, Rognvald/0000-0002-1744-0606; Dryden, Ian/0000-0003-4900-3571 NR 54 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0964-1998 J9 J ROY STAT SOC A STA JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2000 VL 163 BP 284 EP 302 PN 3 PG 19 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 373LM UT WOS:000165291000003 ER PT J AU Xu, RH O'Quigley, J AF Xu, RH O'Quigley, J TI Proportional hazards estimate of the conditional survival function SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE conditional survivorship function; Cox model; Kaplan-Meier integral; multiplicative models; partial likelihood; proportional hazards ID COX REGRESSION-MODEL; CONFIDENCE-INTERVALS; PROGNOSIS AB We introduce a new estimator of the conditional survival function given some subset of the covariate values under a proportional hazards regression. The new estimate does not require estimating the base-line cumulative hazard function. An estimate of the variance is given and is easy to compute, involving only those quantities that are routinely calculated in a Cox model analysis. The asymptotic normality of the new estimate is shown by using a central limit theorem for Kaplan-Meier integrals. We indicate the straightforward extension of the estimation procedure under models with multiplicative relative risks, including non-proportional hazards, and to stratified and frailty models. The estimator is applied to a gastric cancer study where it is of interest to predict patients' survival based only on measurements obtained before surgery, the time at which the most important prognostic variable, stage, becomes known. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. RP Xu, RH (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. RI O'Quigley, John/E-2073-2017 NR 26 TC 14 Z9 16 U1 1 U2 7 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2000 VL 62 BP 667 EP 680 DI 10.1111/1467-9868.00256 PN 4 PG 14 WC Statistics & Probability SC Mathematics GA 362HV UT WOS:000089773300004 ER PT J AU Lee, MLT DeGruttola, V Schoenfeld, D AF Lee, MLT DeGruttola, V Schoenfeld, D TI A model for markers and latent health status SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE acquired immune deficiency syndrome; bivariate Wiener process; disease progression; health status; latent process; marker; prediction; proportional hazards; survival analysis ID CLINICAL-TRIALS; ZIDOVUDINE; TYPE-1 AB We extend the bivariate Wiener process considered by Whitmore and co-workers and model the joint process of a marker and health status. The health status process is assumed to be latent or unobservable. The time to reach the primary end point or failure (death, onset of disease, etc.) is the time when the latent health status process first crosses a failure threshold level. Inferences for the model are based on two kinds of data: censored survival data and marker measurements. Covariates, such as treatment variables, risk factors and base-line conditions, are related to the model parameters through generalized linear regression functions. The model offers a much richer potential for the study of treatment efficacy than do conventional models. Treatment effects can be assessed in terms of their influence on both the failure threshold and the health status process parameters. We derive an explicit formula for the prediction of residual failure times given the current marker level. Also we discuss model validation. This model does not require the proportional hazards assumption and hence can be widely used. To demonstrate the usefulness of the model, we apply the methods in analysing data from protocol 116a of the AIDS Clinical Trials Group. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Lee, MLT (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. NR 16 TC 29 Z9 29 U1 1 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2000 VL 62 BP 747 EP 762 PN 4 PG 16 WC Statistics & Probability SC Mathematics GA 362HV UT WOS:000089773300009 ER PT J AU Gonin, R Lipsitz, SR Fitzmaurice, GM Molenberghs, G AF Gonin, R Lipsitz, SR Fitzmaurice, GM Molenberghs, G TI Regression modelling of weighted kappa by using generalized estimating equations SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE disease index; generalized estimating equations; intraclass correlation coefficient; measure of agreement; ordinal data; unbalanced data; weighted kappa ID LEAST-SQUARES; OBSERVER AGREEMENT; CATEGORICAL-DATA; ORDINAL DATA; RELIABILITY AB In many clinical studies more than one observer may be rating a characteristic measured on an ordinal scale. For example, a study may involve a group of physicians rating a feature seen on a pathology specimen or a computer tomography scan. In clinical studies of this kind, the weighted it coefficient is a popular measure of agreement for ordinally scaled ratings. Our research stems from a study in which the severity of inflammatory skin disease was rated. The investigators wished to determine and evaluate the strength of agreement between a variable number of observers taking into account patient-specific (age and gender) as well as rater-specific (whether board certified in dermatology) characteristics. This suggested modelling kappa as a function of these covariates. We propose the use of generalized estimating equations to estimate the weighted kappa coefficient. This approach also accommodates unbalanced data which arise when some subjects are not judged by the same set of observers. Currently an estimate of overall kappa for a simple unbalanced data set without covariates involving more than two observers is unavailable. In the inflammatory skin disease study none of the covariates were significantly associated with kappa, thus enabling the calculation of an overall weighted a for this unbalanced data set. In the second motivating example (multiple sclerosis), geographic location was significantly associated with kappa. In addition we also compared the results of our method with current methods of testing for heterogeneity of weighted ii coefficients across strata (geographic location) that are available for balanced data sets. C1 Westat WB486, Rockville, MD 20850 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. Limburgs Univ Ctr, Diepenbeek, Belgium. RP Gonin, R (reprint author), Westat WB486, 1441 W Montgomery Ave, Rockville, MD 20850 USA. NR 27 TC 20 Z9 20 U1 0 U2 6 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 2000 VL 49 BP 1 EP 18 DI 10.1111/1467-9876.00175 PN 1 PG 18 WC Statistics & Probability SC Mathematics GA 284UP UT WOS:000085351200001 ER PT J AU Lipsitz, SR Ibrahim, J Molenberghs, G AF Lipsitz, SR Ibrahim, J Molenberghs, G TI Using a Box-Cox transformation in the analysis of longitudinal data with incomplete responses SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE CD4 cell counts; incomplete data; influence graph; maximum likelihood; sensitivity analysis ID JACKKNIFE AB We analyse longitudinal data on CD4 cell counts from patients who participated in clinical trials that compared two therapeutic treatments: zidovudine and didanosine. The investigators were interested in modelling the CD4 cell count as a function of treatment, age at base-line and disease stage at base-line. Serious concerns can be raised about the normality assumption of CD4 cell counts that is implicit in many methods and therefore an analysis may have to start with a transformation. Instead of assuming that we know the transformation (e.g. logarithmic) that makes the outcome normal and linearly related to the covariates, we estimate the transformation, by using maximum likelihood, within the Box-Cox family. There has been considerable work on the Box-Cox transformation for univariate regression models. Here, we discuss the Box-Cox transformation for longitudinal regression models when the outcome can be missing over time, and we also implement a maximization method for the likelihood, assuming that the missing data are missing at random. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Limburgs Univ Ctr, Diepenbeek, Belgium. RP Lipsitz, SR (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 14 Z9 14 U1 0 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 2000 VL 49 BP 287 EP 296 DI 10.1111/1467-9876.00192 PN 2 PG 10 WC Statistics & Probability SC Mathematics GA 314CY UT WOS:000087038300008 ER PT J AU Bernardo, MVP Lipsitz, SR Harrington, DP Catalano, PJ AF Bernardo, MVP Lipsitz, SR Harrington, DP Catalano, PJ TI Sample size calculations for failure time random variables in non-randomized studies SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES D-THE STATISTICIAN LA English DT Article DE exponential distribution; power calculations; proportional hazards model ID REGRESSION-MODEL; CLINICAL-TRIAL; FOLLOW-UP; DURATION AB In non-randomized studies, sample size calculations for failure time random variables are often computed on the basis of the unadjusted log-rank test which assumes that the variable designating group membership is independent of other patient covariates. We show that by extending the methods proposed by Lipsitz and Parzen to time-to-event random variabes the power derived from the unadjusted log-rank test overestimates the true power of the comparison when the variable of interest is correlated with other covariates. We model the hazards by using exponential regression and derive the sample size formulae for both censored and uncensored data. We also present results of a simulation study to assess the validity of the derived formulae when the intended method of analysis is the proportional hazards regression model and the data continue to have an exponential distribution. We apply the methods proposed to the non-Hodgkin's lymphoma prognostic factors project data set. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bernardo, MVP (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0039-0526 J9 J ROY STAT SOC D-STA JI J. R. Stat. Soc. Ser. D-Stat. PY 2000 VL 49 BP 31 EP 40 DI 10.1111/1467-9884.00217 PN 1 PG 10 WC Statistics & Probability SC Mathematics GA 298JK UT WOS:000086135400002 ER PT J AU Ratcliffe, MB Wallace, AW Salahieh, A Hong, J Ruch, S Hall, TS AF Ratcliffe, MB Wallace, AW Salahieh, A Hong, J Ruch, S Hall, TS TI Ventricular volume, chamber stiffness, and function after anteroapical aneurysm plication in the sheep SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CANINE LEFT-VENTRICLE; CONDUCTANCE CATHETER; PATCH REPAIR; SURGERY AB Objective: The success of left ventricular aneurysm plication depends on how the procedure affects both end-systolic elastance and diastolic compliance and how those changes affect ventricular function (stroke work/end-diastolic volume [PRSW] and stroke volume/end-diastolic pressure [Starling] relationships). Methods: Five male Dorsett sheep were surgically instrumented with coronary artery snares, an inferior vena caval occluder, and an ascending aortic ultrasonic flow probe. One week later an anteroapical myocardial infarction was produced by tightening the coronary snares. Ten weeks after myocardial infarction, the left ventricular aneurysm was plicated, Absolute left ventricular volume was measured by long-axis transdiaphragmatic echocardiography, and relative changes in left ventricular volume were measured with a conductance catheter. End-systolic elastance, diastolic compliance, PRSW, and Starling relationships were measured immediately before myocardial infarction, 10 weeks after myocardial infarction (immediately before plication), and immediately after and 6 weeks after aneurysm plication. Results: After plication, end-diastolic and end-systolic left ventricular volumes return to preinfarction values. The slopes of end-systolic elastance, diastolic compliance, and PRSW decrease 10 weeks after myocardial infarction, increase with aneurysm plication, and then decrease 6 weeks after aneurysm plication. The Starling relationship undergoes a downward parallel shift with aneurysm plication. Conclusion: Aneurysm plication abruptly decreases left ventricular volume and diastolic compliance, increases end-systolic elastance and PRSW, but decreases the Starling relationship. The net effect on left ventricular function is mixed. Furthermore, left ventricular remodeling 6 weeks after aneurysm plication causes left ventricular volume, end-systolic elastance, diastolic compliance, PRSW, and the Starling relationship to return to preplication values. C1 San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Div Cardiothorac Surg, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, San Francisco, CA USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, 4150 Clement St, San Francisco, CA 94121 USA. NR 23 TC 38 Z9 39 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 2000 VL 119 IS 1 BP 115 EP 124 DI 10.1016/S0022-5223(00)70225-X PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 276BZ UT WOS:000084856900023 PM 10612769 ER PT J AU Wagner, AW Wolfe, J Rotnitsky, A Proctor, SP Erickson, DJ AF Wagner, AW Wolfe, J Rotnitsky, A Proctor, SP Erickson, DJ TI An investigation of the impact of posttraumatic stress disorder on physical health SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; health; gender; Gulf War ID PERSIAN-GULF-WAR; TRAUMATIC EVENTS; MILITARY PERSONNEL; MISSISSIPPI SCALE; VIETNAM VETERANS; URBAN-POPULATION; SOCIAL SUPPORT; YOUNG-ADULTS; RISK-FACTORS; COMBAT AB In a large sample of Gulf War Veterans (N = 2301) we examined the relations between PTSD symptoms assessed immediately upon returning from the Gulf War and self-reported health problems assessed 18-24 months later PTSD symptomatology was predictive of self-reported health problems over time for both men and women veterans, even after the effects of combat exposure were removed from the analysis. Female veterans reported significantly move health problems than male veterans, however there was no interactive effect of gender and PTSD on health problems. These findings provide further support for the theory that psychological response to stressors impacts health outcome. C1 Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. Boston Univ, Sch Med Psychiat & Psychol, Boston Vet Affairs Med Ctr, Natl Ctr PTSD,Womens Hlth Sci Div, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Sch Med Neurol, Boston Vet Affairs Med Ctr, Boston Environm Hazards Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth Environm Hlth, Boston Vet Affairs Med Ctr, Boston Environm Hazards Ctr, Boston, MA 02215 USA. RP Wagner, AW (reprint author), Univ Wyoming, Dept Psychol, Box 3415, Laramie, WY 82071 USA. NR 42 TC 102 Z9 104 U1 5 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JAN PY 2000 VL 13 IS 1 BP 41 EP 55 DI 10.1023/A:1007716813407 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 299JA UT WOS:000086194200003 PM 10761173 ER PT J AU Kimerling, R Clum, GA Wolfe, J AF Kimerling, R Clum, GA Wolfe, J TI Relationships among trauma exposure, chronic posttraumatic stress disorder symptoms, and self-reported health in women: Replication and extension SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder; trauma; women; health ID SEXUAL ASSAULT HISTORY; PSYCHIATRIC DIAGNOSES; VICTIMIZATION; VETERANS; OUTCOMES; PTSD; IMPACT; PAIN AB Fifty-two women who sewed during the Vietnam era were assessed for war-zone exposure, traumatic life events, posttraumatic stress disorder (PTSD), and self-reported health status. Symptoms of PTSD were examined as mediators in the relationship between traumatic exposure and subsequent reports of health problems. Results showed that PTSD symptoms accounted significantly for variance in health problems reported by women with prior traumatic stressor exposure. When the cardinal symptom domains of PTSD (reexperiencing, numbing, avoidance, hyperarousal) were analyzed separately, the symptom cluster representing hyperarousal accounted uniquely for the variance associated with health complaints, beyond that contributed by other symptom clusters. Discussion of the results focuses on mechanisms underlying the relationship between specific symptoms of PTSD and self-reported health. Implications for intervention within the medical system are also considered. C1 Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA 02130 USA. Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. Univ Georgia, Dept Psychol, Athens, GA 30602 USA. Tufts Univ, Dept Psychiat, Sch Med, Medford, MA 02155 USA. RP Wolfe, J (reprint author), Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, 116B-3,150 S Huntington Ave, Boston, MA 02130 USA. OI Kimerling, Rachel/0000-0003-0996-4212 NR 47 TC 103 Z9 106 U1 1 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JAN PY 2000 VL 13 IS 1 BP 115 EP 128 DI 10.1023/A:1007729116133 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 299JA UT WOS:000086194200008 PM 10761178 ER PT J AU Roehrborn, CG McConnell, J Bonilla, J Rosenblatt, S Hudson, PB Malek, GH Schellhammer, PF Bruskewitz, R Matsumoto, AM Harrison, LH Fuselier, HA Walsh, P Roy, J Andriole, G Resnick, M Waldstreicher, J AF Roehrborn, CG McConnell, J Bonilla, J Rosenblatt, S Hudson, PB Malek, GH Schellhammer, PF Bruskewitz, R Matsumoto, AM Harrison, LH Fuselier, HA Walsh, P Roy, J Andriole, G Resnick, M Waldstreicher, J CA Proscar Long-Term Efficacy Safety TI Serum prostate specific antigen is a strong predictor of future prostate growth in men with benign prostatic hyperplasia SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Urological-Association CY MAY 30-JUN 04, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Urol Assoc DE prostatic hyperplasia; prostate-specific antigen; magnetic resonance imaging; prostate ID ACUTE URINARY RETENTION; FINASTERIDE; SYMPTOMS; VOLUME; FLOW; VARIABILITY; EFFICACY; INDEX; RISK AB Purpose: We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia (BPH) and treated with placebo during 4 years, and determine which baseline parameters were the strongest predictors of growth. Materials and Methods: A total of 3,040 men were enrolled in the 4-year randomized, placebo controlled Proscar Long-Term Efficacy and Safety study. Of these men a subgroup of 10% underwent pelvic magnetic resonance imaging prostate volume measurement at baseline and yearly thereafter. Absolute and percent volume changes during 4 years were calculated in the 164 placebo treated men in the subgroup. The ability of age, baseline prostate volume and prostate specific antigen (PSA) to predict prostate growth in placebo treated patients was assessed by multiple linear regression analyses, receiver operator characteristics curves, and evaluations of growth stratified by tertiles of baseline serum PSA and decades of life. Results: In placebo treated patients a steady increase in mean plus or minus standard deviation prostate volume from year to year was noted (2.5 +/- 6.1, 4.9 +/- 6.8, 6.4 +/- 8.5 and 7.2 +/- 8.8 ml. at years 1, 2, 3 and 4, respectively). Mean volume changes at 4 years ranged from -9 to +30 mi. Mean percent change from baseline ranged from 12.5% to 16.6% for men 50 to 59 years old to those 70 to 79 years old. Baseline serum PSA was a strong predictor of growth with 7.4% to 22.0% change at 4 years from the lowest to highest PSA tertiles. Annualized growth rates from baseline were 0.7 ml. per year for PSA 0.2 to 1.3, 2.1 for PSA 1.4 to 3.2 and 3.3 for PSA 3.3 to 9.9 ng/ml. Multiple Linear regression analysis showed that serum PSA was a stronger predictor of prostate growth than age or baseline prostate volume. All but 1 man with baseline serum PSA greater than 2.0 ng/ml. had prostate growth during 4 years, and 32.6% of men with serum PSA less than 2.0 exhibited a decrease in volume. Conclusions: Serum PSA is a stronger predictor of growth of the prostate in placebo treated patients than age or baseline prostate volume. Since prostate volume is a risk factor for acute urinary retention and the need for BPH related surgery, the ability of PSA to predict prostate growth may be an important factor when considering individual treatment options for BPH. Such use of PSA represents a shift. in paradigm away from focusing solely on symptoms of BPH toward a more comprehensive approach with consideration of predicting and preventing risk factors of BPH related outcomes. C1 Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Vet Adm Med Ctr, Dept Vet Affairs, Bay Pines, FL USA. Irvine Clin Res Ctr, Irvine, CA USA. Jackson Fdn Med Educ & Res, Madison, WI USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Wisconsin, Madison, WI USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Univ Oklahoma, Oklahoma City, OK USA. Washington Univ, St Louis, MO USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Merck Res Labs, Dept Clin Res Endocrinol & Metab, Rahway, NJ USA. RP Roehrborn, CG (reprint author), Univ Texas, SW Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. NR 25 TC 129 Z9 141 U1 1 U2 4 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 2000 VL 163 IS 1 BP 13 EP 20 DI 10.1016/S0022-5347(05)67962-1 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 266XE UT WOS:000084324900004 PM 10604304 ER PT J AU Aronson, WJ Freeland, SJ AF Aronson, WJ Freeland, SJ TI Editorial: Can we lower the mortality rate of black men with prostate cancer? SO JOURNAL OF UROLOGY LA English DT Editorial Material DE prostatic neoplasms; blacks; mortality; prostate-specific antigen; prostatectomy ID WHITE MEN; REFERENCE RANGES; ANTIGEN; SURVIVAL; GENE C1 Univ Calif Los Angeles, Dept Urol, Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90024 USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Dept Urol, Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90024 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 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 2000 VL 163 IS 1 BP 150 EP 151 DI 10.1016/S0022-5347(05)67992-X PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 266XE UT WOS:000084324900044 PM 10604334 ER PT J AU Smith, MR AF Smith, MR TI Successful treatment with mitoxantrone chemotherapy of acute disseminated intravascular coagulation due to metastatic androgen independent prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; mitoxantrone; drug therapy C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 4 TC 12 Z9 12 U1 0 U2 0 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 2000 VL 163 IS 1 BP 248 EP 248 DI 10.1016/S0022-5347(05)68026-3 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 266XE UT WOS:000084324900081 PM 10604368 ER PT J AU Smith, JJ AF Smith, JJ TI Regulatory and legal implications of modifying FDA-approved medical devices SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Food and Drug Administration; medical devices C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Smith, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2000 VL 11 IS 1 BP 19 EP 23 DI 10.1016/S1051-0443(07)61272-X PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 294UD UT WOS:000085928000003 PM 10693709 ER PT J AU Kim, HS Goncalves, NM Henson, JW AF Kim, HS Goncalves, NM Henson, JW TI Glial cell-specific regulation of the JC virus early promoter by large T antigen SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEAR FACTOR-I; HUMAN-BRAIN; TRANSCRIPTION FACTOR-SP1; CPG ISLAND; PROTEIN; REGION; SITES; METHYLATION; ACTIVATION; EXPRESSION AB Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease that results from an oligodendrocyte infection caused by JC virus. The JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, and thus transcriptional regulation constitutes a major mechanism of glial tropism in PML. We have previously demonstrated that T antigen controls the JC virus basal promoter in a glial cell-specific manner, since T antigen repressed the JC virus and simian virus 40 (SV40) early promoters in glioma cells but induced strong activation of the JC virus early promoter in nonglial cells. To further analyze these findings, T antigen and nuclear extracts from glial and nonglial cells were used to examine DNase I footprints on the proximal promoter. T-antigen binding to site II was more extensive than expected based on sequence homology with SV40, and nuclear proteins protected several regions of the proximal promoter in a cell-specific manner. Multiple Sp1 binding domains were identified. Site-directed mutagenesis revealed that T-antigen-mediated activation required a TATA box sequence, a pentanucleotide repeat immediately upstream of the TATA box, and an Sp1 binding site downstream of the TATA box, When footprints were obtained with mutant promoters which blocked T-antigen-induced transactivation, no change in T-antigen binding was observed. These results suggest that T antigen activates the JC virus basal promoter in nonglial cells by interaction with the transcription initiation complex. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS35735] NR 31 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 2 BP 755 EP 763 DI 10.1128/JVI.74.2.755-763.2000 PG 9 WC Virology SC Virology GA 268ND UT WOS:000084421700018 PM 10623737 ER PT J AU Gjoerup, O Chao, H DeCaprio, JA Roberts, TM AF Gjoerup, O Chao, H DeCaprio, JA Roberts, TM TI pRB-dependent, J domain-independent function of simian virus 40 large T antigen in override of p53 growth suppression SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN-VIRUS-40 LARGE-T; LARGE TUMOR-ANTIGEN; MOUSE EMBRYO FIBROBLASTS; P53-MEDIATED TRANSCRIPTIONAL ACTIVITY; P53-DEPENDENT G(1) ARREST; HEAT-SHOCK PROTEIN; CELL-CYCLE ARREST; RNA-POLYMERASE-I; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE AB Simian virus 40 (SV40) large T antigen (LT) can immortalize and transform many cell types. These activities are attributed in large part to the binding and functional inactivation by LT of two major tumor suppressors: p53 and the retinoblastoma protein, pRB. Most effects of LT on pRB have been shown to additionally require an intact J domain, which mediates binding to Hsc70. We show here that the J domain is not required for p53 override in full-length LT. Although LT binds p53, it was shown previously that overcoming a p53-induced cell cycle arrest requires binding to pRB family members (R. S. Quartin et al., J. Virol. 68:1334-1341). We demonstrate that an LT mutant defective for pRB family member binding (K1) can be complemented for efficient override of p53 arrest by a construct encoding the first 135 amino acids of LT with a J domain-inactivating mutation, H42Q. Hence, complementation does not require the J domain, and pRB binding by LT is important for more than dissociating pRB-E2F complexes, which is J dependent. In accordance with this notion, LT alleviates pRB small-pocket-mediated transcriptional repression independently of the J domain. The LT K1 mutant can also be complemented for p53 override by small t antigen (st) in a manner independent of its J domain. Our observations underscore the importance of multiple SV40 functions, two in LT and one in st, that act cooperatively to counteract p53 growth suppression. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA063113, P01-CA50661, CA30002, R37 CA030002, P01 CA050661, R01 CA030002, P0-CA50661] NR 88 TC 25 Z9 25 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 2 BP 864 EP 874 DI 10.1128/JVI.74.2.864-874.2000 PG 11 WC Virology SC Virology GA 268ND UT WOS:000084421700030 PM 10623749 ER PT J AU Shifren, JL Schiff, I AF Shifren, JL Schiff, I TI The aging ovary SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MENOPAUSAL WOMEN; HORMONE LEVELS; ANDROGEN; TESTOSTERONE; AGE AB During reproductive life, ovarian steroid biosynthesis is gonadotropin dependent and occurs in theca and granulosa cells. In the menopausal ovary, there is atresia of ovarian follicles, with sparing of the androgen-producing theca-interstitial cell component. The aging ovary, therefore, produces significantly reduced amounts of estrogen, with continued, though decreased, androgen production. After menopause, ovarian estradiol biosynthesis is minimal, with circulating estrogen being derived principally from peripheral aromatization of ovarian and adrenal androgens. Androgen biosynthesis from the adrenal gland, in addition to that from the ovary, decreases with age. Although ovarian androgen production declines with age, there is not an abrupt decrease as is seen with ovarian estrogen levels at the time of menopause. The biological activity of these steroids, either before or after menopause, depends on the amount of steroid available in the unbound fraction. To this end, sex hormone-binding globulin (SHBG) levels are an important determinant of hormone action. Not only does the concentration of SHBG influence the biological effect of testosterone and estradiol, but these steroids also regulate SHBG concentrations. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Schiff, I (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, VBK 113,55 Fruit St, Boston, MA 02114 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 18 TC 29 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PY 2000 VL 9 SU 1 BP S3 EP S7 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 283PJ UT WOS:000085283700002 PM 10695867 ER PT J AU Fogarty, DG Rich, SS Hanna, L Warram, JH Krolewski, AS AF Fogarty, DG Rich, SS Hanna, L Warram, JH Krolewski, AS TI Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Diabetes-Association CY JUN 13-16, 1998 CL CHICAGO, ILLINOIS SP Amer Diabet Assoc DE albumin excretion; diabetic nephropathy; type 2 diabetes; familial aggregation; heritability; blood pressure ID RENAL-DISEASE; PIMA-INDIANS; NEPHROPATHY; MELLITUS; PREDISPOSITION; SUSCEPTIBILITY; HYPERTENSION; PEDIGREES; AMERICANS; LINKAGE AB Background. Levels of urinary albumin excretion (UAE) are used to define both the diagnosis of diabetic nephropathy and its progression. Predisposition to high blood pressure is also a risk factor for susceptibility to nephropathy, but its relationship with UAE in type 2 diabetes remains unclear. In this study, we have estimated heritabilities of UAE and blood pressure and their correlation attributable to genetic effects using 96 large families ascertained for type 2 diabetes. Methods. In these families, 630 individuals with type 2 diabetes and 639 individuals with normoglycemia were examined. All of them had a determination of UAE as the urinary albumin creatinine ratio (ACR), a convenient index of UAE, together with blood pressure and other variables, such as age, sex, and body mass index. A variance components approach was used to estimate heritability and genetic correlations for ACR and systolic and diastolic blood pressures (SBP and DBP) after adjustment for relevant covariates. Results. In the 96 pedigrees, 6481 usable pairs of relatives were identified. In the total collection of pairs, heritability for ACR (h(2) = 0.27, P < 0.001) was similar to that for blood pressure. When only pairs of diabetic relatives were analyzed (N = 1732), the estimates of heritability increased slightly for ACR (h(2) - 0.31), SEP (h(2) = 0.33), and DBP (h(2) = 0.23). A significant genetic correlation was found between ACR and SEP (r(g) 0.27) and DBP (r(g) 0.26) in all pairs of relatives (P < 0.001). In pairs of diabetic relatives, these values were higher for SEP and DBP, 0.38 and 0.52, respectively. Conclusion. In families with type 2 diabetes, UAE is a heritable trait, with a heritability similar to that for blood pressure. A significant genetic correlation between UAE and blood pressure, particularly in the presence of diabetes, indicates that these traits share common genetic determinants. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. RI Fogarty, Damian/A-8925-2011; OI Fogarty, Damian/0000-0001-8283-2932 FU NHLBI NIH HHS [HL45522]; NIDDK NIH HHS [DK47475, DK53534] NR 29 TC 74 Z9 81 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2000 VL 57 IS 1 BP 250 EP 257 DI 10.1046/j.1523-1755.2000.00833.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 276GN UT WOS:000084868200026 PM 10620206 ER PT J AU Wong, RJ Keel, SB Glynn, RJ Varvares, MA AF Wong, RJ Keel, SB Glynn, RJ Varvares, MA TI Histological pattern of mandibular invasion by oral squamous cell carcinoma SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 17th European Congress of Pathology CY SEP 18-23, 1999 CL BARCELONA, SPAIN DE mandible; histology; squamous cell carcinoma ID LOWER ALVEOLUS; HEAD; NECK; OVEREXPRESSION; EXPRESSION; RECURRENCE; FLOOR; MOUTH AB Objective: Mandibular invasion by oral squamous cell carcinoma may progress by either an infiltrative or an erosive histological pattern. The infiltrative pattern is marked by nests and cords of tumor cells along an irregular tumor front, and the erosive pattern exhibits a broad, pushing tumor front. The objectives of this study were 1) to define the characteristics associated with each histological pattern of mandibular invasion, 2) to assess the relationship between pattern of invasion and clinical outcome as measured by death with disease and disease presence at last follow-up, and 3) to determine whether the cell cycle markers cyclin D1 and Ki-67 are associated with the histological pattern of invasion or are predictive of outcome. Study Design: Retrospective study of 68 patients with mandibular invasion by oral cavity squamous cell carcinoma treated by mandibulectomy, Methods: The clinical records, pathology reports, and original H&E-stained slides were reviewed for each patient. Immunohistochemical staining of cyclin D1 and Ki-67 was performed on slides cut from the paraffin blocks of these patients' specimens. Results: The parameters found to be significantly associated with the infiltrative pattern of mandibular invasion included higher tumor grade, medullary space invasion, positive bone or soft tissue margins, history of previously failed treatment, and postoperative tumor recurrence. The infiltrative pattern had a positive bone margin rate of 47.6% and a primary site recurrence rate of 52.6%. In contrast, the erosive pattern had a positive bone margin rate of 4.9% and a primary site recurrence rate of 16.7%. The infiltrative pattern of invasion gave a fourfold increased risk of death with disease and disease presence at last follow-up in univariate and multivariate analyses when compared with the erosive pattern of invasion. The 3-year disease-free survival was 30% for the infiltrative pattern and 73% for the erosive pattern. The median disease-free survival was 1.5 years for the infiltrative pattern and 5.5 years for the erosive pattern. There was no correlation between cyclin D1 or Ki-67 staining and invasion pattern or clinical outcome. Conclusions: The infiltrative pattern of mandibular invasion by oral squamous cell carcinoma is correlated with a significantly worse prognosis when compared with the erosive pattern of invasion. The infiltrative pattern clearly exhibits a more aggressive behavior with an increased likelihood of positive margins, recurrence, death with disease, and shorter disease-free survival. We recommend that pathologists routinely comment on the histological pattern of invasion when reviewing oral squamous cell carcinoma with mandibular invasion. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA USA. RP Wong, RJ (reprint author), Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Head & Neck Serv, 1275 York Ave, New York, NY 10021 USA. NR 22 TC 39 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2000 VL 110 IS 1 BP 65 EP 72 DI 10.1097/00005537-200001000-00013 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 275DY UT WOS:000084805200013 PM 10646718 ER PT J AU Jyung, RW LeClair, EE Bernat, RA Kang, TS Ung, F McKenna, MJ Tuan, RS AF Jyung, RW LeClair, EE Bernat, RA Kang, TS Ung, F McKenna, MJ Tuan, RS TI Expression of angiogenic growth factors in paragangliomas SO LARYNGOSCOPE LA English DT Article DE vascular endothelial growth factor; platelet-derived; endothelial cell growth factor; hypoxia; tumor vasculature ID FACTOR THYMIDINE PHOSPHORYLASE; VASCULAR-PERMEABILITY FACTOR; THYROID-STIMULATING HORMONE; CAROTID-BODY TUMORS; TYROSINE KINASE; BREAST-CANCER; IN-VITRO; RECEPTORS; HYPOXIA; CELLS AB Objective/Hypothesis: To determine if angiogenic growth factors including vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are expressed in human paragangliomas, Study Design: A histopathologic and molecular examination of paraganglioma specimens obtained from surgical cases or retrieved from the Pathology Department of the Massachusetts Eye and Ear Infirmary, Methods: Fresh tumor or archival, paraffin-embedded paraganglioma specimens were analyzed by immunohistochemistry, Western blotting, and ELISA. Results: Positive immunohistochemical staining for VEGF was observed in five of nine surgical specimens and in six of eight archival specimens (11/17, or 65%). PD-ECGF immunoreactivity was detected in four of five surgical specimens and six of eight archival specimens (10/13, or 77%). The presence of PD-ECGF was confirmed by Western blot assay and ELISA confirmed the presence of VEGF in tumor extract. Conclusions: Both VEGF and PD-ECGF are expressed in paragangliomas and may contribute to the extreme vascularity of these tumors. C1 Temple Univ, Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19140 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Jyung, RW (reprint author), Temple Univ, Sch Med, Dept Otorhinolaryngol, Kresge W Bldg,Rm 102,3440 N Broad St, Philadelphia, PA 19140 USA. FU NIAMS NIH HHS [AR07583]; NICHD NIH HHS [HD08368] NR 55 TC 36 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2000 VL 110 IS 1 BP 161 EP 167 DI 10.1097/00005537-200001000-00029 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 275DY UT WOS:000084805200029 PM 10646734 ER PT S AU Roegener, J Lin, CP AF Roegener, J Lin, CP BE Exarhos, GJ Guenther, AH Kozlowski, MR Lewis, KL Soileau, MJ TI Photomechanical effects - experimental studies of pigment granule absorption, cavitation, and cell damage SO LASER-INDUCED DAMAGE IN OPTICAL MATERIALS: 1999 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 31st Annual Boulder Damage Symposium on Laser-Induced Damage in Optical Materials CY OCT 04-07, 1999 CL BOULDER, CO SP Lawrence Livermore Natl Lab, Univ New Mexico, Ctr High Technol Mat, Univ Cent Florida, Ctr Res & Educ Opt & Lasers, Def Evaluat & Res Agcy, NIST, Pacific NW Natl Lab, SPIE AB Absorption of pulsed laser radiation by individual melanosomes produces localized heating and microcavitation bubble formation around the particles, with transient bubble lifetimes of a few hundred nanoseconds. Intracellular cavitation in the retinal pigment epithelium (REP) leads to prompt cell death. Threshold laser fluence for cavitation bubble formation and RPE cell damage was measured as the exposure spot size was varied from 20 to 200 mu m using a RPE tissue explant model. The threshold energy for cell killing decreased with decreasing spot diameter but the fluence (energy/area) was nearly constant for all spotsizes. How this compares with data from in vivo animal studies is discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Roegener, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. NR 8 TC 13 Z9 13 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 0-8194-3508-2 J9 P SOC PHOTO-OPT INS PY 2000 VL 3902 BP 35 EP 40 DI 10.1117/12.379339 PG 6 WC Materials Science, Multidisciplinary; Optics SC Materials Science; Optics GA BP86M UT WOS:000086446600005 ER PT S AU Rajadhyaksha, M Menaker, G Gonzalez, S AF Rajadhyaksha, M Menaker, G Gonzalez, S BE Anderson, RR Bartels, KE Bass, LS Garrett, CG Gregory, KW Kollias, N Lui, H Malek, RS Peavy, GM Reidenbach, HD Reinisch, L Robinson, DS Tate, LP Trowers, EA Woodward, TA TI Confocal microscopy of excised human skin using acetic acid and crossed polarization: rapid detection of non-melanoma skin cancers SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutics, and Systems X CY JAN 22-25, 2000 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE optical imaging; confocal imaging; microscopy; noninvasive imaging; basal cell cancer; squamous cell cancer; Mohs surgery; skin imaging; dermatopathology; optical diagnosis ID SCANNING LASER MICROSCOPY; IN-VIVO; ROUTINE HISTOLOGY AB Moh's micrographic surgery for basal- and squamous-cell cancers (BCCs, SCCs) involves precise excision of the tumor with minimal damage to the surrounding normal skin. Precise excision is guided by histopathologic examination for tumor margins; typically, 2-4 slices of skin are excised, and there is a waiting time of 15-45 minutes for the surgeon and patient while each slice is being processed for histopathology. We can avoid the processing by using a confocal reflectance microscope; confocal detection of BCCs and SCCs is possible after staining the nuclei in the excised skin with 5% acetic acid, and imaging in crossed polarization. The cancerous nuclei appear bright against the dark surrounding normal dermis. The contrast is due to increased back-scattering as well as increased depolarization from the intra-nuclear structure relative to that from the surrounding normal dermis. As in conventional histopathology, the tumors are first detected at low resolution (section thickness 20 mu m) in a wide field (1-2 mm); nuclear morphology is then viewed at high resolution (section thickness 2 mu m) in a small field (0.25-0.50 mm). Mosaics of images ate assembled to produce confocal maps of the BCCs or SCCs within large excised tissue. Rapid detection (within minutes) is possible. C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. RP Rajadhyaksha, M (reprint author), Massachusetts Gen Hosp, Wellman Labs, Bartlett Hall Ext 630, Boston, MA 02114 USA. EM rajadmil@helix.mgh.harvard.edu NR 22 TC 5 Z9 5 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 0-8194-3523-6 J9 PROC SPIE PY 2000 VL 3907 BP 84 EP 88 DI 10.1117/12.386240 PG 5 WC Optics; Surgery SC Optics; Surgery GA BQ31M UT WOS:000087914600010 ER PT J AU Fowler, AJ AF Fowler, AJ TI Selective photothermolysis in skin by using subcutaneous optical fibers SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE lasers; modeling ID PORT-WINE STAINS; PULSED-LASER TREATMENT; DYE-LASER; HYPERTROPHIC SCARS; BLOOD-VESSELS; PHOTOCOAGULATION; TELANGIECTASIA; DISTRIBUTIONS; WAVELENGTHS; KELOIDS AB Background and Objective: Vascular selective photothermolysis has been shown to be effective in treating hypertrophic scars. Performing selective photothermolysis on the vasculature deep within thick scars requires new methods for delivering laser energy. It is the objective of this study to model the use of subcutaneous fiber optics to perform selective photothermolysis in skin as a possible aid in the treatment of thick scars. S tudy Design/Materials and Methods: A Monte Carlo simulation was performed to study the expected region of vascular necrosis in a two layer skin model when 585-nm radiation is delivered into the dermis by means of subcutaneous optical fibers. Results: The extent of vascular necrosis is independent of fiber diameter for a fixed total energy. A fiber penetrating barely below the epidermis decreases the maximum epidermal fluence by more than an order of magnitude relative to a superficial beam. Using four fibers simultaneously can significantly increase the depth of vascular necrosis, Conclusions: Small diameter fibers are optimum if the maximum fluence tolerable in the dermis is not a limiting factor. Shallowly inserted fibers can significantly decrease epidermal damage to dark-skinned patients undergoing laser (C) 2000 Wiley-Liss, Inc. C1 Univ Massachusetts, Dept Engn Mech, N Dartmouth, MA 02747 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Fowler, AJ (reprint author), Univ Massachusetts, Dept Engn Mech, N Dartmouth, MA 02747 USA. NR 31 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 2000 VL 27 IS 1 BP 10 EP 17 DI 10.1002/1096-9101(2000)27:1<10::AID-LSM2>3.0.CO;2-5 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 339KL UT WOS:000088476200002 PM 10918288 ER PT J AU Brinkmann, R Huttmann, G Rogener, J Roider, J Birngruber, R Lin, CP AF Brinkmann, R Huttmann, G Rogener, J Roider, J Birngruber, R Lin, CP TI Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fast flash photography; fluorescence microscopy; melanosome; pulse stretched laser; RPE-damage; selective photocoagulation; viability assay ID INTERNAL ABSORPTION-COEFFICIENT; STRESS TRANSIENT; BUBBLE FORMATION; MELANIN; INJURY; PHOTOCOAGULATION; MELANOSOME; CAVITATION; THRESHOLD; PARTICLES AB Background and Objective: Selective photodamage of the retinal pigment epithelium (RPE) is a new technique to treat a variety of retinal diseases without causing adverse effects to surrounding tissues such as the neural retina including the photoreceptors and the choroid. In this study, the mechanism of cell damage after laser irradiation was investigated. Study Design/Materials and Methods: Single porcine RPE-melanosomes and RPE cells were irradiated with a Nd:YLF laser (wavelength lambda = 527 nm, adjustable pulse duration tau = 250 nsec-3 mu sec) and a Nd:YAG laser (lambda = 532 nm, tau = 8 nsec). Fast flash photography was applied to observe vaporization at melanosomes in suspension. A fluorescence viability assay was used to probe the cells vitality. Results: The threshold radiant exposures for vaporization around individual melanosomes and for ED50 cell damage are similar at 8-nsec pulse duration. Both thresholds increase with pulse duration; however, the ED50 cell damage radiant exposure is 40% lower at 3 mu sec. Temperature calculations to model the onset of vaporization around the melanosomes are in good agreement with the experimental results when assuming a surface temperature of 150 degreesC to initiate vaporization and a homogeneous melanosome absorption coefficient of 8,000 cm(-1). Increasing the number of pulses delivered to RPE cells at a repetition rate of 500 Hz, the ED50 value decreases for all pulse durations. However, the behavior does not obey scaling laws such as the N-1/4 equation. Conclusion: The origin of RPE cell damage for single pulse irradiation up to pulse durations of 3 mu sec can be described by a damage mechanism in which microbubbles around the melanosomes cause a rupture of the cell structure. The threshold radiant exposure for RPE damage decreases with increasing number of pulses applied. Lasers Surg. Med. 27:451-464, 2000. (C) 2000 Wiley-Liss, Inc. C1 Med Laser Ctr Lubeck GmbH, D-23562 Lubeck, Germany. Univ Regensburg, Eye Clin, D-8400 Regensburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Brinkmann, R (reprint author), Med Laser Ctr Lubeck GmbH, Peter Monnik Weg 4, D-23562 Lubeck, Germany. RI Roider, Johann/E-4513-2010; Huttmann, Gereon/A-9072-2012; Brinkmann, Ralf/E-6701-2012; Birngruber, Reginald/Q-2342-2016 NR 40 TC 124 Z9 127 U1 1 U2 16 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 2000 VL 27 IS 5 BP 451 EP 464 DI 10.1002/1096-9101(2000)27:5<451::AID-LSM1006>3.0.CO;2-1 PG 14 WC Dermatology; Surgery SC Dermatology; Surgery GA 370WU UT WOS:000165146900007 PM 11126439 ER PT J AU Dwyer, PJ White, WM Fabian, RL Anderson, RR AF Dwyer, PJ White, WM Fabian, RL Anderson, RR TI Optical integrating balloon device for photodynamic therapy SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photodynamic therapy; laser; uniform illumination; balloon; cavity ID LIGHT DOSIMETRY; ESOPHAGEAL CANCER; BLADDER; CARCINOMA; TUMORS; HEAD; NECK AB Background and Objectives: It is difficult to deliver light uniformly and efficiently over the complex shapes presented by various organs for photodynamic therapy (PDT). A balloon delivery device for photodynamic therapy was designed and tested for treatment of various anatomic tissues. The device uses the principle of optical integration by multiple internal diffuse reflections to achieve uniform output illumination. Study Design/Materials and Methods: Soft, white, medical-grade silicone balloons were made in various shapes and tested for optical output, uniformity, efficiency, and power capabilities. Balloons were cast to be approximately the shape of the target tissue surface, organ, or cavity. Laser power was introduced into the saline-filled balloon by one or more fiber optics. Devices were constructed and used to illuminate oral mucosa and uterine endometrium for PDT. Results: The balloon walls had low optical absorption, high diffuse reflectivity (80-95%), and low diffuse transmittance (5-20%) in the 500- to 900-nm wavelength region. Optical efficiencies of 65% were typical with emitted light over complex, nonspherical surfaces. Efficiency increased with inflation of the device, such that irradiance (power/area) at the balloon surface was nearly constant with inflation. Conclusion: Optically integrating balloons can provide highly uniform, efficient light exposure over complex tissue surfaces. Uniformity and irradiance were not strongly affected by balloon inflation, and these robust devices are easy to produce in essentially any shape. 2000 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Wellman Labs Photomed, BHX 630,50 Blossom St, Boston, MA 02114 USA. NR 24 TC 14 Z9 14 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 2000 VL 26 IS 1 BP 58 EP 66 DI 10.1002/(SICI)1096-9101(2000)26:1<58::AID-LSM9>3.0.CO;2-V PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 276EY UT WOS:000084863700009 PM 10637004 ER PT J AU Alora, MBT Anderson, RR AF Alora, MBT Anderson, RR TI Recent developments in cutaneous lasers SO LASERS IN SURGERY AND MEDICINE LA English DT Article ID CARBON-DIOXIDE LASER; SWITCHED RUBY-LASER; PULSED-DYE-LASER; PORT-WINE STAINS; NEODYMIUM-YAG LASER; AU-LAIT MACULES; HIGH-ENERGY; DOSE-RESPONSE; HAIR REMOVAL; HUMAN-SKIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02144 USA. RP Anderson, RR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, 50 Blossom St,BHX 620, Boston, MA 02144 USA. NR 74 TC 36 Z9 37 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 2000 VL 26 IS 2 BP 108 EP 118 DI 10.1002/(SICI)1096-9101(2000)26:2<108::AID-LSM2>3.0.CO;2-4 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA 288BT UT WOS:000085542500002 PM 10685084 ER PT J AU Zenzie, HH Altshuler, GB Smirnov, MZ Anderson, RR AF Zenzie, HH Altshuler, GB Smirnov, MZ Anderson, RR TI Evaluation of cooling methods for laser dermatology SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE contact cooling; cryogen spray cooling ID PORT-WINE STAIN; THERMAL RESPONSE; HUMAN SKIN AB Background and Objective: Skin cooling is used to protect the epidermis in a variety of laser dermatology procedures, including leg vein treatment, hair removal, and port wine stain removal. Spray and contact cooling are the two most popular methods, but similarities and differences of these techniques are not well understood. Study Design/Materials and Methods: A theoretical model of skin cooling is presented for two different regimens: "soft" cooling in which freezing of the skin is not permitted and "hard" cooling in which the skin can be frozen to a given depth. Spray and contact cooling were also compared experimentally using an in vitro model. Results: For a fixed skin surface temperature, spray and contact cooling theoretically produce the same cooling profile in the skin. Anatomic depth of cooling depends on the time for which either the spray or contact is applied. In vitro experiments caused temperature at the simulated basal layer to be between -5 and +5 degrees C for both spray (tetrafluoroethane, boiling point -26 degrees C) and contact (-27 degrees C sapphire plate) cooling. The theoretical precooling analysis shows hard mode to be faster and more selective than soft mode; however, cooling time for hard mode must be carefully controlled to prevent irreversible epidermal damage caused by freezing. Conclusions: Both spray and contact cooling provide efficient skin cooling. The choice of cooling method depends on other factors such as the target depth, cost, safety, and ergonomic factors. (C) 2000 Wiley-Liss, Inc. C1 Palomar Med Prod Inc, Burlington, MA 01803 USA. Inst Fine Mech & Opt Laser Ctr, St Petersburg 197101, Russia. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Zenzie, HH (reprint author), Palomar Med Prod Inc, 82 Cambridge St, Burlington, MA 01803 USA. NR 19 TC 85 Z9 85 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 2000 VL 26 IS 2 BP 130 EP 144 DI 10.1002/(SICI)1096-9101(2000)26:2<130::AID-LSM4>3.0.CO;2-J PG 15 WC Dermatology; Surgery SC Dermatology; Surgery GA 288BT UT WOS:000085542500004 PM 10685086 ER PT J AU Pfefer, TJ Smithies, DJ Milner, TE van Gemert, MJC Nelson, JS Welch, AJ AF Pfefer, TJ Smithies, DJ Milner, TE van Gemert, MJC Nelson, JS Welch, AJ TI Bioheat transfer analysis of cryogen spray cooling during laser treatment of port wine stains SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE bioheat transfer; cryogen spray cooling; laser-tissue interaction; light propagation; Monte Carlo; numerical modeling; port wine stains; thermal damage ID BLOOD-VESSELS; THERMAL RESPONSE; SKIN TISSUE; LIGHT; PHOTOTHERMOLYSIS; IRRADIATION; TELANGIECTASIA; DISTRIBUTIONS; CONJUNCTION; ANATOMY AB Background and Objective: The thermal response of port wine stain (PWS) skin to a combined treatment of pulsed laser irradiation and cryogen spray cooling (CSC) was analyzed through a series of simulations performed with a novel optical-thermal model that incorporates realistic tissue morphology. Study Design/Materials and Methods: The model consisted of (1) a three-dimensional reconstruction of a PWS biopsy, (2) a Monte Carlo optical model, (3) a finite difference heat transfer model, and (4) an Arrhenius thermal damage calculation. Simulations were performed for laser pulses of 0.5, 2, and 10 ms and a wavelength of 585 nm. Simulated cryogen precooling spurts had durations of 0, 20, or 60 ms and terminated at laser onset. Continuous spray cooling, which commenced 60 ms before laser onset and continued through the heating and relaxation phases, was also investigated. Results: The predicted response to CSC included maximal preirradiation temperature reductions of 27 degrees C at the superficial surface and 12 degrees C at the dermoepidermal junction. For shorter laser pulses (0.5, 2 ms), precooling significantly reduced temperatures in superficial regions, yet did not effect superficial vessel coagulation. Continuous cooling was required to reduce significantly thermal effects for the 10-ms laser pulse. Conclusions: For the PWS morphology and treatment parameters studied, optimal damage distributions were obtained for a 2-ms laser pulse with a 60-ms precooling spurt. Epidermal and vascular morphology as well as laser pulse duration should be taken into account when planning CSC/laser treatment of PWS. Our novel, realistic-morphology modeling technique has significant potential as a tool for optimizing PWS treatment parameters. (C) 2000 Wiley-Liss, Inc. C1 Univ Texas, Biomed Engn Program, Austin, TX 78712 USA. Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92715 USA. Univ Amsterdam, Acad Med Ctr, Ctr Laser, NL-1105 AZ Amsterdam, Netherlands. RP Pfefer, TJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett 722,55 Fruit St, Boston, MA 02114 USA. RI Pfefer, Josh/I-9055-2012 FU NIAMS NIH HHS [AR43419] NR 39 TC 49 Z9 49 U1 0 U2 5 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 2000 VL 26 IS 2 BP 145 EP 157 DI 10.1002/(SICI)1096-9101(2000)26:2<145::AID-LSM5>3.0.CO;2-0 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA 288BT UT WOS:000085542500005 PM 10685087 ER PT J AU Campos, VB Dierickx, CC Farinelli, WA Lin, TYD Manuskiatti, W Anderson, RR AF Campos, VB Dierickx, CC Farinelli, WA Lin, TYD Manuskiatti, W Anderson, RR TI Ruby laser hair removal: Evaluation of long-term efficacy and side effects SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fluence; hirsutism; hypertrichosis; treatment ID SELECTIVE PHOTOTHERMOLYSIS; FOLLICLES; HIRSUTISM AB Background and Objective: Although several studies on laser-assisted hair removal have been published, data on long-term follow-up are few. The present study investigated the long-term efficacy and safety of normal-mode ruby laser pulses on hair removal. Study Design/Materials and Methods: The normal-mode ruby laser (Epi-laser; 694 nm, 3 msec) was used to treat a wide range of body sites in 51 volunteers. The mean follow-up after the last treatment was 8.37 months. Results: Sixty-three percent of the patients had sparse regrowth. The mean fluence used was 46.5 J/cm(2) in patients who had sparse hair regrowth and 39.3 J/cm(2) in patients who had moderate hair regrowth (P = 0.0127). Transient pigmentary changes occurred most frequently in patients with skin type 4. Conclusion: The normal-mode ruby laser is an efficient and safe method for long-term hair reduction, especially in fair-skinned individuals with dark hair. Higher fluences produce greater long-term efficacy. Adverse effects are minimal and transient. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed Dept Dermatol, Boston, MA 02114 USA. Mahidol Univ, Siriraj Hosp, Dept Dermatol, Bangkok 10700, Thailand. RP Anderson, RR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed Dept Dermatol, 50 Blossom St,Bartlett Extens 6, Boston, MA 02114 USA. NR 19 TC 25 Z9 25 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 2000 VL 26 IS 2 BP 177 EP 185 DI 10.1002/(SICI)1096-9101(2000)26:2<177::AID-LSM8>3.0.CO;2-J PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 288BT UT WOS:000085542500008 PM 10685090 ER PT J AU Zhou, M Gu, L Abshire, TC Homans, A Billett, AL Yeager, AM Findley, HW AF Zhou, M Gu, L Abshire, TC Homans, A Billett, AL Yeager, AM Findley, HW TI Incidence and prognostic significance of MDM2 oncoprotein overexpression in relapsed childhood acute lymphoblastic leukemia SO LEUKEMIA LA English DT Article DE MDM2 oncoprotein; relapsed acute lymphoblastic leukemia ID TOPOISOMERASE-II; P53 MUTATIONS; EXPRESSION; GENE; MALIGNANCIES; APOPTOSIS; DIAGNOSIS; PROTEIN AB MDM2 overexpression by pediatric ALL cells at initial diagnosis has been linked to poor response to therapy, In the present study, we evaluated the incidence of MDM2 overexpression by ALL cells from pediatric patients at first relapse and compared MDM2 protein levels with in vitro response to adriamycin and with duration of initial complete remission (CR1). Since an important role of MDM2 in enhancing cell proliferation and survival appears to be inhibition of p53 activity, we also evaluated the status of p53 in these patients' leukemic cells, MDM2 protein levels were determined by Western blot analysis of leukemic bone marrow cells obtained from 42 patients with B cell precursor (BCP) ALL who relapsed during or following therapy on standard FOG ALL protocols. Twelve of 42 (29%) cases have MDM2 levels greater than or equal to 10-fold higher than those detected in normal bone marrow mononuclear (NMMC) cells, which express relatively low levels of protein, Thirty cases (71%) expressed MDM2 at levels <10-fold those in NMMC, including 24 MDM2-negative cases (57%). P53 mutations were detected by single-strand conformation polymorphism analysis in two cases. Overexpression of MDM2 (greater than or equal to 10-fold) was significantly correlated with adriamycin resistance and decreased duration of CRI. Eight of 12 (75%) overexpressers showed high levels of in vitro resistance to adriamycin, compared to four of 30 (13%) nonoverexpressers (P < 0.005). The median CR1 for MDM2 overexpressers was 20.5 months (range: 3-75 months) compared to 41 months (range: 8-98 months) for non-overexpressers (P < 0.01). Four of 42 patients failed to achieve CR following reinduction: leukemic cells from three of these patients either overexpressed MDM2 or contained a mutant p53, These results indicate that overexpression of MDM2 plays a significant role in refractory pediatric ALL and is associated with early relapse, adriamycin resistance, and failure to respond to re-induction therapy. C1 Emory Univ, Sch Med, Div Pediat Hematol Oncol BMT, Atlanta, GA 30322 USA. Univ Vermont, Coll Med, Burlington, VT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Findley, HW (reprint author), Emory Univ, Sch Med, Div Pediat Hematol Oncol BMT, 2040 Ridgewood Dr NE, Atlanta, GA 30322 USA. FU NCI NIH HHS [CA03161, CA69177, R29CA72020-03] NR 21 TC 61 Z9 63 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2000 VL 14 IS 1 BP 61 EP 67 DI 10.1038/sj.leu.2401619 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 277GX UT WOS:000084925300009 PM 10637478 ER PT J AU Ichinohasama, R Miura, I Takahashi, N Sugawara, T Tamate, E Endoh, K Endoh, F Naganuma, H DeCoteau, JF Griffin, JD Kadin, ME Ooya, K AF Ichinohasama, R Miura, I Takahashi, N Sugawara, T Tamate, E Endoh, K Endoh, F Naganuma, H DeCoteau, JF Griffin, JD Kadin, ME Ooya, K TI Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature SO LEUKEMIA LA English DT Article DE Ph-negative (Ph(-)) non-Hodgkin's lymphoma; Ph-positive chronic myelogenous leukemia; extramedullary localized blast crisis ID CHRONIC MYELOID-LEUKEMIA; T-CELL LYMPHOMA; BONE-MARROW TRANSPLANTATION; CLUSTER REGION REARRANGEMENT; TCR-BETA GENES; PHILADELPHIA-CHROMOSOME; MALIGNANT-LYMPHOMA; LYMPHOBLASTIC TRANSFORMATION; MYELOPROLIFERATIVE DISORDER; BCR AB This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient I was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admired lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admired neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively, DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL, Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs, This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking SCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of ORAL. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph(+) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. C1 Tohoku Univ, Sch Dent, Dept Oral Pathol, Aoba Ku, Sendai, Miyagi 9808575, Japan. Akita Univ, Sch Med, Dept Internal Med 3, Akita, Japan. Furukawa City Hosp, Div Internal Med, Furukawa, Japan. Sendai City Hosp, Div Internal Med, Sendai, Miyagi, Japan. Univ Saskatchewan, Royal Univ Hosp, Dept Pathol, Saskatoon, SK, Canada. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Hosp, Dept Pathol, Boston, MA USA. RP Ichinohasama, R (reprint author), Tohoku Univ, Sch Dent, Dept Oral Pathol, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan. NR 56 TC 19 Z9 23 U1 2 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2000 VL 14 IS 1 BP 169 EP 182 DI 10.1038/sj.leu.2401606 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 277GX UT WOS:000084925300024 PM 10637493 ER PT J AU Stone, M AF Stone, M TI The cancer dictionary. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA USA. RP Stone, M (reprint author), Massachusetts Gen Hosp Lib, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JAN PY 2000 VL 125 IS 1 BP 78 EP 78 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 275DT UT WOS:000084804700043 ER PT J AU Kelly, K AF Kelly, K TI Health and healthcare in the United States: County and metro area data. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp Lib, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JAN PY 2000 VL 125 IS 1 BP 85 EP 85 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 275DT UT WOS:000084804700060 ER PT J AU Nguyen, QD Uy, HS Akpek, EK Harper, SL Zacks, DN Foster, CS AF Nguyen, QD Uy, HS Akpek, EK Harper, SL Zacks, DN Foster, CS TI Choroidopathy of systemic lupus erythematosus SO LUPUS LA English DT Article DE choroidopathy; retinopathy; central nervous system (CNS); nephropathy; systemic lupus erythematosus (SLE); vasculitis; scleritis ID SEROUS RETINAL-DETACHMENT; VISUAL-LOSS; DISEASE; RETINOPATHY; ANTIBODIES; EYE AB Purpose: To describe the ocular and systemic manifestations associated with systemic lupus erythematosus (SLE) choroidopathy. Methods: Three new cases of choroidopathy in patients with active SLE were described. Twenty-five published cases of lupus choroidopathy were summarized. Results: There have been 28 cases of lupus choroidopathy (47 involved eyes) that have been reported in the English literature since 1968, including the three current cases. Only two of the patients were male. The choroidopathy was bilateral in 19 patients (68%), All 28 patients (100%) had active systemic vascular disease at the onset of their choroidopathy; 18 (64%) had nephropathy and 10 (36%) had central nervous system (CNS) lupus vasculitis. All but one of the patients had a known diagnosis of SLE at the onset of choroidopathy. 30 of the 47 involved eyes had presenting visual acuity of 20/40 or better; 14 eyes showed improvement in visual acuity with therapy. 23 patients (82%) had resolution of their choroidopathy when their systemic disease was brought under control. Despite treatment, 4 of the 28 patients (14%) died from complications of SLE. Conclusions: Although less known than retinopathy, lupus choroidopathy may be more common than generally appreciated. It usually serves as a sensitive indicator of lupus activity. The presence of SLE choroidopathy is generally indicative of coexistent (although sometimes occult) nephropathy, CNS vasculitis, and other SLE visceral lesions. Immunomodulation of the systemic disease can lead to improvement and resolution of the systemic vasculitis as well as the choroidopathy. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 24 TC 35 Z9 37 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2000 VL 9 IS 4 BP 288 EP 298 DI 10.1191/096120300680199024 PG 11 WC Rheumatology SC Rheumatology GA 320MZ UT WOS:000087406100009 PM 10866100 ER PT S AU Kyewski, B Rottinger, B Klein, L AF Kyewski, B Rottinger, B Klein, L BE Melchers, F TI Making central T-cell tolerance efficient: Thymic stromal cells sample distinct self-antigen pools SO LYMPHOID ORGANOGENESIS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Lymphoid Organogenesis CY NOV 05-06, 1999 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND HO BASEL INST IMMUNOL ID MEDULLARY EPITHELIUM; INTRATHYMIC EXPRESSION; INTERCELLULAR TRANSFER; PRESENTATION PATHWAY; AUTOIMMUNE-DISEASE; COMPLEX; DELETION; PROTEIN; REPERTOIRE; INDUCTION C1 German Canc Res Ctr, Tumor Immunol Program, D-69120 Heidelberg, Germany. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Kyewski, B (reprint author), German Canc Res Ctr, Tumor Immunol Program, INF 280, D-69120 Heidelberg, Germany. RI Klein, Ludger/G-8785-2011 NR 36 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67569-8 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 251 BP 139 EP 145 PG 7 WC Developmental Biology; Hematology; Immunology; Microbiology SC Developmental Biology; Hematology; Immunology; Microbiology GA BR65F UT WOS:000167097700018 PM 11036769 ER PT S AU Morita, Y Tilly, JL AF Morita, Y Tilly, JL BE Goetzl, EJ Lynch, KR TI Sphingolipid regulation of female gonadal cell apoptosis SO LYSOPHOSPHOLIPIDS AND EICOSANOIDS IN BIOLOGY AND PATHOPHYSIOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Lysophospholipids and Eicosanoids in Cancer and in Cardiovascular and Neurodegenerative Diseases CY JUN 25-28, 1999 CL NEW YORK, NEW YORK SP New York Acad Sci, NIH, NCI, NHLBI ID DAUNORUBICIN-INDUCED APOPTOSIS; CULTURED GRANULOSA-CELLS; GERMINAL DISC REGION; BCL-2 GENE FAMILY; LYSOPHOSPHATIDIC ACID; SPHINGOMYELIN HYDROLYSIS; SPHINGOSINE 1-PHOSPHATE; PRIMORDIAL FOLLICLES; OVARIAN FOLLICLES; OOCYTE APOPTOSIS AB Ceramide and sphingosine-1-phosphate (SIP) are sphingosine-based lipid signaling molecules that have been implicated as key mediators of cellular growth, differentiation, and apoptosis, The cellular response depends on cell type, on the absence or presence of other signals initiated by the same or another stimulus, and on the subcellular location of sphingomyelin hydrolysis leading to ceramide generation. Consistent with mounting evidence Implicating components of the sphingomyelin pathway as mediators of cellular life and death in nonreproductive tissues, recent data have indicated that sphingolipid-based signaling events are also prominent features of cellular development and apoptosis in the fetal and postnatal female gonads. This area of investigation represents a new research avenue of considerable significance for both basic biology and clinical medicine because of the massive levels of developmental death that occur normally in the female germ line, especially during gametogenesis, as well as of the central role of oocyte apoptosis in female gonadal failure resulting from pathologic insults. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01AG12279]; NICHD NIH HHS [R01HD34226]; NIEHS NIH HHS [R01ES08430] NR 86 TC 24 Z9 26 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-213-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 905 BP 209 EP 220 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BQ27A UT WOS:000087758200021 PM 10818455 ER PT J AU Mintorovitch, J Duerinckx, AJ Goldman, MD Meisner, HH AF Mintorovitch, J Duerinckx, AJ Goldman, MD Meisner, HH TI Breathhold cine MRI of left ventricular function in patients with obstructive sleep apnea: work-in-progress SO MAGNETIC RESONANCE IMAGING LA English DT Article DE sleep apnea; sleep disorders; cine MRI; left ventricular dysfunction; wall thickness ID MAGNETIC-RESONANCE; VOLUME; REPRODUCIBILITY; TURBOFLASH; MOTION; LONG AB Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that can cause left ventricular (LV) dysfunction. In patients with OSA, the LV dysfunction is usually evaluated by echocardiography. The purpose of this study was to evaluate whether the use of breathhold cine MRI for the study of LV dysfunction would be feasible and well tolerated by patients with OSA. Six volunteers and five patients underwent a breathhold cine MRI study of the LV using a 1.5 Tesla MR imager. Cine MRI was performed using a breathhold k-space segmented TurboFLASH technique during end-expiration. Systolic thickening of the LV septal wall was 49% +/- 16% in normals vs. 25% +/- 10.5% in patients (p < 0.05). Systolic thickening of the LV free wall was 42% +/- 12% in normals vs. 22% +/- 9% in patients (p < 0.05), There was a significant difference in end-diastolic wall thickness between the two groups. All patients tolerated the procedure well. The total duration of each study was relatively short (less than 11 min). Breathhold MRI techniques can be used to study LV dysfunction in patients with respiratory disability such as OSA. (C) 2000 Elsevier Science Inc. All rights reserved. C1 VA Greater Los Angeles Healthcare Ctr Wadsworth, Serv Radiol, Los Angeles, CA 90073 USA. RP Duerinckx, AJ (reprint author), VA Greater Los Angeles Healthcare Ctr Wadsworth, Serv Radiol, Mail Route W114,MRI Bld 507,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 31 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JAN PY 2000 VL 18 IS 1 BP 81 EP 87 DI 10.1016/S0730-725X(99)00111-3 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 271HB UT WOS:000084587200009 PM 10642105 ER PT J AU Chadwick, BP Leyne, M Gill, S Liebert, CB Mull, J Mezey, E Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Gusella, JF Slaugenhaupt, SA AF Chadwick, BP Leyne, M Gill, S Liebert, CB Mull, J Mezey, E Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Gusella, JF Slaugenhaupt, SA TI Cloning, mapping, and expression of a novel brain-specific transcript in the Familial Dysautonomia candidate region on Chromosome 9q31 SO MAMMALIAN GENOME LA English DT Article ID EXON AMPLIFICATION; GENES; PROTEINS C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NIMH, Genet Lab, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. RP Slaugenhaupt, SA (reprint author), HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Brownstein, Michael/B-8609-2009; Pinkett, Heather/M-9235-2014 FU NINDS NIH HHS [NS36326] NR 15 TC 6 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JAN PY 2000 VL 11 IS 1 BP 81 EP 83 DI 10.1007/s003350010017 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 267EU UT WOS:000084344800017 PM 10603000 ER PT J AU Horner, T Liberthson, R Jellinek, MS AF Horner, T Liberthson, R Jellinek, MS TI Psychosocial profile of adults with complex congenital heart disease SO MAYO CLINIC PROCEEDINGS LA English DT Article ID FOLLOW-UP; YOUNG-ADULTS; CHILDREN; HEALTH; TETRALOGY; ILLNESS; IMPACT; FALLOT AB Objective: Despite the increasing number of adults with congenital heart disease (CHD), little is known of the emotional life of these long-term survivors; hence, we under took a study to establish a psychological profile of these individuals so as to optimize their care, Patients and Methods: We performed psychiatric evaluation by both interview and questionnaire on 29 ambulatory patients with CHD (mean age, 38 years; range, 26-56 years). Results: Although many met symptomatic criteria for psychiatric diagnosis, most were functional in day-to-day life and used denial in adapting to their CHD. In childhood, extended absences from school, cyanosis, scars, and sports restrictions hindered friendships and conflicted with a sense of "normalcy"; teasing and low self-esteem were more notable in boys; girls more readily hid behind makeup, nail polish, and clothing, In adulthood most were concerned about shortened life expectancy, disability, and childbearing and child rearing, Virtually all were highly committed to both school and work performance. All but those with complete, uncomplicated early repair expressed unresolved frustration, anger, and fears of a future that might include further medical complications. Conclusion: Listening to this selected group of patients offers insight that may be helpful to the clinical care of patients with CHD and other patients with lifelong disease. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Westmead Hosp, Westmead, NSW 2145, Australia. Community Serv, Westmead, NSW, Australia. RP Liberthson, R (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 24 TC 78 Z9 79 U1 1 U2 3 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2000 VL 75 IS 1 BP 31 EP 36 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 270ZN UT WOS:000084567200007 PM 10630755 ER PT J AU Felgenhauer, J Hawkins, D Pendergrass, T Lindsley, K Conrad, KU Miser, JS AF Felgenhauer, J Hawkins, D Pendergrass, T Lindsley, K Conrad, KU Miser, JS TI Very intensive, short-term chemotherapy for children and adolescents with metastatic sarcomas SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE sarcoma; metastatic disease; pediatrics; chemotherapy ID LOCALIZED EWINGS-SARCOMA; INTERGROUP RHABDOMYOSARCOMA; DOSE INTENSITY; YOUNG-ADULTS; MESNA UROPROTECTION; MULTIMODAL THERAPY; PEDIATRIC ONCOLOGY; PROGNOSTIC FACTOR; SOFT-TISSUE; STAGE-II AB Background. To improve the prognosis for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), and undifferentiated sarcoma (UDS), we tested the feasibility of a brief, intensive regimen of chemotherapy that maximizes dose intensity. Procedure. Twenty-four children and adolescents with metastatic sarcomas received VAC[ME chemotherapy, consisting of eight courses of vincristine 2 mg/m(2) on day 0; doxorubicin 20 mg/m(2)/day on days 0-3; cyclophosphamide 360 mg/m(2)/day on days 0-4; ifosfamide 1,800 mg/m(2)/day on days 0-4; mesna 2,400 mg/m(2)/day; and etoposide 100 mg/m(2)/day on days 0-4. Doxorubicin was omitted in courses 7 and 8. Granulocyte colony-stimulating factor (GCSF) was used routinely following each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery and resolution of nonhematopoietic toxicities permitted. Surgical resection followed course 6, and radiotherapy followed the completion of all therapy. Results. Thirteen patients achieved a complete response (CRI with chemotherapy alone, and seven more achieved a CR following surgical resection after course 6 (overall CR rate 83%). There was one toxic death. Thirteen patients developed progressive disease, with 2- and 4-year event-free survivals (95% confidence interval) of 50% (30-70%) and 45% (25-65%), respectively. Myelosuppression was severe and cumulative, leading to dose reductions and chemotherapy interval delays. Mucositis was the most common nonhematopoietic toxicity. Conclusions. VACIME chemotherapy was a feasible dose-intensive regimen for pediatric patients with metastatic sarcomas. Cumulative hematopoietic toxicity and severe mucositis limited the delivery of chemotherapy as prescribed. The CR and 2-year event-free survival rates were superior to those of most previously reported regimens. (C) 2000 Wiley-Liss, Inc. C1 Deaconess Med Ctr, Spokane, WA USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed Surg, Seattle, WA 98195 USA. City Hope Natl Med Ctr, Dept Pediat, Duarte, CA 91010 USA. RP Hawkins, D (reprint author), Childrens Hosp & Reg Med Ctr MS, CH29,4800 Sand Point Way, Seattle, WA 98105 USA. NR 50 TC 20 Z9 20 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD JAN PY 2000 VL 34 IS 1 BP 29 EP 38 DI 10.1002/(SICI)1096-911X(200001)34:1<29::AID-MPO6>3.3.CO;2-Z PG 10 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 270VL UT WOS:000084557800006 PM 10611582 ER PT J AU Aron, DC Gordon, HS DiGiuseppe, DL Harper, DL Rosenthal, GE AF Aron, DC Gordon, HS DiGiuseppe, DL Harper, DL Rosenthal, GE TI Variations in risk-adjusted cesarean delivery rates according to race and health insurance SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of the Midwestern Section of the Society-of-General-Internal-Medicine CY NOV, 1997 CL CHICAGO, ILLINOIS SP Soc Gen Internal Med, Midwestern Sect DE cesarean delivery; insurance; insurance; race ID ICD-9-CM ADMINISTRATIVE DATA; CLINICAL COMORBIDITY INDEX; RACIAL ETHNIC-DIFFERENCES; BIRTH CERTIFICATE DATA; CARDIOVASCULAR PROCEDURES; WASHINGTON-STATE; BLACK-AMERICANS; SECTION RATES; NEW-YORK; CARE AB OBJECTIVE. To assess the association between race and insurance and Cesarean delivery rates after adjusting for clinical risk factors that increase the likelihood of cesarean delivery. DESIGN. Retrospective cohort study in 21 hospitals in northeast Ohio. SUBJECTS. 25,697 women without prior cesarean deliveries admitted for labor and delivery January 1993 through June 1995. METHODS. Demographic and clinical data were abstracted from patients' medical records. The risk of cesarean delivery was adjusted for 39 maternal and neonatal risk factors that were included in a previously developed risk-adjustment model using nested logistic regression analysis. MAIN OUTCOME MEASURES. Odds ratios for cesarean delivery in nonwhite patients relative to whites and for patients with government insurance or who were uninsured relative to patients with commercial insurance. RESULTS. The overall rate of cesarean delivery was similar in white and nonwhite patients (15.8% and 16.1%, respectively), but rates varied (P < 0.001) according to insurance (17.0%, 14.2%, 10.7% in patients with commercial insurance, government insurance, and without insurance, respectively). However, after adjusting for clinical factors, the adjusted odds ratio (OR) of cesarean delivery was higher in nonwhite patients (OR = 1.34; 95% CI: 1.14-1.57; P < 0.001), but similar for patients with government insurance (OR = 1.01; 95% CI: 0.90-1.14; P = 0.84) and lower for uninsured patients (OR = 0.65; 95% CI, 0.41, 1.03; P = 0.067), albeit not statistically significant. In analyses stratified according to quintiles of predicted risk of cesarean delivery, racial differences were largely limited to patients in the lower risk quintiles. However, differences in odds ratios for uninsured patients were seen across the risk quintiles, although odds ratios were not statistically significant. CONCLUSION. After adjusting for clinical factors, race and insurance status may independently influence the use of cesarean delivery. The higher rates in nonwhites and lower rates in the uninsured may reflect differences in patient preferences or expectations, differences in physician practice, or unmeasured risk factors. The lower adds of cesarean delivery in uninsured women, particularly women at high risk, may raise the issue of underutilization of services and warrants further study. C1 Louis Stokes Cleveland VA Med Ctr, Educ Off 14 W, Dept Med, Inst Hlth Care Res, Cleveland, OH 44106 USA. Louis Stokes Cleveland VA Med Ctr, Div Clin & Mol Endocrinol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Internal Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Cleveland VA Med Ctr, Dept Med, Cleveland, OH USA. Cleveland VA Med Ctr, Inst Hlth Care Res, Cleveland, OH USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Qual Informat Management Program, Cleveland, OH USA. RP Aron, DC (reprint author), Louis Stokes Cleveland VA Med Ctr, Educ Off 14 W, Dept Med, Inst Hlth Care Res, 10701 E Blvd, Cleveland, OH 44106 USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 71 TC 30 Z9 31 U1 3 U2 7 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 2000 VL 38 IS 1 BP 35 EP 44 DI 10.1097/00005650-200001000-00005 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 270ZG UT WOS:000084566600005 PM 10630718 ER PT J AU DeKay, ML Nickerson, CAE Ubel, PA Hershey, JC Spranca, MD Asch, DA AF DeKay, ML Nickerson, CAE Ubel, PA Hershey, JC Spranca, MD Asch, DA TI Further explorations of medical decisions for individuals and for groups SO MEDICAL DECISION MAKING LA English DT Article DE decision making; expected utility theory; practice guidelines; risk; survey research ID FREQUENCY FORMATS; ANALYTIC MODEL; PHYSICIANS; JUDGMENT; PROBABILITY; DISCREPANCY; GUIDELINES; BEDSIDE; GAMBLES AB Background. Important discrepancies between clinical practice and health policy may be related to the ways in which physicians and others make decisions about individuals and groups. Previous research has found that physicians and laypersons asked to consider an individual patient generally make different decisions than those asked to consider a group of comparable patients, but this discrepancy has not been observed in more recent studies. This study was designed to explore possible reasons for these findings. Methods. Prospective jurors (N = 1,013) each made a recommendation regarding a risky treatment for an incurable blood condition. Perspective (individual vs group) was crossed with uncertainty frame (probability vs frequency) and response wording (original vs revised) in a 2 x 2 x 2 between-participants design. Results. When the strength of participants' recommendations was considered, the effects of perspective, uncertainty frame, and response wording were not statistically significant. When recommendations were dichotomized, participants in the revised-response-wording conditions were more likely to recommend treatment to the group than to the individual. Conclusions. These results conflict with previous findings for this scenario and suggest that reported differences between decisions for individuals and decisions for groups are not robust. C1 Carnegie Mellon Univ, H John Heinz III Sch Publ Policy & Management, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Engn & Publ Policy, Pittsburgh, PA 15213 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Operat & Informat Management, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RAND Corp, Santa Monica, CA USA. RP DeKay, ML (reprint author), Carnegie Mellon Univ, H John Heinz III Sch Publ Policy & Management, Pittsburgh, PA 15213 USA. NR 35 TC 6 Z9 7 U1 1 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-MAR PY 2000 VL 20 IS 1 BP 39 EP 44 DI 10.1177/0272989X0002000105 PG 6 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 272TM UT WOS:000084667100005 PM 10638535 ER PT J AU Earle, CC Wells, GA AF Earle, CC Wells, GA TI An assessment of methods to combine published survival curves SO MEDICAL DECISION MAKING LA English DT Article DE survival analysis; meta-analysis; life tables; proportional hazards models ID INDIVIDUAL PATIENT DATA; CELL LUNG-CANCER; ECONOMIC-EVALUATION; CLINICAL-TRIALS; SUPPORTIVE CARE; OVARIAN-CANCER; META-ANALYSIS; HEALTH-CARE; METAANALYSIS; CHEMOTHERAPY AB Purpose. To assess the accuracies of different techniques for combining published survival curves, for use in disease modeling applications. Methods. Five methods were identified: 1) iterative generalized least-squares (IGLS), 2) meta-analysis of failure-time data with adjustment for covariates (MFD), 3) nonlinear regression (NLR), 4) log relative risk (LRR), and 5) weighted LRR (w-LRR). Each method was used to combine the survival curves from eight single-arm Phase II trials of chemotherapy in 918 patients with advanced non-small-cell lung cancer (NSCLC). The resulting summary curves were compared with the curve calculated from the corresponding individual patient data (IPD). Results. All methods were able to produce accurate summary survival curves statistically similar to the IPD-derived curve. Maximum discrepancies ranged from 1.8% to 4.7%. MFD appeared to be the most accurate when censoring information was complete. Characteristics of the component trials that adversely affected the accuracies of the different techniques were 1) a high proportion of censored observations (MFD); 2) variability in the length of follow-up (IGLS, NLR, LRR, w-LRR); and 3) the heterogeneity of the treatment results (NLR, w-LRR). Conclusions. All methods were able to accurately reproduce summary survival curves from the published literature. The best method depends on characteristics of the data and the purpose of the analysis. C1 Univ Ottawa, Ottawa, ON, Canada. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 454 Brookline Ave, Boston, MA 02115 USA. NR 40 TC 32 Z9 32 U1 0 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-MAR PY 2000 VL 20 IS 1 BP 104 EP 111 DI 10.1177/0272989X0002000113 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 272TM UT WOS:000084667100013 PM 10638543 ER PT S AU Westin, CF Lorigo, LM Faugeras, O Grimson, WEL Dawson, S Norbash, A Kikinis, R AF Westin, CF Lorigo, LM Faugeras, O Grimson, WEL Dawson, S Norbash, A Kikinis, R BE Delp, S DiGioia, AM Jaramaz, B TI Segmentation by adaptive geodesic active contours SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2000 SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 3rd International Conference on Medical Image Computing and Computer-Assisted Intervention CY OCT 11-14, 2000 CL PITTSBURGH, PA ID MEAN-CURVATURE FLOW AB This paper introduces the use of spatially adaptive components into the geodesic active contour segmentation method for application to volumetric medical images. These components are derived from local structure descriptors and are used both in regularization of the segmentation and in stabilization of the image-based vector field which attracts the contours to anatomical structures in the images. They are further used to incorporate prior knowledge about spatial location of the structures of interest. These components can potentially decrease the sensitivity to parameter settings inside the contour evolution system while increasing robustness to image noise. We show segmentation results on blood vessels in magnetic resonance angiography data and bone in computed tomography data. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. INRIA, Sophia Antipolis, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. EM westin@bwh.harvard.edu NR 22 TC 6 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-41189-5 J9 LECT NOTES COMPUT SC PY 2000 VL 1935 BP 266 EP 275 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BT09M UT WOS:000171938700027 ER PT S AU Everett, PC Seldin, EB Troulis, M Kaban, LB Kikinis, R AF Everett, PC Seldin, EB Troulis, M Kaban, LB Kikinis, R BE Delp, S DiGioia, AM Jaramaz, B TI A 3-D system for planning and simulating minimally-invasive distraction osteogenesis of the facial skeleton SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2000 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 3rd International Conference on Medical Image Computing and Computer-Assisted Intervention CY OCT 11-14, 2000 CL PITTSBURGH, PENNSYLVANIA ID IMAGES AB Three-dimensional planning tools will enable the use of minimally-invasive distraction osteogenesis for the correction of craniomaxillofacial deformities by simulating treatment, precisely quantifying movement vectors, and aiding pre and post-treatment evaluation. Current techniques extrapolate 3D surgical movements and outcomes based on standard 2D radiographs. Surgical planning and outcome evaluation would be greatly improved by an accurate, reproducible and reliable 3D treatment planning system. Building upon a software foundation that includes the 3D Slicer of the Brigham & Women's Hospital, and the Visualization Toolkit (VTK) of Schroeder, Martin & Lorensen, we add algorithms that support interactive cutting of large triangulated surface models, collision detection, landmark-based registration, and cephalometric analysis. The oriented bounding-box tree (OBB tree) structure is used throughout to enhance the interactivity of selection, collision detection, and cutting. The cutting tool is notable for its generality and preservation of topological closure in the resultant models. In a retrospective case study, the collision of the proximal fragment of the distracted mandible with the skull base is detected and the resulting 3D bone movements are quantified. The distracted bone volume is computed. In prospective cases, this system will be used to compute the placement and configuration of appropriate buried distractor(s). C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Surg Planning Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Everett, PC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Surg Planning Lab, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-41189-5 J9 LECT NOTES COMPUT SC PY 2000 VL 1935 BP 1029 EP 1039 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BT09M UT WOS:000171938700107 ER PT J AU Aro, A Amarasiriwardena, C Lee, ML Kim, R Hu, H AF Aro, A Amarasiriwardena, C Lee, ML Kim, R Hu, H TI Validation of K x-ray fluorescence bone lead measurements by inductively coupled plasma mass spectrometry in cadaver legs SO MEDICAL PHYSICS LA English DT Article DE bone lead; validation; K x-ray fluorescence (KXRF); ICP-MS ID IN-VIVO; EXPOSURE; METABOLISM; BURDEN; MARKER; BLOOD AB K x-ray fluorescence (KXRF) systems are being used in a growing number of epidemiologic studies to measure bone lead levels as a biological marker of accumulated lead exposure. Although validation of the KXRF technique in lead-doped phantoms and bare bone specimens has been repeatedly demonstrated, few studies have compared KXRF to chemical measurements of actual intact cadaver limbs (with skin and soft tissues). In this study, lead levels in eight amputated human legs were measured by KXRF; after dissection, levels in the bare bones were again measured by KXRF and then by inductively coupled plasma mass spectrometry (ICP-MS). We observed close agreement between the KXRF and ICP-MS measurements with correlation coefficients for both the tibia and patella greater than 0.9. In this study we provide further support for the validity of KXRF measurements, particularly with respect to the patella. (C) 2000 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Aro, A (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, 75 Francis St, Boston, MA 02115 USA. FU NIEHS NIH HHS [5 P42 ES-05947, 2 P30 ES 00002, 2R01-ES 05257-06A1] NR 31 TC 31 Z9 31 U1 0 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2000 VL 27 IS 1 BP 119 EP 123 DI 10.1118/1.598863 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 275VP UT WOS:000084841100016 PM 10659745 ER PT J AU Caviness, VS Takahashi, T Nowakowski, RS AF Caviness, VS Takahashi, T Nowakowski, RS TI Neocortical malformation as consequence of nonadaptive regulation of neuronogenetic sequence SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE neocortical malformations; histogenesis; neuronogenesis; cell cycle; G1 restriction point; primary microcephaly; periventricular nodular heterotopia; holoprosencephaly; tuberous sclerosis ID DEVELOPING CEREBRAL-CORTEX; CELL-CYCLE LENGTH; MICE LACKING; PERIVENTRICULAR HETEROTOPIA; PROLIFERATIVE EPITHELIUM; NEURONAL MIGRATION; BAND HETEROTOPIAS; RESTRICTION POINT; VISUAL-CORTEX; FETAL MONKEY AB Variations in the structure of the neocortex induced by single gene mutations may be extreme or subtle. They differ from Variations in neocortical structure encountered across and within species in that these "normal" structural variations are adaptive (both structurally and behaviorally), whereas those associated with disorders of development are not. Here we propose that they also differ in principle in that they represent disruptions of molecular mechanisms that are not normally regulatory to variations in the histogenetic sequence. We propose an algorithm for the operation of the neuronogenetic sequence in relation to the overall neocortical histogenetic sequence and highlight the restriction point of the G1 phase of the cell cycle as the master regulatory control point for normal coordinate structural variation across species and importantly within species. From considerations based on the anatomic evidence from neocortical malformation in humans, we illustrate in principle how this overall sequence appears to be disrupted by molecular biological linkages operating principally outside the control mechanisms responsible for the normal structural variation of the neocortex. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Caviness, VS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 25 Fruit St, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS33433, NS12005] NR 111 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2000 VL 6 IS 1 BP 22 EP 33 DI 10.1002/(SICI)1098-2779(2000)6:1<22::AID-MRDD4>3.0.CO;2-5 PG 12 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 290XM UT WOS:000085703200004 PM 10899794 ER PT J AU Pomeroy, SL Kim, JYH AF Pomeroy, SL Kim, JYH TI Biology and pathobiology of neuronal development SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE neuron; central nervous system; development; growth factors; inherited disorders ID PLATELET-ACTIVATING-FACTOR; RECEPTOR TYROSINE KINASES; DIEKER LISSENCEPHALY GENE; SONIC-HEDGEHOG; VISUAL-CORTEX; FLOOR PLATE; POSTNATAL-DEVELOPMENT; SIGNALING PROTEIN; CORTICAL-NEURONS; NERVOUS-SYSTEM AB Differentiation of neurons within the central nervous system occurs by the combined effects of intrinsic genetic programs and epigenetic stimuli. Disorders causing mental retardation and other abnormalities of higher cortical function arise by disturbances of the normal developmental sequence. (C) 2000 Wiley-Liss, Inc. C1 Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Pomeroy, SL (reprint author), Childrens Hosp, Dept Neurol, Div Neurosci, Enders 260,300 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24926]; NINDS NIH HHS [NS35701] NR 88 TC 14 Z9 15 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 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2000 VL 6 IS 1 BP 41 EP 46 PG 6 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 290XM UT WOS:000085703200006 PM 10899796 ER PT J AU Roshan, B Tofler, GH Weinrauch, LA Gleason, RE Keough, JA Lipinska, I Lee, AT D'Elia, JA AF Roshan, B Tofler, GH Weinrauch, LA Gleason, RE Keough, JA Lipinska, I Lee, AT D'Elia, JA TI Improved glycemic control and platelet function abnormalities in diabetic patients with microvascular disease SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 59th Scientific Session of the American-Diabetes-Association Annual Meeting CY JUN 18-22, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Diabet Assoc ID VASCULAR-DISEASE; THROMBOXANE SYNTHESIS; VONWILLEBRAND-FACTOR; AUTONOMIC FUNCTION; PLASMA-FIBRINOGEN; INSULIN INFUSION; BLOOD-VISCOSITY; MELLITUS; AGGREGATION; COMPLICATIONS AB Patients with diabetes mellitus have a variety of platelet and coagulation system dysfunctions. At least theoretically, these can contribute to microvascular complications. Intensive glycemic control has been demonstrated to decrease microvascular complications in type 1 diabetics. We studied 16 patients with type 1 diabetes mellitus (11 men and five women; mean age, 39 years) with albuminuria greater than 0.1 g/d and/or proteinuria greater than 0.3 g/d and a creatinine clearance rate higher than 30 mL/min. They received a regimen including three to four injections of insulin per day with or without a weekly infusion of intravenous insulin, and were evaluated for 6 months. We compared the plasma level of von Willebrand factor, platelet aggregation responses to adenosine diphosphate (ADP), epinephrine, and collagen, and platelet adhesion at the beginning of the study and at follow-up intervals. Glycemic control improved significantly. There were no significant differences in the platelet aggregation responses to ADP (1.59 +/- 0.34 v 1.88 +/- 0.23 mmol/L, P = .3; normal, 4.6 +/- 0.2), epinephrine (0.50 +/- 0.20 v 1.11 +/- 0.31 mmol/L, P = .06; normal, 7.6 +/- 1.5), or collagen (92.4 +/- 6.61 v 82.60 +/- 3.78 seconds, P = .6; normal, 79.1 +/- 3.1) or in platelet adhesion (126.31 +/- 16.95 v 195.08 +/- 30.2 platelets, P = .34; normal, 68.6 +/- 1.4). Baseline von Willebrand factor increased, but not significantly (166.38% +/- 10.6% v 142.72% +/- 14.73%, P = .21; normal, 102.0% +/- 6.0%), In type 1 diabetic patients with established microvascular complications of nephropathy, a statistically significant improvement in glycemic control did not improve the in vitro platelet function abnormalities. Improved glycemic control delays the progression of microvascular disease through mechanisms not measured by tests of platelet function. Copyright (C) 2000 by W.B. Saunders Company. C1 Joslin Diabet Ctr, John Cook Renal Unit, Boston, MA 02215 USA. Beth Israel Deaconess Hosp, Dept Med, Boston, MA 02215 USA. Inst Prevent Cardiovasc Dis, Boston, MA USA. Mt Auburn Hosp, Clin Res Sect, Cambridge, MA 02238 USA. Harvard Univ, Sch Med, Boston, MA USA. Picower Inst Med Res, Manhasett, NY USA. RP D'Elia, JA (reprint author), Joslin Diabet Ctr, John Cook Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. OI Weinrauch, Larry/0000-0003-1357-9528 NR 54 TC 16 Z9 16 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2000 VL 49 IS 1 BP 88 EP 91 DI 10.1016/S0026-0495(00)90813-8 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 273XA UT WOS:000084733600014 PM 10647069 ER PT J AU Tanabe, YN Randolph, MA Shimizu, A Lee, WPA AF Tanabe, YN Randolph, MA Shimizu, A Lee, WPA TI Xenotransplantation model for vascularized musculoskeletal tissues in rodents SO MICROSURGERY LA English DT Article ID NATURAL-KILLER-CELLS; TO-RAT HEART; BONE ALLOGRAFTS; SKIN XENOGRAFTS; TRANSPLANTATION; REJECTION; MOUSE; CYCLOSPORINE; INDUCTION; IMMUNOSUPPRESSION AB The purpose of this study was to establish a model and to define the mechanism of rejection for the transplantation of vascularized musculoskeletal xenografts between C57BL/6j (B6) mice and Lewis rats. This was accomplished by using conventional skin xenografts to determine immunologic baseline data between these species and by performing musculoskeletal grafts from the B6 mice transplanted into Lewis rats. After the transplant, the xenografts were examined histologically and the recipients were assessed for immune reaction using in vitro assays to measure both cell-mediated and humoral responses. The results obtained from the skin xenografts showed activation of both cellular and humoral immunologic responses. All musculoskeletal xenografts were rejected between 3 and 4 postoperative days. Histologically, the grafts showed extensive vascular injury manifested by thrombosis and hemorrhage, suggesting an early humoral response. Anti-donor antibody production was detected in the recipient's sera soon after rejection of the xenogeneic tissue. The cell-mediated immune response, although detectable by the in vitro assays, was less pronounced than the humoral response and corroborated the histologic findings of mild lymphocyte infiltration in the rejected tissue. These results demonstrate that humoral rejection plays a predominant role in the rejection of vascularized musculoskeletal xenotransplants between concordant species. This mouse-to-rat vascularized xenograft model will be utilized for further studies on inducing tolerance to vascularized musculoskeletal xenografts. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WACC 452, Boston, MA 02114 USA. NR 27 TC 3 Z9 3 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 0738-1085 J9 MICROSURG JI Microsurgery PY 2000 VL 20 IS 2 BP 59 EP 64 DI 10.1002/(SICI)1098-2752(2000)20:2<59::AID-MICR3>3.0.CO;2-6 PG 6 WC Surgery SC Surgery GA 292KU UT WOS:000085793900003 PM 10702738 ER PT J AU Mathes, DW Randolph, MA Lee, WPA AF Mathes, DW Randolph, MA Lee, WPA TI Strategies for tolerance induction to composite tissue allografts SO MICROSURGERY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Composite Tissue Allotransplantation CY MAY 17-18, 2000 CL LOUISVILLE, KENTUCKY ID BONE-MARROW TRANSPLANTATION; MIXED ALLOGENEIC CHIMERISM; DONOR-SPECIFIC TOLERANCE; RENAL-ALLOGRAFTS; MINIATURE SWINE; CYNOMOLGUS MONKEYS; RADIATION CHIMERAS; CLASS-I; CELL; CD40 AB The emerging field of composite tissue transplantation offers the potential to replace lost tissues from cadaveric sources. Two major obstacles currently limit the future of composite tissue allotransplantation. The first is chronic rejection, attributed to both antibody deposition and cell-mediated destruction of transplanted tissue. The second obstacle is complications associated with the chronic use of immunosuppressive agents. Our laboratory has been investigating several strategies to induce tolerance to limb tissue allografts to provide solutions to many of the current limitations in allotransplantation. Three strategies show promise in the ability to induce tolerance to organ allografts. The first involves genetic matching at the HLA loci followed by a short course of immunosuppression. The second is the application of a "mixed chimerism" regimen followed by transplantation. The third is costimulatory blockade using a short course of monoclonal antibodies, such as anti-CD40 ligand and CTLA4-Ig after transplantation. Inducing a state of tolerance to limb allografts would eliminate the need for chronic immunosuppression and may also prevent the onset of chronic rejection. The ability to induce allograft tolerance would greatly expand the indications for composite tissue transplantation. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WAC-453,15 Parkman St, Boston, MA 02114 USA. OI Mathes, David/0000-0003-4388-1373 NR 36 TC 31 Z9 32 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 0738-1085 J9 MICROSURG JI Microsurgery PY 2000 VL 20 IS 8 BP 448 EP 452 DI 10.1002/1098-2752(2000)20:8<448::AID-MICR17>3.0.CO;2-N PG 5 WC Surgery SC Surgery GA 389MV UT WOS:000166242900016 PM 11150998 ER PT J AU Uchida, T Myers, MG White, MF AF Uchida, T Myers, MG White, MF TI IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION SITES; RECEPTOR SUBSTRATE FAMILY; GROWTH-FACTOR-I; P70 S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; PLECKSTRIN HOMOLOGY; PHOSPHOTYROSINE PROTEIN; INTRACELLULAR CALCIUM; HEMATOPOIETIC-CELLS; CYTOKINE ACTION AB Insulin receptor substrate (IRS) proteins are tyrosine phosphorylated and mediate multiple signals during activation of the receptors for insulin, insulin-like growth factor 1 (IGF-1), and various cytokines. In order to distinguish common and unique functions of IRS-1, IRS-2, and IRS-4, we expressed them individually in 32D myeloid progenitor cells containing the human insulin receptor (32D(IR)). Insulin promoted the association of Grb-2 with IRS-1 and IRS-4, whereas IRS-2 weakly bound Grb-2; consequently, IRS-1 and IRS-4 enhanced insulin-stimulated mitogen-activated protein kinase activity. During insulin stimulation, IRS-1 and IRS-2 strongly bound p850 alpha/beta, which activated phosphatidylinositol (PI) 3-kinase, protein kinase B (PKB)/Akt, and p70(s6k) and promoted the phosphorylation of BAD. IRS-4 also promoted the activation of PKB/Akt and BAD phosphorylation during insulin stimulation; however, it weakly bound or activated p85-associated PI 3-kinase and failed to mediate the activation of p70(s6k), Insulin strongly inhibited apoptosis of interleukin-3 (IL-3)deprived 32D(IR) cells expressing IRS-1 or IRS-2 but failed to inhibit apoptosis of cells expressing IRS-4. Consequently, 32D(IR) cells expressing IRS-4 proliferated slowly during insulin stimulation. Thus, the activation of PKB/Akt and BAD phosphorylation might not be sufficient to inhibit the apoptosis of IL-3-deprived 32D(IR) cells unless p85-associated PI 3-kinase or p70(s6k) are strongly activated. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK38712, R01 DK038712] NR 59 TC 48 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 1 BP 126 EP 138 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265DY UT WOS:000084227100013 PM 10594015 ER PT J AU Kophengnavong, T Michnowicz, JE Blackwell, TK AF Kophengnavong, T Michnowicz, JE Blackwell, TK TI Establishment of distinct MyoD, E2A and twist DNA binding specificities by different basic Region-DNA conformations SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX-LOOP-HELIX; TRANSCRIPTIONAL ACTIVATION; CRYSTAL-STRUCTURE; C-MYC; MUSCLE DEVELOPMENT; GENE ACTIVATION; B/HLH/Z DOMAIN; BHLH PROTEINS; IN-VITRO; RECOGNITION AB Basic helix-loop-helix (bHLH) proteins perform a,wide variety of biological functions. Most bHLH proteins recognize the consensus DNA sequence CAN NTG (the E-box consensus sequence is underlined) but acquire further functional specificity by preferring distinct internal and flanking bases. In addition, induction of myogenesis by MyoD-related bHLH proteins depends on myogenic basic region (BR) and BR-HLH junction residues that are not essential for binding to a muscle-specific site, implying that their BRs may be involved in other critical interactions. We have investigated whether the myogenic residues influence DNA sequence recognition and how MyoD, Twist, and their E2A partner proteins prefer distinct CAN NTG sites. In MyoD, the myogenic BR residues establish specificity for particular CAN NTG sites indirectly, by influencing the conformation through which the BR helix binds DNA. An analysis of DNA binding by BR and junction mutants suggests that an appropriate BR DNA conformation is necessary but not sufficient for myogenesis, supporting the model that additional interactions with this region are important. The sequence specificities of E2A and Twist proteins require the corresponding BR residues. In addition, mechanisms that position the BR allow E2A to prefer distinct half-sites as a heterodimer with MyoD or Twist, indicating that the E2A BR can be directed toward different targets by dimerization with different partners. Our findings indicate that E2A and its partner bHLH proteins bind to CAN NTG sites by adopting particular preferred BR-DNA conformations, from which they derive differences in sequence recognition that can be important for functional specificity. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 60 TC 48 Z9 48 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 1 BP 261 EP 272 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265DY UT WOS:000084227100027 PM 10594029 ER PT J AU O'Reilly, AM Pluskey, S Shoelson, SE Neel, BG AF O'Reilly, AM Pluskey, S Shoelson, SE Neel, BG TI Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; DOMINANT-NEGATIVE MUTANT; CELL-SHAPE CHANGES; MESODERM INDUCTION; MAP KINASE; GASTRULATION MOVEMENTS; SIGNAL-TRANSDUCTION; TERMINAL SEQUENCE; C-CADHERIN; EXPRESSION AB In Xenopus ectodermal explants (animal caps), fibroblast growth factor (FGF) evokes two major events: induction of ventrolateral mesodermal tissues and elongation. The Xenopus FGF receptor (XFGFR) and certain downstream components of the XFGFR signal transduction pathway (e.g., members of the Ras/Raf/MEK/mitogen-activated protein kinase [MAPK] cascade) are required for both of these processes. Likewise, activated versions of these signaling components induce mesoderm and promote animal cap elongation. Previously, using a dominant negative mutant approach, we showed that the protein-tyrosine phosphatase SHP-2 is necessary for FGF-induced MAPK activation, mesoderm induction, and elongation of animal caps. Taking advantage of recent structural information, we now have generated novel, activated mutants of SHP-2. Here, we show that expression of these mutants induces animal cap elongation to an extent comparable to that evoked by FGF. Surprisingly, however, activated mutant-induced elongation can occur without mesodermal cytodifferentiation and is accompanied by minimal activation of the MAPK pathway and mesodermal marker expression. Our results implicate SHP-2 in a pathway(s) directing cell movements in vivo and identify potential downstream components of this pathway. Our activated mutants also may be useful for determining the specific functions of SHP-2 in other signaling systems. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Neel, BG (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, HIM 1047,330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA049152, R01 CA49152]; NIDDK NIH HHS [R01 DK45943, R01 DK045943, R01 DK051729, R01 DK51729] NR 65 TC 82 Z9 84 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 1 BP 299 EP 311 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265DY UT WOS:000084227100030 PM 10594032 ER PT J AU Li, SH Wang, QJ Chakladar, A Bronson, RT Bernards, A AF Li, SH Wang, QJ Chakladar, A Bronson, RT Bernards, A TI Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CELL ADHESION; SMALL GTPASES; E-CADHERIN; BINDING PROTEIN; RHO-GTPASES; MDCK CELLS; CALMODULIN; IDENTIFICATION; DOMAIN; TARGET AB Human IQGAP1 is a widely expressed 190-kDa Cdc42-, Rac1-, and calmodulin-binding protein that interacts with F-actin in vivo and that can cross-link F-actin microfilaments in vitro. Recent results have implicated IQGAP1 as a component of pathways via which Cdc42 or Rad modulates cadherin-based cell adhesion (S, Kuroda et al,, Science 281:832-835, 1998), whereas yeast IQGAP-related proteins have been found to play essential roles during cytokinesis. To identify critical in vivo functions of IQGAP1, we generated deficient mice by gene targeting. We demonstrate that IQGAP1 null mutants arise at normal frequency and show no obvious defects during development or for most of their adult life. Loss of IQGAP1 also does not affect tumor development or tumor progression, but mutant mice exhibit a significant (P < 0.0001) increase in late-onset gastric hyperplasia relative to wild-type animals of the same genetic background. While we cannot exclude that functional redundancy with IQGAP2 contributes to the Lack of developmental phenotypes, the restricted expression pattern of IQGAP2 is not obviously altered in adult IQGAP1 mutant mice. Thus, IQGAP1 does not serve any essential nonredundant functions during murine development but may serve to maintain the integrity of the gastric mucosa in older animals. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Bernards, A (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [CA70294] NR 31 TC 93 Z9 97 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 2 BP 697 EP 701 DI 10.1128/MCB.20.2.697-701.2000 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270VZ UT WOS:000084559000028 PM 10611248 ER PT S AU Gomez-Tortosa, E Irizarry, MC Gomez-Isla, T Hyman, BT AF Gomez-Tortosa, E Irizarry, MC Gomez-Isla, T Hyman, BT BE Growdon, JH Wurtman, RJ Corkin, S Nitsch, RM TI Clinical and neuropathological correlates of dementia with Lewy bodies SO MOLECULAR BASIS OF DEMENTIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging CY FEB 18-20, 2000 CL ZURICH, SWITZERLAND SP Alzheimers Assoc, NIA, Astra Zeneca, Janssen Pharmaceutica ID ALZHEIMERS-DISEASE; BODY DISEASE; PARKINSONS-DISEASE; SENILE DEMENTIA; IMMUNOCYTOCHEMISTRY; HIPPOCAMPUS; NEURITES AB Dementia with Lewy bodies (DLB) is characterized pathologically by widespread Lewy body (LB) neuronal inclusions in the brain, but the contribution of LBs to the clinical syndrome of dementia and parkinsonism is unclear. In a clinical-pathological study of 25 cases with DLB, we examined the regional neuroanatomical distribution of Lewy-related pathology using alpha -synuclein immunostaining to evaluate the relationship between LBs, neuronal loss, Alzheimer-type changes, and the clinical phenotype. Compared to traditional ubiquitin immunostaining, alpha -synuclein immunohistochemistry was more specific and slightly more sensitive, staining about 5% more intracytoplasmic structures. There was a consistent pattern of vulnerability to LB formation across subcortical, paralimbic, limbic, and neocortical structures, which was independent of concomitant Alzheimer-type changes. There were no significant differences in regional LB densities among patients with or without cognitive fluctuations, visual hallucinations, delusions, recurrent falls or parkinsonism. Duration of disease correlated weakly with LB density. There was no neuronal loss in superior temporal sulcus or entorhinal cortex in pure DLB cases compared to nondemented controls. Thus, DLB is characterized by a specific neuroanatomical vulnerability to LB pathology, distinct from AD pathology, with a complicated relationship to clinical symptoms. C1 Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AGO8487, P5O-AGO5134] NR 19 TC 31 Z9 31 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 1-57331-283-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 920 BP 9 EP 15 PG 7 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09W UT WOS:000171939600002 PM 11193181 ER PT S AU Irizarry, MC Rebeck, GW Cheung, B Bales, K Paul, SM Holzman, D Hyman, BT AF Irizarry, MC Rebeck, GW Cheung, B Bales, K Paul, SM Holzman, D Hyman, BT BE Growdon, JH Wurtman, RJ Corkin, S Nitsch, RM TI Modulation of A beta deposition in APP transgenic mice by an apolipoprotein E null background SO MOLECULAR BASIS OF DEMENTIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging CY FEB 18-20, 2000 CL ZURICH, SWITZERLAND SP Alzheimers Assoc, NIA, Astra Zeneca, Janssen Pharmaceutica ID AMYLOID PRECURSOR PROTEIN; SPORADIC ALZHEIMERS-DISEASE; RECEPTOR-RELATED PROTEIN; FIBRIL FORMATION; PEPTIDE DEPOSITION; NEURONAL LOSS; IN-VITRO; ASSOCIATION; ALPHA-2-MACROGLOBULIN; POLYMORPHISM AB Several lines of evidence implicate apolipoprotein E (apoE) and its receptor-the low density lipoprotein receptor related protein (LRP)-in Alzheimer's disease (A beta) pathogenesis, including increased amyloid deposition in human A beta brains of people containing the apoE epsilon4 allele, presence of apoE and LRP in amyloid plaques, and in vitro uptake of amyloid precursor protein (APP) and amyloid P protein (A beta) by LRP. Studies of crosses of apoE knockout mice with APP transgenic mice support a complex interaction between apoE and A beta deposition. In the Tg2576 mice expressing human APP(K670N-M671L), apoE determines the amount, morphology, vascular pattern, and neuropil response to A beta deposits. In the PDAPP mice expressing human APP(V717F) apoE also affects the anatomical localization of cerebral A beta deposits. Thus, APP transgenic mice can serve as models to investigate genetic influences on the amount and timing of cerebral amyloidosis, the morphology of amyloid plaques, and the vulnerability of specific neuroanatomical regions to A beta deposition. C1 Massachusetts Gen Hosp, Alzheimer Dis Res Unit, Boston, MA 02114 USA. Lilly Res Labs, Neurosci Discovery Res, Indianapolis, IN 46202 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp East, Alzheimer Dis Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG00793, AG13956] NR 30 TC 33 Z9 33 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 1-57331-283-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 920 BP 171 EP 178 PG 8 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09W UT WOS:000171939600022 PM 11193147 ER PT S AU Berezovska, O Jack, C McLean, P Aster, JC Hicks, C Xia, WM Wolfe, MS Weinmaster, G Selkoe, DJ Hyman, BT AF Berezovska, O Jack, C McLean, P Aster, JC Hicks, C Xia, WM Wolfe, MS Weinmaster, G Selkoe, DJ Hyman, BT BE Growdon, JH Wurtman, RJ Corkin, S Nitsch, RM TI Rapid Notch1 nuclear translocation after ligand binding depends on presenilin-associated gamma-secretase activity SO MOLECULAR BASIS OF DEMENTIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging CY FEB 18-20, 2000 CL ZURICH, SWITZERLAND SP Alzheimers Assoc, NIA, Astra Zeneca, Janssen Pharmaceutica ID DROSOPHILA PRESENILIN; DIFFERENTIATION; LOCALIZATION; DEPOSITION; MUTATIONS; NEURONS; RELEASE AB Recent data suggest an intimate relationship between the familial Alzheimer disease gene presenilin 1 (PS1) and proteolytic processing of both the amyloid precursor protein (APP) and the important cell signaling molecule, Notch1. We now show, using mammalian cells transfected with full-length Notch1, that the C terminal domain of Notch1 rapidly translocates to the nucleus upon stimulation with the physiologic ligand Delta and initiates a CBF1-dependent signal transduction cascade. Using this assay, we demonstrate that the same aspartate mutations in PS1 that block APP processing also prevent Notch1 cleavage and translocation to the nucleus. Moreover, we show that two APP gamma -secretase inhibitors also diminish Notch1 nuclear translocation in a dose-dependent fashion. However, Notch1 signaling, assessed by measuring the activity of CBF1, a downstream gene, was reduced but not completely abolished in the presence of either aspartate mutations or gamma -secretase inhibitors. Our results support the hypothesis that similar PS1-related enzymatic activity is necessary for both APP and Notch1 processing, yet suggest that Notch Signaling may remain relatively preserved with moderate levels of gamma -secretase inhibition. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Berezovska, O (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Lab, 149-13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG 14744, P0 AG 15379] NR 15 TC 25 Z9 26 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 1-57331-283-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 920 BP 223 EP 226 PG 4 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09W UT WOS:000171939600029 PM 11193154 ER PT S AU Tesco, G Tanzi, RE AF Tesco, G Tanzi, RE BE Growdon, JH Wurtman, RJ Corkin, S Nitsch, RM TI GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin - Effects of the D257/D385A and FAD-linked mutations SO MOLECULAR BASIS OF DEMENTIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging CY FEB 18-20, 2000 CL ZURICH, SWITZERLAND SP Alzheimers Assoc, NIA, Astra Zeneca, Janssen Pharmaceutica ID ALZHEIMERS-DISEASE; PRESENILIN-1; PROTEIN; ACTIVATION AB We have previously shown that the endogenous C-terminal fragment of presenilin 1 co-immunoprecipitates with endogenous beta -catenin. Since PS1 has been suggested to be involved in beta -catenin stabilization, we further investigated whether GSK3 beta, responsible for beta -catenin phosphorylation and degradation, is part of the PS1/beta -catenin complex. In naive H4 and CHO cells, PS1 co-immunoprecipitated with both endogenous beta -catenin and GSK3P. In addition, GSK3 beta endogenously binds to the PS1-CTF/NTF complex and beta -catenin in naive CHO cells. GSK3 beta also co-immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of gamma -secretase activity, we also tested whether PSI endoproteolysis is required for beta -catenin/GSK3 beta /PS1 binding and whether PS1 FAD-linked mutations affect GSK3 beta recruitment in the PS1/beta -catenin complex. GSK3 beta was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, Delta E10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and Delta E10) or the presence of PS1-FAD mutations does not interfere with beta -catenin/GSK3 beta /PS1 complex formation. C1 Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Unit, 149-13th St, Charlestown, MA 02129 USA. NR 16 TC 45 Z9 46 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 1-57331-283-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 920 BP 227 EP 232 PG 6 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09W UT WOS:000171939600030 PM 11193155 ER PT S AU Hock, C Maddalena, A Heuser, I Naber, D Oertel, W Von der Kammer, H Wienrich, M Raschig, A Deng, M Growdon, JH Nitsch, RM AF Hock, C Maddalena, A Heuser, I Naber, D Oertel, W Von der Kammer, H Wienrich, M Raschig, A Deng, M Growdon, JH Nitsch, RM BE Growdon, JH Wurtman, RJ Corkin, S Nitsch, RM TI Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer's disease SO MOLECULAR BASIS OF DEMENTIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging CY FEB 18-20, 2000 CL ZURICH, SWITZERLAND SP Alzheimers Assoc, NIA, Astra Zeneca, Janssen Pharmaceutica ID APOLIPOPROTEIN-E GENOTYPE; INVERSE CORRELATION; CLINICAL-DIAGNOSIS; PRECURSOR PROTEIN; DEMENTIA; TAU; A-BETA-1-42(43); SECRETION; SEVERITY; ASSAY AB Brain amyloid load in Alzheimer's disease (AD) is, at least in genetic forms, associated with overproduction of amyloid beta -peptides (A beta). Thus, lowering A beta production is a central therapeutic target in AD and may be achieved by modulating such key enzymes of amyloid precursor protein (APP) processing as beta-, gamma-, and alpha -secretase activities. Talsaclidine is a selective muscarinic M1 agonist that stimulates the nonamyloidogenic alpha -secretase pathway in model systems. Talsaclidine was administered double-blind, placebo-controlled, and randomized to 24 AD patients and cerebrospinal fluid (CSF) levels of total A beta were quantitated before and after 4 weeks of drug treatment. We observed that talsaclidine decreases CSF levels of A beta significantly over time within the treatment group (n = 20) by a median of 16% as well as compared to placebo (n = 4) by a median of 27%. We conclude that treatment with selective M1 agonists may reduce A beta production and may thus be further evaluated as a potential amyloid-lowering therapy of AD. C1 Univ Zurich, Dept Psychiat Res, CH-8029 Zurich 8, Switzerland. Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Univ Hamburg, Dept Psychiat, Hamburg, Germany. Univ Marburg, Dept Neurol, Marburg, Germany. Univ Hamburg, Ctr Mol Neurobiol, D-2000 Hamburg, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hock, C (reprint author), Univ Zurich, Dept Psychiat Res, Lenggstr 31, CH-8029 Zurich 8, Switzerland. NR 26 TC 39 Z9 41 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 1-57331-283-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 920 BP 285 EP 291 PG 7 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09W UT WOS:000171939600040 PM 11193166 ER PT S AU Cuajungco, MP Faget, KY Huang, XD Tanzi, RE Bush, AI AF Cuajungco, MP Faget, KY Huang, XD Tanzi, RE Bush, AI BE Growdon, JH Wurtman, RJ Corkin, S Nitsch, RM TI Metal chelation as a potential therapy for Alzheimer's disease SO MOLECULAR BASIS OF DEMENTIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging CY FEB 18-20, 2000 CL ZURICH, SWITZERLAND SP Alzheimers Assoc, NIA, Astra Zeneca, Janssen Pharmaceutica ID AMYLOID PRECURSOR PROTEIN; A-BETA; HYDROGEN-PEROXIDE; FREE-RADICALS; NEURODEGENERATIVE-DISORDERS; CEREBROSPINAL-FLUID; INDUCED AGGREGATION; SENILE PLAQUES; BINDING-SITE; ZINC AB Alzheimer's disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer's disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetylcholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer's disease is linked to the characteristic neocortical amyloid-beta deposition, which may be mediated by abnormal metal interaction with A beta as well as metal-mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid-beta plaque formation. This paper reviews recent observations on the possible etiologic role of A beta deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer's disease therapeutics. C1 MGH, Lab Oxidat Biol, Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Bush, AI (reprint author), MGH, Lab Oxidat Biol, Genet & Aging Unit, 13th St Bldg 149, Charlestown, MA 02129 USA. RI Cuajungco, Math/B-2647-2008; Bush, Ashley/A-1186-2007 OI Cuajungco, Math/0000-0003-0749-9564; Bush, Ashley/0000-0001-8259-9069 NR 79 TC 135 Z9 141 U1 1 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-283-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 920 BP 292 EP 304 PG 13 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09W UT WOS:000171939600041 PM 11193167 ER PT B AU Dzik, S AF Dzik, S BE Sibinga, CTS Klein, HG TI CD34+cell analysis: Multicenter cooperative trials SO MOLECULAR BIOLOGY IN BLOOD TRANSFUSION SE DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY LA English DT Proceedings Paper CT 24th International Symposium on Blood Transfusion CY 1999 CL GRONINGEN, NETHERLANDS SP Blood Bank Noord Nederland ID CD34(+) CELL ENUMERATION; LEUKAPHERESIS PRODUCTS; HEMATOPOIETIC STEM; QUALITY ASSURANCE; PROGENITOR CELLS; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; STANDARD C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-6534-8 J9 DEV HEMATOL PY 2000 VL 35 BP 147 EP 158 PG 12 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA BR72N UT WOS:000167335500011 ER PT J AU McCall, MJ Hendry, P Mir, AA Conaty, J Brown, G Lockett, TJ AF McCall, MJ Hendry, P Mir, AA Conaty, J Brown, G Lockett, TJ TI Small, efficient hammerhead ribozymes SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE ribozyme; hammerhead; miniribozyme; minizyme; ribozyme design ID NUCLEASE-RESISTANT RIBOZYMES; MESSENGER-RNA LEVELS; STEM-LOOP-II; IN-VITRO; OLIGONUCLEOTIDE FACILITATORS; CATALYTIC ACTIVITY; MEDIATED CLEAVAGE; ALPHA RIBOZYME; SELF-CLEAVAGE; SITES AB The hammerhead ribozyme is able to cleave RNA in a sequence-specific manner. These ribozymes are usually designed with four basepairs in helix II, and with equal numbers of nucleotides in the 5' and 3' hybridizing arms that bind the RNA substrate on either side of the cleavage site. Here guidelines are given for redesigning the ribozyme so that it is small, but retains efficient cleavage activity. First, the ribozyme may be reduced in size by shortening the 5' arm of the ribozyme to five or six nucleotides; for these ribozymes, cleavage of short substrates is maximal. Second: the internal double-helix of the ribozyme (helix II) may be shortened to one or no basepairs, forming a miniribozyme or minizyme, respectively. The sequence of the shortened helix + loop II greatly affects cleavage rates. With eight or more nucleotides in both the 5' and the 3' arms of a miniribozyme containing an optimized sequence for helix + loop II, cleavage rates of short substrates are greater than for analogous ribozymes possessing a longer helix II. Cleavage of gene-length RNA substrates may be best achieved by miniribozymes. C1 CSIRO Mol Sci, N Ryde, NSW 1670, Australia. NCI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. RI Hendry, Philip/D-5795-2011; McCall, Maxine/H-4707-2013; Lockett, Trevor/H-8970-2013 OI McCall, Maxine/0000-0003-4000-8069; Lockett, Trevor/0000-0002-8063-071X NR 53 TC 9 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JAN PY 2000 VL 14 IS 1 BP 5 EP 17 DI 10.1385/MB:14:1:5 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 306BL UT WOS:000086576200002 PM 10911611 ER PT J AU Damelin, M Silver, PA AF Damelin, M Silver, PA TI Mapping interactions between nuclear transport factors in living cells reveals pathways through the nuclear pore complex SO MOLECULAR CELL LA English DT Article ID GREEN FLUORESCENT PROTEIN; RESONANCE ENERGY-TRANSFER; TRANSCRIPTION FACTOR PHO4; NUCLEOCYTOPLASMIC TRANSPORT; IMPORT; YEAST; LOCALIZATION; NUCLEOPORINS; TRAFFICKING; MICROSCOPY AB The interactions between transport receptors and proteins of the nuclear pore complex (NPC) are fundamental to understanding nucleocytoplasmic transport. In order to delineate the path that a particular transport receptor takes through the NPC, we have employed fluorescence resonance energy transfer (FRET) between enhanced cyan and yellow fluorescent proteins (ECFP, EYFP) in living cells. A panel of yeast strains expressing functional receptor-ECFP and nucleoporin-EYFP fusions has been analyzed with a FRET assay. With this approach, we define points of contact in the NPC for the related importin Pse1/Kap121 and exportin Msn5. These data demonstrate the utility of FRET in mapping dynamic protein interactions in a genetic system. Furthermore, the data indicate that an importin and exportin have overlapping pathways through the NPC. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. NR 34 TC 108 Z9 108 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 2000 VL 5 IS 1 BP 133 EP 140 DI 10.1016/S1097-2765(00)80409-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 281MB UT WOS:000085163400012 PM 10678175 ER PT J AU Birnbaum, RA O'Marcaigh, A Wardak, Z Zhang, YY Dranoff, G Jacks, T Clapp, DW Shannon, KM AF Birnbaum, RA O'Marcaigh, A Wardak, Z Zhang, YY Dranoff, G Jacks, T Clapp, DW Shannon, KM TI Nf1 and Gmcsf interact in myeloid leukemogenesis SO MOLECULAR CELL LA English DT Article ID COLONY-STIMULATING FACTOR; JUVENILE MYELOMONOCYTIC LEUKEMIA; COMMON BETA-SUBUNIT; BONE-MARROW CELLS; NEUROFIBROMATOSIS TYPE-1; SIGNAL-TRANSDUCTION; TRANSGENIC MICE; GM-CSF; RAS; GROWTH AB The NF1 tumor suppressor gene encodes neurofibromin, a GTPase-activating protein (GAP) for p21(ras) (Ras). Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML). Some heterozygous Nf1 mutant mice develop a similar myeloproliferative disorder (MPD), and adoptive transfer of Nf1-deficient fetal liver cells consistently induces this MPD. Human JMML and murine Nf1-deficient cells are hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose cultures. We generated hematopoietic cells deficient in both Nf1 and Gmcsf to test whether GM-CSF is required to drive excessive proliferation of Nf1(-/-) cells in vivo. Here we show that GM-CSF plays a central role in establishing and maintaining the MPD and that recipients engrafted with Nf1(-/-) Gmcsf(-/-) hematopoietic cells are hypersensitive to exogenous GM-CSF. C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Herman B Wells Ctr, Indianapolis, IN 46202 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Shannon, KM (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA74886, CA72614] NR 40 TC 94 Z9 95 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 2000 VL 5 IS 1 BP 189 EP 195 DI 10.1016/S1097-2765(00)80415-3 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 281MB UT WOS:000085163400018 PM 10678181 ER PT S AU Jhala, US Sharma, S Dutta, S Montminy, M AF Jhala, US Sharma, S Dutta, S Montminy, M BE Matschinsky, FM Magnuson, MA TI Molecular mechanisms of PDX-1 regulation SO MOLECULAR PATHOGENESIS OF MODYS SE FRONTIERS IN DIABETES LA English DT Proceedings Paper CT Symposium on Molecular Pathogenesis of MODYs CY NOV 06-08, 1998 CL SCOTTSDALE, AZ SP Amer Diabet Assoc ID PANCREATIC BETA-CELLS; HOMEODOMAIN TRANSCRIPTION FACTOR; INSULIN GENE-TRANSCRIPTION; HOMEOBOX FACTOR STF-1; COOPERATIVE INTERACTIONS; CAENORHABDITIS-ELEGANS; SOMATOSTATIN PROMOTER; RAT PANCREAS; ISLET CELLS; AR42J CELLS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cell Biol, Boston, MA 02115 USA. RP Montminy, M (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cell Biol, Boston, MA 02115 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0251-5342 BN 3-8055-6950-5 J9 FRONT DIABETES JI Front.Diabetes PY 2000 VL 15 BP 181 EP 196 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS67U UT WOS:000170815100013 ER PT S AU Habener, JF Stoffers, DA Elahi, D Hani, E Froguel, P AF Habener, JF Stoffers, DA Elahi, D Hani, E Froguel, P BE Matschinsky, FM Magnuson, MA TI Role of homeodomain transcription factor IPF-1 in the pathogenesis of diabetes mellitus SO MOLECULAR PATHOGENESIS OF MODYS SE FRONTIERS IN DIABETES LA English DT Proceedings Paper CT Symposium on Molecular Pathogenesis of MODYs CY NOV 06-08, 1998 CL SCOTTSDALE, AZ SP Amer Diabet Assoc ID NUCLEAR FACTOR-1-ALPHA GENE; PANCREAS DEVELOPMENT; ISLET CELLS; BETA-CELLS; FACTOR-I; ONSET; DIFFERENTIATION; YOUNG; MICE; EXPRESSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab,Howard Hughes Med Inst, 55 Fruit St,WEL320, Boston, MA 02114 USA. NR 36 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0251-5342 BN 3-8055-6950-5 J9 FRONT DIABETES JI Front.Diabetes PY 2000 VL 15 BP 197 EP 208 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS67U UT WOS:000170815100014 ER PT S AU White, M AF White, M BE Matschinsky, FM Magnuson, MA TI IRS-2 is a common element in peripheral insulin signaling and beta-cell function SO MOLECULAR PATHOGENESIS OF MODYS SE FRONTIERS IN DIABETES LA English DT Proceedings Paper CT Symposium on Molecular Pathogenesis of MODYs CY NOV 06-08, 1998 CL SCOTTSDALE, AZ SP Amer Diabet Assoc ID DEPENDENT DIABETES-MELLITUS; RECEPTOR TYROSINE KINASES; FACTOR-I RECEPTOR; SH2 DOMAIN; PHOSPHOTYROSINE PROTEIN; SUBSTRATE FAMILY; CYTOKINE ACTION; GENE; RAS; RESISTANCE C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. RP White, M (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 42 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0251-5342 BN 3-8055-6950-5 J9 FRONT DIABETES JI Front.Diabetes PY 2000 VL 15 BP 209 EP 218 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS67U UT WOS:000170815100015 ER PT S AU Arystarkhova, E Wetzel, RK Asinovski, NK Sweadner, KJ AF Arystarkhova, E Wetzel, RK Asinovski, NK Sweadner, KJ BE Taniguchi, K Kaya, S TI The renal Na,K-ATPase ancillary gamma subunit: Fine-tuning of substrate ion affinities SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci DE gamma subunit; modulation; kidney; sodium affinity ID PHOSPHOLEMMAN CHANNEL MOLECULES; XENOPUS OOCYTES; NA+,K+-ATPASE; POLYPEPTIDE; EXPRESSION; COMPONENT; INSULIN; CATION; ANION; CELLS AB The renal Na+,K+-ATPase has two necessary subunits, alpha and beta, and a 7.4 kDa protein, the gamma subunit, which is not detected in established cell lines of kidney origin. Here evidence is presented for gamma 's role in the control of the most basic property of Na,K-ATPase, the affinity for Na+ and K+. When stably expressed in NRK-52E cells, gamma decreased affinities for both Na+ and K+. A post-translational modification of gamma selectively eliminated the effect on Na+ affinity, while not affecting the effect on K+ affinity. Thus the mammalian kidney may have at least three quaternary forms of the Na,K-ATPase: alpha beta, alpha beta gamma, and alpha beta gamma*, where the asterisk represents a physiologically important post-translational modification. Confocal microscopy was used to detect gamma in rat renal cortex. Lack of the gamma subunit in some nephron segments, like cortical ascending limb and some cortical collecting tubules, correlated well with higher affinities for Na+ in those segments reported in the literature. Selective expression of the gamma subunit in different parts of nephron as well as susceptibility to post-translational modification is consistent with a modulatory role for the protein in the regulation of Na,K-ATPase in vivo. C1 Massachusetts Gen Hosp, Neurosci Ctr, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Neurosci Ctr, Lab Membrane Biol, 149 13th St,149-6118, Charlestown, MA 02129 USA. NR 18 TC 6 Z9 6 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 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 489 EP 496 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900087 ER PT S AU Sweadner, KJ Rael, E Wetzel, RK Arystarkhova, E AF Sweadner, KJ Rael, E Wetzel, RK Arystarkhova, E BE Taniguchi, K Kaya, S TI Splice variants of the Na,K-ATPase gamma subunit SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci DE gamma subunit; genomics; cDNA; alternative splicing AB The gamma subunit occurs in a splice variant that affects the protein sequence at the N-terminus. Consensus nucleotide and protein sequences were derived for the two splice forms from redundant data in the dbEST database. They were found in independent libraries derived from multiple organ types, and orthologs were found for human, mouse, and rat. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, 1496118,149 13th St,149-6118, Charlestown, MA 02129 USA. NR 7 TC 5 Z9 5 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 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 543 EP 546 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900095 ER PT S AU Ellis, DZ Nathanson, JA Sweadner, KJ AF Ellis, DZ Nathanson, JA Sweadner, KJ BE Taniguchi, K Kaya, S TI Role of nitric oxide and cGMP in modulating Na,K-ATPase activity in secretory epithelium SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci DE Na,K-ATPase; nitric oxide; choroid plexus; cGMP ID DEPENDENT PROTEIN-KINASE; BETA-SUBUNIT ISOFORMS; CHOROID-PLEXUS; BRAIN-BARRIER; ALPHA-SUBUNIT; PHOSPHORYLATION; EXPRESSION; MECHANISM; DOPAMINE; SODIUM AB The free radical nitric oxide (NO) is an inter- and intracellular regulator in a variety of tissues and organs. Unlike other cellular transmitters, NO is not produced, stored and released in response to an extracellular signal. Instead it is synthesized in response to an increase in intracellular calcium, then rapidly diffuses throughout the cell where it binds to its intracellular receptor, soluble guanylate cyclase. Activation of the heterodimeric soluble guanylate cyclase catalyzes the conversion of GTP to cyclic guanosine 5 ' -monophosphate (cGMP). While considerable progress has been made in elucidating the regulation of NO synthesis and in identifying NO's immediate second messenger effecters, such as soluble guanylate cyclase, less is known about its downstream biochemical targets. Recent work has identified the Na,K-ATPase as an effector target for NO. This article provides an overview of the role of the NO/cGMP in mediating Na,K-ATPase activity in secretory epithelium, specifically the choroid plexus. C1 Massachusetts Gen Hosp, Neurosci Ctr, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Ellis, DZ (reprint author), Massachusetts Gen Hosp, Neurosci Ctr, Lab Membrane Biol, 1496118,149 13th St, Charlestown, MA 02129 USA. NR 10 TC 0 Z9 0 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 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 567 EP 570 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900101 ER PT S AU Feschenko, MS Sweadner, KJ AF Feschenko, MS Sweadner, KJ BE Taniguchi, K Kaya, S TI Phosphorylation detection in intact cells with phosphorylation-sensitive antibodies: PKC and PKA phosphorylation of Na,K-ATPase SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci ID PROTEIN-KINASE-C; ALPHA-SUBUNIT; NA+,K+-ATPASE AB The detection of protein phosphorylation with antibodies is a powerful way to assess the level and location of phosphorylation obtained in physiological conditions. Here we describe detection of phosphorylation of Na,K-ATPase a subunit at the PKC site (Ser18) and initial evidence for the absence of phosphorylation at the PKA site (Ser 938) in rat cell lines. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Feschenko, MS (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, 149-6118,149 13th St, Charlestown, MA 02129 USA. NR 11 TC 0 Z9 0 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 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 575 EP 578 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900103 ER PT J AU Sagar, A Daemmrich, A Ashiya, M AF Sagar, A Daemmrich, A Ashiya, M TI The tragedy of the commoners: biotechnology and its publics SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 Harvard Univ, John F Kennedy Sch Govt, Belfer Ctr Sci & Int Affairs, Sci Technol & Publ Policy Program, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sagar, A (reprint author), Harvard Univ, John F Kennedy Sch Govt, Belfer Ctr Sci & Int Affairs, Sci Technol & Publ Policy Program, Cambridge, MA 02138 USA. OI Daemmrich, Arthur/0000-0001-5798-5494 NR 11 TC 36 Z9 37 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2000 VL 18 IS 1 BP 2 EP 4 DI 10.1038/71861 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 273GQ UT WOS:000084699900003 PM 10625342 ER PT J AU Settleman, J AF Settleman, J TI Getting in shape with Rho SO NATURE CELL BIOLOGY LA English DT Article ID DROSOPHILA; GASTRULATION; GTPASE; MEMBER; FAMILY; CDC42; RAC AB The Rho GTPases are potent regulators of the actin cytoskeleton and consequently influence many aspects of cell shape and movement. In vivo, Rho activity appears to be a critical determinant of tissue morphogenesis during several stages of embryonic development. C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Dept Med, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 15 TC 22 Z9 24 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2000 VL 2 IS 1 BP E7 EP E9 DI 10.1038/71390 PG 3 WC Cell Biology SC Cell Biology GA 275WR UT WOS:000084843600005 PM 10620813 ER PT J AU Huettner, CS Zhang, P Van Etten, RA Tenen, DG AF Huettner, CS Zhang, P Van Etten, RA Tenen, DG TI Reversibility of acute B-cell leukaemia induced by BCR-ABL1 SO NATURE GENETICS LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; TRANSGENIC MICE; BCR-ABL; TYROSINE KINASE; GENE-EXPRESSION; BONE-MARROW; P210(BCR/ABL); PROMOTER; ANTIGEN AB Cancer is thought to arise from multiple genetic events that establish irreversible malignancy. A different mechanism might be present in certain leukaemias initiated by a chromosomal translocation. We have taken a new approach to determine if ablation of the genetic abnormality is sufficient for reversion by generating a conditional transgenic model of BCR-ABL1 (also known as BCR-ABL)-induced leukaemia. This oncogene(1) is the of a reciprocal translocation and is associated with differ-ent forms of leukaemia(2). The most common form, p210 BCR-ABL1, is found in more than 90% of patients with chronic myelogenous leukaemia(3,4) (CML) and in up to 15% of adult patients with de novo acute lymphoblastic leukaemia(5) (ALL). Efforts to establish a useful transgenic model have been hampered by embryonic lethality when the oncogene is expressed during embryogenesis(6,7), by reduced penetrance or by extremely long latency periods(8,9). One model uses the 'knock-in' approach to induce leukaemia by p190 BCR-ABL1 (ref. 10). Given the limitations of models with p210, we used a different experimental approach(11) Lethal leukaemia developed within an acceptable time frame in all animals, and complete remission was achieved by suppression of BCR-ABL1 expression, even after multiple rounds of induction and reversion. Our results demonstrate that BCR-ABL1 is required for both induction and maintenance of leukaemia. C1 Harvard Univ, Inst Med, Div Hematol Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Div Hematol Oncol, Cambridge, MA 02138 USA. NR 27 TC 283 Z9 294 U1 1 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2000 VL 24 IS 1 BP 57 EP 60 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 271TH UT WOS:000084609200016 PM 10615128 ER PT J AU Lee, N Bessho, Y Wei, K Szostak, JW Suga, H AF Lee, N Bessho, Y Wei, K Szostak, JW Suga, H TI Ribozyme-catalyzed tRNA aminoacylation SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID ACYL-TRANSFERASE RIBOZYME; TRANSFER-RNA IDENTITY; AMINO-ACIDS; MOLECULAR RECOGNITION; CONFORMATIONAL SWITCH; PROTEIN-SYNTHESIS; RIBOSOMAL-RNA; SELECTION; APTAMERS; INTRONS AB The RNA world hypothesis implies that coded protein synthesis evolved from a set of ribozyme catalyzed acyl-transfer reactions, including those of aminoacyl-tRNA synthetase ribozymes. We report here that a bifunctional ribozyme generated by directed in vitro evolution can specifically recognize an activated glutaminyl ester and aminoacylate a targeted tRNA, via a covalent aminoacyl-ribozyme intermediate. The ribozyme consists of two distinct catalytic domains; one domain recognizes the glutamine substrate and self-aminoacylates its own 5'-hydroxyl group, and the other recognizes the tRNA and transfers the aminoacyl group to the 3'-end. The interaction of these domains results in a unique pseudoknotted structure, and the ribozyme requires a change in conformation to perform the sequential aminoacylation reactions. Our result supports the idea that aminoacyl-tRNA synthetase ribozymes could have played a key role in the evolution of the genetic code and RNA-directed translation. C1 SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Suga, H (reprint author), SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. RI Bessho, Yoshitaka/K-7702-2012 NR 33 TC 113 Z9 120 U1 1 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JAN PY 2000 VL 7 IS 1 BP 28 EP 33 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 276MH UT WOS:000084881200012 PM 10625423 ER PT J AU Fujimoto, JG Pitris, C Boppart, SA Brezinski, ME AF Fujimoto, JG Pitris, C Boppart, SA Brezinski, ME TI Optical coherence tomography: An emerging technology for biomedical imaging and optical biopsy SO NEOPLASIA LA English DT Review DE biopsy; imaging; OCT; optical imaging; optical coherence tomography; tomography ID FIBER LAYER THICKNESS; IN-VIVO; ENDOSCOPIC ULTRASONOGRAPHY; INTRAVASCULAR ULTRASOUND; GASTROINTESTINAL-TRACT; MACULAR EDEMA; LASER SOURCE; SYSTEM; TISSUE; REFLECTOMETRY AB Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. in this paper, we review OCT technology and describe its potential biomedical and clinical applications. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Cardiac Unit, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fujimoto, JG (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-9-RO1-CA75289-02, R01 CA075289]; NEI NIH HHS [NIH-9-RO1-EY11289-13, R01 EY011289]; NHLBI NIH HHS [R29 HL055686]; NIAMS NIH HHS [NIH-RO1-AR44812-02, R01 AR044812] NR 86 TC 366 Z9 376 U1 7 U2 64 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN-APR PY 2000 VL 2 IS 1-2 BP 9 EP 25 DI 10.1038/sj.neo.7900071 PG 17 WC Oncology SC Oncology GA 305BV UT WOS:000086519700002 PM 10933065 ER PT J AU Hochberg, F Grossman, SA Mikkelsen, T Glantz, M Fisher, JD Piantadosi, S AF Hochberg, F Grossman, SA Mikkelsen, T Glantz, M Fisher, JD Piantadosi, S CA NABTT CNS Consortium TI Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma SO NEURO-ONCOLOGY LA English DT Article ID DNA TOPOISOMERASE-I; CAMPTOTHECIN; CHEMOTHERAPY; XENOGRAFTS; INHIBITION; INFUSION; TRIALS; CANCER AB 9-Aminocamptothecin (9-AC) was administered as a 72-h i.v. infusion every 2 weeks to a total of 99 adults with high-grade astrocytomas, Fifty-one patients with newly diagnosed glioblastoma multiforme received 9-AC treatment prior to radiation therapy and 48 patients with high-grade astrocytomas were treated at the time of tumor recurrence. Upon entrance into these research protocols, all patients had measurable disease that was evaluated on a monthly basis with volumetric CT or MRI scans. A partial response was defined by greater than or equal to 50% reduction in the contrast enhancing volume on stable or decreasing doses of glucocorticoids, The study specified that all apparent responders would have central review of their radiologic studies and histopathology, The initial patients treated with 9-AC were also receiving anticonvulsants and were noted to have minimal myelosuppression with this chemotherapy. Thus, 9-AC doses were escalated from the previously reported maximum tolerated dose (MTD) of 850 mug/m(2)/24 h, We then established new MTDs for patients receiving enzyme-inducing anticonvulsants, We defined these MTDs to be 1776 pg/m(2)/24 h for newly diagnosed, previously untreated patients and 1611 pg/m2/24 h for patients with recurrent disease. Twenty-two patients with newly diagnosed glioblastoma multiforme received 9-AC at doses greater than or equal to 1776 mug/m(2)/24 h, Of these, 18 had evaluable disease on central review, and 0 of 18 (0%) demonstrated a partial or complete response. Twenty-one patients with recurrent high-grade astrocytomas were treated at 1611 mug/m(2)/24 h; 20 had evaluable disease and 0 of 20 (0%) had a partial or complete response. Thus, the overall response rate in the 38 evaluable patients treated at the MTD was 0 of 38 (0%), Furthermore, of the 51 evaluable patients who were treated at doses less than the MTD, only one partial response was observed, yielding an overall response rate of 2%, Evidence of drug failure was rapid with tumor progression in one-half of patients after 2 drug cycles. 9-AC lacks evidence of substantial activity in patients with newly diagnosed or recurrent high-grade astrocytomas. C1 Johns Hopkins Oncol Ctr, NABTT Cent Operat Off, Baltimore, MD 21287 USA. Johns Hopkins Univ, Baltimore, MD 21287 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Providence, RI 02903 USA. RP Hochberg, F (reprint author), Johns Hopkins Oncol Ctr, NABTT Cent Operat Off, Room 129,600 N Wolfe St, Baltimore, MD 21287 USA. FU NCI NIH HHS [U01CA6406-07] NR 21 TC 8 Z9 8 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 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2000 VL 2 IS 1 BP 29 EP 33 DI 10.1215/15228517-2-1-29 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 366RZ UT WOS:000090019500005 PM 11302251 ER PT J AU Marota, JJA Mandeville, JB Weisskoff, RM Moskowitz, MA Rosen, BR Kosofsky, BE AF Marota, JJA Mandeville, JB Weisskoff, RM Moskowitz, MA Rosen, BR Kosofsky, BE TI Cocaine activation discriminates dopaminergic projections by temporal response: An fMRI study in rat SO NEUROIMAGE LA English DT Article ID CEREBRAL GLUCOSE-UTILIZATION; RECEPTOR MESSENGER-RNA; VENTRAL TEGMENTAL AREA; LOW-DOSE COCAINE; BLOOD-VOLUME; MOLECULAR MECHANISMS; DEFINES SPECIFICITY; INDUCED LOCOMOTION; BODY-WEIGHT; HUMAN BRAIN AB We applied a sensitive new functional magnetic resonance imaging technique to identify the pattern and determinants of cocaine-induced brain activation in drug-naive rats. At doses greater than 0.1 mg/kg iv cocaine produced robust activation throughout cortex with the largest magnitude increase in frontal neocortex tex. Additionally, we detected selective activation within dopamine-innervated subcortical regions including dorsomedial and ventrolateral striatum, nucleus accumbens region, and dorsal thalamus. All though dose response was similar among activated regions, temporal response differentiated regions along distinct anatomical boundaries with basal ganglia and limbic cortical structures, reaching maximum activation later than frontal neocortex. Pharmacological specificity was demonstrated by blocking cocaine-induced activation with SCH-23390, a selective D1 antagonist. Our data demonstrate the utility of fMRI to identify spatiotemporal patterns of cocaine-induced brain activation and implicate D1 dopaminergic mechanisms in acute cocaine action. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NMR Ctr, MGHE, Charlestown, MA 02119 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Marota, JJA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Moskowitz, Michael/D-9916-2011 FU NIDA NIH HHS [DA-00384, DA-00354] NR 54 TC 132 Z9 137 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2000 VL 11 IS 1 BP 13 EP 23 DI 10.1006/nimg.1999.0520 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 279TW UT WOS:000085062100002 PM 10686113 ER PT J AU Liu, C Reppert, SM AF Liu, C Reppert, SM TI GABA synchronizes clock cells within the suprachiasmatic circadian clock SO NEURON LA English DT Article ID GABAERGIC SYSTEM; NUCLEUS; NEURONS; PERIOD; RAT; RHYTHMICITY; EXPRESSION; MPER1; LIGHT AB The master clock in the suprachiasmatic nuclei (SCN) is composed of multiple, single-cell circadian clocks. We test the postulate that these individual "clock cells" can be synchronized to each other by the inhibitory transmitter gamma-aminobutyric acid (GABA). For these experiments, we monitored the firing rate rhythm of individual clock cells on fixed multielectrode plates in culture and tested the effects of GABA. The results show that the daily variation in responsiveness of the SCN to phase-shifting agents is manifested at the level of individual neurons. Moreover, GABA, acting through A-type receptors, can both phase shift and synchronize clock cells. We propose that GABA is an important synchronizer of SCN neurons in vivo. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. FU NICHD NIH HHS [R37 HD14427] NR 33 TC 195 Z9 199 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN PY 2000 VL 25 IS 1 BP 123 EP 128 DI 10.1016/S0896-6273(00)80876-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 279KP UT WOS:000085043200015 PM 10707977 ER PT J AU Ren, JM Kaplan, PL Charette, MF Speller, H Finkelstein, SP AF Ren, JM Kaplan, PL Charette, MF Speller, H Finkelstein, SP TI Time window of intracisternal osteogenic protein-1 in enhancing functional recovery after stroke SO NEUROPHARMACOLOGY LA English DT Article DE stroke; recovery; rat; ischemia; growth factor; osteogenic protein-1 ID SERINE/THREONINE KINASE RECEPTORS; FIBROBLAST GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; RAT; EXPRESSION; INFARCT; BRAIN; NEURONS AB Osteogenic protein-1 (OP-1, BMP-7) is a member of the bone morphogenetic protein subfamily of the TGF-beta superfamily that selectively stimulates dendritic neuronal outgrowth. In previous studies, we found that the intracisternal injection of OP-1, starting at one day after stroke, enhanced sensorimotor recovery of the contralateral limbs following unilateral cerebral infarct ipn in rats. In the current study, we further explored the time window during which intracisternal OP-1 enhances sensorimotor recovery, as assessed by limb placing tests. We found that intracisternal OP-1 (10 mu g) given 1 and 3 days, or 3 and 5 days, but not 7 and 9 days after stroke, significantly enhanced recovery of forelimb and hindlimb placing. There was no difference in infarct volume between vehicle- and OP-1-treated animals. The mechanism of OP-1 action might be stimulation of new dendritic sprouting in the remaining uninjured brain. (C) 2000 Published by Elsevier Science Ltd. All rights resented. C1 Massachusetts Gen Hosp, Dept Neurol, CNS, Growth Factor Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Creat Biomol Inc, Hopkinton, MA 01748 USA. RP Ren, JM (reprint author), Massachusetts Gen Hosp, Dept Neurol, CNS, Growth Factor Res Lab, Boston, MA 02114 USA. FU NINDS NIH HHS [NS10828] NR 18 TC 42 Z9 45 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 5 BP 860 EP 865 DI 10.1016/S0028-3908(99)00261-0 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 291TA UT WOS:000085751100015 PM 10699451 ER PT J AU Tarazi, FI Kula, NS Zhang, KH Baldessarini, RJ AF Tarazi, FI Kula, NS Zhang, KH Baldessarini, RJ TI Alkylation of rat dopamine transporters and blockade of dopamine uptake by EEDQ SO NEUROPHARMACOLOGY LA English DT Article DE alkylation; autoradiography; [H-3]beta-CIT; caudate-putamen; dopamine transporter; EEDQ ID RECEPTOR TURNOVER; 5-HT RECEPTORS; BINDING-SITES; IN-VIVO; BRAIN; N-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE; RECOVERY; STRIATUM; ASSOCIATION; DISORDER AB Effects of the alkylating agent EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) on levels of dopamine transporter (DA(T)) and function were examined in caudate-putamen (CPu) tissue from rat brain. EEDQ produced profound, dose-dependent decreases in DA(T) binding in homogenates (IC50=78 mu M) and frozen sections (IC75=200 mu M) that were not reversed by washing. EEDQ also blocked uptake of [H-3]DA in CPu synaptosomes (IC50=17 mu M). However, single (10 mg/kg) or repeated administration of EEDQ in vivo (15 mg/kg/dayx3) did not alter DA(T) levels or DA uptake in CPu. Pretreatment of rats with alpha-methyl-p-tyrosine and reserpine to deplete endogenous dopamine also failed to lower DA(T) levels in CPu after injections of EEDQ. EEDQ is an effective alkylating agent for DA(T) in vitro, but not to evaluate metabolic turnover or function of DA(T) in vivo. The results encourage development of selective and in vivo-active DA(T)-alkylating agents. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-19905, MH-47370] NR 34 TC 2 Z9 2 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 11 BP 2133 EP 2138 DI 10.1016/S0028-3908(00)00047-2 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 350AV UT WOS:000089079100020 PM 10963756 ER PT J AU Ali, SO Denicoff, KD Altshuler, LL Hauser, P Li, XM Conrad, AJ Mirsky, AF Smith-Jackson, EE Post, RM AF Ali, SO Denicoff, KD Altshuler, LL Hauser, P Li, XM Conrad, AJ Mirsky, AF Smith-Jackson, EE Post, RM TI A preliminary study of the relation of neuropsychological performance to neuroanatomic structures in bipolar disorder SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID TEMPORAL-LOBE STRUCTURE; MAGNETIC-RESONANCE; MOOD DISORDERS; SIGNAL HYPERINTENSITIES; VENTRICULAR ENLARGEMENT; ELDERLY DEPRESSIVES; BRAIN ABNORMALITIES; COGNITIVE CHANGES; AFFECTIVE-ILLNESS; NORMATIVE DATA AB Objective: To investigate the relation between neuropsychological dysfunction and volumetric measures of neuroanatomic structures in patients with bipolar disorder; Background: Previous research suggests that neuropsychological deficits are associated with neuroanatomic changes in patients with bipolar disorder. Method: Twenty-six outpatients who met Diagnostic and Statistical Manual, Third Edition-Revised criteria for bipolar disorder were administered a battery of neuropsychological tests that assessed, memory, abstracting ability, psychomotor performance, sustained attention, and intelligence. Patients also received a magnetic resonance imaging scan, from which volumes of the temporal lobes, hippocampus, third ventricle, and areas of the lateral ventricles were calculated. Using multiple regression analyses, neuroanatomic structures were compared with neuropsychological test variables. Results: Data suggest that a larger right hippocampal volume is associated with poorer neuropsychological functioning. Conclusions: Further studies are needed to both replicate and examine the relation between potential mechanisms of neuroanatomic alterations and neuropsychological dysfunction in patients with bipolar disorder. C1 NIMH, Psychol Sect, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Psychiat Serv, Baltimore, MD USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Natl Inst Genet, Los Angeles, CA USA. RP Denicoff, KD (reprint author), NIMH, Psychol Sect, Biol Psychiat Branch, Bldg 10,Room 3N212,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ali, Syed/0000-0003-3131-3299 NR 66 TC 53 Z9 54 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JAN PY 2000 VL 13 IS 1 BP 20 EP 28 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 273BZ UT WOS:000084688500004 PM 10645733 ER PT J AU Barrett, AM Schwartz, RL Crucian, GP Kim, M Heilman, KM AF Barrett, AM Schwartz, RL Crucian, GP Kim, M Heilman, KM TI Attentional grasp in far extrapersonal space after thalamic infarction SO NEUROPSYCHOLOGIA LA English DT Article; Proceedings Paper CT 25th Meeting of the International-Neuropsychological-Society CY FEB 05-08, 1997 CL ORLANDO, FLORIDA SP Int Neuropsychol Soc DE thalamus; attention; stroke ID LATERAL HYPOTHALAMIC DAMAGE; UNILATERAL FRONTAL LESION; UTILIZATION BEHAVIOR; SENSORY INATTENTION; HUMAN AUTONOMY; NEGLECT; CORTEX; PROJECTIONS; PATIENT; DISSOCIATION AB Studies of animals and humans with focal brain damage suggest that attention in near and far extrapersonal space may be mediated by anatomically separate systems. Thalamic lesions have been associated with spatial neglect, but whether asymmetric attention specific to near or far space occur after thalamic damage has not been explored. It is also unclear if thalamic injury can induce contralesional defective response inhibition. We tested a woman with a left thalamic infarction who reported that, when driving, she had a tendency to veer towards people or objects on the right side of the road. Our patient and foul controls performed a line bisection task with a laser pointer in near and far extrapersonal space. The experimenter marked each bisection either from the right of the presented line (right-distractor, RD) or the left (left-distractor. LD). RD and LD trials were pseudo-randomized. Our patient performed similarly to controls (mean -0.7 mm, controls -0.6 mm) on the line bisection task in near space. In far space she erred significantly rightward compared to her performance in near space (p < 0.001). Controls performed similarly in neat and far space. The experimenter position did not affect our patient's performance on near line bisections, nor did controls demonstrate a distractor effect for the near condition. In the far condition, however, our patient showed a significant distracter effect (LD -3.3 mm, RD 35.3 mm, p < 0.001). Controls also demonstrated a distractor effect in the far condition (LD -6.4 mm. RD 0.7 mm, p < 0.01), though of much smaller magnitude, Our results suggest that frontal-thalamic systems regulating visual attention may be disrupted by thalamic infarction. Such damage may produce an attentional grasp specific to far extrapersonal space. Published by Elsevier Science Ltd. C1 Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA. VA Med Ctr, Gainesville, FL USA. Univ Florida, Hlth Sci Ctr, Dept Neurol, Jacksonville, FL 32209 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Barrett, AM (reprint author), Penn State Univ, Coll Med, Neurol Sect, POB 850, Hershey, PA 17033 USA. RI Kim, Manho/J-2738-2012; OI Barrett, A.M./0000-0002-0789-2887 FU NINDS NIH HHS [K08 NS002085] NR 42 TC 33 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 6 BP 778 EP 784 DI 10.1016/S0028-3932(99)00144-X PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 296YN UT WOS:000086054500006 PM 10689053 ER PT J AU Anderson, B Mennemeier, M Chatterjee, A AF Anderson, B Mennemeier, M Chatterjee, A TI Variability not ability: another basis for performance decrements in neglect SO NEUROPSYCHOLOGIA LA English DT Article DE neglect; attention; reaction time ID UNILATERAL SPATIAL NEGLECT; SIMPLE REACTION-TIME; VISUAL NEGLECT; SUSTAINED ATTENTION; LINE BISECTION; REHABILITATION; HEMINEGLECT; SEARCH AB Objective: To determine reaction time (RT) and its variability as a function of horizontal spatial position, in subjects with neglect. Background: In neglect, performance is frequently reported a as mean and a decreased ability to perform the task inferred by comparison to control groups. Few studies have examined how consistency and optimal performance relate to spatial neglect. Methods: Ten subjects with brain damage, five with and five without spatial neglect. were assessed on a RT task. Subjects responded by pushing a computer key to the onset of a white square appearing on a black screen. The locations of stimuli were randomly varied along the horizontal meridian. Results. For three of five neglect subjects. optimal RT showed no or little relation to horizontal location. Four of five neglect subjects demonstrated an increased variability in RT that correlated with spatial position and which was not present in our brain damaged subjects without neglect. The relationship was not an artifact of left sided stimuli, in general, being processed differently. For the two neglect subjects with the most trials, a significant correlation between RT variability and spatial position existed for left-sided trials alone. Increased variability was not a consequence of simply looking left proportionately less often, nor could a model of multiple compensatory systems operating in parallel explain the enhanced variability. Neither hemianopsia alone nor brain damage per se could account for the spatial modulation of RT variability. Conclusions. That neglect subjects perform the RT task normally on some trials, even in their 'neglected field, challenges the notion that neglect must reflect an irreparably damaged cognitive system, Performance decrements in neglect call reflect an inability to consistently detect and respond. Evaluating optimal performance and variability of performance can indicate if a capacity has been lost absolutely or merely degraded such that normal performance cannot be sustained. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Alabama, Dept Neurol, Birmingham, AL 35233 USA. Birmingham VA Med Ctr, Neurol Serv, Birmingham, AL USA. Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Anderson, B (reprint author), Univ Alabama, Dept Neurol, Birmingham, AL 35233 USA. NR 30 TC 31 Z9 31 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 6 BP 785 EP 796 DI 10.1016/S0028-3932(99)00137-2 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 296YN UT WOS:000086054500007 PM 10689054 ER PT J AU Savage, CR Deckersbach, T Wilhelm, S Rauch, SL Baer, L Reid, T Jenike, MA AF Savage, CR Deckersbach, T Wilhelm, S Rauch, SL Baer, L Reid, T Jenike, MA TI Strategic processing and episodic memory impairment in obsessive compulsive disorder SO NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Neuroscience CY NOV 07-12, 1998 CL LOS ANGELES, CALIFORNIA SP Soc Neurosci ID FRONTAL-LOBE DYSFUNCTION; GLUCOSE METABOLIC-RATE; PARKINSONS-DISEASE; RECOGNITION MEMORY; HUNTINGTONS-DISEASE; COGNITIVE DEFICITS; PREFRONTAL CORTEX; STRIATAL FUNCTION; RETRIEVAL; NEUROPSYCHOLOGY AB There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149-9102,Bldg 149,13th St, Charlestown, MA USA. FU NIMH NIH HHS [MH01230, MH01215] NR 69 TC 154 Z9 155 U1 16 U2 25 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2000 VL 14 IS 1 BP 141 EP 151 DI 10.1037/0894-4105.14.1.141 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 278ZZ UT WOS:000085020000013 PM 10674806 ER PT J AU O'Connor, TJ Cooper, RA Fitzgerald, SG Dvorznak, MJ Boninger, ML VanSickle, DP Glass, L AF O'Connor, TJ Cooper, RA Fitzgerald, SG Dvorznak, MJ Boninger, ML VanSickle, DP Glass, L TI Evaluation of a manual wheelchair interface to computer games SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE wheelchair; exercise; computer games; fitness; design ID VIDEO-GAME; PAIN AB The sedentary lifestyle of many people with spinal cord injury (SCI) has lead to cardiovascular diseases being a major health concern. A suitable exercise program may help improve the SCI individual's cardiovascular fitness level. GAME(Wheels) is an interface between a custom wheelchair roller system and a computer that enables an individual to control computer video games by driving his or her wheelchair. The purpose of Phase 1 was to evaluate the design of the GAME(Wheels) system and to determine the type of computer video game that is likely to motivate wheelchair users to exercise. Phase 2 included physiologic testing of wheelchair users and the GAME(Wheels) system to investigate whether the system elicits an exercise training response. Thirty-five subjects were recruited to evaluate the GAME(Wheels) by Flaying three commercial computer games (Phase 1) and to identify the computer game that they would prefer to use when exercising. The feedback from Phase 1 was used with test subjects to verify that the GAME(Wheels) system elicits an exercise training effect (Phase 2). Phase 2 included 10 subjects using the GAME(Wheels) system to play Need for Speed II. During game play, physiologic data were collected and the subjects' oxygen consumption and heart rate were analyzed. Analysis showed that the GAME(Wheels) system induced nine subjects to reach their tr;training zone, defined as 50% and 60% of their maximum oxygen consumption and heart rate, respectively. This study demonstrates that the GAME(Wheels) system elicits an exercise training response. C1 VA Pitsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & TEchnol, Pittsburgh, PA 15260 USA. UPMC Hlth Syst, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP O'Connor, TJ (reprint author), VA Pitsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,151R-1, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [P01-HD33989-0151] NR 19 TC 29 Z9 29 U1 1 U2 3 PU DEMOS MEDICAL PUBLISHING PI NEW YORK PA 386 PARK AVE SOUTH, STE 201, NEW YORK, NY 10016 USA SN 0888-4390 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PY 2000 VL 14 IS 1 BP 21 EP 31 DI 10.1177/154596830001400103 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 330MY UT WOS:000087966900003 PM 11228946 ER PT J AU Zhang, K Tarazi, FI Campbell, A Baldessarini, RJ AF Zhang, K Tarazi, FI Campbell, A Baldessarini, RJ TI GABA(B) receptors: Altered coupling to G-proteins in rats sensitized to amphetamine SO NEUROSCIENCE LA English DT Article DE amphetamine; behavioral sensitization; G-proteins; GABA(B) receptors; nucleus accumbens; prefrontal cortex ID MEDIAL PREFRONTAL CORTEX; GAMMA-AMINOBUTYRIC-ACID; VENTRAL TEGMENTAL AREA; METABOTROPIC GLUTAMATE RECEPTORS; NUCLEUS-ACCUMBENS-SEPTI; CENTRAL-NERVOUS-SYSTEM; BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; REPEATED COCAINE; IN-VITRO AB Modified dopamine and glutamate neurotransmission in discrete brain regions is implicated in stimulant-induced behavioral sensitization. Release of both neurotransmitters is influenced by GABAB metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABAB receptors were examined in rats sensitized to amphetamine by measuring receptor density and coupling to G-proteins indicated as [H-3]baclofen binding and baclofen-mediated [S-35]GTP gammaS binding. Repeated treatment with (+)-amphetamine (5 mg/kg per day, i.p., for five days) sensitized the rats to amphetamine challenge (1 mg/kg) at 14 days, but not one day, later. GABAB receptor density was not altered at either time. Baclofen-mediated [S-35]GTP gammaS binding, however, was selectively augmented in the prefrontal cortex and attenuated in the nucleus accumbens at 14 days, but not one day, after amphetamine treatment. Changes in GABAB receptor coupling to G-proteins in rats sensitized to amphetamine, but not in similarly treated but unsensitized rats, lead us to suggest that altered GABAB receptor functioning may contribute to the expression of amphetamine-induced behavioral sensitization. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Zhang, K (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-47370] NR 55 TC 34 Z9 34 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 101 IS 1 BP 5 EP 10 DI 10.1016/S0306-4522(00)00344-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 373AA UT WOS:000165265200002 PM 11068131 ER PT J AU Holschneider, DP Scremin, OU Huynh, L Chen, K Seif, I Shih, JC AF Holschneider, DP Scremin, OU Huynh, L Chen, K Seif, I Shih, JC TI Regional cerebral cortical activation in monoamine oxidase A-deficient mice: Differential effects of chronic versus acute elevations in serotonin and norepinephrine SO NEUROSCIENCE LA English DT Article DE cerebral blood flow; monoamine oxidase; serotonin; norepinephrine; fenfluramine; iodo-antipyrine ID BLOOD-FLOW; D-FENFLURAMINE; SOMATOSENSORY CORTEX; BEHAVIORAL SYNDROME; ADAPTIVE-CHANGES; AMINO-ACIDS; BRAIN; RAT; LACKING; NEURONS AB Mice deficient in monoamine oxidase A have previously been shown to demonstrate a chronic elevation of serotonin and norepinephrine in the brain. Using the autoradiographic [C-14]iodo-antipyrine method, we examined cerebral cortical blood flow in conscious, restrained four- to five-month-old knock-out and wild-type animals following the intraperitoneal administration of either saline or D-fenfluramine. Knock-out animals administered saline, compared to their wild-type counterparts, demonstrated a significantly higher regional cortical blood flow in somatosensory and barrel field neocortex, an area which previous histological studies have shown to be characterized by abnormal serotonergic projection fibers and absent barrel formation. Regional cortical blood how was significantly lower in knock-out than in wild-type mice in the entorhinal and midline motor cortex, with nonsignificant decreases noted in the olfactory, piriform and retrosplenial cortices and the amygdala. We compared the above findings to those obtained in response to D-fenfluramine which, in conjunction with its metabolite D-norfenfluramine, results in acute elevations of brain levels of serotonin and norepinephrine. Administration of D-fenfluramine (21.2 mg/kg) resulted in changes in regional cortical perfusion in most brain regions of both knock-out and wild-type mice that were opposite to the genotypic differences seen in perfusion in response to saline. Fenfluramine significantly increased regional cortical blood flow in the allocortex (olfactory, piriform, entorhinal) and the amygdala, and significantly decreased regional cortical blood flow in the somatosensory, barrel field, midline motor and retrosplenial cortices. Changes in regional perfusion in response to fenfluramine were topographically equivalent in knock-out and wild-type mice, although in knock-out mice such changes were of greater magnitude. Our study suggests that the effects on regional cortical blood how of a lifelong absence of monoamine oxidase A, and the consequent chronic increase in serotonin and norepinephrine, differ from those attributable to acute increases in these neurotransmitters following fenfluramine administration. Such a differential response may reflect neurodevelopmental abnormalities and/or effects of a chronic physiological adaptation on the regulation of cortical activation. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 USC, LAC, Ctr Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. W Los Angeles VAMC, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. Ctr Univ Orsay, Inst Curie, F-91405 Orsay, France. Univ Calif Los Angeles, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA USA. RP Holschneider, DP (reprint author), USC, LAC, Ctr Med, Dept Psychiat & Behav Sci, 1200 N State St, Los Angeles, CA 90033 USA. FU NIA NIH HHS [K12-AG-00521, K12 AG000521]; NIMH NIH HHS [R37 MH39085, R01 MH 37020, R37 MH039085] NR 51 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 101 IS 4 BP 869 EP 877 DI 10.1016/S0306-4522(00)00436-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA 385BZ UT WOS:000165982900007 PM 11113335 ER PT J AU Melone, M Brecha, NC Sternini, C Evans, C Conti, F AF Melone, M Brecha, NC Sternini, C Evans, C Conti, F TI Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex SO NEUROSCIENCE LA English DT Article DE opiate; neurons; immunocytochemistry; rats ID CENTRAL-NERVOUS-SYSTEM; IMMUNOHISTOCHEMICAL LOCALIZATION; INTERNALIZATION; RAT; MORPHINE; PROTEIN; BRAIN; ENDOCYTOSIS; ACTIVATION; MECHANISM AB Imunocytochemical techniques were used to determine whether agonist-induced activation of mu -opioid receptors alters the number and distribution of mu -opioid receptor-positive cells in the rat cerebral cortex. In untreated rats, mu -opioid receptor immunoreactivity was localized to neuronal perikarya and dendrites and to neuropilar punctate structures. mu -Opioid receptor positive neurons were mostly in layers II and III and exhibited a bipolar or bitufted morphology. In rats treated with the mu -opioid receptor agonist etorphine (0.1 mg/kg intraperitoneally) and perfused after different survival periods, there was an enhancement of immunostaining for mu -opioid receptors observed at 15 min, reaching a maximum at 60 min, and which returned to normal at 480 min. Etorphine-induced effects included an increase in the intensity of cellular and neuropil staining; statistical analysis showed that the number of mu -opioid receptor-positive cells in etorphine-treated groups was significantly higher than in controls or saline-treated rats. In animals that received both etorphine and the mu -opioid receptor antagonist naloxone, the pattern of mu -opioid receptors immunoreactivity was similar to that of untreated animals. This study shows that the number of mu -opioid receptor-positive cells is significantly increased following etorphine treatment and suggests that agonist treatment may be exploited to increased immunostaining of mu -opioid receptors and also of other G-protein coupled receptors. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Ancona, Inst Human Physiol, I-60020 Ancona, Italy. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90037 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90037 USA. Univ Calif Los Angeles, Sch Med, CURE, Los Angeles, CA 90037 USA. Univ Calif Los Angeles, Sch Med, Opioid Res Ctr, Los Angeles, CA 90037 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90037 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90037 USA. RP Conti, F (reprint author), Univ Ancona, Inst Human Physiol, I-60020 Ancona, Italy. RI Melone, Marcello/B-3529-2011 OI Melone, Marcello/0000-0003-4173-0774 FU NEI NIH HHS [EY04067]; NIDA NIH HHS [P50 DA005010]; NIDDK NIH HHS [DK54155, DK41301, P30 DK041301] NR 24 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 100 IS 3 BP 439 EP 443 DI 10.1016/S0306-4522(00)00307-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 369JA UT WOS:000165061100001 PM 11098106 ER PT J AU Costantini, LC Isacson, O AF Costantini, LC Isacson, O TI Neuroimmunophilin ligand enhances neurite outgrowth and effect of fetal dopamine transplants SO NEUROSCIENCE LA English DT Article DE behavior; graft; trophic; immunophilin; Parkinson's disease; regeneration ID VENTRAL MESENCEPHALIC GRAFTS; RAT SCIATIC-NERVE; PARKINSONS-DISEASE; NEUROTROPHIC FACTOR; IMMUNOSUPPRESSANT FK506; FUNCTIONAL RECOVERY; NIGRAL TRANSPLANTATION; AXONAL REGENERATION; FIBER OUTGROWTH; SURVIVAL AB Neuroimmunophilin ligands have been shown to enhance neurite outgrowth in several neuronal systems in culture, including primary dopaminergic neurons from fetal ventral mesencephalon. We investigated the ability of neuroimmunophilin ligands to enhance outgrowth of transplanted fetal dopamine neurons in vivo. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopamine system were transplanted with rat embryonic day 14 ventral mesencephalon into the striatum, then treated orally with a neuroimmunophilin ligand (15 mg/kg) or vehicle once per day for 14 days. All transplanted animals regained dopamine function over a 10 week behavioral test period, as indicated by decrease and reversal of amphetamine-induced relation. In addition, neuroimmunophilin ligand-treated animals showed a more pronounced motor response during the first 10 min after amphetamine injection, possibly reflecting increased striatal reinnervation or increased functional capacity. At post-mortem analyses, neuroimmunophilin ligand-treated rats showed a significantly higher density of tyrosine hydroxylase-positive fibers reinnervating the lesioned striatum, both immediately surrounding the transplant (92% of unlesioned density in neuroimmunophilin-treated rats vs 67% of unlesioned levels in vehicle-treated rats) and at some distance from the transplant/host interface. The number of tyrosine hydroxylase-positive cells within the transplants was not different between groups. This study demonstrates that short-term oral administration of a neuroimmunophilin ligand can enhance neurite outgrowth from fetal dopamine neuronal transplants. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 McLean Hosp, Massachusetts Gen Hosp, Dept Neurol & Psychiat, Belmont, MA 02178 USA. Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA. RP Isacson, O (reprint author), McLean Hosp, Massachusetts Gen Hosp, Dept Neurol & Psychiat, 115 Mill St, Belmont, MA 02178 USA. FU NINDS NIH HHS [P50NS39793] NR 50 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 100 IS 3 BP 515 EP 520 DI 10.1016/S0306-4522(00)00312-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 369JA UT WOS:000165061100009 PM 11098114 ER PT J AU Adamec, E Mohan, PS Cataldo, AM Vonsattel, JP Nixon, RA AF Adamec, E Mohan, PS Cataldo, AM Vonsattel, JP Nixon, RA TI Up-regulation of the lysosomal system in experimental models of neuronal injury: Implications for Alzheimer's disease SO NEUROSCIENCE LA English DT Article DE cathepsin D; caspase-3; apoptosis; oncosis; necrosis; neurodegeneration ID IN-SITU IMMUNODETECTION; APOPTOTIC CELL-DEATH; OXIDATIVE STRESS; CATHEPSIN-D; DNA FRAGMENTATION; HUMAN-BRAIN; NEURODEGENERATIVE DISEASES; ABNORMAL DISTRIBUTION; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM AB Previous studies established that the populations of neurons that frequently degenerate in Alzheimer's disease exhibit robust up-regulation of the lysosomal system. In this study, we investigated alterations of the lysosomal system during different forms of experimental injury in rat hippocampal neurons in culture, utilizing a combination of immunocytochemical and biochemical methods. Using triple-label immnocytochemistry for activated caspase-3, fragmentation of DNA and the microtubule-associated protein-2, we characterized treatment paradigms as models of the apoptotic (staurosporine, camptothecin), the oncotic (high-dose menadione, glutamate), and the mixed apoptotic and oncotic (low-dose menadione) pathways of neuronal death. Slowly developing apoptotic or slowly developing mixed apoptotic and oncotic forms of neuronal injury were associated with substantial increases in the number and size of cathepsin D-positive vesicles (late endosomes and mature lysosomes) as determined by immunocytochemistry, and elevated levels of cathepsin D by western blotting. In agreement with our previous findings in Alzheimer's disease, where lysosomal system activation was not restricted to overtly degenerating neurons, up-regulation of this system was also detected quite early during the course of experimental neuronal injury, preceding the development of dystrophic neurites, nuclear segmentation or fragmentation of DNA. These findings implicate lysosomal system activation, both in Alzheimer's disease and in experimental models of neuronal injury, as an important event associated with early stages of neurodegeneration. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 McLean Hosp, Mailman Res Ctr, Belmont, MA 02478 USA. Nathan S Kline Inst Psychiat Res, New York, NY USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA USA. RP Adamec, E (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIA NIH HHS [AG05134, AG00764]; NIMH NIH HHS [MH/NS31862] NR 72 TC 84 Z9 86 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 100 IS 3 BP 663 EP 675 DI 10.1016/S0306-4522(00)00281-5 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 369JA UT WOS:000165061100023 PM 11098128 ER PT J AU Fujikawa, DG Shinmei, SS Cai, B AF Fujikawa, DG Shinmei, SS Cai, B TI Kainic acid-induced seizures produce necrotic, not apoptotic, neurons with internucleosomal DNA cleavage: Implications for programmed cell death mechanisms SO NEUROSCIENCE LA English DT Article DE apoptosis; DNA laddering; necrosis; programmed cell death; status epilepticus; TUNEL ID INDUCED STATUS EPILEPTICUS; NMDA RECEPTOR ANTAGONIST; CENTRAL-NERVOUS-SYSTEM; DEVELOPING RAT-BRAIN; ELECTRICAL-STIMULATION; HIPPOCAMPAL-NEURONS; PROTEIN-SYNTHESIS; CAUTIONARY NOTE; PERFORANT PATH; CYCLIN D1 AB Prolonged seizures (status epilepticus) induced by kainic acid activate programmed cell death mechanisms, and it is believed that kainic acid-induced status epilepticus induces neuronal apoptosis. In order to test this hypothesis, adult rats were subjected to 3-h kainic acid-induced seizures, with 24- or 72-h recovery periods. Neuronal death was assessed by light microscopy with the Hematoxylin and Eosin stain and with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL stain), by electron microscopy, and by agarose gel electrophoresis of DNA extracted from five vulnerable brain regions. Spontaneous and MK-801-induced apoptotic neurons from retrosplenial cortex of neonatal rats, evaluated by light and electron microscopy, were used as positive controls for apoptosis. Surprisingly, the large chromatin clumps of apoptotic neurons were TUNEL negative, whereas the cytoplasm showed light-to-moderate TUNEL staining, consistent with a lack of identifiable nuclear membranes ultrastructurally, and with intermingling of nuclear and cytoplasmic contents. Ultrastructurally, the acidophilic neurons produced by kainic acid-induced status epilepticus, identified with Hematoxylin and Eosin stain, were dark, shrunken and necrotic, with pyknotic nuclei containing small, dispersed chromatin clumps, and with cytoplasmic vacuoles, some of which were swollen, disrupted mitochondria. No apoptotic cells were seen. Acidophilic neurons were found in up to 20 of 23 brain regions examined and comprised 10-25% of the total number of neurons examined. A subset of these neurons (<10% of the total number of neurons in five of 23 regions) had TUNEL-positive nuclei 72 h but not 23 h after status epilepticus. Internucleosomal DNA cleavage (DNA "laddering") occurred in the four most damaged brain regions examined by electron microscopy 24 h after SE and the three most damaged regions 72 h after status epilepticus. Our results demonstrate that kainic acid-induced status epilepticus produces neuronal necrosis and not apoptosis in adult rats. The necrotic neurons show nuclear pyknosis, chromatin condensation and DNA laddering. Programmed cell death mechanisms activated by kainic acid-induced status epilepticus occur in neurons which become necrotic and could contribute to necrotic, as well as apoptotic, neuronal death. Published by Elsevier Science Ltd. C1 VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, Nursing Home Care Unit, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. NR 69 TC 152 Z9 164 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 98 IS 1 BP 41 EP 53 DI 10.1016/S0306-4522(00)00085-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 326NA UT WOS:000087740600005 PM 10858610 ER PT J AU Sternini, C Brecha, NC Minnis, J D'Agostino, G Balestra, B Fiori, E Tonini, M AF Sternini, C Brecha, NC Minnis, J D'Agostino, G Balestra, B Fiori, E Tonini, M TI Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors SO NEUROSCIENCE LA English DT Article DE receptor endocytosis; spare opioid receptors; enteric neurons; mu opioid receptors; opioid peptides; opiates ID GUINEA-PIG ILEUM; MYENTERIC-PLEXUS; NEUROKININ-1 RECEPTOR; MOLECULAR-BIOLOGY; MORPHINE; NEURONS; PEPTIDES; STIMULATION; ENDOCYTOSIS; RELEASE AB Organotypic cultures and ileal neuromuscular preparations were used to determine (i) whether endogenous release of opioids by electrical stimulation induces mu receptor endocytosis, and (ii) whether and under which conditions Ligand-induced mu receptor endocytosis influences the responsiveness of neurons expressing native mu receptor. In longitudinal muscle-myenteric plexus preparations, electrical stimulation at 20 Hz induced a prominent endocytosis of mu receptors in enteric neurons, indicating endogenous release of opioids. A similar massive endocytosis was triggered by exogenous application of the mu receptor agonist, [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin, whereas exogenous application of morphine was ineffective. [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin and morphine induced a concentration-dependent inhibition of neurogenic cholinergic twitch contractions to electrical stimulation at 0.1 Hz. beta-Chlornaltrexamine shifted to the right the inhibitory curve of both agonists with a concentration-dependent reduction of the maximum agonist response, which is consistent with the existence of spare mu opioid receptors. Under these conditions, the induction of mu receptor endocytosis by exogenously applied [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin diminished the inhibitory effect of this agonist on twitch contractions and tritiated acetylcholine release. In contrast, there was no reduction of the inhibitory effect of morphine, which failed to induce mu receptor endocytosis, on neurogenic cholinergic response. These results provide the first evidence for the occurrence of mu receptor endocytosis in neurons by endogenously released opioids and show that agonist-dependent mu receptor endocytosis could serve as a mechanism to regulate mu opioid receptor responsiveness to ligand stimulation when the opioid receptor reserve is reduced. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 CURE Digest Dis Res Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Dept Neurobiol, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Opioid Res Ctr, Los Angeles, CA 90095 USA. Univ Pavia, Sch Pharm, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy. Univ Pavia, Div Clin & Expt Pharmacol, Dept Internal Med & Therapeut, I-27100 Pavia, Italy. RP Sternini, C (reprint author), CURE Digest Dis Res Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Div Digest Dis, Dept Med, Bldg 115,Room 224,VAGLAHS,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NEI NIH HHS [EY04067]; NIDA NIH HHS [P50 DA005010]; NIDDK NIH HHS [DK41301, DK54155] NR 43 TC 44 Z9 45 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 98 IS 2 BP 233 EP 241 DI 10.1016/S0306-4522(00)00118-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 326NC UT WOS:000087740800005 PM 10854754 ER PT J AU Chen, JF Beilstein, M Xu, YH Turner, TJ Moratalla, R Standaert, DG Aloyo, VJ Fink, JS Schwarzschild, MA AF Chen, JF Beilstein, M Xu, YH Turner, TJ Moratalla, R Standaert, DG Aloyo, VJ Fink, JS Schwarzschild, MA TI Selective attenuation of psychostimulant-induced behavioral responses in mice lacking A(2a) adenosine receptors SO NEUROSCIENCE LA English DT Article DE A(2A) adenosine receptor; amphetamine; cocaine; dopamine receptor; quinpirole; SKF81297 ID STRIATAL DOPAMINE RELEASE; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; 6-HYDROXYDOPAMINE-LESIONED RATS; ACETYLCHOLINE-RELEASE; MESSENGER-RNA; IN-VIVO; C-FOS; GLUTAMATE RECEPTORS; ROTATIONAL BEHAVIOR AB A(2A) adenosine receptors are highly expressed in the striatum where they modulate dopaminergic activity. The role of A(2A) receptors in psychostimulant action is less well understood because of the lack of A(2A)-selective compounds with access to the central nervous system. To investigate the A(2A) adenosinergic regulation of psychostimulant responses, we examined the consequences of genetic deletion of A(2A) receptors on psychostimulant-induced behavioral responses. The extent of dopaminergic innervation and expression of dopamine receptors in the striatum were indistinguishable between A(2A) receptor knockout and wild-type mice. However, locomotor responses to amphetamine and cocaine were attenuated in A(2A), knockout mice. In contrast, D-1-like receptor agonists SKF81297 and SKF38393 produced identical locomotor stimulation and grooming, respectively, in wildtype and A(2A) knockout mice. Similarly, the D-2-like agonist quinpirole produced motor-depression and stereotypy that were indistinguishable between A(2A) knockout and wild-type mice. Furthermore, attenuated amphetamine- (but not SKF81297-) induced locomotion was observed in pure 129-Steel as well as hybrid 129-Steel x C57BL/6 mice, confirming A(2A) receptor deficiency land not genetic background) as the cause of the blunted psychostimulant responses in A(2A) knockout mice. These results demonstrate that A(2A) receptor deficiency selectively attenuates psychostimulant-induced behavioral responses and support an important role for the A(2A) receptor in modulating psychostimulant effects. (C) 2000 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Neurol Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Med Coll Penn & Hahnemann Univ, Dept Pharmacol, Philadelphia, PA 19129 USA. RP Chen, JF (reprint author), Massachusetts Gen Hosp E, Mol Neurobiol Lab, 149 13th St, Charlestown, MA 02129 USA. RI Moratalla, Rosario/H-9280-2015; OI Moratalla, Rosario/0000-0002-7623-8010; Turner, Timothy/0000-0001-9770-2647; Standaert, David/0000-0003-2921-8348 FU NIDA NIH HHS [DA07496]; NINDS NIH HHS [NS10828] NR 72 TC 68 Z9 68 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 97 IS 1 BP 195 EP 204 DI 10.1016/S0306-4522(99)00604-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 309DD UT WOS:000086751600019 PM 10771351 ER PT J AU Zhang, K Tarazi, FI Baldessarini, RJ AF Zhang, K Tarazi, FI Baldessarini, RJ TI Dopamine D-4 receptors in rat forebrain: Unchanged with amphetamine-induced behavioral sensitization SO NEUROSCIENCE LA English DT Article DE amphetamine; autoradiography; behavioral sensitization; dopamine D-4 receptors ID NUCLEUS-ACCUMBENS-SEPTI; DIFFERENTIAL REGULATION; ANTIPSYCHOTIC-DRUGS; D-4-LIKE RECEPTORS; D-2-LIKE; EXPRESSION; SUBTYPES; D-1-LIKE; BRAIN AB Dopamine D-2 receptors are implicated in stimulant-induced behavioral sensitization.(7,10) Studies using selective receptor antagonists also implicate the Dq receptor, a member of the dopamine D-2-like receptor family.(3) Accordingly, dopamine D-4 and D-2-like receptor levels in rat forebrain were examined by computed autoradiography after repeated (+)-amphetamine treatment that induced behavioral sensitization. Receptor binding was quantified in critical brain regions including caudate-putamen, nucleus accumbens septi, medial prefrontal cortex and hippocampus. No significant differences in D-4 or D-2-like receptor levels were detected among rats sensitized to amphetamine, those exposed to amphetamine but killed before behavioral sensitization emerged or vehicle-treated controls. The findings indicate that expression of amphetamine-induced behavioral sensitization is not associated with altered D-4 (or D-2) receptor density in rat forebrain. (C) 2000 ZERO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychait, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Zhang, K (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH47370, MH34006]; PHS HHS [M11-19905] NR 19 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 97 IS 2 BP 211 EP 213 DI 10.1016/S0306-4522(00)00082-8 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 314PK UT WOS:000087064400002 PM 10799752 ER PT J AU Ayata, C Shimizu-Sasamata, M Lo, EH Noebels, JL Moskowitz, MA AF Ayata, C Shimizu-Sasamata, M Lo, EH Noebels, JL Moskowitz, MA TI Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha 1A subunit of P/Q type calcium channels SO NEUROSCIENCE LA English DT Article DE electrophysiology; microdialysis; mutant mice; tottering; leaner ID FAMILIAL HEMIPLEGIC MIGRAINE; TRANSCRANIAL MAGNETIC STIMULATION; NEOCORTICAL PYRAMIDAL NEURONS; NETWORK EXCITABILITY DEFECTS; CEREBELLAR PURKINJE-CELLS; LEANER MUTANT MICE; NEUROLOGICAL MUTANT; GLUTAMATE RELEASE; AMINO-ACIDS; SPIKE-WAVE AB The P/Q type voltage-gated Ca2+ channels are involved in membrane excitability and Ca2+-dependent neurotransmitter release within the CNS. Mutations in the CacnalA gene encoding the alpha 1A subunit of the P/Q type Ca2+ channel have recently been reported in tottering mice and a more severely affected allele, leaner. Here we show using in vivo cortical microdialysis that evoked increases of extracellular glutamate levels are markedly attenuated in both mutants upon KCl-induced depolarization compared with wild-type mice. Tottering and leaner mice also show a 10-fold resistance to cortical spreading depression induced by cortical electrical stimulation or KCl application to the pial surface. A slower transcortical propagation speed and failure to sustain regenerative spread of the depolarizing wave were more pronounced in leaner neocortex. Both signaling defects appeared unrelated to the developmental history of repeated cortical spike wave discharges, since neither were observed in the stargazer mouse, a Ca2+ channel gamma 2 subunit mutant with a similar seizure phenotype. These data demonstrate two cortical excitability defects revealed by prolonged depolarization in cerebral networks expressing mutant P/Q type Ca2+ channels, and are the first to identify a gene linked to a spreading depression phenotype. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg & Neurol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg & Neurol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 46 TC 102 Z9 103 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 3 BP 639 EP 645 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 272RE UT WOS:000084664100002 PM 10670432 ER PT J AU Yang, H Yuan, PQ Wang, L Tache, Y AF Yang, H Yuan, PQ Wang, L Tache, Y TI Activation of the parapyramidal region in the ventral medulla stimulates gastric acid secretion through vagal pathways in rats SO NEUROSCIENCE LA English DT Article DE kainate; raphe pallidus; Fos; vagus; TRH mRNA; 5-HT ID THYROTROPIN-RELEASING-HORMONE; DORSAL MOTOR NUCLEUS; INTERMEDIOLATERAL CELL COLUMN; LESION FORMATION; RAPHE PALLIDUS; SUBSTANCE-P; C-FOS; BODY-TEMPERATURE; GENE-EXPRESSION; KAINIC ACID AB Neurons synthesizing thyrotropin-releasing hormone, substance P and serotonin in the medullary caudal raphe nuclei project to the dorsal vagal complex and play a role in the central vagal regulation of gastric function. Neurons in the parapyramidal region in the ventral medulla share similar biochemical coding and projections as those in the caudal raphe nuclei. The role of the parapyramidal region in the autonomic regulation of gastric acid secretion was investigated in urethane-anesthetized rats. Unilateral microinjection of kainate into the parapyramidal region at 10, 15 and 20 ng induced a dose-related stimulation of gastric acid secretion (net increases: 22.2 +/- 11.2, 40.5 +/- 8.5 and 89.8 +/- 19.4 mu mol/60 min, respectively), while injection of vehicle had no effect (net change: -0.1 +/- 1.4 mu mol/60 min). Time-course studies showed a nine-fold peak increase over basal at 30 min after parapyramidal injection of kainate (20 ng) and acid secretion returned to basal level at 70 min. Microinjections of kainate (15-20 ng) outside the parapyramidal region or into the parapyramidal region in vagotomized rats had no effect. Exposure to cold (4 degrees C) for 2 h, which is known to induce vagally mediated gastric secretory and motor responses through medullary thyrotropin-releasing hormone pathways, increased the number of Fos-positive cells in the caudal, middle and rostral parts of the parapyramidal region to 4.3 +/- 0.4, 9.4 +/- 0.9 and 18.4 +/- 1.6/section, respectively, compared with 0.1 +/- 0.1, 0.1 +/- 0.0 and 0.7 +/- 0.6/section, respectively, in rats maintained at room temperature. Most of the Fos-labeled cells co-expressed pro-thyrotropin-releasing hormone messenger RNA signal and/or were serotonin immunoreactive. These data show that chemical activation of neurons in the parapyramidal region results in a vagal-dependent stimulation of gastric acid secretion and that acute cold exposure activates parapyramidal neurons containing pro-thyrotropin-releasing hormone and/or serotonin, suggesting a potential role of the parapyramidal region, in addition to the caudal raphe nuclei, as medullary sites involved in the vagal regulation of gastric function. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Univ Calif Los Angeles, Div Digest Dis, Dept Med,Digest Dis Res Ctr, W Los Angeles Vet Adm Med Ctr,CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), Univ Calif Los Angeles, Div Digest Dis, Dept Med,Digest Dis Res Ctr, W Los Angeles Vet Adm Med Ctr,CURE, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-30110, DK-33061, DK-50255] NR 44 TC 27 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 3 BP 773 EP 779 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 272RE UT WOS:000084664100014 PM 10670444 ER PT J AU Phillips, T Rees, S Augood, S Waldvogel, H Faull, R Svendsen, C Emson, P AF Phillips, T Rees, S Augood, S Waldvogel, H Faull, R Svendsen, C Emson, P TI Localization of metabotropic glutamate receptor type 2 in the human brain SO NEUROSCIENCE LA English DT Article DE metabotropic glutamate receptor; human brain; antibody; western blot; immunohistochemistry; distribution ID CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; NIGRA PARS RETICULATA; SUBTHALAMIC NUCLEUS; IMMUNOHISTOCHEMICAL LOCALIZATION; MOLECULAR CHARACTERIZATION; BASAL GANGLIA; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; CEREBELLAR CORTEX AB Metabotropic glutamate receptors are a heterogeneous family of G-protein-coupled receptors that are linked to multiple second messenger systems to regulate neuronal excitability and synaptic transmission. To elucidate the physiological role of these receptors in human central nervous system function and dysfunction at the receptor protein level requires the use of selective antibodies to determine the phenotype of cells expressing particular receptor subtypes. To this end the present study has examined the regional and cellular localization of the metabotropic glutamate type 2 receptor protein in selected human brain regions. After epitope prediction, antibodies have been generated against a short synthetic peptide corresponding to amino acid residues located in the putative intracellular carboxy-terminus and subsequently applied to an immunohistochemical investigation. Antibodies specifically detected the type 2 receptor in transfected mammalian cells and also recognized a major band of 98,000 mol. wt in western blots of human brain tissue membranes. At the light microscope level immunohistochemical studies have demonstrated that type 2-like immunoreactivity was widely distributed in the human brain, being characterized by the presence of a strong immunoreaction in multiple cortical regions, and in structures comprising the basal ganglia, to include the caudate nucleus, putamen, globus pallidus, substantia nigra and subthalamic nucleus. In the hippocampal formation, immunoreactivity was predominant in selective cell layers of both the dentate gyrus and cornu ammonia, the subicular complex and entorhinal cortex. In the thalamus, multiple subnuclei showed reaction product. In the cerebellar cortex, immunoreactivity was expressed in a number of cell layers and cell types. Furthermore, using double immunofluorescence we confirmed that the type 2 receptor is a product of normal resting astrocytes in the cerebral cortex in particular. This antibody provides a new immunological tool with the potential to evaluate the distribution of human metabotropic glutamate receptor 2 protein in other brain regions and in human central nervous system diseases. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England. Glaxo Wellcome Res & Dev Ltd, Mol Pharmacol Unit, Stevenage SG1 2NY, Herts, England. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Auckland, Dept Anat, Sch Med, Auckland, New Zealand. New Addenbrookes Hosp, MRC, Brain Repair Ctr, Cambridge, England. RP Emson, P (reprint author), Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England. NR 60 TC 27 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 4 BP 1139 EP 1156 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 277EL UT WOS:000084919700022 PM 10682721 ER PT J AU Schmid, CH Brown, EN AF Schmid, CH Brown, EN TI Bayesian hierarchical models SO NUMERICAL COMPUTER METHODS, PART C SE METHODS IN ENZYMOLOGY LA English DT Review ID KALMAN FILTER; LINEAR MODEL; GROWTH; METAANALYSIS; ALGORITHM C1 New England Med Ctr, Div Clin Care Res, Biostat Res Ctr, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Stat Res Lab, MIT,Div Hlth Sci & Technol,Dept Anesthesia & Crit, Boston, MA USA. RP Schmid, CH (reprint author), New England Med Ctr, Div Clin Care Res, Biostat Res Ctr, 750 Washington St, Boston, MA 02111 USA. OI Schmid, Christopher/0000-0002-0855-5313 FU AHRQ HHS [R01-HS08532, R01-HS07782] NR 35 TC 5 Z9 5 U1 1 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 2000 VL 321 BP 305 EP 330 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69J UT WOS:000089207400017 PM 10909064 ER PT J AU Ooi, CJ Podolsky, DK AF Ooi, CJ Podolsky, DK TI Nutrition and Crohn's disease: A case study in ambiguity SO NUTRITION LA English DT Editorial Material ID CONTROLLED TRIAL; INTESTINAL PERMEABILITY; ENTERAL NUTRITION; ELEMENTAL DIET; SMALL BOWEL; METAANALYSIS; REMISSION; RELATIVES; GLUTAMINE C1 Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. Harvard Univ, Ctr Study Inflammatory Bowel Dis, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med,Dept Med, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JAN PY 2000 VL 16 IS 1 BP 76 EP 77 DI 10.1016/S0899-9007(99)00239-7 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 273YE UT WOS:000084736300021 PM 10674246 ER PT J AU Perez, VL Biuckians, A Streilein, JW AF Perez, VL Biuckians, A Streilein, JW TI In-vivo impaired T helper 1 cell development in submandibular lymph nodes due to IL-12 deficiency following antigen injection into the anterior chamber of the eye SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Th1/Th2; lymph node; in-vivo animal model; antigen presentation; cytokines ID IMMUNE DEVIATION; CLONAL EXPANSION; INDUCTION; PRIVILEGE; POPULATION; MECHANISM; INTERLEUKIN-12; APOPTOSIS; TOLERANCE; REQUIRES AB Purpose: To determine the functional properties of antigen-specific T cells that accumulate in lymph nodes following injection of antigen into the anterior chamber ( AC). Methods: Ovalbumin (OVA) specific, CD4(+) transgenic T cell receptor (Tcr) T cells (KJ-126(+)) from DO11.10 mice were adoptively transferred into unirradiated syngeneic BALB/c mice who then received an injection of OVA in the AC or subcutaneously (SC). Three days later, KJ126(+) T cells in draining and non-draining lymph nodes were analyzed for clonal expansion, activation, and cell-cycle status by flow cytometry. In addition, the cells functional phenotype was assessed in vitro by proliferation assays and cytokine production by ELISA. Results: Tcr T cells localized exclusively to draining lymph nodes after injection of OVA into the AC ( neck) and SC (neck, axilla, brachial). In both cases, the KJ126(+) T cells displayed evidence of in-vivo activation and proliferation. T cells from AC-injected donors when stimulated in vitro with OVA produced small amounts of IL-2, but no IFN-gamma, IL-4, IL-5, IL-10, or TGF beta. By contrast, T cells from SC-injected animals displayed a Th1-like phenotype (IL-2, IFN-gamma). The draining lymph nodes of mice that received systemic or intraocular administration of exogenous IL-12 at the time of the AC injection of OVA also contained KJ126(+) T cells that secreted IFN-gamma and IL-2. Conclusion: Antigen attracts antigen-specific T cells to lymph nodes that drain the injection site. Whereas responding T cells in nodes draining SC-injection sites differentiated into Th1-like cells, T cells in nodes draining AC injection failed to differentiated beyond the capacity to secrete IL-2 in response to antigen. Since the failure was reversed by exogenous IL-12, we propose that orderly differentiation of antigen-specific T cells down the Th1 pathway is aborted by the eye, because of a deficit in IL-12 production. C1 Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Streilein, JW (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [EY05678] NR 30 TC 20 Z9 21 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2000 VL 8 IS 1 BP 9 EP 24 DI 10.1076/0927-3948(200003)8:1;1-S;FT009 PG 16 WC Ophthalmology SC Ophthalmology GA 310QV UT WOS:000086839600002 PM 10806431 ER PT S AU Chen, JN Fishman, MC AF Chen, JN Fishman, MC BE NussleinVolhard, C Kratzschmar, J TI Genetic dissection of heart development SO OF FISH, FLY, WORM, AND MAN: LESSONS FROM DEVELOPMENTAL BIOLOGY FOR HUMAN GENE FUNCTION AND DISEASE SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT 29th Ernst-Schering-Research-Foundation Workshop CY JAN 27-29, 1999 CL BERLIN, GERMANY SP Ernst Schering Res Fdn ID LEFT-RIGHT ASYMMETRY; TINMAN-RELATED GENES; ZEBRAFISH EMBRYO; INSERTIONAL MUTAGENESIS; CARDIOVASCULAR-SYSTEM; TRANSCRIPTION FACTOR; VERTEBRATE HEART; INTERNAL ORGANS; HOMEOBOX GENE; DROSOPHILA C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Chen, JN (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. OI Chen, Jau-Nian/0000-0001-8807-3607 NR 48 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-66324-X J9 E SCHERING RES FDN W PY 2000 VL 29 BP 107 EP 122 PG 16 WC Biology; Genetics & Heredity; Medicine, General & Internal SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity; General & Internal Medicine GA BQ01E UT WOS:000086852400007 ER PT J AU Berlin, JD Adak, S Vaughn, DJ Flinker, D Blaszkowsky, L Harris, JE Benson, AB AF Berlin, JD Adak, S Vaughn, DJ Flinker, D Blaszkowsky, L Harris, JE Benson, AB TI A phase II study of gemcitabine and 5-fluorouracil in metastatic pancreatic cancer: An Eastern Cooperative Oncology Group Study (E3296) SO ONCOLOGY LA English DT Article DE gemcitabine; 5-fluorouracil; pancreas cancer; phase II trial AB Gemcitabine has recently been compared favorably to 5-fluorouracil (5-FU) as the standard chemotherapy for advanced pancreas cancer. Based on phase I data that combining gemcitabine with 5-FU is safe and has evidence for clinical activity, a phase II trial was conducted by the Eastern Cooperative Oncology Group (ECOG). Patients with metastatic disease, good performance status and organ function were eligible and enrolled after providing informed consent, Patients were given gemcitabine (1,000 mg/m(2)) followed by 5-FU (600 mg/m(2)) weekly for 3 weeks of every 4. Of 37 patients enrolled over a 3-month period, 36 were eligible. Partial responses were seen in 5 patients (14%). Median survival was 4.4 months with a 1-year survival rate of 8.6%. A randomized trial of the combination of 5-FU and gemcitabine versus gemcitabine alone is currently accruing patients in ECOG. Copyright (C) 2000 S. Karger AG, Basel. C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Mem Hosp Burlington Cty, Mt Holly, NJ USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Berlin, JD (reprint author), 1956 Vanderbilt Clin, Nashville, TN 37232 USA. FU NCI NIH HHS [CA23318, CA15488, CA21076] NR 11 TC 59 Z9 62 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2000 VL 58 IS 3 BP 215 EP 218 DI 10.1159/000012103 PG 4 WC Oncology SC Oncology GA 305UL UT WOS:000086558900006 PM 10765123 ER PT J AU Raje, N Anderson, KC AF Raje, N Anderson, KC TI The Hu/Yahalom article reviewed SO ONCOLOGY-NEW YORK LA English DT Article ID ADVANCED MULTIPLE-MYELOMA; SKELETAL EVENTS; PAMIDRONATE C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Donor Ctr, Dept Adult Oncol & Kraft Family Blood, Boston, MA 02115 USA. RP Raje, N (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2000 VL 14 IS 1 BP 112 EP + PG 2 WC Oncology SC Oncology GA 368QH UT WOS:000090128700018 ER PT J AU Shipley, WU AF Shipley, WU TI The Thompson article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID PROSTATE-CANCER; IRRADIATION; DEFINITION C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Genitourinary Oncol Unit, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2000 VL 14 IS 1 BP 135 EP 136 PG 2 WC Oncology SC Oncology GA 368QH UT WOS:000090128700020 ER PT S AU Krause, M D'Amico, DJ AF Krause, M D'Amico, DJ BE Rol, PO Joos, KM Manns, F TI Ablation of vitreous tissue with a high-repetition-rate-erbium : YAG- laser SO OPHTHALMIC TECHNOLOGIES X SE Proceedings of SPIE LA English DT Proceedings Paper CT 10th Conference on Ophthalmic Technologies CY JAN 22-23, 2000 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE laser- surgery- methods; lasers- therapeutic use; vitreous- body- surgery; vitrectomy- methods; vitreous- body- radiation- effects ID ER-YAG; VITREORETINAL SURGERY; CLINICAL-EXPERIENCE; THERMAL-DAMAGE; MU-M AB The efficacy and predictability of Erbium (Er):YAC laser ablation of vitreous tissue and saline solution were determined. Both substances were ablated in vitro with an Er:YAG laser (pulse duration: 500 mu s) connected to a sapphire fiber with the tip of the fiber placed in air. Pulse energies ranged between 1.0 and 20.8 mJ (vitreous) and 1.0 and 21.2 mJ (saline solution). Pulse repetition rates between 10 and 200 Hz were used. The net ablation rates were determined by weight measurement before and after laser treatment. Untreated control samples were used simultaneously to correct for evaporation. Net ablation rates were considered as the difference in the amounts of weight loss measured with and without laser treatment. Reproducible and constant ablation rates were found for both vitreous and saline solution in each of 3 consecutive measurements at constant laser parameters. Ablation rates did not significantly differ between both substances (p = 0.25). The net ablation rates in both materials were found to increase linearly with increasing pulse frequency and nonlinearly with increasing pulse energy. The present studies suggest directions for the development of instrumentation for enhanced removal of vitreous and other tissues as well. These directions include the use of higher hertz (>200) instruments and appropriately designed endoprobe geometries. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Retina Serv, Cambridge, MA 02138 USA. RP Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Retina Serv, Cambridge, MA 02138 USA. EM krausematthias@hotmail.com NR 27 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 0-8194-3524-4 J9 PROC SPIE PY 2000 VL 3908 BP 157 EP 164 DI 10.1117/12.387519 PG 4 WC Engineering, Biomedical; Ophthalmology; Optics SC Engineering; Ophthalmology; Optics GA BQ51V UT WOS:000088608100020 ER PT S AU Moor, ACE Hamblin, M Molpus, K Duska, LR Rizvi, I Hasan, T AF Moor, ACE Hamblin, M Molpus, K Duska, LR Rizvi, I Hasan, T BE Dougherty, TJ TI Photoimmunotherapy of ovarian cancer SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY IX SE PROGRESS IN BIOMEDICAL OPTICS LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy IX CY JAN 22-23, 2000 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE photoimmunotherapy; chlorin e6; ovarian cancer; CA125 ID PHOTODYNAMIC THERAPY; XENOGRAFT MODEL; CARCINOMA; BIODISTRIBUTION; COMBINATION; CELLS; VIVO AB Photoimmunotherapy (PIT), which involves the antibody-targeted delivery of a photosensitizer and subsequent illumination, might offer a new treatment option for ovarian cancer. Studies from our laboratory and those of others show the specific killing of ovarian cancer cells in vitro and ex vivo by photoimmunoconjugates directed against the ovarian cancer specific antigen CA125. In vivo studies in nude mice with human xenografts, show an increased survival after photoimmunotherapy. In addition, it was shown in ex vivo studies that PIT in combination with cisplatinum, significantly decreases cell viability, especially in platinum-resistant cells. These data suggest further exploration of PIT as an option for the treatment of intraperitoneal disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. EM hasan@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 1017-2661 BN 0-8194-3525-2 J9 PROG BIOM O PY 2000 VL 1 BP 30 EP 33 DI 10.1117/12.659975 PG 4 WC Oncology; Engineering, Biomedical; Optics SC Oncology; Engineering; Optics GA BP94Z UT WOS:000086710500005 ER PT J AU Ring, D Jupiter, JB AF Ring, D Jupiter, JB TI Fractures of the distal humerus SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article AB The quality of elbow function after fracture of the distal humerus is related to the degree to which normal anatomic relationships are restored. This article addresses the issues related to fractures of the distal humerus, including challenges, controversies, surgical exposure, postoperative management, and complications. C1 Massachusetts Gen Hosp, Hand Surg Serv, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jupiter, JB (reprint author), ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 31 TC 53 Z9 71 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JAN PY 2000 VL 31 IS 1 BP 103 EP + DI 10.1016/S0030-5898(05)70131-0 PG 12 WC Orthopedics SC Orthopedics GA 277DT UT WOS:000084918000009 PM 10629336 ER PT J AU Kuhn, V Lochmuller, EM Lill, C Schneider, E Muller, R Barkmann, R Eckstein, F AF Kuhn, V Lochmuller, EM Lill, C Schneider, E Muller, R Barkmann, R Eckstein, F TI Bone strength at clinically relevant skeletal sties displays substantial heterogeneity and is prediced most accurately from site-specific bone densitometry SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract C1 LMU, Inst Anat, Musculoskeletal Res Grp, Munich, Germany. Orthopad Uniklin, Freiburg, Germany. AO Res Inst, Davos, Switzerland. Harvard Univ, Sch Med, Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02115 USA. UKK, Radiol Diagnost Klin, Kiel, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2000 VL 11 SU 3 MA O47 BP 15 EP 15 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 382RZ UT WOS:000165837400049 ER PT J AU Orwoll, ES Bevan, L Phipps, KR AF Orwoll, ES Bevan, L Phipps, KR TI Determinants of bone mineral density in older men SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE bone density; male; osteoporosis ID OSTEOPOROTIC FRACTURES; HIP FRACTURE; ELDERLY MEN; WOMEN; MASS; RISK; WEIGHT; INDEX; LIFE; SIZE AB Although osteoporosis in men is increasingly recognized as an important health issue and bone mass appears to be a major determinant of fracture, there remain few data concerning the determinants of bone mass in men. To determine the correlates of bone density in men, we studied a large group of older subjects recruited from three rural communities in the northwestern United States. Three hundred and fifty-five men over the age of 60 years (mean 71.5 +/- 7.4 years) without known disorders of mineral metabolism were recruited by community advertising. Bone mineral density was measured at the lumbar spine, proximal femur and radius by dual-energy X-ray absorptiometry, and factors potentially related to skeletal status were assessed by direct measurements or questionnaire. In univariate analyses weight (positively) and age (negatively) were associated with bone density. After adjustment for these two factors, alcohol intake, osteoarthritis and thiazide use were associated with higher bone density, while previous fractures, gastrectomy, peptic ulcer disease, rheumatoid arthritis, glucocorticoid use, hypertension, previous hyperthyroidism, height loss since age 20 years, chronic lung disease and smoking were related to lower density. In multivariate models, only weight and a history of cancer were related to higher bone mass, and age, previous fracture, rheumatoid arthritis, gastrectomy and hypertension were associated with lower density. These data contribute to the emerging field of osteoporosis in men, and may help in the clinical identification of men at higher risk of osteopenia. C1 Oregon Hlth Sci Univ, Sch Med, Bone & Mineral Unit, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Res Serv, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Dent, Portland, OR 97201 USA. RP Orwoll, ES (reprint author), Oregon Hlth Sci Univ, Sch Med, Bone & Mineral Unit, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 FU NIDCR NIH HHS [R0I DE 09883] NR 25 TC 65 Z9 67 U1 2 U2 3 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2000 VL 11 IS 10 BP 815 EP 821 DI 10.1007/s001980070039 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 385GT UT WOS:000165996000001 PM 11199184 ER PT J AU Tropitzsch, AS Merchant, SN Kristiansen, AG McKenna, MJ AF Tropitzsch, AS Merchant, SN Kristiansen, AG McKenna, MJ TI In search of connexin 26 mutations in archival temporal bones from individuals with congenital deafness SO OTO-RHINO-LARYNGOLOGIA NOVA LA English DT Article DE connexin 26 mutations; archival temporal bones; sensorineural hearing loss; congenital hearing loss; polymerase chain reaction; direct sequencing ID RECESSIVE DEAFNESS; SENSORINEURAL DEAFNESS; PRELINGUAL DEAFNESS; HIGH PREVALENCE; HEARING-LOSS; GENE; POPULATION; FORM AB Mutations in the connexin 26 gene have been found to be associated with approximately half of all cases of congenital nonsyndromic sensorineural hearing Loss, and represent the single most common cause of genetic sensorineural hearing loss. Seven sets of temporal bones from individuals with congenital sensorineural hearing loss or hearing lass with onset in early childhood were examined for the presence of connexin 26 mutations with the hope of being able to characterize the histopathology of this common disorder. DNA was extracted from temporal bone specimens and analyzed by allele-specific polymerase chain reaction using previously published primer sets and also by direct sequencing. The allele-specific primers resulted in what was initially thought to be mutations in three specimens. However, this could not be confirmed by direct sequencing, which failed to reveal evidence of connexin 26 mutations in any specimens, including those which seemed to be positive by the allele-specific method. Potential problems associated with the molecular analysis of archival human temporal bones are reviewed. Copyright (C) 2001 S. Karger AG, Basel. C1 Harvard Univ, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otol & Laryngol,Dept Otolaryngol, Boston, MA 02114 USA. RP McKenna, MJ (reprint author), Harvard Univ, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Sch Med,Dept Otol & Laryngol,Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1014-8221 J9 OTO RHINO LARYN NOVA JI Oto-Rhino-Laryngol. Nova PY 2000 VL 10 IS 5 BP 232 EP 236 DI 10.1159/000054824 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 405TN UT WOS:000167176400010 ER PT B AU Taylor, AE Hall, JE Adams, JM Martin, KA Welt, CK Crowley, WF AF Taylor, AE Hall, JE Adams, JM Martin, KA Welt, CK Crowley, WF BE Adashi, EY TI The physiology of the human midcycle gonadotropin surge SO OVULATION: EVOLVING SCIENTIFIC AND CLINICAL CONCEPTS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT International Symposium on Ovulation - Evolving Scientific and Clinical Concepts CY SEP 24-27, 1998 CL SALT LAKE CITY, UT SP Serono Symposia USA ID LUTEINIZING-HORMONE SURGE; MENSTRUAL-CYCLE; NORMAL WOMEN; PULSE-GENERATOR; RHESUS-MONKEY; ESTRADIOL; GNRH; SECRETION; RELEASE; PROGESTERONE C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95124-5 J9 SERONO SYMP PY 2000 BP 79 EP 97 PG 19 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA BR70S UT WOS:000167234000007 ER PT J AU Yeh, CH Tsai, JL Li, WJ Chen, HM Lee, SC Yang, CP AF Yeh, CH Tsai, JL Li, WJ Chen, HM Lee, SC Yang, CP TI Use of alternative therapy among pediatric oncology patients in Taiwan SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE alternative therapy; medical help-seeking behavior; oncology; pediatric patient ID GANODERMA-LUCIDUM; CHINESE MEDICINE; UNITED-STATES; CANCER; PREVALENCE; CARE AB Both alter native medicine and western medicine have been commonly used to treat pediatric cancer Patients in Taiwan. Each has its own intrinsic strengths and weaknesses and they can be complementary. Little is known about medical help-seeking behaviors of parents of pediatric cancer patients, especially those related to alternative therapies. This study investigated the extent and parental expectations on use of alternative therapies. All Primary caregivers of 63 eligible patients were interviewed. Use of alternative therapies, regardless of education level or social status of their families, is prevalent (n = 46, 73%) in Taiwan. Commonly used alte,native therapies included, in order of popularity, formulated functional food (n = 22, 48%), temple worship/shamanism (n = 19, 40%), traditional Chinese medicine (n = 9, 20%), secret recipes/herbs (n = 13, 28%), and diet supplements (n = 9, 19%). Such Practices generally occur without medical guidance from oncologists, largely because of poor interactions between pal mts and oncologists. Future efforts should be made to encourage both parents and oncologists to discuss this issue. Nurses may serve as mediators by developing mutual trust and a sharing relationship between these groups. C1 Chang Gung Univ, Grad Inst Nursing Sci, Tao Yuan, Taiwan. Chang Gung Univ, Sch Nursing, Tao Yuan, Taiwan. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. Natl Taipei Coll Nursing, Taipei, Taiwan. RP Yeh, CH (reprint author), Chang Gung Univ, Grad Inst Nursing Sci, 259 Wen Hwa 1 Rd, Tao Yuan, Taiwan. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 28 TC 45 Z9 45 U1 1 U2 3 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD JAN-FEB PY 2000 VL 17 IS 1 BP 55 EP 65 DI 10.1080/088800100276668 PG 11 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 274VG UT WOS:000084785300008 PM 10689715 ER PT J AU Malley, R Vernacchio, L Devincenzo, J Ramilo, O Dennehy, PH Meissner, C Gruber, WC Jafri, HS Sanchez, PJ Macdonald, K Montana, JB Thompson, CM Ambrosino, DM AF Malley, R Vernacchio, L Devincenzo, J Ramilo, O Dennehy, PH Meissner, C Gruber, WC Jafri, HS Sanchez, PJ Macdonald, K Montana, JB Thompson, CM Ambrosino, DM TI Enzyme-linked immunosorbent assay to assess respiratory syncytial virus concentration and correlate results with inflammatory mediators in tracheal secretions SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE enzyme-linked immunosorbent assay; respiratory syncytial virus; tracheal secretions ID IMMUNE GLOBULIN; YOUNG-CHILDREN; TRACT INFECTION; CYTOKINE IL-8; TNF-ALPHA; I RELEASE; HIGH-RISK; INFANTS; RSV; ANTIBODY AB Objective. We developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of respiratory syncytial virus (RSV) in respiratory secretions in intubated patients infected with RSV. Methods. We compared the quantitative ELISA and a standardized plaque assay in intubated children <2 years of age who were mechanically ventilated for severe RSV disease and enrolled in a randomized double blind placebo-controlled treatment trial of a monoclonal antibody to the F protein of RSV (palivizumab; Synagis). We also examined the relationship between the concentrations of virus as measured by ELISA and of three inflammatory indices in respiratory secretions (white blood cell count, myeloperoxidase and eosinophilic cationic protein). Results. Quantitative ELISA and plaque assay were highly correlated for both tracheal aspirates (r = 0.67, P = 0.001) and nasal wash specimens (r = 0.75, P = 0.001). Treatment with palivizumab significantly neutralized RSV in tracheal aspirates as measured by plaque assay. in contrast quantitation of RSV by ELISA was not affected by palivizumab treatment. This finding is consistent with results that were obtained in preliminary studies of RSV-containing media treated with monoclonal antibody, where we found that the ELISA measured virus whether antibody-hound or not. The inflammatory indices were not correlated with RSV concentration measured by ELISA or plaque assay. Conclusions. We conclude that this quantitative ELISA is a potentially useful tool for measurement of RSV concentration in respiratory secretions that may help elucidate the pathophysiology of acute RSV infection. Specific antiviral strategies for the treatment of RSV disease could be evaluated by this method. C1 Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Univ Tennessee, Div Pediat Infect Dis, Memphis, TN USA. St Jude Childrens Res Hosp, Lebonheur Childrens Med Ctr, Memphis, TN 38101 USA. Univ Texas, SW Med Ctr, Div Pediat Infect Dis, Dallas, TX USA. Hasbro Childrens Hosp, Div Pediat Infect Dis, Providence, RI USA. Tufts Univ New England Med Ctr, Div Pediat Infect Dis, Boston, MA 02111 USA. Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Nashville, TN USA. RP Malley, R (reprint author), Childrens Hosp, Dept Med, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM malley@hub.tch.harvard.edu OI Dennehy, Penelope/0000-0002-2259-5370; Vernacchio, Louis/0000-0002-2012-5404 FU NICHD NIH HHS [5T32HD07488-02] NR 16 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2000 VL 19 IS 1 BP 1 EP 7 DI 10.1097/00006454-200001000-00002 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 274KZ UT WOS:000084766200001 PM 10643842 ER PT J AU Lieberman, E Lang, J Richardson, DK Frigoletto, FD Heffner, LJ Cohen, A AF Lieberman, E Lang, J Richardson, DK Frigoletto, FD Heffner, LJ Cohen, A TI Intrapartum maternal fever and neonatal outcome SO PEDIATRICS LA English DT Article DE fever; epidural analgesia; neonatal outcome; neonatal seizures; labor ID EPIDURAL ANALGESIA; FOREBRAIN ISCHEMIA; BRAIN-DAMAGE; LABOR; TERM; HYPERTHERMIA; TEMPERATURE; HYPOTHERMIA; INFECTION; INFANTS AB Objective. Much of fever during term labor may not be infectious but rather a consequence of the use of epidural analgesia. Therefore, we investigated the association of elevated maternal intrapartum temperature with neonatal outcome when the infant does not develop an infection. Methods. We studied 1218 nulliparous women with singleton, term pregnancies in a vertex presentation and spontaneous labor. Women were excluded if their temperature was >99.5 degrees F at admission for delivery, if they were diabetic or had an active genital herpes infection or if their infant developed a neonatal infection, had a congenital infection, or had a major malformation. Maximum intrapartum temperature was categorized as: less than or equal to 100.4 degrees F (afebrile), 100.5 degrees F to 101 degrees F, and >101 degrees F. Results. During labor, 123 women (10.1%) developed a fever >100.4 degrees F; 62 (5.1%) women had a maximum temperature of 100.5 degrees F to 101 F and 61 (5.0%) women had a maximum temperature >101 degrees F. Of febrile women, 97.6% had received epidural analgesia for pain relief. Infants of women developing a fever >100.4 degrees F were more likely to have a 1-minute Apgar score <7 (22.8% for >100.4 degrees F vs 8.0% for afebrile) and to be hypotonic after delivery (4.8% for >100.4 degrees F vs .5% for afebrile). Compared with infants of afebrile women, infants whose mothers' maximum temperature was >101 degrees F were more likely to require bag and mask resuscitation (11.5% vs 3.0%) and to be given oxygen therapy in the nursery (8.2% vs 1.3%). We also found a higher rate of neonatal seizure with fever (3.3% vs.2%), but the number of infants with seizure was small (n = 4). All associations remained essentially the same after controlling for confounding in logistic regression analyses. Conclusions. Intrapartum maternal fever, particularly if >101 degrees F, was associated with a number of apparently transient adverse effects in the newborn. Larger studies are needed to investigate the association of intrapartum fever with neonatal seizures and to determine whether any lasting injury to the fetus may occur. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joint Program Neonatol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Lieberman, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. FU NICHD NIH HHS [R01HD26813] NR 33 TC 102 Z9 108 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 8 EP 13 DI 10.1542/peds.105.1.8 PG 6 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400002 PM 10617697 ER PT B AU Tang, CH Bredow, S Mahmood, U Weissleder, R AF Tang, CH Bredow, S Mahmood, U Weissleder, R BE Fields, GB Tam, JP Barany, G TI In vivo detection of tumor associated protease activity using long circulating fluorescent labeled peptide substrates SO PEPTIDES FOR THE NEW MILLENNIUM LA English DT Proceedings Paper CT 16th American Peptide Symposium CY JUN 26-JUL 01, 1999 CL MINNEAPOLIS, MN SP Amer Peptide Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Tang, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. NR 8 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-6445-7 PY 2000 BP 450 EP 452 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BR58X UT WOS:000166856900179 ER PT J AU Mirela, B Mila, MP Brown, D Ivan, S AF Mirela, B Mila, MP Brown, D Ivan, S TI In colchicine-treated rats, cellular distribution of AQP-1 in convoluted and straight proximal tubule segments is differently affected SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE colchicine; endocytosis; gp330; kidney; microtubules; vacuolar ATPase; water channels ID DARBY CANINE KIDNEY; APICAL MEMBRANE GLYCOPROTEIN; MICROTUBULE DISRUPTION; EPITHELIAL-CELLS; WATER CHANNEL; GP330; ENDOCYTOSIS; RECEPTOR; SURFACE; LOCALIZATION AB In cells along the nephron, the recycling of various components between the plasma membrane and intracellular organelles by vesicle trafficking depends on intact microtubules (MT). Previous studies of rats treated with the MT-disrupting drug colchicine showed that some brush-border membrane (BBM) transporters in renal proximal convoluted tubule cells (PCTC) become internalized in numerous vesicles randomly scattered in the cytoplasm. In this study, we compare the intracellular distribution of MT and several BBM proteins [megalin, vacuolar (V)-ATPase, water channel aquaporin-1 (AQP-1)] as well as endocytosis of the in-vivo-injected fluorescent marker FITC-dextran in PCTC and proximal straight tubule cells (PSTC) in control and colchicine-treated rats. Immunoblotting and immunocytochemical data show that in the PCTC and PSTC colchicine treatment causes: (1) disappearance of MT, (2) strongly diminished endocytosis of FITC-dextran, and (3) marked loss of megalin and V-ATPase from the BBM and their redistribution into intracellular vesicles. Similar pattern was observed for the distribution of AQP-1 in the PCTC. However in thp PSTC thp staining intensity of AQP-1 in the BBM, as well as its intracellular distribution remained unaffected by colchicine treatment. We conclude that in the PSTC, either MT play a minor role in the recycling of AQP-1 between the BBM and intracellular vesicles or BBM AQP-1 turns over much more slowly than in the PCTC. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Zagreb 10001, Croatia. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02119 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02119 USA. RP Ivan, S (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2, Zagreb 10001, Croatia. NR 26 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 2000 VL 439 IS 3 BP 321 EP 330 DI 10.1007/s004240050946 PG 10 WC Physiology SC Physiology GA 269BK UT WOS:000084455700015 ER PT B AU Plesnila, N Moskowitz, MA AF Plesnila, N Moskowitz, MA BE Krieglstein, J Klumpp, S TI Caspases in cerebral ischemia SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 2000 LA English DT Proceedings Paper CT 8th International Symposium on Pharmacology of Cerebral Ischemia CY JUL 23-26, 2000 CL MARBURG, GERMANY SP Deutsch Forsch GmbH, Int Soc Cerebral Blood Flow & Metab, Int Soc Neurochem, Philipps Univ Marburg, Arzneimittelwerk Dresden GmbH, Aventis Behring GmbH, Bayer AG, Boehringer Ingelheim GmbH, Chiron Behring GmbH & Co, Eppendorf Netheler Hinz GmbH, Forchungsinst Angew Neurowissensch, Janssen Cilag, Lichtwer Pharma AG, E Merck, PHOENIX Pharmahandel AG & Co, Pfizer GmbH, Schering AG, Dr Willmar Schwabe Gmbh & Co, SmithKline Beecham Pharma Gmbh, Carl Zeiss Jena ID HIPPOCAMPAL CA1 NEURONS; TRANSIENT FOREBRAIN ISCHEMIA; CYTOCHROME-C; GLOBAL-ISCHEMIA; MESSENGER-RNA; BRAIN-DAMAGE; CELL-DEATH; THERAPEUTIC WINDOW; CONVERTING-ENZYME; SPINAL-CORD C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Plesnila, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. NR 41 TC 1 Z9 1 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-087-4 PY 2000 BP 137 EP 143 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA BR96E UT WOS:000168184000014 ER PT B AU Finkelstein, SP Wada, K AF Finkelstein, SP Wada, K BE Krieglstein, J Klumpp, S TI Update on growth factor treatment for stroke: 2000 SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 2000 LA English DT Proceedings Paper CT 8th International Symposium on Pharmacology of Cerebral Ischemia CY JUL 23-26, 2000 CL MARBURG, GERMANY SP Deutsch Forsch GmbH, Int Soc Cerebral Blood Flow & Metab, Int Soc Neurochem, Philipps Univ Marburg, Arzneimittelwerk Dresden GmbH, Aventis Behring GmbH, Bayer AG, Boehringer Ingelheim GmbH, Chiron Behring GmbH & Co, Eppendorf Netheler Hinz GmbH, Forchungsinst Angew Neurowissensch, Janssen Cilag, Lichtwer Pharma AG, E Merck, PHOENIX Pharmahandel AG & Co, Pfizer GmbH, Schering AG, Dr Willmar Schwabe Gmbh & Co, SmithKline Beecham Pharma Gmbh, Carl Zeiss Jena ID FOCAL CEREBRAL-ISCHEMIA; FIBROBLAST; RECOVERY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CNS Growth Factor Res Lab, Boston, MA 02114 USA. RP Finkelstein, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CNS Growth Factor Res Lab, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE verlagsgesellschaft mbh PI STUTTGART PA POSTFACH 40, BIRKENWALDSTRASSE 44, 70191 STUTTGART, GERMANY BN 3-88763-087-4 PY 2000 BP 371 EP 374 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA BR96E UT WOS:000168184000035 ER PT J AU Barsh, G Gunn, T He, L Schlossman, S Duke-Cohan, J AF Barsh, G Gunn, T He, L Schlossman, S Duke-Cohan, J TI Biochemical and genetic studies of pigment-type switching SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT 17th International Pigment Cell Conference (IPCC) CY OCT 30-NOV 03, 1999 CL NAGOYA, JAPAN DE eumelanin; pheomelanin; Agouti; Mc1r; mahogany/attractin; Agrp ID AGOUTI-RELATED PROTEIN; MOUSE COAT COLOR; MELANOCORTIN RECEPTORS; YELLOW MICE; IN-VITRO; DPPT-L; EXPRESSION; MUTATIONS; MAHOGANY; LOCUS AB Mutations that affect the balance between the synthesis of eumelanin and pheomelanin provide a powerful set of tools with which to understand general aspects of cell signaling, Previous work from our laboratory has demonstrated that pheomelanin synthesis is triggered by the ability of Agouti protein to inhibit signaling through the Melanocortin 1 receptor (Mc1r). In a bioassay based on the Xenopus Mc1r, Agouti protein has two effects, competitive inhibition of receptor occupancy by alpha-MSH and down-regulation of receptor signaling, which are mediated separately by domains in the amino-and carboxy-terminal regions of Agouti protein, respectively. Recently, we have used the genetics of pigmentation as an in vivo system to screen for and analyze other mutations in the Agouti-melanocortin pathway. The pigmentary effects of Agouti are suppressed by the previously existing coat-color mutations mahogany (mg), mahoganoid (md), and Umbrous (U). Double mutant studies, with animals deficient for the Mc1r or those which carry A(y), indicate that mg and Ind are genetically upstream of the Mc1r, and can suppress the effects of A(y) on both pigmentation and body weight. Positional cloning has recently identified the gene mutated in mahogany as a single transmembrane-spanning protein whose ectodomain is orthologous to human Attractin (Atrn). C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, HHMI, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Barsh, G (reprint author), Stanford Univ, Sch Med, Beckman Ctr B271A, Stanford, CA 94305 USA. RI Duke-Cohan, Jonathan/A-5812-2010; OI Duke-Cohan, Jonathan/0000-0002-9478-9609; Gunn, Teresa/0000-0003-2688-6420 FU NIDDK NIH HHS [DK 28506] NR 41 TC 37 Z9 38 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PY 2000 VL 13 SU 8 BP 48 EP 53 DI 10.1034/j.1600-0749.13.s8.10.x PG 6 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 361GA UT WOS:000089714000009 PM 11041357 ER PT J AU Fisher, DE AF Fisher, DE TI Microphthalmia: A signal responsive transcriptional regulator in development SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT 17th International Pigment Cell Conference (IPCC) CY OCT 30-NOV 03, 1999 CL NAGOYA, JAPAN DE Microphthalmia; MSH; Steel factor; c-Kit ID WAARDENBURG SYNDROME; MELANOMA-CELLS; GENE-PRODUCT; MAST-CELL; TYROSINASE; MELANOCYTES; MUTATIONS; IDENTIFICATION; EXPRESSION; ACTIVATION AB The transcription factor Microphthalmia (Mi) is a helix-loop-helix protein which plays an essential role in the development and subsequent function of neural crest-derived melanocytes. Since its discovery as a mutant allele producing mice devoid of viable melanocytes, Mi has emerged as the gene whose mutation is responsible for the human pigmentation condition Waardenburg Syndrome IIa, as well as a variety of cellular defects involving retinal pigment epithelium, osteoclasts, and mast cells. As discussed here, Mi has recently been recognized to be targeted by several signaling pathways of importance to melanocytes, those activated by melanocyte stimulating hormone (MSH) and Steel factor. While these two pathways profoundly modulate Mi activity, they do so via strikingly different mechanisms. The differences and similarities of these responses highlight the likely roles of Mi in influencing both pigmentation and proliferation/survival. These effects are also of significance in human melanoma, a tumor for which Mi appears to be an extremely sensitive and specific marker. C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 24 TC 17 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PY 2000 VL 13 SU 8 BP 145 EP 149 DI 10.1034/j.1600-0749.13.s8.26.x PG 5 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 361GA UT WOS:000089714000025 PM 11041373 ER PT S AU Goulder, PJR AF Goulder, PJR BE Ammann, AJ Rubinstein, A TI Rapid characterization of HIV clade C-specific cytotoxic T lymphocyte responses in infected African children and adults SO PREVENTION AND TREATMENT OF HIV INFECTION IN INFANTS AND CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Global Strategies for the Prevention of HIV Transmission from Mothers to Infants CY SEP 01-06, 1999 CL MONTREAL, CANADA SP Glaxo Welcome ID HUMAN-IMMUNODEFICIENCY-VIRUS; HLA CLASS-I; TYPE-1 INFECTION; CELL RESPONSES; PEPTIDE-BINDING; PREGNANT-WOMEN; VIREMIA; IMMUNODOMINANT; SELECTION; ESCAPE AB Cytotoxic T lymphocytes (CTL) play a central role in successful control of HIV. Induction of effective CTL responses may therefore be an essential requirement of HIV vaccines. Knowledge of CTL epitopes targeted either in natural infection or following vaccination will be critical to understanding the anti-HIV immune response. Until recently, epitope definition was a slow and laborious process that could only be undertaken in laboratories specialized in this work. Recent incremental advances in the technologies that may be applied to this field have transformed what is possible, so that within 48 hours of receipt of a blood sample, novel epitopes may be optimized and the HLA restriction defined. Moreover, these technologies can now be applied in nonspecialized laboratories, so that new epitopes can be characterized locally in sites where the epidemic is most severe. Sub-Saharan Africans and C clade infection have been relatively neglected in terms of the HIV-specific CTL epitopes that have been defined to date. This review summarizes the evidence that cellular immunity is important in successful containment of HIV and describes the novel methods of epitope detection, illustrating their ready application to the study of C-clade infected persons in sub-Saharan Africa. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Goulder, PJR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 13th St,Bldg 149,Rm 5218, Charlestown, MA 02129 USA. NR 75 TC 13 Z9 14 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 1-57331-267-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 918 BP 330 EP 345 PG 16 WC Infectious Diseases; Multidisciplinary Sciences; Pediatrics SC Infectious Diseases; Science & Technology - Other Topics; Pediatrics GA BT09V UT WOS:000171939500036 PM 11131720 ER PT B AU Webb, RH AF Webb, RH BE Gandjbakhiche, AH TI Diagnostic Imaging in living subjects SO PROCEEDINGS OF INTER-INSTITUTE WORKSHOP ON IN VIVO OPTICAL IMAGING AT THE NIH LA English DT Proceedings Paper CT 1st Inter-Institute Workshop on In Vivo Optical Imaging CY SEP 16-17, 1999 CL NIH, BETHESDA, MD SP NICHHD, NCI, NHLBI, NINDS, Off Res Woman Hlth, Opt Soc Amer, Hamamatsu, ISS Inc, Zeiss HO NIH ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Webb, RH (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA BN 1-55752-653-2 PY 2000 BP 4 EP 6 PG 3 WC Engineering, Biomedical; Microscopy; Optics; Spectroscopy SC Engineering; Microscopy; Optics; Spectroscopy GA BT68M UT WOS:000173724500002 ER PT S AU Kung, JH Reft, C Jackson, W Abdalla, I AF Kung, JH Reft, C Jackson, W Abdalla, I BE Enderle, JD TI Intensity Modulated Radiotherapy for a prostate patient with a prosthetic hip SO PROCEEDINGS OF THE 22ND ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 22nd Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY JUL 23-28, 2000 CL CHICAGO, IL SP IEEE, Engn Med & Biol Soc, Amer Assoc Physicists Med, Amer Inst Med & Biol Engn, Int Union Phys & Engn Sci Med, Int Federat Med & Biol Engn, Int Org Med Phys DE prostate carcinoma; Intensity Modulated Radiotherapy; treatment planning AB For a prostate carcinoma patient with a metallic prosthetic hip replacement, a 3D Conformal Radiotherapy (3DCRT) treatment plan is commonly created using only those fields that avoid the prostheses in beam's eye view (BEV). With a limited choice of fields, a resulting plan compromises in dose sparing of rectum and bladder. In this work, we investigate another option with Intensity Modulated Radiotherapy (IMRT). Three patients, previously treated with 3DCRT at the University of Chicago Medical Center for prostate carcinoma with single prostheses, were evaluated in this study. The clinical target volume (CTV=prostate+seminal vesicles), bladder, and rectum were Identified on CT scans. The planning target volume (PTV) was generated by a 3D 1cm expansion of CTV. For comparative studies, plans were generated with the PLUNC 3DCRT and the CORVUS IMRT systems using the CT and contour data. The IMRT plans used 9 equally spaced 6 MV coplanar fields, with each field avoiding the prosthesis. The 3DCRT plans used 5 coplanar 18 MV fields, each field avoiding the prostheses, and a 1cm block margin. The IMRT and 3DCRT plans were normalized so that 100% of a PTV were covered by at least 95% isodose line. Each IMRT plan spared bladder and rectum better than the corresponding 3DCRT plan. In the IMRT plans, a bladder volume getting 80% or greater dose decreased by 19-93 cc, and a rectal volume getting 80% or greater dose decreased by 29-54cc. One negative feature of IMRT plans was the inhomogeneous PTV coverage, which ranged from [95-115]%. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kung, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-6466-X J9 P ANN INT IEEE EMBS PY 2000 VL 22 BP 1546 EP 1548 PN 1-4 PG 3 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BR59S UT WOS:000166896300425 ER PT B AU Befort, K Costigan, M AF Befort, K Costigan, M BE Devor, M Rowbotham, MC WiesenfeldHallin, Z TI Approaches to the study of altered gene expression in pain SO PROCEEDINGS OF THE 9TH WORLD CONGRESS ON PAIN SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 9th World Congress on Pain CY AUG 22-27, 1999 CL VIENNA, AUSTRIA SP Allergan, ASTA Medica AG, Boots Hlthcare Int, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceutica, Medtron Inc, Menarini Int, Neurex Corp, Novartis, Parke Davis, Pfizer Pharmaceut, Procter & Gamble Co, Purdue Pharma LP, UPSA Labs, UPSA Pain Inst ID DIFFERENTIAL DISPLAY; SENSORY NEURONS; SERIAL ANALYSIS; NERVOUS-SYSTEM; DNA CHIPS; CLONING; CHANNEL C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. RP Costigan, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-31-0 J9 PROG PAIN RES MANAG PY 2000 VL 16 BP 163 EP 174 PG 12 WC Medicine, General & Internal; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA BQ56W UT WOS:000088785400015 ER PT B AU Ji, RR Brenner, GJ Schmoll, R Baba, H Woolf, CJ AF Ji, RR Brenner, GJ Schmoll, R Baba, H Woolf, CJ BE Devor, M Rowbotham, MC WiesenfeldHallin, Z TI Phosphorylation of ERK and CREB in nociceptive neurons after noxious stimulation SO PROCEEDINGS OF THE 9TH WORLD CONGRESS ON PAIN SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 9th World Congress on Pain CY AUG 22-27, 1999 CL VIENNA, AUSTRIA SP Allergan, ASTA Medica AG, Boots Hlthcare Int, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceutica, Medtron Inc, Menarini Int, Neurex Corp, Novartis, Parke Davis, Pfizer Pharmaceut, Procter & Gamble Co, Purdue Pharma LP, UPSA Labs, UPSA Pain Inst ID ACTIVATED PROTEIN-KINASE; ELEMENT-BINDING PROTEIN; LONG-TERM POTENTIATION; NEUROPATHIC PAIN; GENE-EXPRESSION; MAP KINASE; PLASTICITY; TRANSCRIPTION; CASCADE; INFLAMMATION C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. RP Ji, RR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. NR 30 TC 6 Z9 6 U1 0 U2 1 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-31-0 J9 PROG PAIN RES MANAG PY 2000 VL 16 BP 191 EP 198 PG 8 WC Medicine, General & Internal; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA BQ56W UT WOS:000088785400017 ER PT B AU Kissin, I AF Kissin, I BE Devor, M Rowbotham, MC WiesenfeldHallin, Z TI Preemptive analgesia: How can we make it work? SO PROCEEDINGS OF THE 9TH WORLD CONGRESS ON PAIN SE PROGRESS IN PAIN RESEARCH AND MANAGEMENT LA English DT Proceedings Paper CT 9th World Congress on Pain CY AUG 22-27, 1999 CL VIENNA, AUSTRIA SP Allergan, ASTA Medica AG, Boots Hlthcare Int, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceutica, Medtron Inc, Menarini Int, Neurex Corp, Novartis, Parke Davis, Pfizer Pharmaceut, Procter & Gamble Co, Purdue Pharma LP, UPSA Labs, UPSA Pain Inst ID POSTOPERATIVE PAIN; NERVE BLOCK; RAT MODEL; POSTHERNIORRHAPHY PAIN; RESPONSE RELATIONSHIPS; RADICAL PROSTATECTOMY; NOCICEPTIVE RESPONSES; RECEPTOR ANTAGONISTS; EPIDURAL ANALGESIA; GENERAL-ANESTHESIA C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Kissin, I (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. NR 44 TC 5 Z9 5 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-31-0 J9 PROG PAIN RES MANAG PY 2000 VL 16 BP 973 EP 985 PG 13 WC Medicine, General & Internal; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA BQ56W UT WOS:000088785400091 ER PT B AU Rosowski, JJ Huang, GT Atencio, CA Peake, WT AF Rosowski, JJ Huang, GT Atencio, CA Peake, WT BE Wada, H Takasaka, T Ikeda, K Koike, T TI Acoustic effects of multiple middle-ear air spaces: Measurements in cats SO PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON RECENT DEVELOPMENTS IN AUDITORY MECHANICS LA English DT Proceedings Paper CT International Symposium on Recent Developments in Auditory Mechanics CY JUL 25-30, 1999 CL SENDAI, JAPAN SP Japan Soc Promot Sci, Aoba Fdn Promot Engn, Charitable Trust Ono Res Fund Acoust, Inoue Fdn Sci, Mikiya Sci & Technol Fdn, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Aloka Co Ltd, Aoba Sci Co Ltd, Asahi Co Ltd, Chemie Co Ltd, Dana Japan Co Ltd, Dowa Min Co Ltd, Honda Motor Co Ltd, J Morita MFG Corp, Kawasaki Steel Corp, Machida Endoscope Co Ltd, Nihon Cochlear Co Ltd, Nihon Kohden Corp, Toshiba Corp, Toyota Motor Corp AB The cat middle-ear air cavity is divided into two air spaces by an incomplete bony septum, such that the two spaces are connected by a narrow foramen. Measurements of middle-ear input admittance and cochlear potentials from cats with intact and modified middle-ear air spaces are used to test two hypotheses concerning the function of middle-ear septa. The data are consistent with the notion that septa act to smooth the middle-ear response at high frequencies by effectively reducing the size of the air spaces at frequencies where the impedance of the foremen is large, but do not support the idea that the septum acts to increase the sensitivity of the ear to high-frequency sounds. The former role may be relevant to the use of high-frequency spectral structure in determining the elevation of sound sources. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-02-4170-4 PY 2000 BP 15 EP 21 PG 7 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS15Z UT WOS:000168874500003 ER PT B AU Ravicz, ME Merchant, SN Rosowski, JJ AF Ravicz, ME Merchant, SN Rosowski, JJ BE Wada, H Takasaka, T Ikeda, K Koike, T TI Effects of middle-ear fluid on umbo motion in human ears SO PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON RECENT DEVELOPMENTS IN AUDITORY MECHANICS LA English DT Proceedings Paper CT International Symposium on Recent Developments in Auditory Mechanics CY JUL 25-30, 1999 CL SENDAI, JAPAN SP Japan Soc Promot Sci, Aoba Fdn Promot Engn, Charitable Trust Ono Res Fund Acoust, Inoue Fdn Sci, Mikiya Sci & Technol Fdn, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Aloka Co Ltd, Aoba Sci Co Ltd, Asahi Co Ltd, Chemie Co Ltd, Dana Japan Co Ltd, Dowa Min Co Ltd, Honda Motor Co Ltd, J Morita MFG Corp, Kawasaki Steel Corp, Machida Endoscope Co Ltd, Nihon Cochlear Co Ltd, Nihon Kohden Corp, Toshiba Corp, Toyota Motor Corp ID MECHANICS AB The mechanisms of hearing loss in otitis media with effusion (OME), a common clinical condition, were investigated by measuring umbo motion with a laser vibrometer while different fluids were introduced into the middle ear of a human temporal bone preparation. Various amounts of saline (to simulate serous effusions) and glycerin (to simulate more viscous mucoid effusions) contacted part or all of the tympanic membrane (TM) and filled part or all of the middle ear. Reductions in umbo motion matched hearing losses reported with OME within 5 dB. Above 700 Hz, reductions depended mostly on the percentage of the TM contacted by fluid; below 700 Hz reductions depended mostly on the reduction in middle-ear air volume by the fluid. Results also suggested that the effects of glycerin viscosity are small (5-10 dB) and important only above 2 kHz. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-02-4170-4 PY 2000 BP 29 EP 35 PG 7 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS15Z UT WOS:000168874500005 ER PT B AU Shera, CA Guinan, JJ AF Shera, CA Guinan, JJ BE Wada, H Takasaka, T Ikeda, K Koike, T TI Frequency dependence of stimulus-frequency-emission phase: Implications for cochlear mechanics SO PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON RECENT DEVELOPMENTS IN AUDITORY MECHANICS LA English DT Proceedings Paper CT International Symposium on Recent Developments in Auditory Mechanics CY JUL 25-30, 1999 CL SENDAI, JAPAN SP Japan Soc Promot Sci, Aoba Fdn Promot Engn, Charitable Trust Ono Res Fund Acoust, Inoue Fdn Sci, Mikiya Sci & Technol Fdn, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Aloka Co Ltd, Aoba Sci Co Ltd, Asahi Co Ltd, Chemie Co Ltd, Dana Japan Co Ltd, Dowa Min Co Ltd, Honda Motor Co Ltd, J Morita MFG Corp, Kawasaki Steel Corp, Machida Endoscope Co Ltd, Nihon Cochlear Co Ltd, Nihon Kohden Corp, Toshiba Corp, Toyota Motor Corp ID EVOKED OTOACOUSTIC EMISSIONS; GUINEA-PIG COCHLEA; BASILAR-MEMBRANE AB Measurements of stimulus-frequency-emission group delay in cats, guinea pigs, and humans provide strong support for the theory of coherent reflection filtering. Application of the theory raises important questions about cochlear tuning and its variation with characteristic frequency and species. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-02-4170-4 PY 2000 BP 381 EP 387 PG 7 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS15Z UT WOS:000168874500054 ER PT B AU Lin, T Guinan, JJ AF Lin, T Guinan, JJ BE Wada, H Takasaka, T Ikeda, K Koike, T TI Organ of Corti vibration in modes: Supporting evidence from auditory-nerve-fiber responses to clicks and clicks with efferent stimulation SO PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON RECENT DEVELOPMENTS IN AUDITORY MECHANICS LA English DT Proceedings Paper CT International Symposium on Recent Developments in Auditory Mechanics CY JUL 25-30, 1999 CL SENDAI, JAPAN SP Japan Soc Promot Sci, Aoba Fdn Promot Engn, Charitable Trust Ono Res Fund Acoust, Inoue Fdn Sci, Mikiya Sci & Technol Fdn, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Aloka Co Ltd, Aoba Sci Co Ltd, Asahi Co Ltd, Chemie Co Ltd, Dana Japan Co Ltd, Dowa Min Co Ltd, Honda Motor Co Ltd, J Morita MFG Corp, Kawasaki Steel Corp, Machida Endoscope Co Ltd, Nihon Cochlear Co Ltd, Nihon Kohden Corp, Toshiba Corp, Toyota Motor Corp ID BASILAR-MEMBRANE; SINGLE-FIBER; GUINEA-PIG; COCHLEA; INTENSITY; MOTION; CAT AB We studied cat single auditory-nerve-fiber responses to clicks. Near-threshold responses followed the classic picture of a single resonant system with temporal jitter reducing high-frequency synchrony. At moderate and high levels, there were two separate level-vs-latency regions of non-classic features and phase reversals, each of which is most simply explained as due to two interacting excitation drives. These data indicate that auditory-nerve fibers are excited by the combination, at some stage in the cochlea, of at least three excitation drives that are derived from the acoustic stimulus. One interpretation of these data is that the organ-of-Corti complex vibrates in resonant modes with each mode producing one excitation drive and the mix of modes varying with sound level. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Lin, T (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-02-4170-4 PY 2000 BP 426 EP 432 PG 7 WC Acoustics; Engineering, Biomedical; Otorhinolaryngology SC Acoustics; Engineering; Otorhinolaryngology GA BS15Z UT WOS:000168874500060 ER PT B AU Anderson, BJ Brackett, J Ho, J Laffel, LMB AF Anderson, BJ Brackett, J Ho, J Laffel, LMB BE Dennis, D TI An intervention to promote family teamwork in diabetes management tasks: Relationships among parental involvement, adherence to blood glucose monitoring, and glycemic control in young adolescents with Type 1 diabetes SO PROMOTING ADHERENCE TO MEDICAL TREATMENT IN CHRONIC CHILDHOOD ILLNESS: CONCEPTS, METHODS, AND INTERVENTIONS LA English DT Proceedings Paper CT Conference on Promoting Adherence to Medical Treatment in Chronic Childhood Illness CY OCT 30-31, 1998 CL CASE WESTERN RESERVE UNIV, CLEVELAND, OH SP Grenetech Fdn Growth & Dev HO CASE WESTERN RESERVE UNIV ID LONGITUDINAL FOLLOW-UP; METABOLIC CONTROL; MELLITUS; CHILDREN; HEALTH; MODEL; IDDM C1 Joslin Diabet Ctr, Mental Hlth Unit, Boston, MA 02215 USA. RP Anderson, BJ (reprint author), Joslin Diabet Ctr, Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. NR 43 TC 17 Z9 17 U1 2 U2 6 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-3348-X PY 2000 BP 347 EP 365 PG 19 WC Medicine, General & Internal; Pediatrics SC General & Internal Medicine; Pediatrics GA BQ82Y UT WOS:000089733600015 ER PT J AU Brawer, MK Ferreri, LF Bankson, DD AF Brawer, MK Ferreri, LF Bankson, DD TI Long-term stability of alpha-1-antichymotrypsin complexed form of prostate specific antigen SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE prostate specific antigen; complexed stability ID PREDICTIVE VALUE; REFERENCE RANGES; SERUM; CANCER; PSA; CARCINOMA; ENHANCE; MEN; PERFORMANCE; HYPERPLASIA AB PSA complexed with alpha-1-anti-chymotrypsin (cPSA(TM)) is the moiety in greatest proportion in the serum of men with prostate cancer (CAP). The performance of this analyte has been established primarily in retrospective archival serum. Studies indicate cPSA(TM) provides the specificity enhancement of the free-to-total PSA ratio, yet obviates the need to measure two markers. In the present investigation we sought to establish the stability of cPSA(TM) with longterm storage. Serum from men undergoing: ultrasound-guided biopsy was utilized. Serum was assayed soon after collection and 18 months later. All serum was initially aliquotted and stored at -80 degreesC There was no freeze-thaw. cPSA(TM) was measured utilizing the Bayer Immune 1 method according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8) and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist between the two determinants (r(2) = 1.0, slope = 1.01, t-test P = 0.9194). These data establish for the first time the long-term stability of cPSA(TM) Retrospective studies performed on archival material should give meaningful results. C1 NW Prostate Inst, Seattle, WA 98133 USA. NW Hosp, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Brawer, MK (reprint author), NW Prostate Inst, 1560 N 115th St,Suite 209, Seattle, WA 98133 USA. NR 34 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PY 2000 VL 3 IS 3 BP 191 EP 194 DI 10.1038/sj.pcan.4500419 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 382QQ UT WOS:000165834100009 ER PT J AU Pirl, WF Roth, AJ AF Pirl, WF Roth, AJ TI Remission of chemotherapy-induced emesis with concurrent olanzapine treatment: A case report SO PSYCHO-ONCOLOGY LA English DT Article ID THERAPY; NAUSEA C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Pirl, WF (reprint author), Erich Lindeman Mental Hlth Ctr, 25 Stanford St, Boston, MA 02114 USA. NR 15 TC 19 Z9 20 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN-FEB PY 2000 VL 9 IS 1 BP 84 EP 87 DI 10.1002/(SICI)1099-1611(200001/02)9:1<84::AID-PON440>3.0.CO;2-T PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 287GX UT WOS:000085499100010 PM 10668063 ER PT J AU Herzog, TA Abrams, DB Emmons, KM Linnan, L AF Herzog, TA Abrams, DB Emmons, KM Linnan, L TI Predicting increases in readiness to quit smoking: A prospective analysis using the contemplation ladder SO PSYCHOLOGY & HEALTH LA English DT Article DE smoking cessation; transtheoretical model; social-cognitive theory; motivation ID WORKING WELL TRIAL; TRANSTHEORETICAL MODEL; CESSATION; STAGE; SMOKERS; WORKPLACE; ADDICTION; BEHAVIOR AB Most smokers are not motivated to quit. The transtheoretical model posits mechanisms (processes of change and pros and cons) by which smokers might increase their stage of readiness to quit. While cross-sectional relationships among the stages of change, processes of change, and pros and cons are well established, there is little evidence that processes of change and pros and cons predict progressive stage movements. This study uses data from a large worksite-based cancer prevention study (the Working Well Trial) to test the hypothesis that processes of change and the pros and cons of smoking predict progressive movement up the contemplation ladder, which is an alternative measure of motivation to quit smoking based on social cognitive theory. The results indicate that experiential processes of change promote increases in readiness to quit smoking. This study provides further evidence for the predictive validity of the contemplation ladder and sheds light on how unmotivated, nonvolunteer smokers can be motivated to consider cessation. C1 H Lee Moffit Canc Ctr & Res Inst, Tobacco Res & Intervent Program, Tampa, FL 33617 USA. Miriam Hosp, Div Behav & Prevent Med, Providence, RI 02906 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Herzog, TA (reprint author), H Lee Moffit Canc Ctr & Res Inst, Tobacco Res & Intervent Program, 4115 E Fowler Ave, Tampa, FL 33617 USA. NR 35 TC 42 Z9 43 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0887-0446 J9 PSYCHOL HEALTH JI Psychol. Health PY 2000 VL 15 IS 3 BP 369 EP 381 DI 10.1080/08870440008401999 PG 13 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 322BT UT WOS:000087490900006 ER PT J AU Baer, L Jacobs, DG Meszler-Reizes, J Blais, M Fava, M Kessler, R Magruder, K Murphy, J Kopans, B Cukor, P Leahy, L O'Laughlen, J AF Baer, L Jacobs, DG Meszler-Reizes, J Blais, M Fava, M Kessler, R Magruder, K Murphy, J Kopans, B Cukor, P Leahy, L O'Laughlen, J TI Development of a brief screening instrument: The HANDS SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE depression; screening; rating scales; validity; psychometrics ID DEPRESSION AB Background: The present study was designed to develop a briefer screening scale of approximately 10 items which maintained the validity of the Zung Self-Rating Depression Scale in a sample similar to that attending National Depression Screening Day (NDSD), as well as a more general audience. Methods: We first administered 70 items from a variety of existing rating sea les to 40 subjects who answered an ad for depressed subjects and 55 who answered an ad for non-depressed subjects, all of whose diagnoses were confirmed by the Structured Clinical Interview for DSM-IV (SCID). Based on the correlation between each item and the diagnostic criterion, we reduced the number of items to 17 which we then administered to another 45 subjects who answered an ad similar to that used for NDSD and also underwent a SCID interview. Based on these results, we arrived at the final 10-item Harvard Department of Psychiatry/NDSD scale (HANDS) with the assistance of the item-response theory. The items are scored for frequency of occurrence of each symptom over the past 2 weeks. Total scores range from 9 to 30, Results: The 10-item scale (HANDS) has good internal consistency and validity: a cutpoint score of 9 or greater gave sensitivity of at least 95% in both studies. Although specificity was lower for all scales in the self-selected population, the HANDS performed at least as well as the 20-item Zung Scale, the 21-item Beck Depression Inventory-ii and the 15-item Hopkins Symptom Depression Checklist. Conclusion: The 10-item HANDS performs as well as other widely used longer self-report scales and has the advantage of briefer administration time. Copyright(C) 2000 S. Karger AG, Basel. C1 Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. RP Baer, L (reprint author), Massachusetts Gen Hosp East, 13th St,Bldg 149,9th Floor, Charlestown, MA 02129 USA. NR 14 TC 60 Z9 61 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD JAN-FEB PY 2000 VL 69 IS 1 BP 35 EP 41 DI 10.1159/000012364 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 269LN UT WOS:000084478900004 PM 10601833 ER PT J AU Bosch, JL Hunink, MGM AF Bosch, JL Hunink, MGM TI Comparison of the Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D in patients treated for intermittent claudication SO QUALITY OF LIFE RESEARCH LA English DT Article DE EuroQol EQ-5D (EQ-5D); health-related quality-of-life; Health Utilities Index (HUI); intermittent claudication; randomized controlled trial; rating scale; SF-36; standard gamble; time tradeoff ID QUALITY-OF-LIFE; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED CONTROLLED TRIAL; ARTERY OCCLUSIVE DISEASE; STENT PLACEMENT; CLINICAL-TRIAL; VALIDITY; QUESTIONNAIRE; OUTCOMES; SF-36 AB The Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D (EQ-5D) were compared to each other and to other quality-of-life (QoL) measures in patients treated for intermittent claudication. A total of 88 patients with intermittent claudication completed the HUI3, EQ-5D, RAND 36-Item Health Survey 1.0, time tradeoff, standard gamble, and rating scale before revascularization and at follow-up at 1 month, 3 months, and 1 year. The effect of treatment on the HUI3 and EQ-5D dimensions and the overall scores, calculated using published formulas based on societal preferences, were compared. After 1 month of treatment, the majority of patients showed improvement on the HUI3 dimensions ambulation and pain and on the EQ-5D dimensions mobility, usual activities, and pain/discomfort. The mean HUI3 score was significantly higher than the mean EQ-5D score (0.66 and 0.57, respectively, p < 0.01) before treatment. After treatment, however, they were not significantly different from each other (e.g., 12 months after treatment: 0.77 and 0.75, respectively (p > 0.05). After 1 month, the scores did not change significantly over time (p > 0.05). The intraclass correlation coefficient between changes over time in the HUI3 and EQ-5D scores was 0.30, with other health-related quality-of-life (HRQoL) measures the correlations for HUI3 and EQ-5D were very similar. In conclusion, both the HUI3 and EQ-5D demonstrated an effect of treatment in patients with intermittent claudication; in addition, they showed similar relationships with other (HRQoL) measures. To demonstrate the effect of revascularization in patients with intermittent claudication, however, clinicians and researchers should be aware of the differences in the mean HUI3 and EQ-5D scores. C1 Massachusetts Gen Hosp, Dept Radiol, HMS, Boston, MA 02114 USA. Erasmus Med Ctr Rotterdam, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Erasmus Med Ctr Rotterdam, Dept Radiol, Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Boston, MA 02115 USA. RP Bosch, JL (reprint author), Massachusetts Gen Hosp, Dept Radiol, HMS, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. RI van Doorn, Louk/G-5326-2010 OI van Doorn, Louk/0000-0003-1493-0973 NR 37 TC 61 Z9 62 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2000 VL 9 IS 6 BP 591 EP 601 DI 10.1023/A:1008929129537 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 392QH UT WOS:000166422500001 PM 11236850 ER PT J AU Silverman, SL AF Silverman, SL TI The Osteoporosis Assessment Questionnaire (OPAQ): A reliable and valid disease-targeted measure of health-related quality of life (HRQOL) in osteoporosis SO QUALITY OF LIFE RESEARCH LA English DT Article; Proceedings Paper CT Conference on the 1st International State of the Art Meeting on Health Outcome Assessment for Post-Menopausal Women CY NOV 09-10, 1998 CL VENICE, ITALY DE osteoporosis; vertebral fracture; health-related quality of life; OPAQ ID OF-LIFE AB The Osteoporosis Assessment Questionnaire (OPAQ) is a reliable and valid disease-targeted self assessment questionnaire of health-related quality of life (HRQOL) in osteoporosis first developed in 1993. OPAQ has been used in two international multicenter trials. OPAQ structure includes 14-18 domains which may be grouped into four dimensions: physical function, emotional status, symptoms and social interaction. OPAQ exists in two long versions: OPAQ 1.0 (73 questions) and OPAQ 2.0 (60 questions) OPAQ also exists as a short version: OPAQ-SV (34 questions) with three dimensions: physical function, emotional status and back pain. OPAQ detects changes in HRQOL with prevalent vertebral and nonvertebral fracture. Decreases in HRQOL are seen with increasing numbers of prevalent vertebral fractures. OPAQ is sensitive to changes in HRQOL of incident vertebral fracture. C1 OMC Clin Res Ctr, OMC Res Div, Beverly Hills, CA 90211 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Silverman, SL (reprint author), OMC Clin Res Ctr, OMC Res Div, 8641 Wilshire Blvd,Suite 301, Beverly Hills, CA 90211 USA. NR 13 TC 25 Z9 25 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2000 VL 9 IS 6 SU S BP 767 EP 774 DI 10.1023/A:1008934208764 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 401QM UT WOS:000166939800011 ER PT J AU Burruss, JW Hurley, RA Taber, KH Rauch, RA Norton, RE Hayman, LA AF Burruss, JW Hurley, RA Taber, KH Rauch, RA Norton, RE Hayman, LA TI Functional neuroanatomy of the frontal lobe circuits SO RADIOLOGY LA English DT Article DE brain, anatomy; brain, cortex; brain, function; brain, injuries; brain, MR; special reports ID SUBCORTICAL CIRCUITS; CORTEX AB This article summarizes the current theories regarding the locations and functions of the three primary frontal lobe circuits. It forms the framework for structuring functional magnetic resonance imaging investigations. It can be used to assist in (a) detecting subtle lesions of the frontal circuits and (b)applying the current theories of neuropsychiatry to assess prognosis and to plan rehabilitation. C1 Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Psychiat Serv, Houston, TX USA. Houston NW Med Ctr, Dept Radiol, Houston, TX USA. RP Hayman, LA (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, 1 Baylor Plaza, Houston, TX 77030 USA. NR 13 TC 57 Z9 57 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2000 VL 214 IS 1 BP 227 EP 230 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 268LD UT WOS:000084414400037 PM 10644129 ER PT J AU Grant, EG Duerinckx, AJ El Saden, SM Melany, ML Hathout, GM Zimmerman, PT Marumoto, AK Cohen, SN Baker, JD AF Grant, EG Duerinckx, AJ El Saden, SM Melany, ML Hathout, GM Zimmerman, PT Marumoto, AK Cohen, SN Baker, JD TI Ability to use duplex US to quantify internal carotid arterial stenoses: Fact or fiction? SO RADIOLOGY LA English DT Article DE angiography, comparative studies; carotid arteries, angiography; carotid arteries, stenosis or obstruction; carotid arteries, US ID ENDARTERECTOMY TRIAL; COST-EFFECTIVENESS; CRITERIA; 70-PERCENT; ULTRASOUND; SONOGRAPHY; ULTRASONOGRAPHY; ACCURACY; DISEASE AB PURPOSE: To determine if duplex ultrasonography (US) can help predict the degree of internal carotid arterial (ICA) stenosis. MATERIALS AND METHODS: ICA peak systolic velocity (PSV) and the:ratio Of the PSV in the ICA to that in the ipsilateral common carotid artery (VICA/VCCA) were compared with the degree of arteriographically measured stenosis. ICAs were arteriographically subgrouped at 10% incremental levels' of stenosis and broader ranges. Mean PSV, VICA/VCCA, and SDs were calculated for each category Histograms showing the numbers of-stenotic ICAs in subgroups and for vessels with stenoses of greater than or equal to or less than 70% narrowing were:constructed. The number of vessels correctly subgrouped with typical Doppler US thresholds was calculated. RESULTS: Mean PSV and VICA/VCCA increased with stenosis level (P < .01); SDs were wide. Histograms showed Doppler US values in the central groups across all disease levels. Histograms differentiating at least or less than 70% stenosis showed minimal overlap. PSV and VICA/VCCA helped classify respectively, 185 and 181 of 204 vessels with stenoses of less than 50%, 15 and 21 of 46 vessels with stenoses of 50%-69%, and 73 and 67 of 84 vessels with stenoses of 70% or greater. When classifying stenoses as 69% or less or 70% or more, PSV and VICA/VCCA were correct in 90.6% and 90.3% of vessels. CONCLUSION: Doppler US is excellent for classifying stenoses as above or below a single deg ree of severity but does not function well in stenosis subclassification. C1 W Los Angeles Vet Affairs Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP Grant, EG (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 29 TC 51 Z9 55 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2000 VL 214 IS 1 BP 247 EP 252 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 268LD UT WOS:000084414400040 PM 10644132 ER PT S AU Bues, M Kooy, HM Hacker, FL Tarbell, NJ Chapman, P Loeffler, JS AF Bues, M Kooy, HM Hacker, FL Tarbell, NJ Chapman, P Loeffler, JS BE Kondziolka, D TI Micro intensity-modulated radiotherapy for intracranial tumors: A case study SO RADIOSURGERY 1999 SE RADIOSURGERY (SERIES) LA English DT Proceedings Paper CT 4th International-Stereotactic-Radiosurgery-Society Congress CY FEB 23-26, 1999 CL SYDNEY, AUSTRALIA SP Int Stereotact Radiosurg Soc ID STEREOTAXIC RADIOSURGERY; CONFORMAL THERAPY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Bues, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1024-2651 BN 3-8055-6922-X J9 RADIOSURG PY 2000 VL 3 BP 64 EP 72 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BS67V UT WOS:000170815200007 ER PT J AU Kohane, DS Lu, NT Gokgol-Kline, AC Shubina, M Kuang, Y Hall, S Strichartz, GR Berde, CB AF Kohane, DS Lu, NT Gokgol-Kline, AC Shubina, M Kuang, Y Hall, S Strichartz, GR Berde, CB TI The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE ED50; LD50; local anesthetic; peripheral nerve; saxitoxin; sciatic; tetrodotoxin ID SODIUM-CHANNELS; EXCITABLE-MEMBRANES; TETRODOTOXIN; MECHANISM; DURATION AB Background and objectives. Saxitoxin and its homologues are naturally occurring compounds that block the sodium channel with high potency. They have the potential for providing prolonged duration local anesthesia when coinjected with vasoconstrictors or conventional local anesthetics and are devoid of local neurotoxicity. Here, we compare sciatic nerve block with saxitoxin to those with neosaxitoxin, decarbamoyl saxitoxin, and tetrodotoxin (TTX), in a search for even safer compounds. Methods. Rats received percutaneous sciatic nerve block with toxins. The compounds were compared in terms of lethality, onset and duration of action for thermal analgesia (hot-plate testing), and motor block (weight-bearing). Data were expressed as medians with 25th and 75th percentiles, and median effective concentrations were determined. Results. The median concentrations at which analgesia of 60 minutes duration was achieved were neosaxitoxin, 34 +/- 2 mu mol/L; saxitoxin, 58 +/- 3 mu mol/L; TTX, 92 +/- 5 mu mol/L; and decarbamoyl saxitoxin, 268 +/-; 8 mu mol/L. Similar trends were observed for other measures of effectiveness (block duration of 90 minutes, maximal block), and for lethality so thar the therapeutic indices were similar. No toxin had a marked predominance of sensory or motor block. The potency of TTX was intermediate between those of the saxitoxins, and its therapeutic index was slightly better. No difference was observed in time to onset of nerve blockade among the toxins. Conclusions. Substitutions on the saxitoxin nucleus result in large differences in incidence and duration of block, and toxicity. The therapeutic indices of the saxitoxins are similar; that of TTX is slightly better. C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. US FDA, Off Seafood, Washington Seafood Lab Branch, Washington, DC 20204 USA. Brigham & Womens Hosp, Dept Anesthesia & Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Childrens Hosp, Dept Anesthesia, 300 Longwood Ave,Room 555, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 35647] NR 24 TC 38 Z9 39 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JAN-FEB PY 2000 VL 25 IS 1 BP 52 EP 59 DI 10.1016/S1098-7339(00)80011-5 PG 8 WC Anesthesiology SC Anesthesiology GA 276RW UT WOS:000084892000010 PM 10660241 ER PT J AU Choy, E Philips, M AF Choy, E Philips, M TI Expression and activity of human prenylcysteine-directed carboxyl methyltransferase SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID ENDOPLASMIC-RETICULUM; SIGNAL TRANSDUCTION; MEMBRANES; PROTEINS; RAS; METHYLATION; NEUTROPHILS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Choy, E (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI036224] NR 13 TC 2 Z9 2 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 2000 VL 325 BP 101 EP 114 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BR04L UT WOS:000165500200010 PM 11036596 ER PT J AU Johnson, DC AF Johnson, DC TI Importance of adjusting carbon monoxide diffusing capacity (DLCO) and carbon monoxide transfer coefficient (KCO) for alveolar volume SO RESPIRATORY MEDICINE LA English DT Article DE asthma; DLCO; DLCO/VA; emphysema; interstitial lung disease; KCO; lung volume; normals; sarcoidosis ID LUNG-VOLUME; REFERENCE VALUES; DISEASE; ADJUSTMENT; FREQUENCY; EXERCISE; HISTORY; DL(CO) AB The volume dependence of single breath carbon monoxide diffusing capacity (DLCO) and carbon monoxide transfer coefficient (KCO) was determined in 24 healthy subjects. The change in DLCO [fraction of DLCO measured at total lung capacity (TLC)] to change in alveolar volume [fraction of alveolar volume (V-A) at TLC] closely fitted a simple linear regression and matched a theoretical model. As V-A decreased, DLCO fell linearly and KCO increased as expected from the relation of DLCO to V-A. The equations for adjustment of predicted DLCO and KCO for alveolar volume are: DLCO/D-L COtlc = 0.58 +/- 0.42VA/VAtlc KCO/KCOtlc = 0.42 + 0.58/(VA/VAtlc) DLCO and KCO were evaluated in 2313 patients. Subgroups of patients with asthma, emphysema, extrapulmonary lung disease, interstitial lung disease and lung resection were identified. Unadjusted DLCO and KCO percent predicted values showed large differences and much variability, so can be misleading As expected, KCO and DLCO percent predicted values adjusted for alveolar volume were nearly identical. Subgroups have characteristic patterns of V-A and unadjusted and adjusted DLCO and KCO. Changes in DLCO and KCO with alveolar volume are relevant for accurate interpretation of diffusion in patients with low lung volumes. Adjusting predicted DLCO and KCO for alveolar volume provides a better assessment of lung function. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Pulm Funct Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, DC (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Pulm Funct Lab, Boston, MA 02114 USA. NR 34 TC 46 Z9 47 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JAN PY 2000 VL 94 IS 1 BP 28 EP 37 DI 10.1053/rmed.1999.0740 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 287HZ UT WOS:000085501600004 PM 10714476 ER PT J AU Frederick, AR AF Frederick, AR TI A new instrument for scleral buckling procedures SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE scleral buckle; instrumentation; Watzke sleeve; encircling band C1 Massachusetts Eye & Ear Infirm, Ctr Eye Res & Teaching, Ophthalm Consultants Boston, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Frederick, AR (reprint author), Ophthalm Consultants Boston, 50 Staniford St,6th Floor, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 2000 VL 20 IS 4 BP 426 EP 426 PG 1 WC Ophthalmology SC Ophthalmology GA 403QU UT WOS:000167054600033 PM 10950436 ER PT B AU Sodroski, JG AF Sodroski, JG BE Girard, M Dodet, B TI Stabilization of soluble human immunodeficiency virus envelope glycoprotein trimers SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 12th Cent Gardes Meeting on Retroviruses of Human Aids and Related Animal Diseases CY OCT 25-27, 1999 CL PARIS, FRANCE ID GP41; ECTODOMAIN C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-173-7 PY 2000 BP 5 EP 7 PG 3 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BP90T UT WOS:000086564300001 ER PT B AU Walker, BD AF Walker, BD BE Girard, M Dodet, B TI Effects of treatment and treatment interruption on cellular immune responses in acute HIV infection SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 12th Cent Gardes Meeting on Retroviruses of Human Aids and Related Animal Diseases CY OCT 25-27, 1999 CL PARIS, FRANCE C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-173-7 PY 2000 BP 55 EP 55 PG 1 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BP90T UT WOS:000086564300011 ER PT B AU Ruprecht, RM AF Ruprecht, RM BE Girard, M Dodet, B TI Complete protection against oral SHIV challenge with a triple combination of human neutralizing IgG monoclonal antibodies SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 12th Cent Gardes Meeting on Retroviruses of Human Aids and Related Animal Diseases CY OCT 25-27, 1999 CL PARIS, FRANCE ID INFECTION; MONKEYS; VIRUS C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-173-7 PY 2000 BP 155 EP 157 PG 3 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BP90T UT WOS:000086564300036 ER PT J AU Liu, RH Barrick, JE Szostak, JW Roberts, RW AF Liu, RH Barrick, JE Szostak, JW Roberts, RW TI Optimized synthesis of RNA-protein fusions for in vitro protein selection SO RNA-LIGAND INTERACTIONS, PART B SE METHODS IN ENZYMOLOGY LA English DT Review ID EUKARYOTIC MESSENGER-RNA; CELL-FREE SYNTHESIS; IN-VITRO; PEPTIDE LIBRARIES; IDENTIFYING LIGANDS; ENHANCE TRANSLATION; ESCHERICHIA-COLI; INITIATION; EVOLUTION; SEQUENCE C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. RP Liu, RH (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI Barrick, Jeffrey/A-3046-2012 NR 46 TC 110 Z9 112 U1 0 U2 10 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 2000 VL 318 BP 268 EP 293 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69H UT WOS:000089206400019 PM 10889994 ER PT J AU Cubilla, AL Meijer, CJLM Young, RH AF Cubilla, AL Meijer, CJLM Young, RH TI Morphological features of epithelial abnormalities and precancerous lesions of the penis SO SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY LA English DT Article; Proceedings Paper CT Consensus Conference on Public Health and Clinical Significance of Premalignant Alterations in the Genito-Urinary Tract CY JUN 08-10, 2000 CL STOCKHOLM, SWEDEN SP European Commiss, Europe Against Canc DE epithelial abnormalities; morphology; penis; precancerous lesions ID SQUAMOUS-CELL-CARCINOMA; HUMAN PAPILLOMAVIRUS; BOWENOID PAPULOSIS; INTRAEPITHELIAL NEOPLASIA; PREVALENCE; DISEASE AB There is a heterogenous spectrum of abnormalities and atypical lesions in the penile epithelium. The terminology used to designate precursor lesions is variable but squamous intraepithelial lesions of low and high grade or penile intraepithelial neoplasia I, II and III are the recommended terms. Other probable precursor lesions are squamous hyperplasia and bowenoid papulosis. Low- and high-grade squamous intraepithelial lesions may be classified into squamous or simplex, the most frequent types, or warty (condylomatous) and basaloid. There is a striking morphological correspondence between precancerous lesions of the penis and their respective invasive lesions. The presence of two groups of lesions in the precancerous as well as invasive carcinomas, the squamous typical and the warty basaloid, is consistent with the bimodal hypothesis of the existence of non-HPV (the typical squamous) and HPV-related (warty or basaloid) tumors. C1 Univ Nacl Asuncion, Fac Ciencias Med, Inst Patol & Invest, Asuncion, Paraguay. Free Univ Amsterdam Hosp, Dept Pathol, Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Homer Wright Labs Pathol, Boston, MA USA. RP Cubilla, AL (reprint author), Univ Nacl Asuncion, Fac Ciencias Med, Inst Patol & Invest, Brizuela 325 & Ayala Velazquez, Asuncion, Paraguay. NR 28 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0036-5599 J9 SCAND J UROL NEPHROL JI Scand. J. Urol. Nephrol. PY 2000 VL 34 SU 205 BP 215 EP 219 DI 10.1080/00365590050509940 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 377RA UT WOS:000165526100021 ER PT J AU Kaufman, JS AF Kaufman, JS TI Antithrombotic agents and the prevention of access thrombosis SO SEMINARS IN DIALYSIS LA English DT Review ID HEMODIALYSIS VASCULAR ACCESS; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ARTERIOVENOUS-SHUNT THROMBOSIS; MUSCLE CELL-PROLIFERATION; LOW-DOSE ASPIRIN; DOUBLE-BLIND; INTIMAL HYPERPLASIA; STENT IMPLANTATION; INTRAVASCULAR ULTRASOUND; PLATELET-AGGREGATION C1 VA Boston Healthcare Syst, Renal Sect 111RE, Dept Med, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kaufman, JS (reprint author), VA Boston Healthcare Syst, Renal Sect 111RE, Dept Med, 150 S Huntington Ave, Boston, MA 02130 USA. NR 89 TC 17 Z9 17 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 2000 VL 13 IS 1 BP 40 EP 46 DI 10.1046/j.1525-139x.2000.00012.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 282WB UT WOS:000085242500012 PM 10740671 ER PT J AU Anderson, KC AF Anderson, KC TI Thalidomide: Therapeutic potential in hematologic malignancies SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID ERYTHEMA-NODOSUM LEPROSUM; BONE-MARROW; MULTIPLE-MYELOMA; ANGIOGENESIS; BLOOD; CELLS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St,Room DL189, Boston, MA 02115 USA. NR 27 TC 8 Z9 8 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2000 VL 37 IS 1 SU 3 BP 1 EP 4 DI 10.1016/S0037-1963(00)90076-3 PG 4 WC Hematology SC Hematology GA 296RB UT WOS:000086037100001 ER PT J AU Alexanian, R Anderson, KC Barlogie, B Stirling, DI Thomas, DA AF Alexanian, R Anderson, KC Barlogie, B Stirling, DI Thomas, DA TI Thalidomide in hematologic malignancies: Future directions SO SEMINARS IN HEMATOLOGY LA English DT Article ID MULTIPLE-MYELOMA; ACUTE-LEUKEMIA; THERAPY; SURVIVAL; CANCER; ANGIOGENESIS; PROGNOSIS; CHEMOTHERAPY; SARCOIDOSIS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Celgene Corp, Warren, NJ USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St,Room DL189, Boston, MA 02115 USA. NR 42 TC 5 Z9 5 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2000 VL 37 IS 1 SU 3 BP 35 EP 39 DI 10.1016/S0037-1963(00)90081-7 PG 5 WC Hematology SC Hematology GA 296RB UT WOS:000086037100006 ER PT J AU Rosen, HR Martin, P AF Rosen, HR Martin, P TI Hepatitis B and C in the liver transplant recipient SO SEMINARS IN LIVER DISEASE LA English DT Review DE hepatitis B; hepatitis C; viral recurrence ID VIRUS-INFECTION; INTERFERON-ALPHA; IMMUNE GLOBULIN; CHOLESTATIC HEPATITIS; ALLOGRAFT CIRRHOSIS; REJECTION EPISODES; UNITED-STATES; RECURRENCE; DISEASE; PROPHYLAXIS AB Liver disease related to chronic viral hepatitis is the leading indication for orthotopic fiver transplantation (OLT) worldwide. The evolution of our understanding of hepatitis B and C infection in the OLT recipient has been rapid in the last decade. The spontaneous risk for viral recurrence after transplantation is high but has been effectively decreased in hepatitis B infected recipients with the use of HBIG and lamivudine with dramatic improvements in patient and graft survivals, HCV recurrence as defined by histologic injury is almost universal although graft or patient outcomes for the first decade after OLT do not appear to be limited by HCV infection for most patients. However; individual patients do suffer severe graft injury and even graft loss due to recurrent HCV With longer follow up into the second decade, the prevalence of HCV-related graft failure is likely to increase. In addition, the role of different immunosuppressive protocols on disease recurrence requires further study. Thus, although hepatitis B recurrence has been effectively contained by use of HBIG with or without lamivudine, the more intractable problem of managing recurrent HCV has as yet no obvious solutions. Optimal antiviral strategies for hepatitis C post-OLT have yet to be identified. C1 Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland VA Med Ctr, Portland, OR 97207 USA. Portland Vet Adm, Liver Transplantat Program, Portland, OR 97207 USA. Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Dumont Transplant Program, Ctr Hlth Sci, Los Angeles, CA USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland VA Med Ctr, POB 1034,111-A,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 122 TC 12 Z9 12 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PY 2000 VL 20 IS 4 BP 465 EP 480 DI 10.1055/s-2000-13156 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 392EY UT WOS:000166399100006 PM 11200416 ER PT J AU Anzueto, A AF Anzueto, A TI Treatment of acute exacerbations of chronic bronchitis: Antibiotic therapy SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE antibiotics; acute exacerbation of chronic bronchitis; marcrolides; fluoroquinolones; cephalosporins; penicillins ID OBSTRUCTIVE PULMONARY-DISEASE; STREPTOCOCCUS-PNEUMONIAE; DOUBLE-BLIND; HAEMOPHILUS-INFLUENZAE; TOPOISOMERASE-IV; PRIMARY TARGET; DNA GYRASE; FLUOROQUINOLONES; RESISTANCE; CONTROVERSIES AB Acute exacerbation of chronic bronchitis (AECB) is a condition associated with increased morbidity and mortality. Bacterial infections are the most frequent cause of exacerbations. The most common bacterial etiologies include Haemophilus influenzae, Moraxella catarrhalis, and Streptococeus pneumonia. The diagnosis of AE:CB is often based on the clinical presentation, but microbiological assessment, including Gram stain and sputum culture should be done. Antibiotic therapy should be used in patients with the following characteristics: underlying lung disease, frequent exacerbations, and comorbid conditions. Penicillins, erythromycin, beta-lactamase inhibitors, and trimethoprim-sulfamethoxazole have been the preferred antibiotics. However, because of the increasing prevalence of resistance among respiratory pathogens, mainly the production of beta-lactamase by H. influenzae and IM. catarrhalis, and the emergence of multidrug-resistant S. pneumonia, new generation macrolides and fluoroquinolones should be the first line of treatment in selected patients. These drugs have increased efficacy and safety. C1 Univ Texas, Hlth Sci Ctr, VA Med Ctr 111 E, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Anzueto, A (reprint author), Univ Texas, Hlth Sci Ctr, VA Med Ctr 111 E, 7400 Mentor Minter Blvd, San Antonio, TX 78284 USA. NR 34 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 2000 VL 21 IS 2 BP 97 EP 106 DI 10.1055/s-2000-9843 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 336KX UT WOS:000088301400005 PM 16088723 ER PT J AU Angel, L Homma, A Levine, SM AF Angel, L Homma, A Levine, SM TI Bronchiolitis obliterans SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE bronchiolitis obliterans; constrictive bronchiolitis; lung transplantation; bone marrow transplantation; panbronchiolitis ID BONE-MARROW TRANSPLANTATION; INTERSTITIAL LUNG-DISEASE; SYSTEMIC LUPUS-ERYTHEMATOSUS; AIR-FLOW OBSTRUCTION; SILO-FILLERS DISEASE; TERM FOLLOW-UP; DIFFUSE PANBRONCHIOLITIS; ORGANIZING PNEUMONIA; RISK-FACTORS; SMALL AIRWAYS AB Bronchiolitis obliterans (BO) is a fibrotic lung disease involving the small conducting airways. BO may be classified by etiology and underlying disease or, more commonly, by histopathological pattern. The two major histopathological categories are (1) BO organizing pneumonia (BOOP) and proliferative bronchiolitis and (2) constrictive bronchiolitis. The former is often idiopathic in nature and may also be associated with connective tissue diseases and inhalation injury Characteristic findings on chest imaging include alveolar infiltrates and ground glass opacities and pulmonary function tests (PFTs) usually reveal restrictive dysfunction. Constrictive bronchiolitis is associated with organ transplantation, infections, connective tissue diseases, inhalation injury, and drugs and may also have an idiopathic origin. The radiographic characteristic is a mosaic pattern on high-resolution computed tomography (HRCT) and PFTs most often reveal obstructive dysfunction. This article will attempt to review constrictive BO, including histopathology, clinical presentation, radiographic appearance, and physiological findings, for both idiopathic diseases, as well as specific clinical-associated entities. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Levine, SM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 100 TC 6 Z9 6 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 2000 VL 21 IS 2 BP 123 EP 134 DI 10.1055/s-2000-9846 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 336KX UT WOS:000088301400008 PM 16088726 ER PT J AU Fink, JB Dhand, R AF Fink, JB Dhand, R TI Aerosol therapy in mechanically ventilated patients: Recent advances and new techniques SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE aerosols; nebulizers; pulmonary mechanics; bronchodilators; beta-agonists ID METERED-DOSE INHALER; AIR-FLOW OBSTRUCTION; INSTILLED EXOGENOUS SURFACTANT; RESPIRATORY-DISTRESS-SYNDROME; BRONCHODILATOR DELIVERY; CYSTIC-FIBROSIS; LUNG INJURY; NEBULIZED ALBUTEROL; IPRATROPIUM BROMIDE; NONUNIFORM PATTERN AB Therapeutic aerosols are commonly used in mechanically ventilated patients, yet information regarding their efficacy and optimal technique of administration has been limited. The advantages of aerosol therapy include a smaller dose, efficacy comparable with that observed with systemic administration of the drug, and a rapid onset of action. Inhaled drugs are delivered directly to the respiratory tract, their systemic absorption is limited, and systemic side effects are minimized. Inhaled bronchodilators are routinely used with mechanically ventilated patients in the intensive care unit, but a variety of drugs ranging from antibiotics to surfactants has been administered. Nebulizers and metered-dose inhalers (MDIs) are commonly used aerosol generators because they produce respirable particles with a mass median aerodynamic diameter (MMAD) between 1 and 5 mu m. Due to the limitation of available formulations, MDIs are chiefly used to deliver bronchodilators and steroids, whereas nebulizers have greater versatility and can he used to administer bronchodilators, antibiotics, surfactant, mucokinetic agents, and other drugs. The delivery of inhaled drugs in mechanically ventilated patients differs from that in ambulatory patients in several respects. Until recently, the consensus of opinion was that the efficiency of aerosol delivery to the lower respiratory tract in mechanically ventilated patients was much lower that that in ambulatory patients. Data suggest that this might be overly pessimistic and that the endotracheal tube may actually facilitate greater aerosol delivery compared with the normal airway when a variety of variables effecting aerosol delivery during mechanical ventilation are optimized. C1 Aerogen, Resp Program, Sunnyvale, CA 94089 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Chicago Stritch Sch Med, Hines, IL USA. RP Fink, JB (reprint author), Aerogen, Resp Program, 1310 Orleans Dr, Sunnyvale, CA 94089 USA. NR 84 TC 10 Z9 10 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 2000 VL 21 IS 3 BP 183 EP 201 DI 10.1055/s-2000-9854 PG 19 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 345GM UT WOS:000088808300006 PM 16088731 ER PT J AU Batra, RK Sharma, S Dubinett, SM AF Batra, RK Sharma, S Dubinett, SM TI New gene and cell-based therapies for lung cancer SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE lung cancer; gene therapy; immunotherapy ID WILD-TYPE P53; COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; IFN-GAMMA PRODUCTION; DOWN-REGULATION; TUMOR-CELLS; ADENOVIRAL VECTORS; IMMUNE-RESPONSES AB Lung cancer is the leading cause of cancer-related mortality in men and women in the United States, in part, because of the poor treatment options available. New treatment strategies that specifically target discreet steps in the molecular and cellular pathogenesis of this disease are under development. This review highlights many of the basic defects that result in the cellular transformation and subsequent progression of lung cancer, and how the understanding of those fundamental defects lead to the formulation of rational gene-based or cell-based therapies. C1 Univ Calif Los Angeles, Sch Med, Vet Adm Greater Los Angeles Hlth Care Syst, Div Pulm & Crit Care Med,Wadsworth Pulm Immunol L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles VA Med Ctr,Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, Sch Med, Vet Adm Greater Los Angeles Hlth Care Syst, Div Pulm & Crit Care Med,Wadsworth Pulm Immunol L, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 124 TC 1 Z9 1 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PY 2000 VL 21 IS 5 BP 463 EP 472 DI 10.1055/s-2000-9455 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 362AJ UT WOS:000089756200011 PM 16088747 ER PT J AU Hunault, M Bauer, KA AF Hunault, M Bauer, KA TI Recombinant factor VIIa for the treatment of congenital factor VII deficiency SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE factor VIIa; factor VII deficiency; bleeding disorder ID COAGULATION-FACTOR-VII; ACTIVATED FACTOR-VII; BOVINE FACTOR-VII; TISSUE FACTOR; FACTOR-IX; CONTINUOUS-INFUSION; BLOOD-COAGULATION; HAGEMAN-FACTOR; PLASMA; QUANTITATION AB Factor VII deficiency is a rare autosomal bleeding disorder with a highly variable hemorrhagic predisposition, Severe bleeding, including hemarthroses, may be encountered when plasma factor VII levels are below 1%, Patients have prolonged prothrombin times, and the final diagnosis is established by quantitative factor VII assays. Some patients have true deficiencies, that is, very low factor VII activity and low factor VII antigen (crossreacting material) levels (CRM-); others have normal antigen levels but low activity (CRM+). Still others have reduced antigen levels (CRMR). There is a rather poor correlation between clinical symptoms and factor VII activity levels in plasma. Treatment of these patients consists of fresh frozen plasma, prothrombin complex concentrates, or factor VII concentrates. Recombinant activated factor VII (rFVIIa) is a very useful alternative, and several patients have been treated successfully. Because of the short half-life of factor VIIa, repeated doses have to be administered, and continuous infusion may be even better, Antibodies to factor VII have been reported but seem to be rather rare. From the available data it appears that rFVIIa is a safe and effective treatment modality for patients with congenital factor VII deficiency. C1 VA Boston Healthcare Syst, Dept Med, Hematol Oncol Sect, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. CHU Angers, Serv Malad Sang, Angers, France. RP Bauer, KA (reprint author), Vet Adm Med Ctr W Roxbury, 1400 VFW Pkwy, Boston, MA 02132 USA. NR 40 TC 41 Z9 44 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PY 2000 VL 26 IS 4 BP 401 EP 405 DI 10.1055/s-2000-8459 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 375LC UT WOS:000165399900008 PM 11092215 ER PT S AU Newburg, DS Shen, ZJ Warren, CD AF Newburg, DS Shen, ZJ Warren, CD BE Koletzko, B Michaelsen, KF Hernell, O TI Quantitative analysis of human milk oligosaccharides by capillary electrophoresis SO SHORT AND LONG TERM EFFECTS OF BREAST FEEDING ON CHILD HEALTH SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 9th International Conference of the International-Society-for-Research-in-Human-Milk-and-Lactation (ISRHML) CY OCT 02-06, 1999 CL MUNICH, GERMANY SP WHO, WHO, Reg Off Europe, UNICEF, Danish Int Dev Agcy, Swedish Int Dev Cooperat Agcy, Swedish Natl Food Adm, Swedish Natl Board Hlth & Welfare, Child Hlth Fdn DE capillary electrophoresis; oligosaccharides; acidic oligosaccharides; analysis; human milk C1 Shriver Ctr, Program Glycobiol, Waltham, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Newburg, DS (reprint author), Shriver Ctr, Program Glycobiol, Waltham, MA USA. NR 5 TC 6 Z9 6 U1 0 U2 2 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46405-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2000 VL 478 BP 381 EP 382 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BR25S UT WOS:000165949900037 PM 11065092 ER PT J AU Kochevar, IE Redmond, RW AF Kochevar, IE Redmond, RW TI Photosensitized production of singlet oxygen SO SINGLET OXYGEN, UV-A, AND OZONE SE METHODS IN ENZYMOLOGY LA English DT Review ID PLASMA-MEMBRANE; DYE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. FU NCI NIH HHS [CA68524]; NIGMS NIH HHS [GM30755] NR 8 TC 125 Z9 128 U1 4 U2 22 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 2000 VL 319 BP 20 EP 28 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ66A UT WOS:000089101100002 PM 10907495 ER PT J AU Masih, S Sorenson, SM Gentili, A Seeger, LL AF Masih, S Sorenson, SM Gentili, A Seeger, LL TI Atypical adult non-calcified pilomatricoma SO SKELETAL RADIOLOGY LA English DT Article DE MRI; neoplasms, MRI; soft tissues, MRI; soft tissue neoplasms; skin, neoplasms; MRI, pilomatricoma (histology) ID CALCIFYING EPITHELIOMA; MALHERBE AB We present a rare case of a non-calcified pilomatricoma in a 67-year-old man. This tumor was extremely large in size, and its location, in the lower extremity, was very unusual. The clinical, radiographic, and histopathological features are described in detail. The role of magnetic resonance imaging (MRI) in the diagnosis of this entity is discussed. Definite internal reticulations and septations were observed. A possible explanation for this observation is that the high signal intensity reticulations may represent edematous stroma surrounding basaloid cells. C1 W Los Angeles Vet Affairs Med Ctr, Dept Radiol 114, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Masih, S (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Radiol 114, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 8 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JAN PY 2000 VL 29 IS 1 BP 54 EP 56 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 282DC UT WOS:000085200400010 PM 10663591 ER PT J AU Fortunel, N Hatzfeld, J Kisselev, S Monier, MN Ducos, K Cardoso, A Batard, P Hatzfeld, A AF Fortunel, N Hatzfeld, J Kisselev, S Monier, MN Ducos, K Cardoso, A Batard, P Hatzfeld, A TI Release from quiescence of primitive human hematopoietic stem/progenitor cells by blocking their cell-surface TGF-beta type II receptor in a short-term in vitro assay SO STEM CELLS LA English DT Article DE hematopoiesis; stem/progenitor cell; HPP-Q in vitro assay; quiescence; TGF-beta receptor ID GROWTH-FACTOR-BETA; HUMAN-BONE-MARROW; CHRONIC LYMPHOCYTIC-LEUKEMIA; GASTRIC-CANCER CELLS; PROGENITOR CELLS; STEM-CELLS; RETINOBLASTOMA CELLS; PANCREATIC-CANCER; STROMAL CELLS; CYCLE STATUS AB Genetic alterations of the signaling cascade of transforming growth factor-beta (TGF-beta) are often associated with neoplastic transformation of primitive cells. This demonstrates the key role for this pleiotropic factor in the control of quiescence and cell proliferation in vivo. In the high proliferative potential-quiescent cell (HPP-Q) in vitro assay, the use of TGF-beta 1 blocking antibodies (anti-TGF-beta 1) allows the detection within two to three weeks of primitive hematopoietic cells called HPP-Q, which otherwise would not grow. However, the possibility of triggering cell proliferation by blocking the cell-surface TGF-beta receptors has not been investigated until now, We have tested here the efficiency of a blocking antibody against TGF-beta RII (anti-TGF-beta RII) on CD34(+)CD38(-) hematopoietic cells, a subpopulation enriched in primitive stem/progenitor cells, and compared its effect with that of anti-TGF-beta 1, About twice as many HPP colony-forming cells were detected in the presence of anti-TGF-beta 1 or anti-TGF-beta RII, compared to the control (p < 0.02). Moreover, anti-TGF-beta RII was as efficient as anti-TGF-beta 1 for activating multipotent HPP-granulocyte erythroid macrophage megakaryocyte and HPP-Mix, bipotent HPP-granulocyte-macrophage (GM) and unipotent HPP-Q, HPP-M and HPP-BFU-E, We therefore propose the use of anti-TGF-beta RII: to release primitive cells from quiescence in the HPP-Q assay, This strategy could be extended to nonhematopoietic tissues, as TGF-beta 1 may be a pleiotropic regulator of somatic stem cell quiescence. C1 CNRS, Lab Biol Cellules Souches Somat Humaines, Villejuif, France. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Hatzfeld, J (reprint author), UPR 1983, 7 rue Guy Moquet, F-94800 Villejuif, France. RI HATZFELD, Antoinette/I-2341-2013; HATZFELD, Jacques/I-2346-2013 OI HATZFELD, Antoinette/0000-0002-9147-533X; HATZFELD, Jacques/0000-0002-3468-6659 NR 68 TC 51 Z9 53 U1 0 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2000 VL 18 IS 2 BP 102 EP 111 DI 10.1634/stemcells.18-2-102 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 302QA UT WOS:000086375600005 PM 10742382 ER PT J AU van Os, R Robinson, S Sheridan, T Mauch, PM AF van Os, R Robinson, S Sheridan, T Mauch, PM TI Granulocyte-colony stimulating factor impedes recovery from damage caused by cytotoxic agents through increased differentiation at the expense of self-renewal SO STEM CELLS LA English DT Article DE hematopoiesis; primitive stem cells; G-CSF; cytotoxic agents; BCNU; cobblestone area-forming cell ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; HIGH-DOSE CHEMOTHERAPY; CYTO-TOXIC AGENTS; COMPETITIVE REPOPULATION; PROGENITOR-CELL; CYCLOPHOSPHAMIDE; ENGRAFTMENT; THERAPY; BLOOD AB G-CSF is routinely used to hasten recovery from chemotherapy-induced neutropenia. We have recently shown that G-CSF, when combined with stem cell-damaging cytotoxic agents, results in enhanced stem cell damage and lass of marrow reserve, To investigate the mechanisms of stem cell damage caused by G-CSF, we gave C57BL/6 (B6) mice repeated doses of cyclophosphamide ([CY] 84 mg/kg) or carmustine ([BCNU] 13.2 mg/kg) and G CSF (250 mu g/kg/day) for either four days or eight days. Two different regimens of G-CSF were chosen to study the influence of increased proliferation on hematopoiesis which was measured at the end of the first, third and sixth 14-day cycle of each cytotoxic agent and 7 and 20 weeks after completion of all cycles. A spectrum of hematopoietic indices was measured including WBC, bone marrow cellularity, granulocyte/macrophage-colony-forming cells (GM-CFC), colony-forming cells with high proliferative-potential (HPP-CFC), cobblestone area-forming cells ([CAFC]-day 7 and CAFC-day 28), and long-term marrow repopulating ability in vivo. Despite the absence of differences in peripheral blood cell counts or bone marrow cellularity 14 days after each dose, progenitor cell levels (HPP-CFC, GM-CFC, and CAFC-7) were increased up to 2.5-fold with cytotoxic agent and G-CSF administration compared with cytotoxic agent administration alone. Mice given G-CSF for eight days had the greatest number of progenitors suggesting a dose-response relationship for G-CSF administration. G-CSF resulted in a decrease in hematopoietic stem cell (CAFC-28) content when measured two weeks after each cycle of saline, CY, and BCNU. Twenty weeks after six cycles of BCNU, the reduction in stem cell levels persisted and was further decreased when G-CSF was added to BCNU for four or eight days. Data from this study suggest that the most likely explanation for the damaging effects of G-CSF is that G-CSF directly or indirectly induces stem cells to differentiate into more committed hematopoietic cells resulting in a loss of marrow reserve. This effect is enhanced in animals with an already compromised hematopoietic stem cell compartment as seen with repeated doses of BCNU. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP van Os, R (reprint author), Leiden Univ, Med Ctr, Dept Hematol, Bldg 1,C2-R,POB 9600, NL-2300 RC Leiden, Netherlands. RI van Os, Ronald/I-1516-2013 FU NCI NIH HHS [R01 CA 10941-28] NR 32 TC 32 Z9 32 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2000 VL 18 IS 2 BP 120 EP 127 DI 10.1634/stemcells.18-2-120 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 302QA UT WOS:000086375600007 PM 10742384 ER PT J AU Rebel, VI Hartnett, S Denham, J Chan, M Finberg, R Sieff, CA AF Rebel, VI Hartnett, S Denham, J Chan, M Finberg, R Sieff, CA TI Maturation and lineage-specific expression of the coxsackie and adenovirus receptor in hematopoietic cells SO STEM CELLS LA English DT Article DE adenovirus; gene transfer; hematopoietic cells; coxsackie adenovirus receptor ID MEDIATED GENE-TRANSFER; SERUM-FREE CULTURES; BLOOD STEM-CELLS; EX-VIVO CULTURE; CORD-BLOOD; BONE-MARROW; IN-VIVO; ADHESION MOLECULES; REPOPULATING CELLS; PROGENITOR CELLS AB Adenovirus vectors have been used to transfer genes into both hematopoietic progenitor cells and tumor cells, including carcinoma cells that have metastasized to bone marrow (BM), However, the relative susceptibility of different subsets of hematopoietic cells is unknown, In permissive cells adenoviral-mediated gene transfer is mediated by the coxsackievirus and adenovirus receptor (CAR) protein and a,integrins expressed on the cell surface of the target cells. This prompted us to investigate the expression of CAR on subpopulations of hematopoietic cells, determine whether this protein played a role in adenovirus-mediated gene transfer of hematopoietic cells and whether we could modulate CAR to enhance gene transfer efficiency. in this report we show that CAR is expressed on approximately 40% of all human BM cells, including erythroid and myeloid cells, but not lymphoid cells. Of the CD34(+) cells, 10%-15% expressed CAR, but this did not include most colony-forming progenitor cells, nor the most primitive CD38(-) subpopulation. The presence of CAR correlated well with gene transfer efficiency, but we were unable to induce CAR expression on immature, noncommitted progenitor cells, in conclusion, our results show that primitive hematopoietic progenitor cells lark CAR expression, but that expression is acquired during erythroid and myeloid differentiation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Infect Dis, Boston, MA 02115 USA. RP Sieff, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 NR 33 TC 68 Z9 78 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2000 VL 18 IS 3 BP 176 EP 182 DI 10.1634/stemcells.18-3-176 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 319AA UT WOS:000087315800004 PM 10840070 ER PT J AU Lang-Lazdunski, L Matsushita, K Hirt, L Waeber, C Vonsattel, JPG Moskowitz, MA AF Lang-Lazdunski, L Matsushita, K Hirt, L Waeber, C Vonsattel, JPG Moskowitz, MA TI Spinal cord ischemia - Development of a model in the mouse SO STROKE LA English DT Article DE ischemia; mice; spinal cord ID NITRIC-OXIDE SYNTHASE; AORTIC-ANEURYSM REPAIR; CEREBRAL-ISCHEMIA; THORACOABDOMINAL AORTA; THORACIC AORTA; BLOOD-FLOW; NEUROLOGICAL DEFICITS; SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; BRAIN INJURY AB Background and Purpose-Spinal cord ischemia with resulting paraplegia is a devastating complication of thoracoabdominal aortic surgery. Experimental models of spinal cord ischemia have been developed in primate, dog, pig, rabbit, and rat with variable reproducibility, but none has been developed in mouse. Because genetically engineered mice have become important to examine the impact of specific genes in ischemic pathophysiology, we sought to develop a reproducible mouse model of spinal cord ischemia. Methods-C57BL/6NCrlBR mice were subjected to cross-clamping of the aortic arch, left subclavian artery, and internal mammary artery for 9 minutes (group A; n=8) or 11 minutes (group B; n=29) followed by reperfusion for 24 or 48 hours. Mean distal arterial blood pressure (left femoral artery) and lumbar (L1) spinal cord blood flow (laser-Doppler flowmetry) were measured for the duration of the procedure. The arterial blood supply of the spinal cord was visualized by intravascular perfusion of carbon black ink. We evaluated motor function in the hind limbs at 0, 1, 3, 6, and 24 hours after reperfusion using a rating scale of 0 (normal function) to 6 (total absence of movement). Spinal cord histopathology was evaluated after 24 and 48 hours of reperfusion by Luxol fast blue-hematoxylin and eosin. Results-The vascular anatomy of the mouse and human spinal cord appeared similar in that blood was supplied by I anterior and 2 posterior spinal arteries and heterosegmental radicular arteries. During combined occlusion of aortic arch and left subclavian artery, mean distal arterial blood pressure dropped to 10+/-5 mm Hg, and spinal cord blood flow at the L1 level decreased to 27+/-7% of baseline. All animals recovered from anesthesia with acute paraplegia, Animals in the 9-minute group (group A) showed steady recovery of hind Limb function over the ensuing 24 hours, whereas the majority (80%) in the 11-minute group (group B) remained paralyzed with maximum deficit throughout the postoperative period. Mortality was 0% and 21% in groups A and B, respectively. Maximal ischemic damage was observed at the lower thoracic and higher lumbar spinal levels in both groups. In group A (9 minutes), tissue damage was mild, affecting predominantly dorsal horns and intermediate gray matter, whereas ventral horns were minimally involved. All mice in group B (11 minutes) showed extensive gray matter lesions particularly involving dorsal horns and intermediate areas; in ventral horns, >50% of motor neurons died. White matter lesions were present in the most severely damaged cords only. Conclusions-Spinal cord ischemia caused by aortic arch plus left subclavian artery cross-clamping provides a mouse model useful for the study of spinal cord injury and of potential relevance to the complications following thoracoabdominal aortic surgery in humans. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol & Neurosurg, Stroke & Neurovasc Regulat Lab,Neurosci Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci,Lab Mol Neuropathol, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol & Neurosurg, Stroke & Neurovasc Regulat Lab,Neurosci Ctr, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009; Hirt, Lorenz/G-3553-2010 OI Waeber, Christian/0000-0001-6078-0027; Hirt, Lorenz/0000-0002-2921-5000 FU NINDS NIH HHS [1 RO1 NS374141-01, NS10828] NR 45 TC 73 Z9 79 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 BP 208 EP 213 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100041 PM 10625739 ER PT J AU Ay, I Sugimori, H Finklestein, SP AF Ay, I Sugimori, H Finklestein, SP TI Basic fibroblast growth factor (bFGF) decreases DNA fragmentation and increases Bcl-2 expression following stroke in rats SO STROKE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2000 VL 31 IS 1 MA 36 BP 282 EP 282 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 271HX UT WOS:000084589100094 ER EF