FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LENFANT, C AF LENFANT, C TI NHLBI FUNDING POLICIES - ENHANCING STABILITY, PREDICTABILITY, AND COST CONTROL SO CIRCULATION LA English DT Editorial Material DE CARDIOVASCULAR NEWS; FUNDING RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 1 EP 1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700001 PM 8025982 ER PT J AU GILLIGAN, DM GUETTA, V PANZA, JA GARCIA, CE QUYYUMI, AA CANNON, RO AF GILLIGAN, DM GUETTA, V PANZA, JA GARCIA, CE QUYYUMI, AA CANNON, RO TI SELECTIVE LOSS OF MICROVASCULAR ENDOTHELIAL FUNCTION IN HUMAN HYPERCHOLESTEROLEMIA SO CIRCULATION LA English DT Article DE CHOLESTEROL; BRADYKININ; ACETYLCHOLINE; NITRIC OXIDE; G PROTEINS ID DEPENDENT VASCULAR RELAXATION; FOREARM RESISTANCE VESSELS; PORCINE CORONARY-ARTERIES; LOW-DENSITY LIPOPROTEINS; RABBIT AORTA; L-ARGININE; SMOOTH-MUSCLE; ATHEROSCLEROSIS; ACETYLCHOLINE; VASODILATION AB Background Endothelial dysfunction is increasingly recognized as an early and important feature of vascular disease. Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia, although it is unknown whether this defect is selective for some pathways of nitric oxide production or indicates a more generalized abnormality of endothelial function. The aim of this study was to further elucidate the nature of endothelial dysfunction in human hypercholesterolemia by comparing vascular responses of agonists that use different signal transduction pathways to activate production of nitric oxide. Methods and Results Forearm flow was measured in 12 hypercholesterolemic patients (total cholesterol, 286+/-35 mg/dL [mean+/-SD]) aged 50+/-11 years and in 12 healthy subjects (total cholesterol, 173+/-27 mg/dL) aged 48+/-7 years using strain-gauge plethysmography and brachial artery drug infusions. The endothelium-dependent vasodilators used were acetylcholine (7.5, 15, and 30 mu g/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin (100, 200, and 400 ng/min), which uses a pertussis toxin-insensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside (0.8, 1.6, and 3.2 mu g/min) was used to test endothelium-independent vasodilation. The maximum flow in response to acetylcholine was markedly impaired in patients compared with healthy subjects (8.0+/-5.1 versus 17.5+/-7.7 mL.min(-1).100 mL(-1), P=.002). However, the maximum forearm flow in response to bradykinin was similar in the two groups (13.01+/-4.5 versus 16.2+/-5.5 mL.min(-1).100 mL(-1), P=.14), as was the maximum flow in response to sodium nitroprusside (7.0+/-2.8 versus 8.4+/-2.2 mL.min(-1).100 mL(-1), P=.13). NG-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, reduced the maximum forearm vasodilation induced by bradykinin to the same extent in patients and in healthy subjects (-29+/-8% versus -32+/-6% reduction in peak flow, P=.80), with similar maximum flows in response to bradykinin (9.2+/-4.0 versus 10.4+/-2.6 mL.min(-1).100 mL(-1), P=.35). Conclusions Hypercholesterolemic patients are capable of normal nitric oxide bioavailability in response to bradykinin. Impairment of microvascular endothelial vasodilator function in human hypercholesterolemia is selective, and the defect occurs at the level of the acetylcholine receptor or its signal transduction pathway. C1 NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. NR 35 TC 123 Z9 126 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 35 EP 41 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700009 PM 8026018 ER PT J AU AGUIRRE, FV MCMAHON, RP MUELLER, H KLEIMAN, NS KERN, MJ DESVIGNENICKENS, P HAMILTON, WP CHAITMAN, BR AF AGUIRRE, FV MCMAHON, RP MUELLER, H KLEIMAN, NS KERN, MJ DESVIGNENICKENS, P HAMILTON, WP CHAITMAN, BR TI AGE ON CLINICAL OUTCOME AND POSTLYTIC MANAGEMENT STRATEGIES IN PATIENTS TREATED WITH INTRAVENOUS THROMBOLYTIC THERAPY - RESULTS FROM THE TIMI-II STUDY SO CIRCULATION LA English DT Article DE AGE; CLINICAL TRIALS; THROMBOLYTIC AGENTS; INFARCTION ID ACUTE MYOCARDIAL-INFARCTION; LUMINAL CORONARY ANGIOPLASTY; TISSUE PLASMINOGEN-ACTIVATOR; ANGIOGRAPHY; MORTALITY; IMMEDIATE; TRIAL; STREPTOKINASE; PREDICTOR; PROGNOSIS AB Background Few thrombolytic studies have assessed whether patient age is an indication for routine postlytic cardiac catheterization and revascularization or evaluated the impact of age on 1-year outcome differences after acute myocardial infarction. Methods and Results A secondary analysis of 3339 patients enrolled in the TIMI II trial was performed to identify differences in clinical and coronary angiographic findings and 1-year cardiac event rates among 841 patients <50 years old, 1639 patients 50 to 64 years old, and 859 patients 65 to 75 years old. Differences in 1-year clinical outcome were assessed among patients randomly assigned to an invasive or a conservative postlytic strategy within each age group. The percentages of patients with a prior history of myocardial infarction, angina, congestive heart failure, hypertension, or diabetes mellitus or an infarction complicated at the time of study entry by shock, pulmonary edema, hypotension, rales more than one third of lung fields, or atrial fibrillation as well as the percentage of female patients (all P<.001) increased with age. Fewer older patients (65 to 75 years) received early tie, less than or equal to within 2 hours after symptom onset) treatment with recombinant tissue-type plasminogen activator (rTPA), and fewer were eligible for random assignment to immediate or deferred beta-blocker therapy (P=.01). The location of the infarct-related artery and the percentage of patients with patent tie, TIMI flow grade 2 or 3) or ''complete'' tie, TIMI flow grade 3) infarct-related artery flow did not vary with age. The percentage of patients with multivessel disease was greatest in the older patients (P=.001). Cumulative 1-year mortality was low in the youngest patients (2.8%; 99% confidence interval [CI], 1.6% to 4.7%) regardless of whether the infarct location was anterior (3.7%) or nonanterior (1.6%). The highest 1-year mortality occurred in the older patients (13.6%; 99% CI, 10.9% to 16.9%), particularly when the infarct location was anterior (18%). The 42-day rates of reinfarction (P=.85), death (P=.95), or death or reinfarction (P=.99) were similar in patients assigned to the invasive or conservative postlytic treatment strategy, regardless of age group. Conclusions Among patients with acute myocardial infarction treated with intravenous rTPA, heparin, and aspirin, there were age-related differences in time to treatment with thrombolytic therapy, use of beta-blockers, extent of coronary artery disease, and 1-year cardiac event rates. Routine use of cardiac catheterization and coronary revascularization does not improve immediate or 1-year outcome in terms of mortality or reinfarction compared with a more conservative strategy in young, middle-aged, or elderly patients similar to those enrolled in TIMI II. C1 ST LOUIS UNIV HOSP,ST LOUIS,MO. MARYLAND MED RES INST,BALTIMORE,MD. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,BRONX,NY 10467. BAYLOR COLL MED,HOUSTON,TX 77030. NHLBI,BETHESDA,MD 20892. ST JOHNS MERCY MED CTR,ST LOUIS,MO 63141. RI McMahon, Robert/C-5462-2009 NR 37 TC 33 Z9 34 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 78 EP 86 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700014 PM 8026055 ER PT J AU POST, WS LARSON, MG LEVY, D AF POST, WS LARSON, MG LEVY, D TI IMPACT OF LEFT-VENTRICULAR STRUCTURE ON THE INCIDENCE OF HYPERTENSION - THE FRAMINGHAM HEART-STUDY SO CIRCULATION LA English DT Article DE HYPERTENSION; LEFT VENTRICLE; HYPERTROPHY; FRAMINGHAM HEART STUDY; ECHOCARDIOGRAPHY ID FUTURE BLOOD-PRESSURE; ECHOCARDIOGRAPHIC ASSESSMENT; MYOCARDIAL HYPERTROPHY; CARDIAC SIZE; MASS; TWINS; PERFORMANCE; MUSCATINE; CHILDREN; GEOMETRY AB Background Left ventricular hypertrophy is often found very early in the course of hypertension. It is not known whether increased left ventricular mass contributes to the pathogenesis of hypertension. The purpose of this study was to examine the impact of left ventricular mass and other echocardiographically assessed cardiac structural features on the incidence of hypertension. Methods and Results Subjects for this investigation included participants in the Framingham Heart Study and the Framingham Offspring Study who were normotensive at the baseline examination (systolic blood pressure, <140 mm Hg; diastolic blood pressure, <90 mm Hg; not receiving antihypertensive medications) and free of coronary heart disease, congestive heart failure, valvular heart disease, hypertrophic cardiomyopathy, diabetes mellitus, and renal insufficiency. The study sample included 1121 men (mean age, 44.4 years) and 1559 women (mean age, 45.6 years). Four years after the baseline examination, 202 men (18.0%) and 257 women (16.5%) were hypertensive (systolic blood pressure, greater than or equal to 140 mm Hg; diastolic blood pressure, greater than or equal to 90 mm Hg; or use of antihypertensive medications). Baseline echocardiographic left ventricular mass (P=.01) and the sum of septal and posterior left ventricular wail thicknesses (P=.02) were associated with progression to hypertension. After adjusting for sex, baseline age, systolic and diastolic blood pressures, body mass index, alcohol intake, and systolic blood pressure from an examination 8 years earlier, the odds ratio for developing hypertension for a 1-SD increment in left ventricular mass index was 1.20 (95% confidence interval, 1.04 to 1.39), and the odds ratio for a 1-SD increment in left ventricular wall thickness was 1.16 (95% confidence interval, 1.02 to 1.33). Conclusions In these normotensive adults, increased left ventricular mass and wall thickness were associated with the development of hypertension. Further studies are warranted to examine the utility of echocardiography in determining the need for antihypertensive therapy and to assess the effect of earlier intervention an the course of progression to hypertension. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC-38038] NR 49 TC 92 Z9 97 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 179 EP 185 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700027 PM 8025994 ER PT J AU ARRIGHI, JA DILSIZIAN, V PERRONEFILARDI, P DIODATI, JG BACHARACH, SL BONOW, RO AF ARRIGHI, JA DILSIZIAN, V PERRONEFILARDI, P DIODATI, JG BACHARACH, SL BONOW, RO TI IMPROVEMENT OF THE AGE-RELATED IMPAIRMENT IN LEFT-VENTRICULAR DIASTOLIC FILLING WITH VERAPAMIL IN THE NORMAL HUMAN HEART SO CIRCULATION LA English DT Article DE VERAPAMIL; AGING HEART FUNCTION TESTS; DIASTOLE ID CORONARY-ARTERY DISEASE; HYPERTROPHIC CARDIOMYOPATHY; SARCOPLASMIC-RETICULUM; CONTRACTION DURATION; SYSTOLIC FUNCTION; RAT MYOCARDIUM; PRESSURE; RELAXATION; INDEXES; ADULT AB Background Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired active LV relaxation as well as to structural alterations, we hypothesized that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects. Methods and Results We studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and after 3 to 4 days of oral verapamil therapy. Indexes of global LV function were derived from analysis of background-corrected time-activity curves. Subjects were recruited from three age groups: young (26+/-4 years, n=10), middle-aged (46+/-5 years, n=9), and elderly (66+/-3 years, n=8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per second) was reduced in the middle-aged group (5.8+/-1.2, P<.01) and the elderly group (4.3+/-1.0, P<.01) compared with the young group (7.8+/-1.2). With verapamil, resting heart rate, peak systolic wall stress, LV ejection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8+/-1.5 SV/s, P<.01) and the elderly group (to 5.7+/-1.0 SV/s, P<.01) but did not change in the young group (8.0+/-1.4 SV/s). Also, time to peak filling rate decreased with verapamil in the elderly group (from (1)85+/-31 to 147+/-15 milliseconds, P<.01). The magnitude of change in filling rate was correlated positively with age (r=.55, P<.005). Conclusion Verapamil selectively enhances LV diastolic filling in middle-aged and elderly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairment of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 45 TC 39 Z9 39 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 213 EP 219 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700031 PM 8025999 ER PT J AU HAIGNEY, MCP LAKATTA, EG STERN, MD SILVERMAN, HS AF HAIGNEY, MCP LAKATTA, EG STERN, MD SILVERMAN, HS TI SODIUM-CHANNEL BLOCKADE REDUCES HYPOXIC SODIUM LOADING AND SODIUM-DEPENDENT CALCIUM LOADING SO CIRCULATION LA English DT Article DE CALCIUM; SODIUM; CHANNELS; HYPOXIA; ISCHEMIA ID RAT VENTRICULAR MYOCYTES; ISOLATED RABBIT HEART; INTRACELLULAR SODIUM; CARDIAC MYOCYTES; CONTRACTILE FAILURE; NA+-CA-2+ EXCHANGE; OXYGEN PARADOX; ISCHEMIA; CELLS; REPERFUSION AB Background Studies have shown that the rise in intracellular ionized calcium, [Ca2+](i), in hypoxic myocardium is driven by an increase in sodium, [Na+](i), but the source of Na+ is not known. Methods and Results Inhibitors of the voltage-gated Na+ channel were used to investigate the effect of Naf channel blockade on hypoxic Na+ loading, Na+-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated adult rat cardiac myocytes. Single electrically stimulated (0.2 Hz) cells were loaded with either SBFI (to index [Na+](i)) or indo-1. (to index [Ca2+](i)) and exposed to glucose-free hypoxia (Po-2 < 0.02 mm Hg). Both [Na+](i) and [Ca](i) increased during hypoxia when cells became inexcitable following ATP-depletion contracture. The hypoxic rise in [Na+](i) and [Ca2+](i) was significantly attenuated by 1 mu mol/L R 56865. Tetrodotoxin (60 mu mol/L), a selective Na+-channel blocker, also markedly reduced the rise in [Ca2+](i) during hypoxia and reoxygenation. Reoxygenation-induced cellular hypercontracture was reduced from 83% (45 of 54 cells) under control conditions to 12% (4 of 32) in the presence of R 56865 (P < .05). Lidocaine reduced hypercontracture dose dependently with 13% of cells hypercontracting in 100 mu mol/L lidocaine, 42% in 50 mu mol/L lidocaine, and 93% in 25 mu mol/L lidocaine. The Na+-K+ exchange blocker, ethylisopropylamiloride (10 mu mol/L) was also effective, limiting hypercontracture to 12%. R 56865, lidocaine, and ethylisopropylamiloride were also effective in preventing hypercontracture in normoxic myocytes induced by 75 mu mol/L veratridine, an agent that impairs Na+ channel inactivation. Ethylisopropylamiloride prevented the veratridine-induced rise in [Ca2+](i) without affecting Na+-Ca2+ exchange, suggesting that amiloride derivatives can reduce Ca2+ loading by blocking Na+ entry through Na+ channels, an action that may in part underlie their ability to prevent hypoxic Na+ and Ca2+ loading. Conclusions Na+ influx through the voltage-gated Na+ channel is an important route of hypoxic Na+ loading, Na+-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated rat cardiac myocytes. Importantly, the Na+ channel appears to serve as a route for hypoxic Na+ influx after myocytes become inexcitable. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. FU NHLBI NIH HHS [K08-HL-02539, P50-HL-17655, R01-HL-42050] NR 46 TC 158 Z9 172 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 391 EP 399 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700053 PM 8026023 ER PT J AU THOM, TJ EPSTEIN, FH AF THOM, TJ EPSTEIN, FH TI HEART-DISEASE, CANCER, AND STROKE MORTALITY TRENDS AND THEIR INTERRELATIONS - AN INTERNATIONAL PERSPECTIVE SO CIRCULATION LA English DT Article DE CANCER; CEREBROVASCULAR DISORDERS HEART DISEASES; MORTALITY AB Background Changes in mortality from heart disease, cancer, and stroke over recent decades in many countries have received much attention. However, comprehensive and concurrent analyses of these trends and their effect on total mortality have been lacking. Moreover, the extent to which the trends for one disease may relate to those for another disease is unknown. Concordance of trends for major diseases would suggest that they have common causes and thus may be responsive to the same preventive measures. Methods and Results Age-adjusted death rates for total mortality and mortality from heart disease, stroke, lung cancer, and cancer other than lung cancer were obtained for the years 1950 to 1987 in 27 countries by sex and ages 35 to 74 years from the World Health Organization statistical reports. Concordance of mortality trends was assessed for ages 35 to 74 between 1950 and 1983 through visual inspection and semiquantitative measurements of percentage change over time. The epidemic increase in heart disease mortality ended in the 1960s or 1970s in most industrialized countries; death rates often declined very steeply. Stroke mortality also changed from an increase to a decline or from a modest to a steep decline in the 1960s or 1970s. Lung cancer mortality slopes generally changed from a steep increase to either a modest increase, a hat trend, or a decline; the changes in slope are lagging behind those for heart disease and stroke. These improvements influenced trends for total mortality. Cancer other than lung cancer trends are less distinct than those for the three other causes of mortality. Yet, testing them for concordance with heart disease trends reveals that they are mostly concordant on a time-lag analysis that assumes that heart disease responds more rapidly to a change in lifestyle or environment than cancer. Trends for heart disease and lung cancer in men also tend to be concordant on time-lag analysis. Heart disease and stroke trends have become more concordant with time. Conclusions Trends for mortality from heart disease, stroke, lung cancer, and, less distinctly, cancer other than lung cancer, tend to be similar in different countries, leading to a corresponding similarity in total mortality trends. An analysis of trends for pairs of diseases within countries indicates a tendency toward concordance of trends, suggesting the existence of common causes amenable to the same preventive measures. This analysis of international mortality trends is intended to stimulate further research along these lines, as a guide to preventive and therapeutic action. C1 UNIV ZURICH,INST SOCIAL & PREVENT MED,CH-8006 ZURICH,SWITZERLAND. RP THOM, TJ (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892, USA. NR 26 TC 80 Z9 82 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1994 VL 90 IS 1 BP 574 EP 582 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700073 PM 8026045 ER PT J AU BOLUYT, MO ONEILL, L MEREDITH, AL BING, OHL BROOKS, WW CONRAD, CH CROW, MT LAKATTA, EG AF BOLUYT, MO ONEILL, L MEREDITH, AL BING, OHL BROOKS, WW CONRAD, CH CROW, MT LAKATTA, EG TI ALTERATIONS IN CARDIAC GENE-EXPRESSION DURING THE TRANSITION FROM STABLE HYPERTROPHY TO HEART-FAILURE - MARKED UP-REGULATION OF GENES ENCODING EXTRACELLULAR-MATRIX COMPONENTS SO CIRCULATION RESEARCH LA English DT Article DE HEART FAILURE; SPONTANEOUSLY HYPERTENSIVE RATS; MYOSIN HEAVY CHAIN; MYOSIN LIGHT CHAIN; ALPHA-ACTIN; SARCOPLASMIC RETICULUM CA2+-ATPASE; FIBRONECTIN; COLLAGEN; TRANSFORMING GROWTH FACTOR-BETA ID SPONTANEOUSLY HYPERTENSIVE RATS; SARCOPLASMIC-RETICULUM CA-2+-ATPASE; MESSENGER-RNA; SKELETAL-MUSCLE; FIBRONECTIN EXPRESSION; ATPASE ACTIVITY; ANGIOTENSIN-II; ADULT-RAT; COLLAGEN; GROWTH AB The failing heart is characterized by impaired cardiac muscle function and increased interstitial fibrosis. Our purpose was to determine whether the functional impairment of the failing heart is associated with changes in levels of mRNA encoding proteins that modulate parameters of contraction and relaxation and whether the increased fibrosis observed in the failing heart is related to elevated expression of genes encoding extracellular matrix components. We studied hearts of 18- to 24-month-old spontaneously hypertensive rats with signs and symptoms of heart failure (SHR-F) or without evidence of failure (SHR-NF) and of age-matched normotensive Wistar-Kyoto (WKY) rats. Compared with WKY rats, SHR-NF exhibited left ventricular (LV) hypertrophy (2.2-fold) and right ventricular (RV) hypertrophy (1.5-fold), whereas SHR-F were characterized by comparable LV hypertrophy (2.1-fold) and augmented RV hypertrophy (2.4-fold; all P<.01). Total RNA was isolated from ventricles and subjected to Northern blot analysis. In SHR-F hearts, the level of alpha-myosin heavy chain mRNA was decreased in both ventricles to 1/3 and 1/5 of the SHR-NF and WKY values, respectively (both P<.01). Levels of beta-myosin heavy chain, alpha-cardiac actin, and myosin light chain-2 mRNAs were not significantly altered in hearts of SM-NF or SHR-F. Levels of alpha-skeletal actin were twofold greater in SHR-NF hearts compared with WKY hearts and were intermediate in SHR-F hearts. Levels of atrial natriuretic factor (ANF) mRNA were elevated threefold in the LV of SHR-NF (P<.05) but were not significantly increased in the RV of SHR-NF compared with WKY rats. During the transition to failure (SHR-F versus SHR-NF), ANF mRNA levels increased an additional 1.6-fold in the LV and were elevated 4.7-fold in the RV (both P<.05), Levels of sarcoplasmic reticulum Ca2+ ATPase (SRCA) mRNA were maintained in the LV of hypertensive and failing hearts at levels not significantly different from WKY values. In contrast, the level of RV SRCA mRNA was 24% less in SHR-NF compared with WKY rats, and during the transition to failure, this difference was not significantly exacerbated (29% less than the WKY value). The levels of fibronectin and pro-alpha 1(I) and pro-alpha 1(III) collagen mRNAs were not significantly elevated in either ventricle of the SHR-NF group but were fourfold to fivefold higher in both ventricles of SHR-F (all P<.05). The increase in fibronectin gene expression was at least partially explained by an elevation in the level of the EIIIA-containing isoform, an alternatively spliced variant expressed during wound healing and pressure overload hypertrophy. Transforming growth factor-beta(1) (TGF-beta(1)) mRNA abundance was not elevated in ventricles of SHR-NF but increased 1.3-fold in the LV and twofold in the RV during the transition to heart failure compared with SHR-NF values (both P<.05). The decrease in alpha-myosin heavy chain mRNA levels in SHR-F hearts represents a pretranslational basis for the slowed contraction previously observed in cardiac muscle from these hearts. The survey of specific contractile protein mRNAs provides no evidence of a downregulation of these genes during the transition to heart failure. The increase in fibronectin and collagen mRNA levels suggests that the previously observed increase in interstitial fibrosis in cardiac muscles of failing hearts is regulated at the level of gene expression. The increase in abundance of TGF-beta(1) mRNA in conjunction with the upregulation of fibronectin and collagen genes suggests that activation of TGF-beta(1) gene expression may be a mechanism initiating interstitial fibrosis during the transition from stable hypertrophy to failure. C1 VET AFFAIRS MED CTR,DEPT MED,BOSTON,MA. RP BOLUYT, MO (reprint author), NIH,GERONTOL RES CTR,CARDIOVASC SCI LAB,ROOM 3-E-10,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 58 TC 273 Z9 279 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1994 VL 75 IS 1 BP 23 EP 32 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NV031 UT WOS:A1994NV03100004 PM 8013079 ER PT J AU PAULY, RR PASSANITI, A BILATO, C MONTICONE, R CHENG, L PAPADOPOULOS, N GLUZBAND, YA SMITH, L WEINSTEIN, C LAKATTA, EG CROW, MT AF PAULY, RR PASSANITI, A BILATO, C MONTICONE, R CHENG, L PAPADOPOULOS, N GLUZBAND, YA SMITH, L WEINSTEIN, C LAKATTA, EG CROW, MT TI MIGRATION OF CULTURED VASCULAR SMOOTH-MUSCLE CELLS THROUGH A BASEMENT-MEMBRANE BARRIER REQUIRES TYPE-IV COLLAGENASE ACTIVITY AND IS INHIBITED BY CELLULAR-DIFFERENTIATION SO CIRCULATION RESEARCH LA English DT Article DE SMOOTH MUSCLE CELLS; CHEMOTAXIS; MATRIX METALLOPROTEINASES; EXTRACELLULAR MATRIX; BASEMENT MEMBRANE ID RAT CAROTID-ARTERY; PLASMINOGEN-ACTIVATOR; GROWTH-FACTOR; CORONARY ANGIOPLASTY; EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; TUMOR INVASION; EXPRESSION; ATHEROSCLEROSIS; IDENTIFICATION AB The migration of vascular smooth muscle cells (VSMCs) from the tunica media to the neointima is a key event in the development and progression of many vascular diseases and a highly predictable consequence of mechanical injury to the blood vessel. In vivo, VSMCs are surrounded by and embedded in a variety of extracellular matrices (ECMs) that must be traversed during migration. One of the principal barriers to cell movement in the intact vessel is the basement membrane (BM) that surrounds each VSMC and separates the VSMC-containing medial cell layer from the endothelium. We have used a Boyden chamber to monitor the ability of VSMCs to degrade a BM barrier as they migrate toward a chemoattractant and to define the role of extracellular proteases in this process. We show that cultured VSMCs can migrate across a BM barrier and that this ability was dependent on the phenotypic state of the cell. VSMCs maintained in a proliferating or ''synthetic'' state readily migrated across a BM toward a chemoattractant, whereas the migration of serum-starved/differentiated VSMCs was suppressed by >80% (P<.001). By use of a number of peptides that inhibit matrix metalloproteinase (MMP) activity, the migration of proliferating VSMCs across the BM barrier was inhibited by >80% (P<.0001), whereas migration that occurred in the absence of the barrier was unaffected. Northern blotting and zymographic analyses indicated that 72-kD type IV collagenase (MMP2) was the principal MMP expressed and secreted by these cells. Accordingly, antisera capable of selectively neutralizing MMP2 activity also inhibited VSMC migration across the barrier without significantly affecting the migration of VSMCs in the absence of the barrier. Finally, MMP2 activity was also regulated by the phenotypic state of the cells in that MMP2 activity expressed by serum-starved/differentiated VSMCs was 15% of that measured in proliferating VSMCs. Extrapolating to the in vivo situation in which VSMCs reside in an ECM composed of various BM barriers, these results suggest that VSMC migration in vivo may be dependent on MMP2 activity. That activity, in turn, could be regulated by the phenotypic state of VSMCs and increase as these cells undergo the transition from a quiescent and differentiated state to that of a dedifferentiated, proliferating, and motile phenotype after injury to the vessel. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,BIOL CHEM LAB,BALTIMORE,MD 21224. RI Papadopoulos, Nickolas/K-7272-2012 NR 59 TC 258 Z9 265 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1994 VL 75 IS 1 BP 41 EP 54 PG 14 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NV031 UT WOS:A1994NV03100006 PM 8013081 ER PT J AU LEE, KN CSAKO, G BERNHARDT, P ELIN, RJ AF LEE, KN CSAKO, G BERNHARDT, P ELIN, RJ TI RELEVANCE OF MACRO CREATINE-KINASE TYPE-1 AND TYPE-2 ISOENZYMES TO LABORATORY AND CLINICAL-DATA SO CLINICAL CHEMISTRY LA English DT Article DE ELECTROPHORESIS, AGAROSE; ENZYME-IMMUNOGLOBULIN COMPLEX; ISOENZYMES; PREVALENCE; PROGNOSIS; ETIOLOGY; AUTOIMMUNITY; CANCER ID MYOCARDIAL-INFARCTION; HEALTHY-INDIVIDUALS; SERUM; BB; MARKER; MB; DIFFERENTIATION; MACROENZYMES; PREVALENCE; DIAGNOSIS AB From 8322 patients for whom creatine kinase (OK; EC 2.7.3.2) isoenzyme analysis was ordered, we identified 136 patients with macro OK isoenzyme in their serum. There were 36 cases with type 1 (prevalence: 0.43%) and 100 cases with type 2 isoenzyme (prevalence: 1.20%). About three-fourths of the patients were ambulatory at the time of testing, and similar to 90% of the first 68 patients identified survived at least 1 year after macro CK was found in their serum. Age and gender did not differ significantly between the two groups. The serum total CK was significantly higher (P <0.0005), and an increased OK-MR proportion (>0.05 of total CK) was also significantly more common (P <0.0005) in patients with macro OK type 1 than in those with type 2. On average, macro CK type 2 accounted for similar to 25% and macro CK type 1 for similar to 10% of the serum total CK activity. Patients with macro CK type 1 most often had myositis, whereas those with macro CK type 2 most commonly had a malignancy. We conclude that the presence of macro CK isoenzymes has a low prognostic value for impending death, but may support the diagnosis of an autoimmune process (type 1) or malignant cell proliferation (type 2). C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BETHESDA,MD 20892. NR 40 TC 48 Z9 53 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 1994 VL 40 IS 7 BP 1278 EP 1283 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NW103 UT WOS:A1994NW10300012 PM 8013099 ER PT J AU CONE, EJ HILLSGROVE, M DARWIN, WD AF CONE, EJ HILLSGROVE, M DARWIN, WD TI SIMULTANEOUS MEASUREMENT OF COCAINE, COCAETHYLENE, THEIR METABOLITES, AND CRACK PYROLYSIS PRODUCTS BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO CLINICAL CHEMISTRY LA English DT Article DE ABUSED DRUGS; DRUG METABOLISM; DRUG MONITORING ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; ECGONINE METHYL-ESTER; BASIC DRUGS; HUMAN-URINE; BENZOYLECGONINE; PLASMA; QUANTITATION; CONFIRMATION; ALCOHOL AB We developed a sensitive and specific assay for the simultaneous measurement of cocaine, cocaethylene, six of their metabolites, and anhydroecgonine methyl ester, a pyrolysis product, in biological fluids. The assay involves solid-phase extraction columns containing a copolymeric bonded phase for isolation of cocaine analytes, derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide and 10 g/L trimethylchlorosilane, and measurement with gas chromatography-mass spectrometry operating in the selected-ion monitoring mode. Detector responses for analytes were linear over a concentration range of 3.1-1000 mu g/L. The limits of detection were similar to 1 mu g/L for cocaine, ecgonine methyl ester, and benzoylecgonine and 3-6 mu g/L for the remaining analytes. Hydrolysis of cocaine and artifact formation of anhydroecgonine methyl ester during extraction and assay was <1%. Cocaine and its derivatives appear in different proportions in plasma, saliva, and urine according to the biological fluid and time of measurement. Each biological fluid provides unique information on the disposition of cocaine in human subjects. RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 124 Z9 125 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 1994 VL 40 IS 7 BP 1299 EP 1305 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NW103 UT WOS:A1994NW10300016 PM 8013103 ER PT J AU UYESAKA, N HASEGAWA, S NAKAMURA, T HONGO, AT SCHECHTER, AN SHIO, H AF UYESAKA, N HASEGAWA, S NAKAMURA, T HONGO, AT SCHECHTER, AN SHIO, H TI PATHOPHYSIOLOGIC SIGNIFICANCE OF MECHANICAL FRAGILITY OF RED-BLOOD-CELLS SO CLINICAL HEMORHEOLOGY LA English DT Article DE RED BLOOD CELLS (RBC); MECHANICAL FRAGILITY; OSMOTIC FRAGILITY; HEMATOCRIT; HEINZ BODIES; HEMOLYTIC ANEMIA ID INCREASED INTRACELLULAR CALCIUM; DECREASED DEFORMABILITY; ERYTHROCYTE-MEMBRANE; CEREBRAL INFARCTION; HEMATOCRIT; RELEVANCE; PROTEINS AB To elucidate the pathophysiologic significance of the mechanical fragility of red blood cells (RBC), we have developed a simple quantitative technique, the impact-force method, for measuring mechanical hemolysis; the method makes use of the instantaneous falling of a metal bar due to gravity. The mechanical hemolysis thus induced was accompanied by cell fragmentation and echinocytosis. The method can be performed under near physiologic conditions. We found that mechanical hemolysis increased with a rise in hematocrit (Hct) value; in particular, the hemolysis rapidly increased above a Hct value of around 50%, thereby suggesting that the mechanical fragility determined by this method reflects the rheologic characteristics of the RBC suspension, such as cell-cell interactions, as well as membrane stability. Using the impact-force method, we found that the mechanical fragility of rat RBC was greater than that of human RBC, whereas there was little difference between the two species in osmotic fragility. Although osmotic hemolysis was strongly reduced by low concentrations of chlorpromazine, this drug promoted mechanical hemolysis at all concentrations examined. More interestingly, Heinz body-forming RBC from a patient with unstable hemoglobin disease and hemolytic anemia showed a marked increase in mechanical fragility, but a pronounced decrease in osmotic fragility due to dehydration of the cells. This suggests the pathophysiologic importance of the mechanical fragility of RBC, specifically in the pathogenesis of hemolytic disease. It is, therefore, likely that this mechanical fragility test could be of value in various related fields of clinical medicine, as well as hematology. C1 NIDDKD,CHEM BIOL LAB,BETHESDA,MD. SHIGA MED CTR ADULT DIS,SHIGA,JAPAN. RP UYESAKA, N (reprint author), NIPPON MED COLL,DEPT PHYSIOL,1-1-5 SENDAGI,BUNKYO KU,TOKYO 113,JAPAN. OI Schechter, Alan N/0000-0002-5235-9408 NR 32 TC 1 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5198 J9 CLIN HEMORHEOL JI Clin. Hemorheol. PD JUL-AUG PY 1994 VL 14 IS 4 BP 557 EP 570 PG 14 WC Hematology SC Hematology GA NZ091 UT WOS:A1994NZ09100011 ER PT J AU HASEGAWA, S NOMURA, T IINO, M SHIO, H SCHECHTER, AN UYESAKA, N AF HASEGAWA, S NOMURA, T IINO, M SHIO, H SCHECHTER, AN UYESAKA, N TI CAUSAL ROLE OF DENSE MICROSPHEROCYTES IN THE ANEMIA OF HEREDITARY SPHEROCYTOSIS - CLINICAL IMPORTANCE OF FILTERABILITY MEASUREMENTS THROUGH 3-MU-M PORES SO CLINICAL HEMORHEOLOGY LA English DT Article DE RED BLOOD CELL (RBC); DEFORMABILITY; MICROSPHEROCYTE; SPLENIC CONDITIONING; HEMOLYTIC ANEMIA; HEREDITARY SPHEROCYTOSIS ID RED-CELL DEFORMABILITY; ERYTHROCYTE FILTERABILITY; MEMBRANE-SKELETON; HEMOLYTIC-ANEMIA; SPLEEN; SPECTRIN; PROTEINS; PASSAGE; DISEASE; LIPIDS AB To elucidate the pathogenesis of hemolysis in hereditary spherocytosis (HS), we studied the heterogeneity and deformability of red blood cells (RBCs), before and after splenectomy, in a typical patient with HS. RBC deformability was measured with our recently developed nickel mesh filter with both 3 mum and 5 mum pores. HS RBCs showed a marked increase in osmotic fragility with a ''tailed'' osmotic-fragility curve; consistently, the density distribution of HS RBCs was markedly shifted to heavier cells, with a biphasic profile. HS RBCs, the dense cells in particular, showed a marked impairment in filterability through the 3-mum pore nickel mesh compared with that through the 5-mum pores. It is, therefore, likely that the impaired deformability of HS RBCs arises from the decrease in the cell surface area to volume ratio and the high mean corpuscular hemoglobin concentration. After splenectomy, the dense microspherocytes disappeared, and there was a marked improvement in RBC filterability through 3-mum pores. This suggests that dense cells were microspherocytes that received splenic conditioning in the walls of splenic sinuses. Correspondingly, splenectomy markedly improved clinical manifestations and ameliorated hemolysis. Thus, the laboratory measurement (i.e., the 3-mum filtration test) reflected the patient's clinical state. The use of both 5- and 3-mum filtration measurements can make a practical contribution to determining the differential diagnosis of hereditary hemolytic anemias. The 3-mum filter is useful in determing the clinical severity and indications for splenectomy in HS. C1 NIPPON MED COLL, DEPT PHYSIOL, TOKYO 113, JAPAN. SHIGA MED CTR ADULT DIS, SHIGA, JAPAN. NIDDKD, CHEM BIOL LAB, BETHESDA, MD USA. RP HASEGAWA, S (reprint author), NIPPON MED COLL, DEPT INTERNAL MED 3, 1-1-5 SENDAGI, BUNKYO KU, TOKYO 113, JAPAN. OI Schechter, Alan N/0000-0002-5235-9408 NR 36 TC 4 Z9 5 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0271-5198 J9 CLIN HEMORHEOL JI Clin. Hemorheol. PD JUL-AUG PY 1994 VL 14 IS 4 BP 571 EP 584 PG 14 WC Hematology SC Hematology GA NZ091 UT WOS:A1994NZ09100012 ER PT J AU GAYDOS, CA EIDEN, JJ OLDACH, D MUNDY, LM AUWAERTER, P WARNER, ML VANCE, E BURTON, AA QUINN, TC AF GAYDOS, CA EIDEN, JJ OLDACH, D MUNDY, LM AUWAERTER, P WARNER, ML VANCE, E BURTON, AA QUINN, TC TI DIAGNOSIS OF CHLAMYDIA-PNEUMONIAE INFECTION IN PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA BY POLYMERASE CHAIN-REACTION ENZYME-IMMUNOASSAY SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID STRAIN TWAR; POPULATION; DISEASE AB We conducted a prospective study of 385 patients who had community-acquired pneumonia with use of a modified polymerase chain reaction (PCR) assay that detects amplified DNA by enzyme immunoassay (EIA). We used PCR-EIA to improve detection of Chlamydia pneumoniae infection and to differentiate C. pneumoniae infection from other chlamydial infections. Cultures of throat swab specimens from four patients yielded Chlamydia species (C. pneumoniae, one patient; Chlamydia species, two patients; and C. psittaci, one patient). C. pneumoniae was repeatedly detected by PCR-EIA for thirteen (3.4%) of these 385 patients. Six of these 13 patients were infected with the human immunodeficiency virus. Ten (76.9%) of the patients who were positive by PCR-EIA had IgG titers of greater than or equal to 1:16, and two (15.4%) of the 13 patients had Ige titers of <1:16; no sera was available in one case. Other pathogens were recovered in eight (61.5%) of the 13 cases in which C. pneumoniae was detected by PCR-EIA. In addition, for 46 (11.9%) of the 385 patients the titers of antibody were considered diagnostic of C. pneumoniae infection; however, as 36 of the 46 patients were infected with the human immunodeficiency virus (which may have affected their serological response to C. pneumoniae), interpretation of these titers was problematic. As PCR-EIA was more sensitive than was culture for detecting C. pneumoniae infection in this study, this method may be a valuable tool for the prompt diagnosis of this infection. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010 NR 16 TC 56 Z9 56 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1994 VL 19 IS 1 BP 157 EP 160 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX665 UT WOS:A1994NX66500026 PM 7948521 ER PT J AU PIZZO, PA WILFERT, C AF PIZZO, PA WILFERT, C TI ANTIRETROVIRAL THERAPY FOR INFECTION DUE TO HUMAN-IMMUNODEFICIENCY-VIRUS IN CHILDREN SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; HIV-1 REVERSE-TRANSCRIPTASE; AIDS-RELATED COMPLEX; POLYMERASE CHAIN-REACTION; RECOMBINANT SOLUBLE CD4; PLACEBO-CONTROLLED TRIAL; INFUSION ZIDOVUDINE THERAPY; HIGH-LEVEL RESISTANCE; P24 ANTIGEN LEVELS; PHASE-I TRIAL AB Infection with human immunodeficiency virus type 1 (HIV-1) in children presents problems that greatly differ from those seen in adults. The great majority of children are infected either during gestation or at the time of birth. As Drs. Pizzo and Wilfert note in their AIDS Commentary, this results in rapid development of immunosuppression and clinical manifestations in patients whose immune systems are in the process of maturing. Thus, a thorough understanding of the pharmacokinetics of antiretroviral agents in infants and small children is required. This AIDS Commentary provides a comprehensive review of the current state of our knowledge and possible future directions for the management of HIV-1 infection in this young population. C1 DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. RP PIZZO, PA (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 178 TC 16 Z9 16 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1994 VL 19 IS 1 BP 177 EP 196 PG 20 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX665 UT WOS:A1994NX66500032 PM 7948527 ER PT J AU POLLARD, HB ROJAS, E ARISPE, N AF POLLARD, HB ROJAS, E ARISPE, N TI BETA-AMYLOID IN ALZHEIMERS-DISEASE - THERAPEUTIC IMPLICATIONS SO CNS DRUGS LA English DT Article ID PRECURSOR PROTEIN; BILAYER-MEMBRANES; PEPTIDE; CALCIUM; NEURONS; CHROMOSOME-14; DERIVATIVES; METABOLISM; MECHANISM; TOXICITY AB Recent evidence has been accumulating to suggest that the peptide beta-amyloid may be implicated as a causative agent in Alzheimer's disease. This compound is known to accumulate in the cerebral plaques that are characteristic of the disease. Whether beta-amyloid is toxic per se is yet to be established, but several options are available which may reduce the toxicity of the agent and, thus, have potential in the treatment of Alzheimer's disease. Prevention of the generation of beta-amyloid from the amyloid precursor protein (APP) and inhibition of the possible neurotoxic effects of the compound are being explored. A recent finding that has gained much attention is that beta-amyloid can form ion channels that are cation-specific. An increase in intracellular calcium levels can occur via these channels, which may be neurotoxic and cause inflammatory responses. The use of channel blocking agents, such as trometamol (tromethamine), may prevent neurotoxicity, while anti-inflammatory drugs may also prove to be useful therapeutic agents. RP NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. NR 39 TC 10 Z9 10 U1 0 U2 1 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PD JUL PY 1994 VL 2 IS 1 BP 1 EP 6 PG 6 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NX347 UT WOS:A1994NX34700001 ER PT J AU MILLER, W BOGUSKI, M AF MILLER, W BOGUSKI, M TI A NOTE ABOUT COMPUTING ALL LOCAL ALIGNMENTS SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Note ID RAS; FARNESYLTRANSFERASE; ALGORITHM; PROTEINS AB A recent paper in this journal by G. Barton proposed an efficient algorithm for locating locally optimal alignments between two sequences. Although the paper claims that all such alignments are found, the approach frequently fails to detect some of the significant matches. This note explains the deficiency. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP MILLER, W (reprint author), PENN STATE UNIV,DEPT COMP SCI & ENGN,UNIVERSITY PK,PA 16802, USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUL PY 1994 VL 10 IS 4 BP 455 EP 456 PG 2 WC Computer Science, Interdisciplinary Applications SC Computer Science GA PD680 UT WOS:A1994PD68000013 PM 7804880 ER PT J AU TATUSOV, RL KOONIN, EV AF TATUSOV, RL KOONIN, EV TI A SIMPLE TOOL TO SEARCH FOR SEQUENCE MOTIFS THAT ARE CONSERVED IN BLAST OUTPUTS SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Note C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NR 6 TC 23 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUL PY 1994 VL 10 IS 4 BP 457 EP 459 PG 3 WC Computer Science, Interdisciplinary Applications SC Computer Science GA PD680 UT WOS:A1994PD68000014 PM 7804881 ER PT J AU SNYDER, DS AF SNYDER, DS TI NEUROTOXINS AND NEURODEGENERATIVE DISEASE - LANGSTON,JW, YOUNG,A SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP SNYDER, DS (reprint author), NATL INST AGING,BETHESDA,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD JUL PY 1994 VL 39 IS 7 BP 754 EP 756 PG 3 WC Psychology, Multidisciplinary SC Psychology GA NW991 UT WOS:A1994NW99100045 ER PT J AU SUFFREDINI, AF AF SUFFREDINI, AF TI CURRENT PROSPECTS FOR THE TREATMENT OF CLINICAL SEPSIS SO CRITICAL CARE MEDICINE LA English DT Article DE SEPTIC SHOCK; TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-1; ENDOTOXIN; TUMOR NECROSIS FACTOR RECEPTOR; INTERLEUKIN-1 RECEPTOR; CRITICAL ILLNESS; CYTOKINES; INFECTION ID TUMOR-NECROSIS-FACTOR; NEGATIVE SEPTIC SHOCK; HUMAN MONOCLONAL-ANTIBODY; FACTOR-ALPHA; ESCHERICHIA-COLI; IMMUNOGLOBULIN PREPARATION; FACTOR CACHECTIN; DOUBLE-BLIND; INTERLEUKIN-1; ENDOTOXIN AB Objectives: To review the role of antimediator therapy in the inflammatory cascade associated with sepsis, and to review the status of animal and clinical studies being conducted on novel therapies for septic shock. Data Sources: Information presented at the 22nd Educational and Scientific Meeting of the Society of Critical Care Medicine on June 9-13, 1993 in New York City was reviewed, along with supportive documentation from the English language literature. Study Selection: Controlled animal studies that provide evidence for the effectiveness of antiendotoxin and anticytokine therapies. The preliminary results of selected clinical trials are also presented. Data Extraction: This review focuses on data describing the potential role of mediator antagonists in the treatment of septic shock. Data Synthesis: Information concerning the effectiveness and tolerability of these therapies has been integrated into a description of emerging therapies for septic shock. Conclusions: Clinical trials of antiendotoxin antibodies have not shown them to have therapeutic benefit. New agents that neutralize or antagonize the cellular effects of endotoxin may provide an alternative means to inhibit endotoxin effects during severe Gram-negative infections. Anti-interleukin-1 and antitumor necrosis factor-alpha therapies have demonstrated efficacy in animal models, but the results have been inconsistent in human trials. Preliminary results from clinical trials of cytokine antagonists suggest that these therapies may be effective in the most severely ill patients. Further clinical trials will be required to determine the therapeutic role of these agents in septic shock. RP SUFFREDINI, AF (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,ROOM 7D-43,BETHESDA,MD 20892, USA. NR 51 TC 36 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1994 VL 22 IS 7 BP S12 EP S18 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA PA696 UT WOS:A1994PA69600022 PM 8026188 ER PT J AU METZGER, H AF METZGER, H TI IMMUNOGLOBULIN RECEPTORS - HANDICAPPING THE IMMUNE-RESPONSE SO CURRENT BIOLOGY LA English DT Note ID HIGH-AFFINITY RECEPTOR; FC-GAMMA RECEPTOR; CELL-RECEPTOR; IGE RECEPTOR; T-CELL; SUBUNIT; ASSOCIATION; TAIL; RI AB Gene targeting experiments that 'knock out' the expression of cellular Fe receptors for immune complexes have confirmed previous assumptions about the receptors' function but have also revealed some surprises. RP METZGER, H (reprint author), NIAMS,BETHESDA,MD 20892, USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 1 PY 1994 VL 4 IS 7 BP 644 EP 646 DI 10.1016/S0960-9822(00)00143-3 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NX678 UT WOS:A1994NX67800015 PM 7953545 ER PT J AU WALDBILLIG, RJ JONES, BE SCHOEN, TJ MOSHAYEDI, P HEIDERSBACH, S BITAR, MS VANKUIJK, FJGM DEJUAN, E KADOR, P CHADER, GJ AF WALDBILLIG, RJ JONES, BE SCHOEN, TJ MOSHAYEDI, P HEIDERSBACH, S BITAR, MS VANKUIJK, FJGM DEJUAN, E KADOR, P CHADER, GJ TI VITREAL INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS) ARE INCREASED IN HUMAN AND ANIMAL DIABETICS SO CURRENT EYE RESEARCH LA English DT Article DE DIABETIC RETINOPATHY; RETINA; INSULIN-LIKE GROWTH FACTOR (IGF); INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS (IGFBPS); STREPTOZOTOCIN; GALACTOSEMIA; VITREOUS HUMOR ID PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL-CELLS; NEURAL RETINA; RECEPTORS; GALACTOSE AB Although patients with diabetic retinopathy have been reported to have elevated vitreal IGF-I levels, it is not known whether diabetes also affects the levels of vitreal IGF binding proteins (IGFBPs) which control IGF's bioavailability. To address this issue, vitreal IGFBP levels were assayed in human diabetics, rats with streptozotocin-induced diabetes and galactose-fed dogs with diabetic-like retinopathy. Using I-125-IGF-II ligand blots, it was found that human diabetics have a 4-fold increase in vitreal IGFBP levels. Also, western blots on human diabetic vitreous reveal increased levels of IGFBP-2 and proteolytic fragments of IGFBP-3. IGF binding assays on vitreous from streptozotocin-treated rats (three months in duration) also indicate a 5-fold increase in IGF binding activity. IGF ligand blots using vitreous from rats with a shorter duration of diabetes (one month) show a 63% increase in IGFBP binding and a marked decrease in serum IGFBP binding. IGF ligand blots and IGFBP-2 and -4 western blots using vitreous from galactose-fed dogs with diabetic-like retinopathy exhibit a 6-fold increase in vitreal IGFBPs. The observation that vitreal IGFBPs are elevated in diabetic humans and rats without overt retinopathy suggests that these increases are not the result of a preexisting end-stage retinopathy but rather are an early ocular event in the diabetic process. Increases in vitreal IGFBPs thus could participate in the proliferative aspects of diabetic retinopathy by virtue of their putative intrinsic bioactivity or their capacity to alter IGF bioavailability. C1 NEI,BETHESDA,MD 20892. PENN COLL PODIAT MED,DEPT PHYSIOL SCI,PHARMACOL SECT,PHILADELPHIA,PA 19107. MONTANA STATE UNIV,DEPT CHEM & BIOCHEM,BOZEMAN,MT 59717. DUKE UNIV,DEPT OPHTHALMOL,DURHAM,NC 27710. FU NEI NIH HHS [NEI EY-08818] NR 22 TC 35 Z9 37 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUL PY 1994 VL 13 IS 7 BP 539 EP 546 DI 10.3109/02713689408999886 PG 8 WC Ophthalmology SC Ophthalmology GA NW758 UT WOS:A1994NW75800009 PM 7523030 ER PT J AU BERG, M FRAKER, DL ALEXANDER, HR AF BERG, M FRAKER, DL ALEXANDER, HR TI CHARACTERIZATION OF DIFFERENTIATION FACTOR LEUKEMIA INHIBITORY FACTOR EFFECT ON LIPOPROTEIN-LIPASE ACTIVITY AND MESSENGER-RNA IN 3T3-L1 ADIPOCYTES SO CYTOKINE LA English DT Article DE CACHEXIA; CANCER; CYTOKINES; LIPID METABOLISM ID TUMOR-NECROSIS-FACTOR; CULTURED BROWN ADIPOCYTES; IL-6 SIGNAL TRANSDUCER; CANCER CACHEXIA; ADIPOSE-TISSUE; CELLS; MICE; INTERLEUKIN-6; CACHECTIN; RECEPTOR C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NR 47 TC 53 Z9 55 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL PY 1994 VL 6 IS 4 BP 425 EP 432 DI 10.1016/1043-4666(94)90067-1 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA NW099 UT WOS:A1994NW09900012 PM 7948751 ER PT J AU CHEN, H WALKER, GE TAYLOR, SL MCKEON, C AF CHEN, H WALKER, GE TAYLOR, SL MCKEON, C TI PROXIMAL ENHANCER OF THE HUMAN INSULIN-RECEPTOR GENE BINDS THE TRANSCRIPTION FACTOR SP1 SO DIABETES LA English DT Article ID SV40 EARLY PROMOTER; MESSENGER-RNA; REGION; DIFFERENTIATION; EXPRESSION; IDENTIFICATION; INITIATION; SEQUENCES; KINASE; CELLS AB The insulin receptor is a growth regulator present on the surface of most cells that transmits a mitogenic signal in response to insulin. Thus, the gene for the insulin receptor is constitutively expressed at low levels in all cells. We characterize a constitutive enhancer element that is present in the proximal promoter of the human insulin receptor gene. We have localized the enhancer to a 26- base-pair (26-bp) sequence from -528 to -503. When this sequence is inserted into the proximal promoter, a three- to fourfold increase in promoter activity is observed, and when two copies are inserted, a five- to sixfold increase is seen. Electrophoretic mobility shift analysis demonstrates that nuclear factors binding to this sequence are found in many different cell types. At least two proteins with different specificities bind within this 26-bp sequence. The identity of the predominant binding protein is Sp1, because an oligonucleotide composed of an Sp1 consensus binding sequence can compete for several of the DNA-protein complexes. in addition, we demonstrate that purified Sp1 can bind to the 26-bp oligonucleotide and that this complex comigrates with a DNA-protein complex formed with a HeLa nuclear extract. Finally, an antibody to human Sp1 protein is able to bind to the enhancer DNA/HeLa protein complex and supershift this complex. These findings suggest that this sequence corresponds to a general element that may contribute to the ubiquitous expression of the human insulin receptor gene. C1 NIDDKD,DIABET BRANCH,METAB DIS & GENE THERAPY RES PROGRAM,BETHESDA,MD 20892. NR 27 TC 5 Z9 6 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1994 VL 43 IS 7 BP 884 EP 889 DI 10.2337/diabetes.43.7.884 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU593 UT WOS:A1994NU59300008 PM 8013752 ER PT J AU QUON, MJ COCHRAN, C TAYLOR, SI EASTMAN, RC AF QUON, MJ COCHRAN, C TAYLOR, SI EASTMAN, RC TI NON-INSULIN-MEDIATED GLUCOSE DISAPPEARANCE IN SUBJECTS WITH IDDM - DISCORDANCE BETWEEN EXPERIMENTAL RESULTS AND MINIMAL MODEL ANALYSIS SO DIABETES LA English DT Article ID SENSITIVITY INDEX; LABELED IVGTT; DIABETES-MELLITUS; TOLERANCE TEST; CLAMP; RESISTANCE; DISPOSAL; INVIVO; VALUES AB Both insulin and glucose contribute to the regulation of glucose metabolism in vivo. We directly measured the ability of glucose per se to promote glucose disposal in subjects with insulin-dependent diabetes mellitus (IDDM). We compared our results with predictions of the minimal model of glucose metabolism. To identify minimal model parameters, a frequently sampled intravenous glucose tolerance test (FSIVGTT) was administered to each subject,while they were connected to a Biostator (a device that monitors blood glucose and gives insulin to mimic normal insulin secretion). Data from this test reflected normal glucose tolerance and were in excellent agreement with minimal model predictions. The FSIVGTT was then repeated without the Biostator in the same diabetic subjects in order to directly measure the effect of glucose per se to promote glucose disposal in the absence of an incremental insulin effect (a basal insulin drip was maintained). To compare these results with minimal model predictions, the equations describing glucose disappearance in the absence of an incremental insulin effect were solved using parameters identified hom the Biostator experiment. The glucose disappearance measured in the absence of an incremental insulin response was much slower than the minimal model predictions. Thus, the minimal model appears to overestimate the effect of glucose per se on glucose uptake and underestimate the contribution of incremental insulin. RP QUON, MJ (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892, USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 19 TC 74 Z9 75 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1994 VL 43 IS 7 BP 890 EP 896 DI 10.2337/diabetes.43.7.890 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU593 UT WOS:A1994NU59300009 PM 8013753 ER PT J AU OTONKOSKI, T BEATTIE, GM RUBIN, JS LOPEZ, AD BAIRD, A HAYEK, A AF OTONKOSKI, T BEATTIE, GM RUBIN, JS LOPEZ, AD BAIRD, A HAYEK, A TI HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR HAS INSULINOTROPIC ACTIVITY IN HUMAN FETAL PANCREATIC-CELLS SO DIABETES LA English DT Article ID SCATTER FACTOR; MET PROTOONCOGENE; TISSUE-CULTURE; FACTOR-ALPHA; EPITHELIAL-CELLS; TRANSGENIC MICE; GENE-EXPRESSION; FACTOR RECEPTOR; FACTOR-BETA; TGF-ALPHA AB Fetal mesenchyme-derived factors are likely to play an important role in pancreatic islet development and growth. We have used primary cultures of human fetal pancreatic tissue to identify growth factors that have morphogenic, mitogenic, and insulinotropic activity. The formation of islet-like cell clusters (ICCs) during a 6-day culture was stimulated two- to threefold by hepatocyte growth factor/scatter factor (HGF/SF), basic fibroblast growth factor (FGF)-2, and to a lesser extent by keratinocyte growth factor (FGF-7) and insulin-like growth factor-II (IGF-II). In contrast, transforming growth factor-beta (TGF-beta) had a strong inhibitory effect, The ICCs formed during HGF/SF stimulation consisted mainly of epithelial cells, whereas FGF-2-induced ICCs were predominantly nonepithelial. Furthermore, although both FGF-2 and HGF/SF increased the total insulin content of the cultures, only HGF/SF increased the insulin content per DNA. Quantitatively, HGF/SF stimulated a 2.3-fold increase in the proportion of insulin-positive cells and a 3-fold higher number of replicating beta-cells. Blocking of the IGF-I receptor inhibited ICC formation but did not affect their insulin content. Immunoneutralizing TGF-beta resulted in increased cell growth and insulin content, indicating the presence of an endogenous inhibitory TGF-beta activity in the model system. Our results suggest that HGF/SF may be an important component of the fetal mesenchyme-derived factors responsible for pancreatic islet development. HGF/SF also may prove valuable for supporting the in vitro growth of islet cells. C1 WHITTIER INST DIABET & ENDOCRINOL,LUCY THORNE WHITTIER CHILDRENS CTR,LA JOLLA,CA 92037. WHITTIER INST DIABET & ENDOCRINOL,DEPT MOLEC & CELLULAR GROWTH BIOL,LA JOLLA,CA 92037. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Otonkoski, Timo/F-1189-2011 FU NIDDK NIH HHS [R01-DK-39087, DK-18811] NR 55 TC 128 Z9 130 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1994 VL 43 IS 7 BP 947 EP 953 DI 10.2337/diabetes.43.7.947 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU593 UT WOS:A1994NU59300018 PM 8013761 ER PT J AU COWIE, CC PORT, FK RUST, KF HARRIS, MI AF COWIE, CC PORT, FK RUST, KF HARRIS, MI TI DIFFERENCES IN SURVIVAL BETWEEN BLACK-AND-WHITE PATIENTS WITH DIABETIC END-STAGE RENAL-DISEASE SO DIABETES CARE LA English DT Article ID DIALYSIS; TRANSPLANTATION; NEPHROPATHY; AMERICANS; MELLITUS AB OBJECTIVE - To evaluate whether the longer survival of blacks with diabetic end-stage renal disease (ESRD) relative to whites is due to racial differences in type of diabetes, comorbidity at ESRD onset, and ESRD treatment modality and to examine whether survival differences between blacks and whites occur only in certain population subgroups. RESEARCH DESIGN AND METHODS - The Michigan Kidney Registry was used to ascertain all blacks and whites (n = 594) with diabetic ESRD in south-eastern Michigan, with ESRD onset at age < 65 years during 1974-1983. Patients were followed through 1988. Medical records were abstracted for type of diabetes, comorbidity at ESRD onset, and other factors. RESULTS - Median survival among insulin-dependent diabetes mellitus patients was 27 months in blacks and 17 months in whites, and among non-insulin-dependent diabetes mellitus patients was 30 months in blacks and 16 months in whites. After adjustment for confounding factors by Cox proportional hazards analysis, the death rate was 45% lower in blacks than in whites on dialysis (relative death rate [RDR] = 0.55, 95% confidence interval [CI] = 0.44-0.69), but was similar in blacks and whites with a renal transplant (RDR = 0.99, 95% CI = 0.64-1.52). Compared with dialysis, transplantation was associated with lower mortality in both races (whites, RDR = 0.50, 95% CI = 0.36-0.70; blacks, RDR = 0.89, 95% CI = 0.60-1.34), although the effect was not statistically significant in blacks. Racial differences in survival did not vary by type of diabetes or any additional factor. CONCLUSIONS - Survival airer ESRD onset is longer in blacks than in whites treated with dialysis, even after adjusting for comorbidity and other factors that affect survival. Survival does not differ by race among transplant patients. C1 NIDDKD,BETHESDA,MD 20892. UNIV MICHIGAN,MICHIGAN KIDNEY REGISTRY,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. WESTAT CORP,ROCKVILLE,MD. RP COWIE, CC (reprint author), SOCIAL & SCI SYST INC,7101 WISCONSIN AVE,SUITE 1300,BETHESDA,MD 20814, USA. FU NIDDK NIH HHS [T32-DK07445] NR 26 TC 42 Z9 42 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1994 VL 17 IS 7 BP 681 EP 687 DI 10.2337/diacare.17.7.681 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU592 UT WOS:A1994NU59200008 PM 7924777 ER PT J AU HARRIS, MI EASTMAN, RC SIEBERT, C AF HARRIS, MI EASTMAN, RC SIEBERT, C TI THE DCCT AND MEDICAL-CARE FOR DIABETES IN THE US SO DIABETES CARE LA English DT Editorial Material ID UNITED-STATES POPULATION; BLOOD-GLUCOSE; COMPLICATIONS; RETINOPATHY; NEUROPATHY; PHYSICIANS; ADULTS; TRIAL RP HARRIS, MI (reprint author), NIDDKD,WESTWOOD BLDG,ROOM 620,BETHESDA,MD 20892, USA. NR 16 TC 43 Z9 43 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1994 VL 17 IS 7 BP 761 EP 764 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU592 UT WOS:A1994NU59200021 PM 7924790 ER PT J AU COLLEN, MJ JENSEN, RT AF COLLEN, MJ JENSEN, RT TI IDIOPATHIC GASTRIC-ACID HYPERSECRETION - COMPARISON WITH ZOLLINGER-ELLISON SYNDROME SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE IDIOPATHIC GASTRIC ACID HYPERSECRETION; ZOLLINGER-ELLISON SYNDROME ID NONULCER DYSPEPSIA; DUODENAL-ULCER; SECRETION; MANAGEMENT; OUTPUT; PAIN AB Many patients with acid-peptic disease have idiopathic gastric acid hypersecretion defined as a basal acid output >10.0 meq/hr; however, a significant proportion have basal acid outputs >15.0 meq/hr, which is within the range found in Zollinger-Ellison syndrome. Although idiopathic gastric acid hypersecretion is more common than Zollinger-Ellison syndrome, it is important that these two disorders be differentiated because of differences in treatment and natural history. In the present study, we compared 124 patients with idiopathic gastric acid hypersecretion and 137 patients with Zollinger-Ellison syndrome. There were no significant differences with regard to age at diagnosis, history of upper gastrointestinal hemorrhage, nausea, vomiting, and family history of duodenal ulcer and other acid-peptic disease. However,;significant differences were observed between patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome with regard to percentage of males: 77% compared to 64% (P = 0.008), mean serum gastrin: 60 pg/ml compared to 3679 pg/ml (normal <100 pg/ml) (P < 0.001), mean basal acid output: 15.4 meq/hr compared to 47.0 meq/hr (P < 0.001), mean age at onset of symptoms: 33 years compared to 41 years (P < 0.001), mean duration of symptoms before diagnosis: 11 years compared to five years (P < 0.001), percentage with abdominal pain: 67% compared to 82% (P = 0.00004), percentage with diarrhea: 12% compared to 75% (P < 0.000001), percentage with pyrosis: 58% compared to 40% (P = 0.003), percentage with duodenal ulcer: 53% compared to 74% (P < 0.000001), and percentage with esophagitis: 31% compared to 42% (P = 0.0004). The differences in clinical features could be attributed to difference in mean basal acid output, and/or differences in levels of basal acid output used for diagnosis of idiopathic gastric acid hypersecretion (basal acid output >10.0 meq/hr) and Zollinger-Ellison syndrome (basal acid output >15.0 meq/hr). When 45 patients with idiopathic gastric acid hypersecretion and 39 patients with Zollinger-Ellison syndrome with basal acid outputs 15.1-30.0 meq/hr were compared, the main significant differences were with regard to mean serum gastrin: 69 pg/ml compared to 655 pg/ml (P < 0.001), percentage of male gender: 82% compared to 62% (P = 0.03), and percentage with diarrhea: 16% compared to 64% (P = 0.000005). These results indicate that in general patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome often have similar clinical features that can be difficult to distinguish. However, the increased frequency of diarrhea and female gender should lead to a strong suspicion of Zollinger-Ellison syndrome, which can be distinguished in almost every case by measurement of serum gastrin. C1 LOMA LINDA UNIV,MED CTR,DEPT MED,DIV GASTROENTEROL,LOMA LINDA,CA. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 27 TC 12 Z9 13 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 1994 VL 39 IS 7 BP 1434 EP 1440 DI 10.1007/BF02088045 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NW939 UT WOS:A1994NW93900009 PM 8026253 ER PT J AU SUGIYAMA, K NAGATA, K GILLETTE, JR DARBYSHIRE, JF AF SUGIYAMA, K NAGATA, K GILLETTE, JR DARBYSHIRE, JF TI THEORETICAL KINETICS OF SEQUENTIAL METABOLISM IN-VITRO - STUDY OF THE FORMATION OF 16-ALPHA-HYDROXYANDROSTENEDIONE FROM TESTOSTERONE BY PURIFIED RAT P450 2C11 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; IDENTIFICATION; PURIFICATION AB P450 2C11 from rat liver is known to metabolize testosterone to 2 alpha-, 16 alpha-, and 6 beta-hydroxytestosterone, and to androstenedione and 16 alpha-hydroxyandrostenedione. Because Waxman (J. Biol. Chem. 259, 15481-15490) has reported that the enzyme converts androstenedione to 16 alpha-hydroxyandrostenedione, it seemed likely that the metabolite was formed from testosterone by way of androstenedione. Indeed, we have found that P450 2C11 does not convert 16 alpha-hydroxytestosteone to 16 alpha-hydroxyandrostenedione to any significant extent and, therefore, that the metabolite is formed from testosterone almost solely by way of androstenedione. To determine whether some of the 16 alpha-hydroxyandrostenedione might be formed directly from the androstenedione-enzyme complex, we developed an approach by which it is possible to calculate the amount of the androstenedione, released into the medium, relative to the amount of the androstenedione enzyme complex that is converted directly to 16 alpha-hydroxyandrostenedione under initial conditions when the concentration of released androstenedione will be negligible. The approach uses two factors: factor A is the androstenedione/(androstenedione + 16 alpha-hydroxyandrostenedione) present at the end of the incubation, and factor B corrects for the amount of released androstenedione that recombines with the enzyme and is converted to 16 alpha-hydroxyandrostenedione. Although the values of both factors A and B will vary with the concentrations of testosterone and preformed androstenedione present in the incubation mixtures and with the duration of incubation, the value of A*B will be independent of these parameters. Using this approach, we calculated that similar to 85% of the androstenedione-enzyme complex dissociated to androstenedione and that similar to 15% was converted directly to 16 alpha-hydroxyandrostenedione before the complex dissociated to androstenedione. The approach may be used with virtually any enzyme-substrate combination in which product formation is irreversible, and the secondary metabolite is formed solely from a single precursor. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 9 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL-AUG PY 1994 VL 22 IS 4 BP 584 EP 591 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ025 UT WOS:A1994NZ02500013 PM 7956734 ER PT J AU HERSHFIELD, B CHADER, G AQUIRRE, G AF HERSHFIELD, B CHADER, G AQUIRRE, G TI A POLYMERASE CHAIN REACTION-BASED METHOD FOR THE IDENTIFICATION OF DNA SAMPLES FROM COMMON VERTEBRATE SPECIES SO ELECTROPHORESIS LA English DT Article ID ELISA-ABC METHOD; ARBITRARY PRIMERS; BLOODSTAINS; BLOOD; HEMOGLOBIN; SEQUENCES; ANTIBODY; MARKERS; GENOMES AB Polymerase chain reaction (PCR) amplification of vertebrate genomic DNAs using a (CAC)(n) primer was found to generate species-specific patterns which are resolvable by agarose gel electrophoresis. Of the thirteen species tested (trout, frog, chicken, mouse, rat, cow, dog, African green monkey, chimpanzee, orangutan, gorilla, rhesus macaque, and human), all species showed discrete amplification products ranging in size from 1.0 to 3.2 kbp although trout and frogs had only weak (CAC)(n) amplification products. Most species had three to six bands except rodents, who had eight bands, and cows, who had a single band at 2.2 kbp. Importantly, within a single species, different unrelated individuals had highly similar amplification band patterns although the relative intensities of the bands varied. This held true even when different unrelated humans of different racial backgrounds were tested. We conclude that this technique is potentially useful for identifying which vertebrate species contributed DNA to a given biological sample (e.g., bloodstains, semen, hair) and that only a very small amount of sample is necessary for the analysis. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP HERSHFIELD, B (reprint author), CORNELL UNIV,JAMES A BAKER INST ANIM HLTH,CTR CANINE GENET & REPROD,ITHACA,NY 14853, USA. NR 19 TC 3 Z9 3 U1 1 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1994 VL 15 IS 7 BP 880 EP 884 DI 10.1002/elps.11501501125 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PC634 UT WOS:A1994PC63400002 PM 7813391 ER PT J AU WHEELER, DL CHRAMBACH, A AF WHEELER, DL CHRAMBACH, A TI A COMPUTER-SIMULATION ACCOUNTING FOR DISSIMILAR ELECTROPHORETIC BEHAVIOR BETWEEN 2 SIMILARLY CURVED DNA FRAGMENTS DUE TO A DIFFERENCE IN ARC-LENGTH SO ELECTROPHORESIS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; LINEAR DNA AB Arc-shaped bent DNA fragments of the same predicted planar curvature but differing in length by 20% were compared in regard to their mobilities in 3 to 10% polyacrylamide. The longer (155 bp) fragment is retarded far more severely than the shorter (124 bp) fragment. The effect of gel concentration in promoting the retardation is far more pronounced for the 155 bp than for the 124 bp fragment. Moreover, a temperature change from 25 degrees C to 4 degrees C does not substantially affect the gel concentration dependent mobility of the 124 bp fragment while it increases the retardation of the 155 bp fragment greatly. The strong increase in retardation brought about by a mere 20% increase in the length of the are was accounted for by a simple computer simulation of gel electrophoresis which considered the rate of passage of are-shaped objects through a two-dimensional array of disc-shaped obstacles. Since the simulation relies exclusively on geometric factors, its success in predicting the behavior of the 124 and 155 bp DNA fragments suggests that geometric factors are largely responsible for their electrophoretic properties. The simulation can account for the strong temperature effect on the retardation of a model of the 155 bp DNA in polyacrylamide gels by showing that a decreased degree of random motion has a profound effect on the modeled 155 bp particle, but not on the modeled 124 bp DNA. RP WHEELER, DL (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1994 VL 15 IS 7 BP 885 EP 889 DI 10.1002/elps.11501501126 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PC634 UT WOS:A1994PC63400003 PM 7813392 ER PT J AU CSAKO, G NAGY, B COSTELLO, R CASTELLI, JC HRUSZKEWYCZ, AM AF CSAKO, G NAGY, B COSTELLO, R CASTELLI, JC HRUSZKEWYCZ, AM TI POISED-FIELD GEL-ELECTROPHORESIS FOR THE SEPARATION OF LARGE PROTEIN MOLECULES EXEMPLIFIED BY THE ISOFORMS OF APOLIPOPROTEIN (A) SO ELECTROPHORESIS LA English DT Article ID LP(A) GLYCOPROTEIN PHENOTYPES; PLASMA; LIPOPROTEIN(A); INHERITANCE AB The performance of pulsed-field gel electrophoresis (PFGE) was assessed for the separation of protein molecules. The allelic isoforms of apolipoprotein (a) (apo[a]) served as a model for this study because apo(a) is an unusually large protein, consisting of a variable number of repeating units. PFGE and, for comparison, conventional electrophoresis of human sera were carried out under reducing conditions in agarose gel. After blotting proteins onto nitrocellulose membrane, a combination of monospecific rabbit anti-apo(a) antibody and alkaline phosphatase-conjugated protein A detected apo(a) isoforms in all sera tested. The various apo(a) isoforms were effectively resolved within two repeating units (''kringles'') by both PFGE and conventional electrophoresis, but the type of agarose gel used greatly affected the speed of electrophoretic separation. In a series of 89 human sera, 59 double-band and 30 single-band patterns were seen using either electrophoretic system. However, one specimen produced double bands with PFGE, while only a single band could be detected by conventional electrophoresis, and with another specimen the opposite occurred. A total of 22 different apo(a) isoforms were identified among these patterns. It is concluded that the increasingly available PFGE technology is a practical alternative to conventional agarose electrophoresis for the separation of large protein molecules. RP CSAKO, G (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CHEM CLIN,CLIN CHEM SERV,BLDG 10,RM 2C-407,BETHESDA,MD 20892, USA. RI Nagy, Balint/F-6943-2012 NR 14 TC 3 Z9 3 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1994 VL 15 IS 7 BP 926 EP 929 DI 10.1002/elps.11501501134 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PC634 UT WOS:A1994PC63400011 PM 7813396 ER PT J AU LANDAU, D DOMENE, H SHENORR, Z ESHET, R LARON, Z KOCH, Y LEROITH, D ROBERTS, CT AF LANDAU, D DOMENE, H SHENORR, Z ESHET, R LARON, Z KOCH, Y LEROITH, D ROBERTS, CT TI EFFECT OF GH STATUS ON RENAL INSULIN-LIKE GROWTH-FACTOR-I (IGF-I), IGF-I RECEPTOR, IGF-BINDING PROTEIN (IGFBP) AND GH RECEPTOR MESSENGER-RNA LEVELS IN PREPUBERTAL RATS SO ENDOCRINE LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; DIFFERENTIAL REGULATION; UNILATERAL NEPHRECTOMY; HORMONE GH; KIDNEY; CLONING; HYPOPHYSECTOMY; IMMATURE; LIVER AB Both locally produced and circulating growth factors are thought to be important in the growth and development of many tissues. The action of insulin-like growth factors (IGFs) in particular has been implicated in kidney growth. The kidney has been shown to express the genes encoding the IGFs, the IGF-I receptor and several IGF-binding proteins (IGFBPs). This local production may, however, be influenced by circulating agents such as growth hormone (GH), that also regulates the synthesis of IGFs and some IGFBPs. To address this issue, we have determined the effect of hypophysectomy and GH treatment on the expression of the IGF-I, IGF-I receptor, GH receptor and IGFBP-1, 2, 3 and 4 genes in the kidneys of prepubertal rats. Hypophysectomy decreased the kidney to body weight ratio, an effect which was partially reversed by GH treatment. This was correlated with decreases in IGF-I (55.7 +/- 11.1% of control; P < 0.05) and IGFBP-2 (64.7 +/- 14.2% of controls; P < 0.05) gene expression in hypophysectomized animals that were reversed by GH treatment. IGF-I receptor, GH receptor, and IGFBP-3 and -4 mRNA levels did not change, whereas IGFBP-1 mRNA levels were significantly increased (161.5 +/- 20.2% of control; P < 0.05) after hypophysectomy. These findings suggest that in prepubertal animals, as was previously shown in postpubertal animals, GH status may influence kidney growth through changes in both hepatic and renal IGF-I gene expression. Decreased IGFBP-2 gene expression may also contribute to these changes, whereas increased IGFBP-1 gene expression may represent a compensatory mechanism. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT NEPHROL,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. PETACH TIKVA & SACKLER FAC MED,CHILDRENS MED CTR ISRAEL,DEPT PEDIAT ENDOCRINOL & DIABET RES,TEL AVIV,ISRAEL. WEIZMANN INST SCI,DEPT HORMONE RES,IL-76100 REHOVOT,ISRAEL. NR 41 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0969-711X J9 ENDOCRINE JI Endocrine PD JUL PY 1994 VL 2 IS 7 BP 611 EP 616 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QV191 UT WOS:A1994QV19100007 ER PT J AU YANOVSKI, JA CUTLER, GB AF YANOVSKI, JA CUTLER, GB TI PITFALLS IN THE USE OF INFERIOR PETROSAL SINUS SAMPLING FOR THE DIFFERENTIAL-DIAGNOSIS OF ACTH-DEPENDENT CUSHINGS-SYNDROME SO ENDOCRINOLOGIST LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; STIMULATION TEST; DISEASE; ADRENOCORTICOTROPIN; SECRETION; BLOOD; HYPERCORTISOLISM; MICROADENOMAS; CORTISOL AB Inferior petrosal sinus sampling is highly accurate in distinguishing pituitary from ectopic sources of ACTH in Cushing's syndrome. However, this test may give misleading results in several clinical situations. These include patients in whom hypercortisolism is the result of a pseudo-Cushing state, patients who have ACTH-independent Cushing's syndrome, patients with episodic or mild hypercortisolism that is insufficient to suppress ACTH secretion of the normal pituitary corticotrophs, and patients who have disparate results between inferior petrosal sinus sampling and the noninvasive tests used to distinguish Cushing's disease from die ectopic ACTH syndrome. Due to these limitations, petrosal sinus sampling should be reserved for patients with clear clinical and biochemical evidence of ACTH-dependent Cushing's syndrome, and must be interpreted cautiously whenever the results conflict with those of the noninvasive tests of differential diagnosis. RP YANOVSKI, JA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10 ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 40 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JUL PY 1994 VL 4 IS 4 BP 245 EP 251 DI 10.1097/00019616-199407000-00004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NZ313 UT WOS:A1994NZ31300006 ER PT J AU MASTICK, CC KATO, H ROBERTS, CT LEROITH, D SALTIEL, AR AF MASTICK, CC KATO, H ROBERTS, CT LEROITH, D SALTIEL, AR TI INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I RECEPTORS SIMILARLY STIMULATE DEOXYRIBONUCLEIC-ACID SYNTHESIS DESPITE DIFFERENCES IN CELLULAR PROTEIN-TYROSINE PHOSPHORYLATION SO ENDOCRINOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; KINASE-ACTIVITY; AUTOPHOSPHORYLATION; CELLS; PATHWAYS; MUTANT; SPECIFICITY; EXPRESSION; ACTIVATION; MUTATIONS AB Signal transduction pathways stimulated by insulin or insulin-like growth factor-I (IGF-I) were compared in transfected NIH3T3 fibroblast cell lines expressing the human insulin receptor, IGF-I receptor, or a chimeric IGF-I receptor with its carboxy-terminal tail replaced with that of the insulin receptor (-1 X 10(6) receptors/cell). Although receptor autophosphorylation was very similar in the three cell lines overexpressing receptors (EC(50) = 1-3 nM), there were differences detected in the protein tyrosine phosphorylation stimulated by insulin and IGF-I in these cells. Although no substrates specific for the insulin receptor were detected, phosphorylation of a 170-kilodalton (kDa; IRS1) and a 70-kDa protein was 10 times more sensitive to insulin than to IGF-I (EC(50) = 1.5-2.5 us. 14-23 nM). The chimeric receptor stimulated significantly lower levels of phosphorylation of several proteins relative to the wild-type IGF-I receptor. Activation of phosphatidylinositol 3 '-kinase paralleled phosphorylation of the 170- and 70-kDa proteins. Despite these differences in protein tyrosine phosphorylation, stimulation of mitogen-activated protein (MAP) kinase and DNA synthesis were very similar in the three cell lines overexpressing receptors. Little difference was detected in She phosphorylation or MAP kinase activation through the three receptors, although activation of MAP kinase was more efficiently coupled to the platelet-derived growth factor receptor than to any of the overexpressed receptors. All three receptors stimulated DNA synthesis to levels comparable to 10% serum, with similar sensitivities (EC(50) = 1.5-3.5 nM). C1 WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES DIV, ANN ARBOR, MI 48105 USA. NIDDK, DIABET BRANCH, BETHESDA, MD 20892 USA. UNIV MICHIGAN, SCH MED, DEPT PHYSIOL, ANN ARBOR, MI 48109 USA. OI Saltiel, Alan/0000-0002-9726-9828; Roberts, Charles/0000-0003-1756-5772 NR 33 TC 43 Z9 44 U1 0 U2 2 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 JUL PY 1994 VL 135 IS 1 BP 214 EP 222 DI 10.1210/en.135.1.214 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU811 UT WOS:A1994NU81100030 PM 7516864 ER PT J AU CAPSONI, S VISWANATHAN, M DEOLIVEIRA, AM SAAVEDRA, JM AF CAPSONI, S VISWANATHAN, M DEOLIVEIRA, AM SAAVEDRA, JM TI CHARACTERIZATION OF MELATONIN RECEPTORS AND SIGNAL-TRANSDUCTION SYSTEM IN RAT ARTERIES FORMING THE CIRCLE OF WILLIS SO ENDOCRINOLOGY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; OVINE PARS TUBERALIS; ADENYLATE-CYCLASE; GUANINE-NUCLEOTIDES; VASORELAXING ACTION; BINDING-SITES; SMOOTH-MUSCLE; BRAIN; FORSKOLIN; RELAXATION AB The aims of this study were to characterize the melatonin receptors in rat brain arteries forming the circle of Willis. Saturation studies performed using in vitro autoradiography and [I-125]iodomelatonin revealed the presence of two binding sites: one with a K-d of 13 pM, and the second characterized by a K-d of 832 pM. Coincubation with a nonhydrolyzable guanine nucleotide analog [guanosine-5'-O-(3-thiotriphosphate)l inhibited 2-[I-125]iodomelatonin binding in a concentration-dependent manner, whereas adenine nucleotide adenosine-5'-O(3-thiotriphosphate) was ineffective. In saturation studies performed in the presence of guanosine-5'-O-(3-thiotriphosphate), the high affinity site was no longer detectable, and the affinity of the receptor was decreased to the high picomolar range. Melatonin, at nanomolar concentrations, was able to inhibit forskolin-stimulated cAMP production in rat circle of Willis arteries. Preincubation with pertussis toxin counteracted the effect of melatonin. Our results demonstrate that melatonin receptors in rat cerebral arteries are linked to their second messenger through a pertussis toxin-sensitive G-protein, similar to what has been described for melatonin receptors in different areas of vertebrate brain. C1 NIMH, CLIN SCI LAB, PHARMACOL SECT, BETHESDA, MD 20892 USA. OI Capsoni, Simona/0000-0003-2670-8237 NR 40 TC 70 Z9 70 U1 0 U2 0 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 JUL PY 1994 VL 135 IS 1 BP 373 EP 378 DI 10.1210/en.135.1.373 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU811 UT WOS:A1994NU81100051 PM 8013371 ER PT J AU DAVIS, VL COUSE, JF GOULDING, EH POWER, SGA EDDY, EM KORACH, KS AF DAVIS, VL COUSE, JF GOULDING, EH POWER, SGA EDDY, EM KORACH, KS TI ABERRANT REPRODUCTIVE PHENOTYPES EVIDENT IN TRANSGENIC MICE EXPRESSING THE WILD-TYPE MOUSE ESTROGEN-RECEPTOR SO ENDOCRINOLOGY LA English DT Article ID NUCLEAR-BINDING; BREAST-CANCER; GAP-JUNCTIONS; GENE; RAT; METALLOTHIONEIN; PARTURITION; PREGNANCY; INTRONS; UTERUS AB The estrogen receptor (ER) acts as a transcription factor to regulate multiple cellular functions involved in normal physiology, differentiation, and reproduction. To date, there is no known animal model for studying aberrant ER expression. Therefore, we created transgenic mice expressing the wild-type mouse ER under the control of the mouse metallothionein-I (MT) promoter to determine whether overexpression of the ER would disrupt normal reproductive processes. Five male and one female founder mice were produced, and all were fertile. The progeny from these mice were screened for MT-mER expression by the ribonuclease protection assay. Mice in all six lines were found to express the transgene in a variety of tissues, although generally at low levels. The highest level of expression was observed in the female reproductive tract of line E. Females in all six lines demonstrated aberrant reproductive phenotypes involving processes at parturition and, with some of the lines, a tendency toward reduced fertility. Gestational length was prolonged up to 4 days beyond the normal gestation of 19 days, providing evidence of delayed parturition. In addition, prolonged labor (up to 3 days in length to deliver all pups) and labors requiring cesarean sections for maternal survival demonstrated the occurrence of dystocia in the MT-mER females. As maternal age increased, the incidence of stillborn litters, delayed parturition, and dystocia approached 100% in the transgenic dams. Difficulties at parturition were not observed in nontransgenic control females. These phenotypes suggest that the mechanisms regulating parturition may be perturbed by improper expression of the ER. The MT-mER transgenic mice may provide a novel approach for studying the estrogen-regulated signals involved in parturition and fertility as well as a unique animal model for the human reproductive phenotypes of delayed parturition and dystocia. C1 NIEHS, REPROD & DEV TOXICOL LAB, RECEPTOR BIOL SECT, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 41 TC 30 Z9 30 U1 0 U2 0 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 JUL PY 1994 VL 135 IS 1 BP 379 EP 386 DI 10.1210/en.135.1.379 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU811 UT WOS:A1994NU81100052 PM 8013372 ER PT J AU CHEGINI, N ZHAO, Y WILLIAMS, RS FLANDERS, KC AF CHEGINI, N ZHAO, Y WILLIAMS, RS FLANDERS, KC TI HUMAN UTERINE TISSUE THROUGHOUT THE MENSTRUAL-CYCLE EXPRESSES TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1), TGF-BETA-2, TGF-BETA-3, AND TGF-BETA TYPE-II RECEPTOR MESSENGER-RIBONUCLEIC-ACID AND PROTEIN AND CONTAINS [I-125] TGF-BETA-1-BINDING SITES SO ENDOCRINOLOGY LA English DT Article ID PERIIMPLANTATION PERIOD; INSITU HYBRIDIZATION; SIGNAL-TRANSDUCTION; MOUSE UTERUS; CELL TYPE; BINDING; LOCALIZATION; ESTROGEN; CLONING; RNA AB The use of isoform-specific transforming growth factor-beta (TGF beta) primers, S-35-labeled 40-mer oligonucleotide probes and polyclonal antibodies, reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemical observations has revealed that human uterine tissue at various reproductive stages expresses TGF beta s and TGF beta type II receptor messenger RNAs (mRNAs) and proteins. The reverse transcription-polymerase chain reaction revealed the predicted 443-, 310-, 524-, and 431-basepair fragments for TGF beta 1, TGF beta 2, TGF beta 3, and TGF beta type II receptor, respectively in both endometrial and myometrial tissues, which were further verified by restriction enzyme analysis. In situ hybridization and immunohistochemical observations indicated that all uterine cell types express TGF beta s mRNAs and proteins. In the functionalis region, endometrial luminal and glandular epithelial cells are the primary cell types expressing TGF beta s mRNAs and proteins, with lesser expression in stromal cells, whereas in the basalis region, they are equally expressed in both cell types. In myometrium, TGF beta mRNA and protein expression in smooth muscle cells occurs at a substantially lower level than in endometrial tissue. In endometrial tissue, the highest level of TGF beta mRNA and protein expression appeared in the late proliferative and early to midsecretory phases of the menstrual cycle, with a considerable reduction during the late secretory and postmenopausal periods. The pattern and cellular distribution of TGF beta type II receptor protein were similar to those seen with TGF beta isoforms in both endometrial and myometrial tissues. Quantitative autoradiography (net grain density per 100 mu m(2)) of specific binding of [I-125]TGF beta 1 for different uterine cell types indicated that the stromal cells contain a higher grain density than other uterine cell types (P < 0.05), without a significantly different density in the proliferative, compared with the secretory, phase of the menstrual cycle. These data suggest that TGF beta s acting through their specific receptors may play an important role in a variety of uterine functions in an autocrine/paracrine manner, and ovarian steroids may also regulate their expression in endometrial tissue. C1 NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP CHEGINI, N (reprint author), UNIV FLORIDA, COLL MED, DEPT OBSTET & GYNECOL, BOX 100294, GAINESVILLE, FL 32610 USA. NR 45 TC 123 Z9 125 U1 0 U2 2 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 JUL PY 1994 VL 135 IS 1 BP 439 EP 449 DI 10.1210/en.135.1.439 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU811 UT WOS:A1994NU81100060 PM 8013382 ER PT J AU WEINBERG, CR AF WEINBERG, CR TI THE INFLUENCE OF OCCUPATIONAL ACTIVITY ON THE MENSTRUAL-CYCLE AND FECUNDABILITY SO EPIDEMIOLOGY LA English DT Letter RP WEINBERG, CR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1994 VL 5 IS 4 BP 476 EP 476 DI 10.1097/00001648-199407000-00019 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NT868 UT WOS:A1994NT86800019 PM 7802800 ER PT J AU CAMERA, L KINUYA, S GARMESTANI, K BRECHBIEL, MW WU, CC PAI, LH MCMURRY, TJ GANSOW, OA PASTAN, I PAIK, CH CARRASQUILLO, JA AF CAMERA, L KINUYA, S GARMESTANI, K BRECHBIEL, MW WU, CC PAI, LH MCMURRY, TJ GANSOW, OA PASTAN, I PAIK, CH CARRASQUILLO, JA TI COMPARATIVE BIODISTRIBUTION OF INDIUM-LABELED AND YTTRIUM-LABELED B3 MONOCLONAL-ANTIBODY CONJUGATED TO EITHER 2-(P-SCN-BZ)-6-METHYL-DTPA (1B4M-DTPA) OR 2-(P-SCN-BZ)-1,4,7,10-TETRAAZACYCLODODECANE TETRAACETIC ACID (2B-DOTA) SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE INDIUM; YTTRIUM; BIODISTRIBUTION; MONOCLONAL ANTIBODIES; LIGANDS ID BIFUNCTIONAL CHELATE TECHNIQUES; CARCINOMA XENOGRAFTS; NUDE-MICE; CANCER-THERAPY; Y-90; RADIOIMMUNOTHERAPY; DTPA; TUMOR; IN-111; AGENT AB The biodistribution of indium-111/yttrium-88-labeled B3 monoclonal antibody, a murine IgG1k, was evaluated in non-tumor-bearing mice. B3 was conjugated ted to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M) or 2-(p-SCN-Bz)-1,4,7,10 tetraazacyclododecane tetra-acetic acid (2B-DOTA) and labeled with In-111 at 1.4-2.4 mCi/mg and Y-88 at 0.1-0.3 mCi/mg. Non-tumor-bearing nude mice were co-injected i.v. with 5-10 mu Ci/4-10 mu g of (111)n/Y-88-labeled B3 conjugates and sacrificed at 6 h and daily up to 168 h post-injection. Mice injected with In-111/Y-88-(1B4M)-B3 showed a similar biodistribution of the two radiolabels in all tissues except the bones, where significantly higher accretion of Y-88 than In-111 was observed, with 2.8% +/- 0.2% vs 1.3% +/- 0.16% ID/g in the femur at 168 h, respectively (P<0.0001). In contrast, mice receiving the In-111/Y-88-(DOTA)-B3 conjugate showed significantly higher accumulation of In-111 than Y-88 in most tissues, including the bones, with 2.0% +/- 0.1% vs 1.2% +/- 0.09% ID/g in the femur at 168 h, respectively (P<0.0001). Whereas the ratios of the areas underneath the curve (%ID x h/g) in the blood, liver, kidney and bone were 0.96, 1.12, 1.13, and 0.74 for In-111/Y-88-(1B4M)-B3 and 0.84, 1.23, 1.56, and 1.31 for In-111/Y-88-(DOTA)-B3, respectively, ratios approximate to 1 were observed between In-111-(1B4M)-B3 and Y-88-(DOTA)-B3. In summary, while neither 1B4M nor DOTA was equally stable for In-111 and Y-88, the fate of Y-88-(DOTA)-B3 could be closely traced by that of In-111-(1B4M)-B3. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. IST NAZL TUMORI G PASCALE,DIV NUCL MED,I-80131 NAPLES,ITALY. NIH,RADIAT ONCOL BRANCH,CHEM SECT,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 42 TC 27 Z9 28 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD JUL PY 1994 VL 21 IS 7 BP 640 EP 646 DI 10.1007/BF00285586 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NW292 UT WOS:A1994NW29200008 PM 7957350 ER PT J AU WASSERMANN, EM PASCUALLEONE, A HALLETT, M AF WASSERMANN, EM PASCUALLEONE, A HALLETT, M TI CORTICAL MOTOR REPRESENTATION OF THE IPSILATERAL HAND AND ARM SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE MOTOR CORTEX; IPSILATERAL; TRANSCRANIAL MAGNETIC STIMULATION; HUMAN ID TRANSCRANIAL MAGNETIC STIMULATION; ELECTRICAL-STIMULATION; CORTICOSPINAL TRACT; MACAQUE MONKEY; CORTEX; REORGANIZATION; RESPONSES; MUSCLES; PATHWAYS; RECOVERY AB We sought to determine whether motor evoked potentials (MEPs) as well as silent periods could be produced in hand and shoulder muscles by transcranial magnetic stimulation (TMS) of the ipsilateral cerebral hemisphere and, if so, whether their cortical representations could be mapped with respect to those of contralateral muscles. In six normal subjects, we delivered ten stimuli each to a grid of sites 1 cm apart on the scalp. The EMG was recorded and averaged from the contralateral first dorsal interosseous (FDI) and risorius (facial) muscles at rest and the ipsilateral FDI muscle, which was voluntarily contracted. In four of these subjects and an additional subject, we used the same mapping technique and recorded from the deltoid muscle on the right and left sides and the contralateral FDI during activation of the ipsilateral deltoid. In all subjects, the cortical representation of the contralateral risorius was anterolateral to that of the FDI. The contralateral deltoid could be activated in only three subjects. In them, its representation was slightly medial to that of the FDI. All subjects had at least one scalp site where TMS produced MEPs in the ipsilateral FDI. Two subjects had rich ipsilateral hand representations with multiple ipsilateral MEP sites. Both had ipsilateral MEP sites near the representation of the contralateral FDI, but the largest ipsilateral MEPs occurred with TMS at more lateral sites, which were near the representation of the contralateral risorius. In these subjects, the ipsilateral deltoid was preferentially activated at sites medial and posterior to those activating the contralateral muscle. Ipsilateral TMS also produced silent periods in the FDI in all subjects. These silent periods were much more frequent than the ipsilateral MEPs and tended to occur with TMS near the representation of the contralateral FDI. The excitatory cortical representation of the ipsilateral arm muscles is accessible to TMS in normal subjects and is different from that of the homologous contralateral muscles. The hand may have two ipsilateral representations, one of which produces silent periods and the other MEPs at the same stimulus intensity. RP WASSERMANN, EM (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892, USA. NR 35 TC 158 Z9 158 U1 1 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1994 VL 100 IS 1 BP 121 EP 132 PG 12 WC Neurosciences SC Neurosciences & Neurology GA PB514 UT WOS:A1994PB51400012 PM 7813640 ER PT J AU COHEN, RM GROSS, M SEMPLE, WE NORDAHL, TE SUNDERLAND, T AF COHEN, RM GROSS, M SEMPLE, WE NORDAHL, TE SUNDERLAND, T TI THE METABOLIC BRAIN PATTERN OF YOUNG SUBJECTS GIVEN SCOPOLAMINE SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; ATTENTION; THALAMUS; BASAL GANGLIA; HUMAN ID POSITRON EMISSION TOMOGRAPHY; VISUAL EVOKED-POTENTIALS; ALZHEIMERS-DISEASE; GLUCOSE-UTILIZATION; CHOLINERGIC SYSTEM; MEMORY; ATTENTION; DEMENTIA; PERFORMANCE; NEURONS AB The effect of an intravenous dose of 0.5 mg of scopolamine on the functional brain activity of normal subjects performing auditory discrimination (CPT) was determined in two independent positron emission tomography studies with [F-18] 2-fluoro-deoxyglucose. In the first preliminary study, the most significant effect found was a reduction in the functional activity of the thalamus. In the second ''hypothesis-testing'' study, an equally prominent effect on thalamic functional activity was seen. Because the second study was performed on a high-resolution scanner with improved methodology, we re-examined scopolamine's effects on those brain regions established as determinants of CPT. Of the regions affected, the reduction in cingulate and the increase in basal ganglia metabolic rates were the most notable. We concluded that scopolamine's effects on the functions of thalamic, cingulate and basal ganglia are the likely causes of scopolamine's well-described attention-altering properties. Alterations in these same brain structures could be responsible for scopolamine's effects on other cognitive functions, e.g., memory. Alternatively, scopolamine's effects on other brain structures such as the hippocampus and frontal cortex could underlie scopolamine's effects on these other cognitive functions. Studies of scopolamine's regional metabolic effects in subjects performing these other cognitive tasks at more than a single dose and at more than one post-drug time are needed to discriminate between these two possibilities. C1 NIMH,LCS,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. RP COHEN, RM (reprint author), NIMH,IRP,LCM,CLIN BRAIN IMAGING SECT,BLDG 10-4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 65 TC 17 Z9 17 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1994 VL 100 IS 1 BP 133 EP 143 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PB514 UT WOS:A1994PB51400013 PM 7813641 ER PT J AU OXFORD, JT DOEGE, KJ HORTON, WE MORRIS, NP AF OXFORD, JT DOEGE, KJ HORTON, WE MORRIS, NP TI CHARACTERIZATION OF TYPE-II AND TYPE-XI COLLAGEN-SYNTHESIS BY AN IMMORTALIZED RAT CHONDROCYTE CELL-LINE (IRC) HAVING A LOW-LEVEL OF TYPE-II COLLAGEN MESSENGER-RNA EXPRESSION SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PRO-ALPHA-1(XI) COLLAGEN; CHAINS; GENE; PROCOLLAGEN; CARTILAGE; CDNA; IDENTIFICATION; REVEALS; PROTEIN; HETEROGENEITY AB The biosynthesis of type XI and type II collagens was examined using a stable rat chondrocyte cell line established by W. E. Horton et al. (1988, Exp. Cell Res. 178, 457-468.). These cells (IRC; immortalized rat chondrocytes) were created by transformation with a murine retrovirus carrying the v-myc and v-raf oncogenes. They grow in suspension culture as multicellular aggregates and synthesize typical cartilage proteins, aggrecan and link protein. Type II collagen is absent or synthesized at severely reduced levels, as shown by Northern analysis of mRNA. Thus, this cell type represents a unique model in which to study cartilage matrix protein interactions in the absence of type II collagen. A more detailed look at the proteins secreted into the medium by metabolically labeled IRC cells revealed the presence of collagenase-sensitive bands when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The bands were identified as the alpha 1, alpha 2, and alpha 3 chains of heterotrimeric type XI collagen by electrophoretic migration after pepsin digestion, by CNBr peptide mapping, and by immunoprecipitation with antibodies to rat alpha 1(XI). mRNA for all three chains was detected by Northern blot analysis. The data indicate that the low level of alpha 1(II) mRNA previously detected in these cells is translated into pro alpha 3(XI) polypeptide chains which are incorporated into molecules of type XI. Under normal culture conditions, homotrimers of type II collagen were not detected. The carboxyl propeptide domain of the fibrillar collagens directs chain selection and molecular assembly of the trimeric molecules. The sequence of the carboxyl propeptide domain from pro alpha 3(XI) of IRC cells was found to be identical to this domain from pro alpha 1(II) of swarm rat chondrosarcoma, supporting previous evidence that pro alpha 3(XI) and pro alpha 1(II) have the same primary structure. When cultured in the presence of 50 mM arginine, IRC cells could be induced to synthesize pro alpha 1(II) chains in excess over pro alpha 1(XI) and pro alpha 2(XI). Only under these conditions were type II collagen molecules detected, suggesting a preferential association of pro alpha 1(II) with the pro alpha 1 and/or pro alpha 2 chains of type XI collagen. (C) 1994 Academic Press, Inc. C1 OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,DEPT BIOCHEM & MOLEC BIOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,DEPT CELL BIOL & ANAT,PORTLAND,OR 97201. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. FU NIGMS NIH HHS [R29 GM38862] NR 36 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL PY 1994 VL 213 IS 1 BP 28 EP 36 DI 10.1006/excr.1994.1169 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA NV448 UT WOS:A1994NV44800004 PM 8020600 ER PT J AU ZHANG, MH THORGEIRSSON, SS AF ZHANG, MH THORGEIRSSON, SS TI MODULATION OF CONNEXINS DURING DIFFERENTIATION OF OVAL CELLS INTO HEPATOCYTES SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID LIVER EPITHELIAL-CELLS; JUNCTIONAL INTERCELLULAR COMMUNICATION; TRANSFORMING GROWTH FACTOR-BETA-1; HEPATIC GAP-JUNCTIONS; RAT-LIVER; ALPHA-FETOPROTEIN; V-RAF; NEOPLASTIC TRANSFORMATION; REGENERATING LIVER; TUMOR PROGRESSION AB The connexins are a family of related gap-junction proteins, implicated in embryonic development, cell growth control, and cellular differentiation. To identify connexins involved in liver cell differentiation, both in vivo and in vitro systems were employed to study expression of connexins 26, 32, and 43. Northern blot analysis and in situ hybridization were used to measure the levels of connexin expression and cellular localization of the transcripts, respectively. Normal liver expressed high connexin 32, low connexin 26, and barely detectable connexin 43. In vivo proliferation and differentiation of oval cells was at first accompanied by increased connexin 43 and decreased connexin 32 expression; later as the oval cells differentiated into hepatocytes, connexin 43 disappeared and connexin 32 increased to control levels. In situ hybridization showed that both oval cells and bile duct epithelial cells, but not hepatocytes, expressed connexin 43. A switch from connexin 43 to connexin 32 expression was observed following in vitro transformation and differentiation of rat liver epithelial cells toward the hepatocytic lineage. These results suggest that early progenitor cells in the liver express connexin 43 and a switch from connexin 43 to connexin 32 may signal commitment to hepatocytic differentiation. (C) 1994 Academic Press, Inc. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 42 TC 66 Z9 66 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL PY 1994 VL 213 IS 1 BP 37 EP 42 DI 10.1006/excr.1994.1170 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA NV448 UT WOS:A1994NV44800005 PM 7517369 ER PT J AU RHODES, N HICKS, R KASENALLY, AB INNES, CL PAULES, RS PROPST, F AF RHODES, N HICKS, R KASENALLY, AB INNES, CL PAULES, RS PROPST, F TI V-MOS-TRANSFORMED CELLS FAIL TO ENTER QUIESCENCE BUT GROWTH ARREST IN G1 FOLLOWING SERUM WITHDRAWAL SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTO-ONCOGENE PRODUCT; MURINE SARCOMA-VIRUS; C-MOS; MEIOTIC MATURATION; OOCYTE MATURATION; XENOPUS-OOCYTES; PROTOONCOGENE PRODUCT; KINASE-ACTIVITY; MEIOSIS-II; MAP KINASE AB The product of the mos protooncogene normally functions in the induction of meiosis and regulation of cell-cycle progression in oocytes. Here we have investigated the cell-cycle progression of NIH3T3 cells transformed by the v-mos gene. Flow cytometric analysis showed that logarithmically growing v-mos-transformed cells do not differ from their nontransformed counterparts in the distribution of cells in the G1, S, and G2/M phases. Likewise, after serum withdrawal for 48 h, both normal and v-mos-transformed NIH3T3 cells have essentially ceased proliferation, as analyzed by flow cytometry, [H-3]thymidine and BrdU incorporation into newly synthesized DNA, and mitotic indexes. However, while the normal NIH3T3 cells are arrested in a quiescent state, the v-mos-transformed cells are arrested in early to mid G1, prior to the point where cells require certain amino acids for proliferation (V point). In agreement with these different arrest points, the v-mos-transformed cells enter 8 phase following serum stimulation within about 8 h, without the additional 4-to 6-h lag period characteristically displayed by the parental NIH3T3 cells. In addition, we show a lack of expression of a growth arrest-specific gene product, gas1, in the serum-arrested v-mos-transformed cells. These data demonstrate that v-mos-transformed cells display growth characteristics that differ fundamentally from those of normal cells or cells transformed by overexpression of nye [1]. Our results suggest that the v-mos oncoprotein transforms cells, at least in part, by preventing exit from the cell cycle into quiescence. (C) 1994 Academic Press, Inc. C1 NIEHS,GROWTH CONTROL & CANC GRP,POB 12233,RES TRIANGLE PK,NC 27709. COUTAULD INST BIOCHEM,IMPERIAL CANC RES FUND,HUMAN TUMOR IMMUNOL GRP,LONDON W1P 8BT,ENGLAND. ST MARYS HOSP,SCH MED,LUDWIG INST CANC RES,LONDON W2 1PG,ENGLAND. NR 42 TC 8 Z9 8 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL PY 1994 VL 213 IS 1 BP 210 EP 217 DI 10.1006/excr.1994.1192 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA NV448 UT WOS:A1994NV44800027 PM 8020593 ER PT J AU CHEPELINSKY, AB SHINOHARA, T TSUI, LC AF CHEPELINSKY, AB SHINOHARA, T TSUI, LC TI BREITMAN,MARTIN,LESLIE (1952-1994) - IN-MEMORIAM SO EXPERIMENTAL EYE RESEARCH LA English DT Item About an Individual C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HOSP SICK CHILDREN,DEPT GENET,TORONTO M5G 1X8,ON,CANADA. RP CHEPELINSKY, AB (reprint author), NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Tsui, Lap-chee/A-1081-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 1994 VL 59 IS 1 BP 1 EP 2 PG 2 WC Ophthalmology SC Ophthalmology GA PB369 UT WOS:A1994PB36900001 ER PT J AU SARKADI, B MULLER, M HOMOLYA, L HOLLO, Z SEPRODI, J GERMANN, UA GOTTESMAN, MM PRICE, EM BOUCHER, RC AF SARKADI, B MULLER, M HOMOLYA, L HOLLO, Z SEPRODI, J GERMANN, UA GOTTESMAN, MM PRICE, EM BOUCHER, RC TI INTERACTION OF BIOACTIVE HYDROPHOBIC PEPTIDES WITH THE HUMAN MULTIDRUG TRANSPORTER SO FASEB JOURNAL LA English DT Article DE MDR1; P-GLYCOPROTEIN; PEPTIDES; MULTIDRUG TRANSPORTER; ATPASE ACTIVITY; FLUORESCENT DYE EXTRUSION ID P-GLYCOPROTEIN; RESISTANCE PUMP; INSECT CELLS; GENE; VINCRISTINE; EXPRESSION; INVITRO AB In this report we demonstrate that various biologically active hydrophobic peptide derivatives, e.g., proteinase inhibitors, chemoattractants, ionophores, enkephalins, and immunosuppressants, stimulate a membrane ATPase activity associated with the human multidrug transporter (MDR1). The stimulation of the MDR1-ATPase by these agents does not correlate with their known biochemical or pharmacological activities but rather with their hydrophobicity. The peptides that show high-affinity interaction with the MDR1-ATPase also interfere strongly with fluorescent dye extrusion catalyzed by the multidrug transporter in intact cells and some have been shown to reverse drug resistance in cultured cells. These data suggest that several hydrophobic peptides behave as substrates of the multidrug transporter and may be used to modulate the chemotherapy resistance of tumor cells. C1 SEMMELWEIS UNIV MED,INST BIOCHEM 1,BUDAPEST,HUNGARY. NCI,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27599. RP SARKADI, B (reprint author), NATL INST HAEMATOL BLOOD TRANSFUS & IMMUNOL,DAROCZI 24,H-1113 BUDAPEST,HUNGARY. RI Sarkadi, Balazs/I-5024-2013; Homolya, Laszlo/N-1154-2016 NR 25 TC 87 Z9 87 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1994 VL 8 IS 10 BP 766 EP 770 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NY350 UT WOS:A1994NY35000015 PM 7914178 ER PT J AU PURCELL, RH AF PURCELL, RH TI HEPATITIS-C VIRUS - HISTORICAL-PERSPECTIVE AND CURRENT CONCEPTS SO FEMS MICROBIOLOGY REVIEWS LA English DT Article; Proceedings Paper CT FEMS Symposium on the Hepatitis C Virus and its Infection CY JUN 29-JUL 01, 1993 CL ISTANBUL, TURKEY SP FEDERAT EUROPEAN MICROBIOL SOC DE HEPATITIS C; FLAVIVIRUS; NON-A NON-B HEPATITIS; TRANSMISSION STUDIES ID NON-B-HEPATITIS; HUMAN NON-A; EXPERIMENTALLY INFECTED CHIMPANZEES; POLYMERASE CHAIN-REACTION; 5' NONCODING REGION; TRANSMITTED NON-A; POSTTRANSFUSION HEPATITIS; VIRAL-HEPATITIS; AUSTRALIA ANTIGEN; SEQUENCE-ANALYSIS AB Over the past 30 years, hepatitis C has emerged from shadowy enigma to important public health problem. The existence of the etiological agent of this disease was first appreciated two decades ago but significant progress in its understanding had to await its molecular characterization within the past 5 years. The virus is a member of the family Flaviviridae and is the cause of approximately 20% of clinical viral hepatitis in the United States, While the control of the transmission of hepatitis C virus in blood and blood products has been nothing less than spectacular, the control of community-acquired hepatitis C will be a major challenge to the scientific and medical communities. RP PURCELL, RH (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 202,BETHESDA,MD 20892, USA. NR 104 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD JUL PY 1994 VL 14 IS 3 BP 181 EP 191 DI 10.1016/0168-6445(94)90031-0 PG 11 WC Microbiology SC Microbiology GA NX639 UT WOS:A1994NX63900002 PM 8086193 ER PT J AU BATISTA, MC CARTLEDGE, TP ZELLMER, AW NIEMAN, LK LORIAUX, DL MERRIAM, GR AF BATISTA, MC CARTLEDGE, TP ZELLMER, AW NIEMAN, LK LORIAUX, DL MERRIAM, GR TI THE ANTIPROGESTIN RU486 DELAYS THE MIDCYCLE GONADOTROPIN SURGE AND OVULATION IN GONADOTROPIN-RELEASING HORMONE-INDUCED CYCLES SO FERTILITY AND STERILITY LA English DT Article DE RU486; PROGESTERONE; OVULATION; GONADOTROPIN; GONADOTROPIN-RELEASING HORMONE ID FEMALE RHESUS-MONKEY; FOLLICULAR PHASE; LH-RELEASE; PROGESTERONE; WOMEN; SECRETION; RU-486; ESTRADIOL; PLASMA AB Objective: To investigate whether the antiprogestin RU486 acts primarily on the hypothalamus to delay the midcycle gonadotropin surge and thus gain insight into the site(s) of action of P in the control of ovulation. Design: Prospective, crossover, single-blinded clinical study. Setting: Outpatient clinic in an academic research environment. Patients: Women with hypothalamic amenorrhea. Interventions: RU486 or a placebo was given orally at a low dose of 1 mg/d for 5 days, starting when the dominant follicle reached 14 to 16 mm, to women with hypothalamic amenorrhea undergoing ovulation induction with GnRH pulses of unvarying frequency and dose. Blood samples and ovarian ultrasounds were obtained daily in the late follicular phase and every 3 to 4 days in the remainder of the cycle. C1 NICHHD,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 20 TC 36 Z9 38 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1994 VL 62 IS 1 BP 28 EP 34 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA NT072 UT WOS:A1994NT07200004 PM 8005300 ER PT J AU WAALKES, MP REHM, S AF WAALKES, MP REHM, S TI CHRONIC TOXIC AND CARCINOGENIC EFFECTS OF CADMIUM CHLORIDE IN MALE DBA/2NCR AND NFS/NCR MICE - STRAIN-DEPENDENT ASSOCIATION WITH TUMORS OF THE HEMATOPOIETIC SYSTEM, INJECTION SITE, LIVER, AND LUNG SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DIETARY ZINC-DEFICIENCY; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; B6C3F1 MOUSE-LIVER; TESTICULAR CADMIUM; BINDING PROTEINS; RENAL TOXICITY; INBRED MICE; METALLOTHIONEIN; RESISTANCE AB Although the acute toxic effects of cadmium in mice vary greatly with strain, relatively little is known about strain differences in cadmium carcinogenesis. Therefore, this work was performed to assess the chronic toxic and carcinogenic effects of cadmium in two strains of mice generally thought to be susceptible to the acute effects of cadmium. Male DBA/2NCr (DBA) and NFS/NCr (NFS) mice were given CdCl2, (40 mu mol/kg, sc) either as a single dose (1 X 40) or as weekly doses for 16 weeks (16 X 40) starting at 8 weeks of age. Controls received saline. The animals were observed for the next 104 weeks and mice at risk were defined as those surviving to the time of appearance of a particular tumor. Cadmium-induced dose-related increases in lymphoma (primarily follicular center cell) incidence (1 X 40, 11 cases/23 mice at risk; 16 x 40, 16/28) over control (7/27) in DBA mice but not in NFS mice. Only NFS mice receiving repeated cadmium injections (16 X 40) showed sarcoma development at the injection site (9/35), as no sarcomas occurred in control NFS mice or any group of DBA mice. On the other hand, cadmium-treated (16 X 40) NFS mice, but not DBA mice, had more hepatocellular adenomas and carcinomas (9/27) than control (1/15) but only at the high dose (16 X 40). More cadmium-treated NFS mice had pulmonary tumors than controls, but only at the lower dose (1 x 40). Although testicular tumors were rare, nonneoplastic lesions (fibrosis and mineralization) were induced by cadmium to a similar extent in both strains. Clearly cadmium carcinogenicity varies widely with strain, indicating a genetic basis to susceptibility. The basis of these strain differences deserves further study. (C) 1994 Society of Toxicology. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,MOLEC PATHOL WORKING,FREDERICK,MD 21702. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INORGAN CARCINOGENESIS SECT,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 49 TC 43 Z9 44 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1994 VL 23 IS 1 BP 21 EP 31 DI 10.1006/faat.1994.1074 PG 11 WC Toxicology SC Toxicology GA NY559 UT WOS:A1994NY55900003 PM 7958559 ER PT J AU HASEMAN, JK BOURBINA, J EUSTIS, SL AF HASEMAN, JK BOURBINA, J EUSTIS, SL TI EFFECT OF INDIVIDUAL HOUSING AND OTHER EXPERIMENTAL-DESIGN FACTORS ON TUMOR-INCIDENCE IN B6C3F1 MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DIETARY RESTRICTION; BODY-WEIGHT; F344/N RATS; CALORIE RESTRICTION; CELL-PROLIFERATION; CORN-OIL; CARCINOGENESIS; VARIABILITY; GROWTH; CANCER AB The effects of individual housing and other experimental design factors on body weight, survival, and tumor incidence in 72 control groups of B6C3F1 mice were evaluated. Individually housed males showed a greatly reduced incidence of dermal/subcutaneous tumors and an improved survival relative to group-housed animals. However, there were significant body weight increases in individually housed males and females and an associated marked increase in liver tumor incidence in both sexes and a lesser increase in lung neoplasms in males. Body weights of mice as young as 19 weeks of age were predictive of subsequent liver tumor incidence. There were no major differences in tumor rates among the various types of control groups, and differences in tumor rates among laboratories were not significant for most tumors. Differences among animal suppliers may have contributed to the time-related decreased incidence of malignant lymphoma observed in control mice, particularly in females. Comparisons with earlier control tumor rates suggest that there has been little change in tumor incidence for control groups having approximately equivalent body weights. However, control groups with heavier animals have shown a striking increase in the incidence of liver tumors. The National Toxicology Program recently returned to its earlier practice of group-housing female mice, and this should reduce the incidence of liver tumors in this sex-species group. However, if measures are not taken to reduce body weights, male mice (which continue to be individually housed because of fighting problems among group-housed animals) will likely continue to show a high incidence of liver tumors and possibly also lung neoplasms. (C) 1994 Society of Toxicology. C1 NIEHS,EXPTL TOXICOL PROGRAM,PATHOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CHAPEL HILL,NC 27514. RP HASEMAN, JK (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 70 Z9 71 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1994 VL 23 IS 1 BP 44 EP 52 DI 10.1006/faat.1994.1077 PG 9 WC Toxicology SC Toxicology GA NY559 UT WOS:A1994NY55900006 PM 7958562 ER PT J AU BRIZUELA, BJ ELFRING, L BALLARD, J TAMKUN, JW KENNISON, JA AF BRIZUELA, BJ ELFRING, L BALLARD, J TAMKUN, JW KENNISON, JA TI GENETIC-ANALYSIS OF THE BRAHMA GENE OF DROSOPHILA-MELANOGASTER AND POLYTENE CHROMOSOME SUBDIVISIONS 72AB SO GENETICS LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; DOSAGE-DEPENDENT MODIFIERS; DNA-BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION; HOMEOTIC GENES; GLOBAL ACTIVATOR; SNF6 PROTEINS; MUTATIONS; EXPRESSION; ENCODES AB The brahma gene is required for activation of the homeotic genes of the Antennapedia and bithorax complexes in Drosophila, We have isolated and characterized 21 mutations in brahma. We show that both maternal and zygotic functions of brahma are required during embryogenesis. In addition, the severe abnormalities caused by loss of maternal brahma expression show that the homeotic genes are not the only targets for brahma activation. The complex pattern of interallelic complementation for the 21 brahma alleles suggests that brahma may act as a multimer. In addition to mutations in brahma, we have isolated mutations in four other essential genes within polytene chromosome subdivisions 72AB. Based on a compilation of similar studies that include about 24% of the genome, we estimate that about 3600 genes in Drosophila can mutate to cause recessive lethality, with fewer than 900 additional genes essential only for gametogenesis. We have identified three times more transcripts than lethal complementation groups in 72AB. One transcript in 72AB is the product of the essential arflike gene and encodes a member of the ARF subfamily of small GTP-binding proteins. Two other transcripts are probably the products of a single gene whose protein products are similar to the catalytic subunits of cAMP-dependent protein kinases. C1 GEORGE WASHINGTON UNIV,GENET PROGRAM,WASHINGTON,DC 20052. UNIV CALIF SANTA CRUZ,DEPT BIOL,SANTA CRUZ,CA 95064. RP BRIZUELA, BJ (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 70 TC 96 Z9 96 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 1994 VL 137 IS 3 BP 803 EP 813 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA NU308 UT WOS:A1994NU30800021 PM 7916308 ER PT J AU GUAN, XY MELTZER, PS TRENT, JM AF GUAN, XY MELTZER, PS TRENT, JM TI RAPID GENERATION OF WHOLE CHROMOSOME PAINTING PROBES (WCPS) BY CHROMOSOME MICRODISSECTION SO GENOMICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; SATELLITE DNA; LIBRARIES; TRANSLOCATIONS; INTERPHASE; METAPHASE; PCR; AMPLIFICATION; MELANOMA; LECTURE AB A strategy for rapid construction of whole chromosome painting probes (WCPs) by chromosome microdissection has recently been developed. WCPs were prepared from 20 copies of each target chromosome microdissected from normal human metaphase chromosomes and then directly amplified by PCR using a universal primer. Fifteen WCPs, including chromosomes 1, 3, 6, 7, 9, 12, 13, 14, 15, 17, 19, 20, 21, 22, and X, have been generated using this strategy. The probe complexity and hybridization specificity of these WCPs have been characterized by gel electrophoresis and fluorescence in situ hybridization. Analysis of WCPs constructed by chromosome microdissection indicated that microdissected WCPs invariably provide strong and uniform signal intensity with no cytologically apparent cross-hybridization. To demonstrate the application of WCPs generated from microdissection, we have used these probes to detect complex chromosome rearrangements in a melanoma cell line, UM93-007. Two different translocations involving three chromosomes [t(1;3;13) and t(1;7; 13)] have been identified, both of which were undetectable by conventional banding analysis. Further application of these WCPs (including generation of WCPs from mouse and other species) should greatly facilitate the cytogenetic analysis of complex chromosome rearrangements. (C) 1894 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 35 TC 80 Z9 88 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1994 VL 22 IS 1 BP 101 EP 107 DI 10.1006/geno.1994.1350 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NW898 UT WOS:A1994NW89800013 PM 7959755 ER PT J AU VANAGAITE, L SAVITSKY, K ROTMAN, G ZIV, Y GERKEN, SC WHITE, R WEISSENBACH, J GILLETT, G BENHAM, FJ RICHARD, CW JAMES, MR COLLINS, FS SHILOH, Y AF VANAGAITE, L SAVITSKY, K ROTMAN, G ZIV, Y GERKEN, SC WHITE, R WEISSENBACH, J GILLETT, G BENHAM, FJ RICHARD, CW JAMES, MR COLLINS, FS SHILOH, Y TI PHYSICAL LOCALIZATION OF MICROSATELLITE MARKERS AT THE ATAXIA-TELANGIECTASIA LOCUS AT 11Q22-Q23 SO GENOMICS LA English DT Note ID HUMAN GENOME; LINKAGE MAP; HYBRIDS AB The autosomal recessive disorder ataxia-telangiectasia (A-T) is genetically heterogeneous, with four complementation groups. The genes for the two major groups (ATA and ATC) have been mapped to 11q22-q23. Genetic analysis of the disease has been con ducted to date using biallelic polymorphisms. We have physically mapped to this region eight new microsatellite markers that were generated by three laboratories that construct whole-genome linkage maps. These markers should be valuable for refined localization and positional cloning of the A-T genes and for diagnostic purposes. The results demonstrate the value of integrating genetic and physical maps generated by different laboratories. (C) 1994 Academic Press, Inc. C1 UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112. UNIV LONDON UNIV COLL,DEPT HUMAN GENET,LONDON NW1 2HE,ENGLAND. UNIV LONDON UNIV COLL,MRC,HUMAN BIOCHEM GENET UNIT,GALTON LAB,LONDON NW1 2HE,ENGLAND. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. CTR ETUD POLYMORPHISME HUMAIN,F-75010 PARIS,FRANCE. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP VANAGAITE, L (reprint author), TEL AVIV UNIV,SACKLER FAC MED,DEPT HUMAN GENET,IL-69978 TEL AVIV,ISRAEL. NR 15 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1994 VL 22 IS 1 BP 231 EP 233 DI 10.1006/geno.1994.1370 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NW898 UT WOS:A1994NW89800033 PM 7959777 ER PT J AU LUNDEGARDH, G EKBOM, A MCLAUGHLIN, JK NYREN, O AF LUNDEGARDH, G EKBOM, A MCLAUGHLIN, JK NYREN, O TI GASTRIC-CANCER RISK AFTER VAGOTOMY SO GUT LA English DT Article ID HELICOBACTER-PYLORI INFECTION; PEPTIC-ULCER SURGERY; DUODENAL-ULCER; PARTIAL GASTRECTOMY; STOMACH-CANCER; TIME TRENDS; WISTAR RATS; CIMETIDINE; COHORT; MORTALITY AB The risk of gastric cancer after vagotomy for benign gastric and duodenal disease was examined in a population based cohort of 7198 patients operated on during 1971-79 and followed up until 1988, After exclusion of the first year of follow up there were 34 cases of gastric cancer compared with 25.6 expected (standardised incidence ratio (SIR)=1.33; 95% confidence intervals (CI) 0.92 to 1.86). Separate analyses by duration of follow up, sex, age at operation, underlying diagnosis, and operative procedures did not show any significant increased or decreased risk of gastric cancer in any of the subgroups. In conclusion, decreased gastric acid secretion after vagotomy does not increase the risk of gastric cancer in the first 10 years after operation or in the subgroup followed up for 10-18 years. A longer follow-up is needed before an excess risk can be excluded. C1 UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 53 TC 27 Z9 27 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD JUL PY 1994 VL 35 IS 7 BP 946 EP 949 DI 10.1136/gut.35.7.946 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NV151 UT WOS:A1994NV15100014 PM 8063222 ER PT J AU SELBY, DM STOCKER, JT WACLAWIW, MA HITCHCOCK, CL ISHAK, KG AF SELBY, DM STOCKER, JT WACLAWIW, MA HITCHCOCK, CL ISHAK, KG TI INFANTILE HEMANGIOENDOTHELIOMA OF THE LIVER SO HEPATOLOGY LA English DT Article ID ALPHA-FETOPROTEIN; TUMORS AB Clinical and morphological findings in 91 patients with infantile hemangioendothelioma of the liver are reported. The study comprised 56 girls and 35 boys ranging in age from premature infant to 3 yr; one outlier patient was 18 yr old. Most patients with infantile hemangioendothelioma (87%) were first seen before the age of 6 mo. Congestive heart failure was evident in 15%. Skin hemangiomas were noted in 11%. Anemia, hyperbilirubinemia and increased AST level were present. Solitary lesions were more common than multiple ones (3:2). Immunohistochemical staining of tumor cells for factor VIII was positive in 20 of 21 cases tested; testing for blood group antigen was positive in 8 of 28 cases. Cytokeratin staining verified the presence of bile ducts, some of which appeared to be the result of transformation of injured liver. No pericytes were identified on electron microscopy. The 6-mo survival rate, based on 71 cases, was 70%. Average time of follow-up for the survivors was 7.7 yr. All deaths occurred during the initial presentation/hospitalization of infants, with the exception of two patients who died 3 mo and 7 mo after diagnosis. More recent analytic methods, including immunohistochemical stains and how cytometric studies, do not contribute to the practical assessment of this tumor. Covariates with significant value in predicting death 6 mo after diagnosis included presence of congestive heart failure, jaundice, multiple tumor nodules and absence of cavernous differentiation. C1 ARMED FORCES INST PATHOL,OFF DEPUTY DIRECTOR,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT PEDIAT PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT HEPAT PATHOL,WASHINGTON,DC 20306. NHLBI,BETHESDA,MD 20892. NR 21 TC 62 Z9 68 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 1994 VL 20 IS 1 BP 39 EP 45 DI 10.1002/hep.1840200108 PN 1 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NV026 UT WOS:A1994NV02600007 PM 8020903 ER PT J AU BUKH, J MILLER, RH AF BUKH, J MILLER, RH TI DIAGNOSTIC AND CLINICAL IMPLICATIONS OF THE DIFFERENT GENOTYPES OF HEPATITIS-C VIRUS SO HEPATOLOGY LA English DT Note ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; NON-A; SEQUENCE-ANALYSIS; HCV GENOME; ASSAY; ANTIBODIES; DISTINCT; SUBTYPES; PROTEIN AB Hepatitis C virus (HCV) samples in 155 sera, from patients with chronic non-A, non-B liver disease and blood donors, were grouped into four genotypes (I, II, III, and IV) by amplification of core-gene sequences by polymerase chain reaction with type-specific primers. HCV genotypes were compared wth various HCV-associated antibodies detectable by the first-generation ELISA (ELISA-1) with C100-3 protein and those to its subsequence (5-1-1) were detected in 13 (93%) and 12 (86%), respectively, of 14 sera with genotype I HCV; 56 (79%) and 58 (82%) of 71 sera with genotype II; 13 (34%) and 6 (16%) o 38 sera with genotype III; and 11 (34%) and 4 (13%) of 32 sera with genotype IV. Amino acid sequences of C100-3 of genotype I HCV are conserved by 90% in genotype II, but only by 75% in genotypes III and IV. The sensitivity o ELISA-1, therefore, would be influenced by heterogeneity in C100-3 sequences of different genotypes. RP BUKH, J (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 31 TC 13 Z9 13 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 1994 VL 20 IS 1 BP 256 EP 259 DI 10.1016/0270-9139(94)90163-5 PN 1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NV026 UT WOS:A1994NV02600038 PM 7517384 ER PT J AU TORREY, EF AF TORREY, EF TI VIOLENT BEHAVIOR BY INDIVIDUALS WITH SERIOUS MENTAL-ILLNESS SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article; Proceedings Paper CT 45th Institute on Hospital and Community Psychiatry CY OCT 03-12, 1993 CL BALTIMORE, MD ID COUNTY JAIL; ILL; SCHIZOPHRENIA; DISORDER; CRIME; PERCEPTIONS; MEDICATION; ACCURACY AB Objective: The perceived association between violent behavior and serious mental illness was explored to determine the validity of claims by mental health advocates that individuals with serious mental illness are no more dangerous than members of the general population. Methods: The author reviewed recent studies and media accounts Of violent behavior by individuals with serious mental illness, with emphasis given to the most recent studies. Results and conclusions: Although the vast majority of individuals with serious mental illness are not more dangerous than members of the general population, recent findings suggest the existence of a subgroup that is more dangerous. A history of violent behavior, noncompliance with medications, and substance abuse are important predictors of violent behavior in this subgroup. The findings imply that the criteria for involuntary hospitalization, involuntary medication, outpatient commitment, the monitoring of medication compliance, and other mandated follow-up procedures may need to be revised. The existence of a subgroup of seriously mentally ill patients who exhibit violent behavior undermines efforts by mental health advocates to reduce the stigma of mental illness by denying an association with violence. Until the problem of violence by this subgroup is addressed, it will be difficult to substantially decrease the stigma associated with serious mental illness. RP TORREY, EF (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,2700 MARTIN LUTHER KING AVE SE,WASHINGTON,DC 20032, USA. NR 102 TC 133 Z9 134 U1 1 U2 15 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD JUL PY 1994 VL 45 IS 7 BP 653 EP 662 PG 10 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA NU776 UT WOS:A1994NU77600006 PM 7927289 ER PT J AU KOTIN, RM AF KOTIN, RM TI PROSPECTS FOR THE USE OF ADENOASSOCIATED VIRUS AS A VECTOR FOR HUMAN GENE-THERAPY SO HUMAN GENE THERAPY LA English DT Review ID TRANSMEMBRANE CONDUCTANCE REGULATOR; STRUCTURAL PROTEINS REQUIRES; ADENOASSOCIATED VIRUS; MAMMALIAN-CELLS; DETROIT-6 CELLS; BINDING-PROTEIN; DNA; INTEGRATION; EXPRESSION; SITE C1 GENET THERAPY INC,GAITHERSBURG,MD 20878. RP KOTIN, RM (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,RM 7D18,BETHESDA,MD 20892, USA. RI kotin, robert/B-8954-2008 NR 64 TC 203 Z9 208 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 1994 VL 5 IS 7 BP 793 EP 801 DI 10.1089/hum.1994.5.7-793 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NY715 UT WOS:A1994NY71500002 PM 7981305 ER PT J AU ELKINS, KL ENNIST, DL WINEGAR, RK WEIR, JP AF ELKINS, KL ENNIST, DL WINEGAR, RK WEIR, JP TI IN-VIVO DELIVERY OF INTERLEUKIN-4 BY A RECOMBINANT VACCINIA VIRUS PREVENTS TUMOR-DEVELOPMENT IN MICE SO HUMAN GENE THERAPY LA English DT Article ID STIMULATORY FACTOR-I; IMMUNODEFICIENT MICE; NECROSIS-FACTOR; GAMMA-INTERFERON; GENE-THERAPY; CELL-GROWTH; VECTOR; EXPRESSION; INFECTION; INVIVO AB To study the immunotherapeutic potential of interleukin-4 (IL-4) delivered in vivo via a recombinant vaccinia virus, a thymidine kinase-negative (TK-) vaccinia virus that expressed the murine IL-4 gene (VV1/IL-4) was constructed. When mice were inoculated with 10(7) plaque-forming units (pfu) of VV1/IL-4 subcutaneously (s.c.), 10(5) pfu/cm(2) were found in skin, and smaller numbers in liver and kidney between 1 and 7 days after infection; few viral pfu were found in spleen and lung, or in any organ after intravenous infection. This suggested that recombinant vaccinia viruses might be most efficient at delivery of cytokine genes to the skin. Because IL-4 has recently been found to have potent anti-tumor activity, the effect of recombinant virus infection on the development of s.c. tumors was studied. A single s.c. inoculation with VV1/IL-4 delayed the development of NCTC 2472 tumors, but when VV1/IL-4 was inoculated s.c. weekly for 8 weeks, turner development was completely prevented in 93% of mice. Similarly, the development of M-3 melanoma tumors was also prevented by weekly s.c. inoculations of VV1/IL-4. About 40% of mice treated with control VV2/beta gal by the same regimen also failed to develop tumors. Weekly virus treatment did not prevent NCTC 2472 tumor development in athymic nu/nu mice, suggesting that mature T cells are required for expression of VV1/IL-4 induced antitumor activity. Thus, recombinant vaccinia viruses may be especially well suited for convenient therapeutic delivery of immunomodulator genes to skin-related sites. C1 WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,ROCKVILLE,MD 20852. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. RP ELKINS, KL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,ENTER & SEXUALY TRANSMITTED DIS LAB,BETHESDA,MD 20852, USA. NR 48 TC 28 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 1994 VL 5 IS 7 BP 809 EP 820 DI 10.1089/hum.1994.5.7-809 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NY715 UT WOS:A1994NY71500004 PM 7981307 ER PT J AU BRODY, SL METZGER, M DANEL, C ROSENFELD, MA CRYSTAL, RG AF BRODY, SL METZGER, M DANEL, C ROSENFELD, MA CRYSTAL, RG TI ACUTE RESPONSES OF NONHUMAN-PRIMATES TO AIRWAY DELIVERY OF AN ADENOVIRUS VECTOR CONTAINING THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR CDNA SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; RECOMBINANT ADENOVIRUS; B VACCINE; PATHOGENESIS; TYPE-5; INVIVO; IMMUNOGENICITY; IDENTIFICATION; PNEUMONIA; EXPRESSION AB Recombinant human adenovirus (Ad) vectors are leading candidates for human gene therapy for cystic fibrosis (CF) based on demonstration of efficient transfer of exogenous genes to rodent respiratory epithelium in vivo and human respiratory cells in vitro. The safety of Ad-mediated gene transfer to the respiratory epithelium and acute (up to 21 days) clinical responses to airway delivery of a replication-deficient recombinant, E1(-), E3(-) Ad type 5-based vector containing the human cystic fibrosis transmembrane conductance regulator cDNA (Ad-CFTR) were evaluated in rhesus monkeys. Airway delivery of an Ad vector with the lacZ marker gene demonstrated beta-galactosidase expression in epithelial cells. Animals administered intratracheal AdCFTR demonstrated human CFTR cDNA expression in airway epithelial cells. Animals administered AdCFTR intranasal, and 24 hr later, intrabronchial [2 x 10(7) to 5 x 10(10) plaque-forming units (pfu), n = 12], in a fashion similar to a proposed human protocol, or only intrabronchial (10(11) pfu, n = 3), had no significant changes in clinical parameters compared to vehicle controls (n = 6). Microscopic analysis of the lung by necropsy or bronchoalveolar lavage demonstrated a dose-dependent increase in inflammatory cells, primarily lymphocytes, in the area where AdCFTR was delivered, which persisted for at least 2 months in some animals. Serum anti-Ad type 5 neutralizing antibody titers did not rise and shed Ad was not detected. The presence of AdCFTR DNA, analyzed by the polymerase chain reaction (PCR), was not detected in organs outside the lung. These data demonstrate that AdCFTR is well tolerated in non-human primates, although there is dose-dependent inflammation in the lung not clinically apparent. This suggests that delivery of Ad vectors for human gene therapy may be dose limited. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NR 45 TC 136 Z9 138 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 1994 VL 5 IS 7 BP 821 EP 836 DI 10.1089/hum.1994.5.7-821 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NY715 UT WOS:A1994NY71500005 PM 7526901 ER PT J AU OSHAUGHNESSY, JA COWAN, KH NIENHUIS, AW MCDONAGH, KT SORRENTINO, BP DUNBAR, CE CHIANG, YW WILSON, W GOLDSPIEL, B KOHLER, D COTTLERFOX, M LEITMAN, S GOTTESMAN, M PASTAN, I DENICOFF, A NOONE, M GRESS, R AF OSHAUGHNESSY, JA COWAN, KH NIENHUIS, AW MCDONAGH, KT SORRENTINO, BP DUNBAR, CE CHIANG, YW WILSON, W GOLDSPIEL, B KOHLER, D COTTLERFOX, M LEITMAN, S GOTTESMAN, M PASTAN, I DENICOFF, A NOONE, M GRESS, R TI RETROVIRAL-MEDIATED TRANSFER OF THE HUMAN MULTIDRUG-RESISTANCE GENE (MDR-1) INTO HEMATOPOIETIC STEM-CELLS DURING AUTOLOGOUS TRANSPLANTATION AFTER INTENSIVE CHEMOTHERAPY FOR METASTATIC BREAST-CANCER SO HUMAN GENE THERAPY LA English DT Article ID BONE-MARROW CELLS; PERIPHERAL-BLOOD; TRANSGENIC MICE; DRUG-RESISTANCE; PROTECTION; EXPRESSION AB Patients with metastatic breast cancer will receive 4-5 cycles of induction chemotherapy on one of the ongoing Medicine Branch protocols. Patients achieving at least a partial response, and who do not have evidence of bone marrow involvement and who do not have metastatic bone disease, will undergo PBSC and bane marrow harvest when hematologic recovery has occurred. Patients who have not achieved a PR, but who are responding to therapy, may be treated with additional cycles of therapy in an attempt to achieve a PR. Such patients will be eligible for transplant if a PR is obtained. 70% of the bone marrow and PBSC will be cryopreserved. The CD34(+) subpopulation from the remaining 30% of the bone marrow and PBSC harvest will be obtained using an anti-CD34(+) antibody and immunoabsorption column. The bone marrow and peripheral blood CD34 cells will be transduced with a retroviral vector expressing the human MDR-1 cDNA. Patients with positive bone scans or histologic evidence of bone marrow involvement will be excluded from the gene transfer component of the protocol. The MDR-1 transduced CD34 cells will be reinfused along with the non-transduced bone marrow and PBSC into patients following high dose ICE chemotherapy. Serial peripheral blood and bone marrow samples will be obtained to study hematopoietic reconstitution with MDR-1 transduced cells. Patients with residual or progressive disease after ABMT will be treated with taxol or vinblastine. In these relapsed patients, peripheral blood and bone marrow samples will be obtained to study whether chemotherapy amplifies the proportion of hematopoietic cells containing the MDR-1 provirus. We will monitor the nadir blood counts of each patient receiving salvage chemotherapy for evidence of myeloprotection and correlate this data with changes in the mean proviral copy number. Sites of relapsed tumor will be biopsied to test for the presence of the MDR-1 provirus. C1 UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. GENET THERAPY INC, GAITHERSBURG, MD USA. NHLBI, CHB, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, BETHESDA, MD 20892 USA. NIH, CTR CLIN, BETHESDA, MD 20892 USA. NIH, DEPT TRANSFUS MED, BETHESDA, MD 20892 USA. NCI, DIV CANC BIOL & DIAG, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP OSHAUGHNESSY, JA (reprint author), ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. NR 27 TC 67 Z9 69 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 1994 VL 5 IS 7 BP 891 EP 911 DI 10.1089/hum.1994.5.7-891 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NY715 UT WOS:A1994NY71500010 PM 7526902 ER PT J AU KISHIDA, T YAO, M CHEN, F ORCUTT, ML LERMAN, MI ZBAR, B AF KISHIDA, T YAO, M CHEN, F ORCUTT, ML LERMAN, MI ZBAR, B TI A NOVEL DONOR SPLICE-SITE MUTATION ASSOCIATED WITH 2 MESSENGER-RNAS IN VONHIPPEL-LINDAU-DISEASE SO HUMAN MOLECULAR GENETICS LA English DT Note ID JUNCTIONS; GENE C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV P,FREDERICK,MD 21702. RP KISHIDA, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,IMMUNOBIOL LAB,FREDERICK,MD 21702, USA. NR 4 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1994 VL 3 IS 7 BP 1191 EP 1192 DI 10.1093/hmg/3.7.1191 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NX341 UT WOS:A1994NX34100031 PM 7981696 ER PT J AU SCHAFF, Z HSIA, CC SAROSI, I TABOR, E AF SCHAFF, Z HSIA, CC SAROSI, I TABOR, E TI OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA IN HEPATOCELLULAR-CARCINOMA AND FOCAL NODULAR HYPERPLASIA FROM EUROPEAN PATIENTS SO HUMAN PATHOLOGY LA English DT Article DE TRANSFORMING GROWTH FACTOR-ALPHA; LIVER; HEPATOCELLULAR CARCINOMA; FOCAL NODULAR HYPERPLASIA; HEPATITIS B VIRUS ID MESSENGER-RNA; HUMAN KERATINOCYTES; GASTRIC-CARCINOMA; TRANSGENIC MICE; FACTOR RECEPTOR; MAMMARY-GLAND; TGF-ALPHA; LIVER; EXPRESSION; CELLS C1 NCI,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. SEMMELWEIS UNIV MED,DEPT PATHOL & EXPTL CANC RES 1,H-1085 BUDAPEST,HUNGARY. NR 30 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1994 VL 25 IS 7 BP 644 EP 651 DI 10.1016/0046-8177(94)90296-8 PG 8 WC Pathology SC Pathology GA NX227 UT WOS:A1994NX22700004 PM 8026823 ER PT J AU OEHNINGER, S SUELDO, C LANZENDORF, S MAHONY, M BURKMAN, LJ ALEXANDER, NJ HODGEN, GD AF OEHNINGER, S SUELDO, C LANZENDORF, S MAHONY, M BURKMAN, LJ ALEXANDER, NJ HODGEN, GD TI A SEQUENTIAL-ANALYSIS OF THE EFFECT OF PROGESTERONE ON SPECIFIC SPERM FUNCTIONS CRUCIAL TO FERTILIZATION IN-VITRO IN INFERTILE PATIENTS SO HUMAN REPRODUCTION LA English DT Article DE ASTHENOZOOSPERMIA; FERTILIZATION; PROGESTERONE; TERATOZOOSPERMIA ID HUMAN FOLLICULAR-FLUID; ACROSOME REACTION; HUMAN-SPERMATOZOA; HYPERACTIVATED MOTILITY; HEMIZONA ASSAY; PELLUCIDA; RECEPTOR; SURFACE; CALCIUM; BINDING AB The objective of these studies was to evaluate the modulatory effect(s) of progesterone on sperm functions crucial to fertilization in infertile men with abnormal sperm parameters. A prospective, controlled study applying a sequential diagnostic analysis capable of identifying specific dysfunctions of the male gamete was performed. Patients (n = 14) were allocated to the study group if they had a history of infertility of >1 year duration and after semen evaluation showed teratozoospermia (< 14% normal sperm forms as diagnosed by strict criteria) or terato-asthenozoospermia (<50% progressive motility). After swim-up separation of the motile sperm fraction, the following functions were assessed with and without previous exposure to progesterone (1.0 mu g/ml): acrosome reaction (using Pisum sativum agglutinin), hyperactivated motility (using a computerized semen analyser), sperm-zona pellucida binding (in the hemizona assay), sperm-zona pellucida penetration (in a sperm-zona penetration assay), and sperm-oocyte penetration (using the hamster zona-free oocyte/sperm penetration assay). Progesterone did not affect the percentage of acrosome-reacted spermatozoa after 1 or 3 h of incubation. Hyperactivated motility was significantly enhanced by progesterone after Ih (12 +/- 4 versus 6 +/- 2% in controls; P < 0.02). Although progesterone did not affect sperm-zona binding, it significantly enhanced both sperm-zona pellucida penetration (27 versus 12% in controls; P = 0.03) and sperm-oocyte penetration (15 versus 8% in controls; P < 0.05). Because those sperm functions enhanced by progesterone are crucial to fertilization, the steroid may have value in the treatment of some male-factor patients undergoing assisted reproductive therapy. C1 UNIV CALIF SAN FRANCISCO,DEPT OBSTET & GYNECOL,SAN FRANCISCO,CA 93703. LIFE TECHNOL INC,GIBCO LABS,GRAND ISL,NY 14072. NICHHD,CTR POPULAT RES,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892. RP OEHNINGER, S (reprint author), EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,601 COLLEY AVE,NORFOLK,VA 23507, USA. NR 25 TC 40 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 1994 VL 9 IS 7 BP 1322 EP 1327 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA NY297 UT WOS:A1994NY29700028 PM 7962441 ER PT J AU BAKER, E SAYERS, TJ SUTHERLAND, GR SMYTH, MJ AF BAKER, E SAYERS, TJ SUTHERLAND, GR SMYTH, MJ TI THE GENES ENCODING NK-CELL GRANULE SERINE PROTEASES, HUMAN TRYPTASE-2 (TRYP2) AND HUMAN GRANZYME-A (HFSP), BOTH MAP TO CHROMOSOME-5Q11-Q12 AND DEFINE A NEW LOCUS FOR CYTOTOXIC LYMPHOCYTE GRANULE TRYPTASES SO IMMUNOGENETICS LA English DT Note ID TARGET; LYSIS C1 AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOTOX LAB,HEIDELBERG,VIC 3084,AUSTRALIA. WOMENS & CHILDRENS HOSP,CTR GENET MED,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Sutherland, Grant/D-2606-2012; Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU Wellcome Trust NR 14 TC 31 Z9 31 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUL PY 1994 VL 40 IS 3 BP 235 EP 237 DI 10.1007/BF00167085 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA NX396 UT WOS:A1994NX39600010 PM 8039831 ER PT J AU MACKS, J AF MACKS, J TI SENIOR MEMBER COMMENTS ON 25TH ANNIVERSARY ISSUE SO INDUSTRIAL ENGINEERING LA English DT Letter RP MACKS, J (reprint author), NIH,CTR CLIN,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST INDUSTRIAL ENGINEERS PI NORCROSS PA 25 TECHNOLOGY PARK/ATLANTA, NORCROSS, GA 30092 SN 0019-8234 J9 IND ENG PD JUL PY 1994 VL 26 IS 7 BP 6 EP 6 PG 1 WC Engineering, Industrial SC Engineering GA NW684 UT WOS:A1994NW68400002 ER PT J AU FRACASSO, MP PORGES, SW LAMB, ME ROSENBERG, AA AF FRACASSO, MP PORGES, SW LAMB, ME ROSENBERG, AA TI CARDIAC ACTIVITY IN INFANCY - RELIABILITY AND STABILITY OF INDIVIDUAL-DIFFERENCES SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE VAGAL TONE; HEART PERIOD; INFANT CARDIAC ACTIVITY ID RESPIRATORY SINUS ARRHYTHMIA; SUSTAINED VISUAL-ATTENTION; HEART-RATE-VARIABILITY; VAGAL TONE; LIFE; TEMPERAMENT; REACTIVITY; PATTERNS; NEWBORN; STRESS AB The goals of this study were to examine: (a) normative developmental changes in heart period and cardiac vagal tone; and (b) the reliability and stability over time of individual differences in the two measures. When the 73 infants participating in this short-term longitudinal study were 5, 7, 10, and 13 months old, a 5-min sample of cardiac activity was collected while the infants sat on their mothers' laps in a quiet, attentive state. A second 5-min sample of cardiac activity was also collected at 7, 10, and 13 months following a 20-min long battery of emotion-eliciting stimuli. Significant developmental increases were observed in heart period but not in the measure of cardiac vagal tone. Stress-related decreases in cardiac vagal tone and increases in heart rate were observed after the emotion-eliciting stimuli ended. Individual differences in measures of heart period and cardiac vagal tone were stable over 2- and 3-month periods. C1 UNIV MARYLAND,COLLEGE PK,MD 20742. NATL ACAD SCI,WASHINGTON,DC 20418. RP FRACASSO, MP (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 32 TC 47 Z9 48 U1 0 U2 2 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD JUL-SEP PY 1994 VL 17 IS 3 BP 277 EP 284 DI 10.1016/0163-6383(94)90006-X PG 8 WC Psychology, Developmental SC Psychology GA PN499 UT WOS:A1994PN49900006 ER PT J AU TAMISLEMONDA, CS DAMAST, AM BORNSTEIN, MH AF TAMISLEMONDA, CS DAMAST, AM BORNSTEIN, MH TI WHAT DO MOTHERS KNOW ABOUT THE DEVELOPMENTAL NATURE OF PLAY SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Note DE PLAY; MATERNAL JUDGMENTS; DEVELOPMENTAL SEQUENCES ID CHILDRENS AB Mothers of 21-month-olds were given a list of 24 child play acts and asked to rank order the acts in terms of relative difficulty. Included were exploratory behaviors (e.g., mouthing), nonsymbolic acts (e.g., nesting cups), and symbolic acts (e.g., drinking from an empty cup). In general, mothers' rankings matched scalings of play established in the developmental literature. These findings represent a first step in elucidating mothers' knowledge about development in the domain of child play. C1 NICHHD,BETHESDA,MD 20892. RP TAMISLEMONDA, CS (reprint author), NYU,DEPT APPL PSYCHOL,239 GREEN ST,5TH FLOOR,NEW YORK,NY 10003, USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD JUL-SEP PY 1994 VL 17 IS 3 BP 341 EP 345 DI 10.1016/0163-6383(94)90014-0 PG 5 WC Psychology, Developmental SC Psychology GA PN499 UT WOS:A1994PN49900014 ER PT J AU DILL, JA GREENSPAN, BJ MELLINGER, KH ROYCROFT, JH DUNNICK, J AF DILL, JA GREENSPAN, BJ MELLINGER, KH ROYCROFT, JH DUNNICK, J TI DISPOSITION OF INHALED CADMIUM-OXIDE AEROSOL IN THE RAT SO INHALATION TOXICOLOGY LA English DT Article ID INHALATION; CLEARANCE; EXPOSURE AB Male F344/N rats were exposed to target air concentrations of 0.0, 0.10, 0.25, or 1.0 mg CdO/m(3) for approximately 6 h/day, 5 days/wk, for 13 wk. The lung burdens of Cd, the concentration of Cd in whole blood, and the concentration oi Cd in the kidneys from exposure groups were determined at study days 3, 9, 30, and 93. Accumulated lung burdens were not directly proportional to the exposure concentration, but became progressively less than expected when exposure concentrations were increased. This was attributed to differences in exposure material deposition at different exposure concentrations, although the basis for these differences was not determined. Based on lung burden measurements made during the study, the lung clearance rate of Cd in F344 rats agreed well with values reported in the literature for Long-Evans and Wistar rats. Lung clearance half-lives did not change significantly with exposure concentration. Estimation of the deposition rate and the clearance rate constant allowed calculation of the equilibrium lung burdens expected in each of the exposure groups after long-term exposure. The concentration of Cd in blood was found to be very low in all exposure groups studied. Evidence suggests that the low blood concentration is most likely a result of rapid clearance from the blood to the kidney, and possibly the liver. The amount of Cd observed in the kidneys of exposed animals represented a significant fraction of the accumulated lung burden, and the concentration of Cd in the kidney was linearly proportional to the accumulated lung burden. Based on a linear model, projected accumulation of Cd in the kidneys of rats indicated that kidney Cd concentrations should be well below the toxic threshold when lung burdens reach steady state. However, this extrapolation will most likely underestimate accumulation of Cd in the kidney after steady-state lung burdens are achieved. C1 NATL INST ENVIRONM HLTH SCI, RES TRIANGLE PK, NC USA. RP DILL, JA (reprint author), PACIFIC NW LAB, POB 999, RICHLAND, WA 99352 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD JUL-AUG PY 1994 VL 6 IS 4 BP 379 EP 393 DI 10.3109/08958379409003034 PG 15 WC Toxicology SC Toxicology GA PD617 UT WOS:A1994PD61700005 ER PT J AU NARA, T MATSUMOTO, N JANECHARUT, T MATSUDA, H YAMAMOTO, K IRIMURA, T NAKAMURA, K AIKAWA, M OSWALD, I SHER, A KITA, K KOJIMA, S AF NARA, T MATSUMOTO, N JANECHARUT, T MATSUDA, H YAMAMOTO, K IRIMURA, T NAKAMURA, K AIKAWA, M OSWALD, I SHER, A KITA, K KOJIMA, S TI DEMONSTRATION OF THE TARGET MOLECULE OF A PROTECTIVE IGE ANTIBODY IN SECRETORY GLANDS OF SCHISTOSOMA-JAPONICUM LARVAE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE BACTERIAL EXPRESSION; CDNA CLONING; PARAMYOSIN; SCHISTOSOMIASIS; VACCINE DEVELOPMENT ID MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; PARAMYOSIN; IMMUNITY; MANSONI; VACCINE; MICE; ANTIGEN; INDUCTION; RESISTANCE AB We have demonstrated that a mouse monoclonal IgE antibody, SJ18epsilon.1, recognizes a 97 kDa surface molecule (Sj97) of Schistosoma japonicum larvae and that the antibody induces partial but significant protection against the skin to lung-stage of S. japonicum infection. The antibody stimulates eosinophil- and macrophage-mediated killing of schistosomula in vitro. In the present study, we isolated the putative full-length cDNA of Sj97 by screening a lambdagt11 cDNA library from S. japonicum adult worms with SJ18epsilon.1. The predicted amino acid sequence of the cDNA showed highly significant homology to that of S. mansoni paramyosin, a potential vaccine candidate for schistosomiasis. The deletion mutants of S. japonicum paramyosin were expressed in Escherichia coli and the translation product of 443 amino acid residues of paramyosin was found to be recognized by the antibody. Moreover, we observed by immunoelectron microscopy the presence of paramyosin in the postacetabular gland as well as in the tegument and muscle layers of the larvae. These results suggest that paramyosin is a secretory protein which may be incorporated into the tegument during the development of schistosomula, thus becoming a target for protective immunity during the migratory phase of the parasite. C1 UNIV TOKYO,INST MED SCI,DEPT PARASITOL,TOKYO 108,JAPAN. UNIV TOKYO,FAC PHARMACEUT SCI,DEPT CHEM TOXICOL & IMMUNOCHEM,TOKYO 113,JAPAN. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RI OSWALD, Isabelle/A-8497-2013; OI Kita, Kiyoshi/0000-0002-0426-4308; OSWALD, Isabelle/0000-0001-9918-277X NR 30 TC 54 Z9 55 U1 0 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 1994 VL 6 IS 7 BP 963 EP 971 DI 10.1093/intimm/6.7.963 PG 9 WC Immunology SC Immunology GA NY685 UT WOS:A1994NY68500005 PM 7947464 ER PT J AU ELSON, LH SHAW, S VANLIER, RAW NUTMAN, TB AF ELSON, LH SHAW, S VANLIER, RAW NUTMAN, TB TI T-CELL SUBPOPULATION PHENOTYPES IN FILARIAL INFECTIONS - CD27 NEGATIVITY DEFINES A POPULATION GREATLY ENRICHED FOR T(H)2 CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD27; FILARIASIS; IL-4; IL-5; LYMPHOCYTE MARKERS ID PROTECTIVE IMMUNITY; SOLUBLE FORM; HELMINTH INFECTIONS; ACTIVATION ANTIGEN; INTERFERON-GAMMA; SUBSETS; HELPER; CD4+; INTERLEUKIN-4; INVITRO AB Three-color flow cytometric analysis was used to define surface markers which identify the T(h)2-type CD4+ cells responsible for the eosinophilia and elevated serum IgE typical of tissue invasive helminth infections. A group of six mAbs to well known cell surface markers were screened for differential expression on CD4+ CD45RO+ lymphocytes from normal individuals (NL; n = 6) and filaria-infected patients (PT; n = 10). The majority of markers were expressed equally by both groups, but the CD4+ CD45RO+ cells in the PTs showed significantly higher levels of expression of HLA-DR than those of NLs (P = 0.014). This CD4+ HLA-DR+ subpopulation was then studied further for its expression of an additional 10 activation and adhesion molecules. CD27 showed a trend for lower intensities of expression on PT CD4+ HLA-DR+ cells than on those of NLs. Analysis of the serum from both NLs and PTs revealed that PTs had significantly higher levels of soluble CD27 and CD25 (IL-2R) in the serum than NLs (P < 0.01 and P = 0.022 respectively) indicating a general state of immune activation and differentiation. Functional analysis of the CD4+ HLA-DR+ and the CD4+ CD27- subpopulations revealed that the CD4+ HLA-DR+ cells produced significantly higher levels of IL-5 than the CD4+ HLA-DR- cells (P = 0.04), and the CD4+ CD27- cells produced significantly higher levels of both IL-4 and IL-5 than the CD4+ CD27+ cells (P <0.05 and P < 0.001 respectively). Thus, while the CD4+ CD27- and CD27+ subpopulations contain T(h)1 and T(h)O cells, only the CD4+ CD27- population contains the T(h)2 cells (producing both IL-4 and IL-5). C1 NCI,EXPTL IMMUNOL LAB,BETHESDA,MD 20892. NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,AMSTERDAM,NETHERLANDS. RP ELSON, LH (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. OI van Lier, Rene/0000-0002-3201-7144 NR 32 TC 28 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 1994 VL 6 IS 7 BP 1003 EP 1009 DI 10.1093/intimm/6.7.1003 PG 7 WC Immunology SC Immunology GA NY685 UT WOS:A1994NY68500010 PM 7947453 ER PT J AU TOPALIAN, SL RIVOLTINI, L MANCINI, M NG, J HARTZMAN, RJ ROSENBERG, SA AF TOPALIAN, SL RIVOLTINI, L MANCINI, M NG, J HARTZMAN, RJ ROSENBERG, SA TI MELANOMA-SPECIFIC CD4+ T-LYMPHOCYTES RECOGNIZE HUMAN-MELANOMA ANTIGENS PROCESSED AND PRESENTED BY EPSTEIN-BARR VIRUS-TRANSFORMED B-CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; AUTOLOGOUS TUMOR; CYTOKINE SECRETION; LYMPH-NODES; INVIVO; RESPONSES; RELEASE; ALLELES AB While much emphasis has been placed on the role of MHC class I-restricted CD8(+) T cells in the recognition of tumor-specific antigens (Ag), evidence has accumulated that CD4(+) T cells also play a critical role in the anti-tumor immune response. However, little information exists on the nature of MHC class II-restricted human tumor Ag. In an attempt to develop in vitro systems to characterized such Ag, we examined the ability of Epstein-Barr virus(EBV)-transformed B cells to present melanoma-associated Ag to melanoma-specific CD4(+) cells. CD4(+) T cells cultured from lymphocytes infiltrating a s.c. melanoma metastasis secreted TNF-alpha and GM-CSF specifically in response to autologous cultured melanoma cells expressing MHC class II molecules. These CD4(+) cells also recognized MHC class II-compatible EBV-B cells pulsed with extracts of autologous melanoma cells, but failed to recognize EBV-B cells pulsed with autologous non-transformed cells or a variety of allogeneic tumors normal cells. B cells pre-fixed with paraformaldehyde were incapable of Ag presentation, suggesting that intracellular processing events were occurring. Antibody-blocking studies defined HLA-DR as the dominant if not exclusive restriction locus in this T-B interaction, and HLA-DR genotyping revealed DRBI *0404 to be the probable restriction element. In a second patient, CD4(+) T-cell clone cultured from a melanoma lesion recognized autologous tumor Ag presented by autologous EBV-B; no cross-reactivity was observed with the other tumor system investigated, nor with autologous CD4(+) T cells specific for tetanus toxoid. These findings demonstrate that tumor Ag can be processed and presented by EBV-transformed B cells to MHC class II-restricted tumor-specific CD4(+) T cells. They also provide a model system for direct identification of these tumor-derived antigens. (C) 1994 Wiley-Liss, Inc.* C1 USN,MED RES INST,CW BILL YOUNG MARROW DONOR RECRUITMENT & RES PROG,BETHESDA,MD 20889. RP TOPALIAN, SL (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,ROOM 2B47,BETHESDA,MD 20892, USA. OI Rivoltini, Licia/0000-0002-2409-6225 NR 28 TC 78 Z9 78 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 1994 VL 58 IS 1 BP 69 EP 79 DI 10.1002/ijc.2910580113 PG 11 WC Oncology SC Oncology GA NU741 UT WOS:A1994NU74100012 PM 7516926 ER PT J AU SOLARY, E LING, YH PEREZSOLER, R PRIEBE, W POMMIER, Y AF SOLARY, E LING, YH PEREZSOLER, R PRIEBE, W POMMIER, Y TI HYDROXYRUBICIN, A DEAMINATED DERIVATIVE OF DOXORUBICIN, INHIBITS MAMMALIAN DNA TOPOISOMERASE-II AND PARTIALLY CIRCUMVENTS MULTIDRUG-RESISTANCE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MULTIPLE-DRUG RESISTANCE; CELLS; ADRIAMYCIN; AGENT; CYTOTOXICITY; CARCINOMA; CLEAVAGE; LEUKEMIA; ANALOGS AB In vivo effectiveness of doxorubicin remains restricted due to toxicity and drug resistance. Hydroxyrubicin is a synthetic analog of doxorubicin in which the basic amino group at the C-3' has been replaced by a hydroxyl group in order to overcome recognition by the multidrug resistant (MDR) P-glycoprotein and limit cardiotoxicity. The present study shows that hydroxy-rubicin is a less potent intercalator than doxorubicin. Induction of topoisomerase II-mediated DNA cleavage in the human c-myc origin by the two drugs was similar, reaching a maximum at 0.5 mu M. Results from the NCI Cell Screening program indicate a relatively good correlation between the cytotoxicity of the 2 drugs on 55 cell lines of various origins (r = 0.723). Using a clonogenic assay, we observed that hydroxyrubicin was 20-fold more cytotoxic against the MDR KB-VI cell line than doxorubicin and was slightly more cytotoxic than doxorubicin in the sensitive KB3.1 cell line. Uptake studies showed that doxorubicin was retained up to 1 hr in KB3.1 cells and rapidly eliminated from resistant KB-V1 cells. In contrast, hydroxyrubicin was rapidly eliminated from both sensitive KB3.1 and MDR-positive KB-V1 cells. Both drugs induced protein-linked DNA single-strand breaks (SSBs) in both KB3.1 and KB-V1 cells, which is consistent with topoisomerase inhibition. However, the kinetics of DNA SSBs induced by both drugs was very different. DNA breaks disappeared quickly in both KB3.1 and KB-VI cell lines after hydroxyrubicin removal while DNA breaks induced by doxorubicin disappeared very slowly in KB3.1 cells and rapidly in KB-V1 cells. We conclude that removal of the basic amino group at the C-3' of doxorubicin modifies drug transport and partially circumvents MDR without changing topoisomerase II inhibition when compared with doxorubicin. (C) 1994 Wiley-Liss, Inc. C1 NCI, DIV CANC TREATMENT, MOLEC PHARMACOL LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT THORAC HEAD & NECK MED ONCOL, HOUSTON, TX 77030 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT CLIN INVEST, HOUSTON, TX 77030 USA. FU NCI NIH HHS [CA 55320] NR 23 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 1994 VL 58 IS 1 BP 85 EP 94 DI 10.1002/ijc.2910580115 PG 10 WC Oncology SC Oncology GA NU741 UT WOS:A1994NU74100014 PM 8014019 ER PT J AU REITER, Y KREITMAN, RJ BRINKMANN, U PASTAN, I AF REITER, Y KREITMAN, RJ BRINKMANN, U PASTAN, I TI CYTOTOXIC AND ANTITUMOR-ACTIVITY OF A RECOMBINANT IMMUNOTOXIN COMPOSED OF DISULFIDE-STABILIZED ANTI-TAC FV FRAGMENT AND TRUNCATED PSEUDOMONAS EXOTOXIN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SINGLE-CHAIN FV; ESCHERICHIA-COLI; PROTEIN; DOMAINS; TOXINS; CELLS AB Disulfide-stabilized Fv (dsFv)-immunotoxins are recombinant immunotoxins in which the inherently unstable Fv moiety, composed of the VH-VL heterodimer, is stabilized by a disulfide bond engineered between structurally conserved framework positions of VH and VL. Anti-Tac(dsFv)-PE38KDEL is composed of such a dsFv, directed to the alpha subunit of the IL2 receptor (IL2R), and containing a truncated form of Pseudomonas exotoxin to be indistinguishable in its in vitro activity and specificity from its single-chain immunotoxin counterpart, anti-Tac(Fv)-PE38KDEL. We have now examined the therapeutically relevant factors, including stability, pharmacokinetics, and antitumor activity of this new disulfide-stabilized Fv-immunotoxin. We found that anti-Tac(dsFv)-PE38KDEL was specifically cytotoxic to human activated T-lymphocytes in addition to IL2R bearing cell lines. Anti-Tac(dsFv)-PE38KDEL was considerably more stable at 37 degrees C in human serum and in buffered saline than the single-chain immunotoxin, anti-Tac(Fv)-PE38KDEL. The half-life in blood was similar for both immunotoxins (approx. 20 min). The therapeutic potential of the disulfide-stabilized immunotoxin was evaluated using an animal model of immunodeficient mice bearing subcutaneous tumor xenografts of human IL2R-bearing cells. Anti-Tac(dsFv)-PE38KDEL caused complete regression of tumors with no toxic effects in mice. Because dsFv-immunotoxins are more stable and can be produced with significantly improved yields compared to scFv-immunotoxins, dsFv-immunotoxin may be more useful for therapeutic applications. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 25 TC 47 Z9 48 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 1994 VL 58 IS 1 BP 142 EP 149 DI 10.1002/ijc.2910580123 PG 8 WC Oncology SC Oncology GA NU741 UT WOS:A1994NU74100022 PM 8014011 ER PT J AU REGIER, DA AF REGIER, DA TI ECA CONTRIBUTIONS TO NATIONAL POLICY AND FURTHER RESEARCH SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE MENTAL HEALTH POLICY; MENTAL HEALTH EPIDEMIOLOGY; MENTAL HEALTH SERVICES RESEARCH ID CATCHMENT-AREA-PROGRAM; MENTAL-DISORDERS; UNITED-STATES; ADDICTIVE-DISORDERS; EPIDEMIOLOGY; SERVICES; SYSTEM AB This paper provides a brief review of accomplishments from a research program that has now been in place for about 15 years at the National Institute of Mental Health (NIMH). The program's purpose has been to advance epidemiological and health services research in the field of mental and addictive disorders; its centerpiece has been the Epidemiologic Catchment Area (ECA) study. This paper assesses the achievements of the ECA in terms of its contribution to government health services policy, to the development of psychiatric nosology and to laying the groundwork for future research. These achievements are discussed in the context of the degree to which they have realized, and how they contribute to, some of the classic 'uses of epidemiology' enunciated by Morris (1970): conducting community diagnosis; assessing individual risks; completing the clinical picture; identifying new syndromes; clarifying the working of the health system. RP REGIER, DA (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,10-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 17 TC 4 Z9 4 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1049-8931 J9 INT J METHOD PSYCH JI Int. J. Methods Psychiatr. Res. PD JUL PY 1994 VL 4 IS 2 BP 73 EP 80 PG 8 WC Psychiatry SC Psychiatry GA NX621 UT WOS:A1994NX62100002 ER PT J AU LIANG, BC NEWTON, HB JUNCK, L GREENBERG, HS AF LIANG, BC NEWTON, HB JUNCK, L GREENBERG, HS TI HERPES-ZOSTER AND PROCARBAZINE THERAPY IN PATIENTS WITH MALIGNANT GLIOMA SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE HERPES ZOSTER; PROCARBAZINE; MALIGNANT GLIOMA ID BRAIN-TUMORS; PHASE-II; COMBINATION CHEMOTHERAPY; SYSTEMIC CHEMOTHERAPY; VINCRISTINE PCV; SIMPLEX VIRUSES; CCNU; RADIOTHERAPY; BCNU; ASTROCYTOMAS AB Procarbazine is effective in the treatment of malignant gliomas. We retrospectively reviewed all glioma patients treated with procarbazine at a dose of 150 mg/m2 daily for 28 days, every eight weeks, to determine incidence and prognostic factors associated with the development of Herpes Zoster. Ten of sixty-four (16%) patients developed Herpes Zoster infections; this group was found to have received a greater number of courses of procarbazine (5.1+/-1.2 v. 1.6+/-.2, p<.001) and have significantly less neutropenia when compared to the group receiving procarbazine who did not develop the infection. Infection developed at a median of 4.1+/-1.1 courses. Herpes Zoster infection is common in brain tumor patients taking procarbazine, and is associated with multiple drug courses and a normal WBC count. Immune function studies that could identify patients at high risk for Herpes Zoster might lead to the prophylactic use of acyclovir. C1 UNIV MICHIGAN,MED CTR,DEPT NEUROL,1914 TAUBMAN CTR 0316,1500 E MED CTR DR,ANN ARBOR,MI 48109. NIH,NCHGR,CANC GENET LAB,BETHESDA,MD 20892. OHIO STATE UNIV HOSP,DEPT NEUROL,COLUMBUS,OH 43210. NR 28 TC 0 Z9 0 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 1994 VL 5 IS 1 BP 97 EP 100 PG 4 WC Oncology SC Oncology GA NR643 UT WOS:A1994NR64300013 PM 21559563 ER PT J AU JOHNSTONE, PA WEXLER, LH VENZON, DJ JACOBSON, J YANG, JC HOROWITZ, ME DELANEY, TF AF JOHNSTONE, PA WEXLER, LH VENZON, DJ JACOBSON, J YANG, JC HOROWITZ, ME DELANEY, TF TI SARCOMAS OF THE HAND AND FOOT - ANALYSIS OF LOCAL-CONTROL AND FUNCTIONAL RESULT WITH COMBINED-MODALITY THERAPY IN EXTREMITY PRESERVATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE SARCOMA; HAND; FOOT; RADIATION THERAPY; COMBINED MODALITY THERAPY; LIMB PRESERVATION ID SOFT-TISSUE SARCOMAS; EWINGS-SARCOMA; RADIATION-THERAPY; RHABDOMYOSARCOMA; CHEMOTHERAPY; RADIOTHERAPY; INTERGROUP; MANAGEMENT; SURGERY; WRIST AB Purpose: The records of 28 patients with sarcomas of the hand and foot treated at the National Cancer Institute (NCI) between 1977 and 1992 were reviewed to assess local control and functional results. Methods and Materials: Histologic types included 15 cases of the Ewing's sarcoma family of tumors, 7 cases of alveolar rhabdomyosarcoma, and 6 cases of nonrhabdomyosarcoma soft tissue sarcomas. Median age of all patients was 18 years (range 4-61), with a median potential follow-up of 114 months following diagnosis. Surgery varied from incisional biopsies for Ewing's Sarcoma and rhabdomyosarcoma lesions to complete excision when possible for nonrhabdomyosarcoma soft tissue sarcoma lesions. Amputation was not primarily performed, except in two patients who underwent ray resections of hand lesions (patients 13 and 24). Radiotherapy generally consisted of 50 Gy/25 fractions (fx)/5 weeks for Ewing's Sarcoma, 54 Gy/30 fx/6 weeks for rhabdomyosarcoma, and 63 Gy/35 fx/7 weeks for nonrhabdomyosarcoma soft tissue sarcomas. Chemotherapy was administered on various NCI protocols. Results: Actuarial local control for Ewing's Sarcoma was 84% at 5 and 10 years. All but one survivor are capable of hand/foot function for routine activities without orthotic requirements. Five of six patients (83%) who died of metastatic disease had functional distal extremities. Actuarial local control for rhabdomyosarcomas was 100% at 5 years, with similar function. Three patients (60%) died of distant disease progression with functional distal extremities. Five-year actuarial local control for nonrhabdomyosarcoma soft tissue sarcomas was 100%, with equivalent function. No patient developed a second malignancy in the treatment field. Conclusions: Although equivalent local control may be achieved in these lesions with either amputation or radiotherapy, a prudent management course would be to defer amputation for management of local recurrences. Many patients with these lesions fail in distant sites only and die without local failure. For these patients and for those who remain long-term survivors, we believe a functional hand and foot provides a better quality of life than a prosthesis. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP JOHNSTONE, PA (reprint author), USN,MED CTR,DIV RADIAT ONCOL,SAN DIEGO,CA 92134, USA. RI Venzon, David/B-3078-2008 NR 17 TC 27 Z9 29 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1994 VL 29 IS 4 BP 735 EP 745 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NZ482 UT WOS:A1994NZ48200013 PM 8040019 ER PT J AU SINDELAR, WF TEPPER, JE KINSELLA, TJ BARNES, M DELUCA, AM TERRILL, R MATTHEWS, D ANDERSON, WJ BOLLINGER, BK JOHNSTONE, PAS AF SINDELAR, WF TEPPER, JE KINSELLA, TJ BARNES, M DELUCA, AM TERRILL, R MATTHEWS, D ANDERSON, WJ BOLLINGER, BK JOHNSTONE, PAS TI LATE EFFECTS OF INTRAOPERATIVE RADIATION-THERAPY ON RETROPERITONEAL TISSUES, INTESTINE, AND BILE-DUCT IN A LARGE ANIMAL-MODEL SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE AORTA; BILE DUCT; INTESTINE; INTRAOPERATIVE RADIOTHERAPY; LATE EFFECTS; NORMAL TISSUE EFFECTS; RETROPERITONEUM; URETER; VENA CAVA ID RADIOTHERAPY; TOLERANCE AB Purpose: The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Methods and Materials: Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Results and Conclusion: Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses greater than or equal to 30 Gy. Radiation changes were present in the aorta and vena sava at doses greater than or equal to 40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. C1 NCI, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NCI, OFF LAB ANIM SCI, BETHESDA, MD 20892 USA. NIH, NATL CTR RES RESOURCES, VET RESOURCES PROGRAM, BETHESDA, MD 20892 USA. TERRE HAUTE CTR MED EDUC, DEPT ANAT, TERRE HAUTE, IN 47809 USA. NATL NAVAL MED CTR, DIV SURG PATHOL, BETHESDA, MD 20889 USA. RP NCI, SURG BRANCH, BLDG 10, BETHESDA, MD 20892 USA. NR 7 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1994 VL 29 IS 4 BP 781 EP 788 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NZ482 UT WOS:A1994NZ48200019 PM 8040025 ER PT J AU DAMASSA, AJ TULLY, JG ROSE, DL PITCHER, D LEACH, RH COTTEW, GS AF DAMASSA, AJ TULLY, JG ROSE, DL PITCHER, D LEACH, RH COTTEW, GS TI MYCOPLASMA-AURIS SP-NOV, MYCOPLASMA-COTTEWII SP-NOV, AND MYCOPLASMA-YEATSII SP-NOV, NEW STEROL-REQUIRING MOLLICUTES FROM THE EXTERNAL EAR CANALS OF GOATS SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CLINICALLY NORMAL GOATS AB Three mycoplasma strains, designated GIH(T) (T = type strain), UIA(T), and VIST, were isolated from the external ear canals of goats and were shown to be serologically distinct from each other and from previously described Acholeplasma, Entomoplasma, Mesoplasma, and Mycoplasma species. Using light and transmission electron microscopy, we showed that the cells of these organisms were small, pleomorphic, coccoid, nonmotile, and nonhelical and that each cell was surrounded by a single cytoplasmic membrane. There was no evidence of a cell wall, and the organisms grew freely in media containing penicillin at concentrations of 1,000 U/ml or more and thallous acetate (final concentration, 1:4,000) and produced the ''fried-egg'' morphology typical of most mollicutes. Growth occurred both aerobically and anaerobically (as determined by the GasPak method). The ability to catabolize glucose and mannose and the ability to hydrolyze arginine varied among the three strains. All three strains required sterol for growth, and none of the strains hydrolyzed urea. The guanine-plus-cytosine contents of the DNAs of strains UIA(T), VIST, and GIH(T) were determined to be 26.9, 27.0, and 26.6 mol%, respectively. Our data indicate that the three strains represent new Mycoplasma species, for which we propose the names Mycoplasma auris, Mycoplasma cottewii, and Mycoplasma yeatsii. The type strain of M auris is UIA (= ATCC 51348 = NCTC 11731), the type strain of M. cottewii is VIS (= ATCC 51347 = NCTC 11732), and the type strain of M. yeatsii is GIH (= ATCC 51346 = NCTC 11730). C1 NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,FREDERICK,MD 21702. CENT PUBL HLTH LAB,RESP & SYST INFECT LAB,LONDON NW9 5HT,ENGLAND. CENT PUBL HLTH LAB,NATL COLLECT TYPE CULTURES,LONDON NW9 5HT,ENGLAND. CSIRO,DIV ANIM HLTH,ANIM HLTH RES LAB,PARKVILLE,VIC 3052,AUSTRALIA. RP DAMASSA, AJ (reprint author), LAWRENCE LIVERMORE NATL LAB,SCH VET MED,DEPT POPULAT HLTH & REPROD,DAVIS,CA 95616, USA. NR 31 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1994 VL 44 IS 3 BP 479 EP 484 PG 6 WC Microbiology SC Microbiology GA NW043 UT WOS:A1994NW04300014 PM 8068541 ER PT J AU GERY, I CHANAUD, NP ANGLADE, E AF GERY, I CHANAUD, NP ANGLADE, E TI RECOVERIN IS HIGHLY UVEITOGENIC IN LEWIS RATS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Note DE RECOVERIN; CA-BINDING PROTEINS; CANCER-ASSOCIATED RETINOPATHY (CAR); EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU); S-ANTIGEN (ARRESTIN) ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; CANCER-ASSOCIATED RETINOPATHY; RETINOID-BINDING PROTEIN; ANTIGEN; UVEITIS AB Purpose. Recoverin, a calcium-binding protein that selectively localizes to the retina and pineal gland, has been identified as the target for the putative pathogenic autoimmune process of cancer-associated retinopathy (CAR). The present study was aimed at testing the capacity of recoverin to induce experimental autoimmune uveoretinitis and pinealitis in Lewis rats. Methods. Lewis rats were immunized against recombinant myristoylated recoverin by a single footpad injection of the protein, at various doses, emulsified in complete Freund's adjuvant. Development of uveoretinitis was monitored by clinical and histologic examinations, whereas pinealitis was detected by histologic examination. Results. Immunization with recoverin induced severe panuveitic changes that closely resemble those induced by S-antigen (arrestin). The effect was dose-dependent, with 10 mu g/rat the lowest immunopathogenic dose. Rats immunized with recoverin also developed pineal inflammation. Conclusion. Recoverin is highly immunopathogenic in Lewis rats. Although the ocular changes induced in rats differ from those seen in CAR, the data recorded here are in line with the concept that recoverin can initiate pathogenic autoimmune processes in the eye. RP GERY, I (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N208,BETHESDA,MD 20892, USA. NR 11 TC 61 Z9 65 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1994 VL 35 IS 8 BP 3342 EP 3345 PG 4 WC Ophthalmology SC Ophthalmology GA NY460 UT WOS:A1994NY46000028 PM 8045724 ER PT J AU ZINOVIEVA, RD TOMAREV, SI PIATIGORSKY, J AF ZINOVIEVA, RD TOMAREV, SI PIATIGORSKY, J TI CRYSTALLINS OF CEPHALOPODS AND VERTEBRATES ARE EVOLUTIONARY RELATED TO THE HEAT-SHOCK AND STRESS-INDUCED PROTEINS SO IZVESTIYA AKADEMII NAUK SERIYA BIOLOGICHESKAYA LA Russian DT Article ID ALPHA-B-CRYSTALLIN; GLUTATHIONE-S-TRANSFERASE; CUBOMEDUSAN JELLYFISH; LENS CRYSTALLINS; EXPRESSION; SQUID; GENE; RECRUITMENT; TISSUES; DEHYDROGENASE AB The lenses of cephalopods and vertebrates are a classical example of convergent evolution. In the course of evolution vertebrates and cephalopods used the same strategy of recruitment of ancestral proteins (primarily enzymes, whose activity is related with stress and detoxification) for structural functions in the lens. Crystallins are defined as water soluble proteins, that form the lenses of cephalopods and vertebrates. In vertebrates. only the beta/gamma-crystallin genes are lens-specific. The other crystallin classes (alpha-, beta-, etc) are overexpressed in the lens, having the various noticeable expression levels in the other tissues as well. Almost all the crystallins, forming squid lens are referred to a single class, namely S-crystallins. The latters are encoded by a family of genes, consisting of at least 10 members S-crystallins of the squid and the octopus are related, but not identical to glutathione S-transferases. S-crystallins show no enzymatic activity, though they have 42-44% homology with a squid glutathione-S-transferase (GST), which we have structurally characterized. Genes of GST and S-crystallins have similar ''on-intron structures (5-6 exons), whereas their 5' nanking regions are different. Promoters of both of S-crystallin genes and of some vertebrate crystallin genes bear the similar regulatory element (AP1-site), that must take part in regulation of their lens-specific expression. Besides S-crystallins, octopus lens contains a major polypeptide, omega-crystallin, that was characterized in detail. Though omega-crystallin is related to aldehyde dehydrogenase (ALDG), it has no enzymatic activity. Genes coding for omega- and S-crystallins were shown to be expressed only in the lens cells of squid and octopus. In some mammals ALDG is known to serve as a crystallin (eta-crystallin of elephant shrew). Thus, octopus omega-crystallin and eta-crystallin of elephant shrew - are the first example of similarity between vertebrate and cephalopod crystallins. C1 NEI,BETHESDA,MD 20892. RP ZINOVIEVA, RD (reprint author), NK KOLTSOV INST DEV BIOL,MOSCOW,RUSSIA. NR 42 TC 2 Z9 2 U1 0 U2 4 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0002-3329 J9 IZV AKAD NAUK BIOL+ JI Izv. Akad. Nauk Ser. Biol. PD JUL-AUG PY 1994 IS 4 BP 566 EP 576 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA PJ218 UT WOS:A1994PJ21800008 PM 7987197 ER PT J AU BURNS, DN LANDESMAN, S MUENZ, LR NUGENT, RP GOEDERT, JJ MINKOFF, H WALSH, JH MENDEZ, H RUBINSTEIN, A WILLOUGHBY, A AF BURNS, DN LANDESMAN, S MUENZ, LR NUGENT, RP GOEDERT, JJ MINKOFF, H WALSH, JH MENDEZ, H RUBINSTEIN, A WILLOUGHBY, A TI CIGARETTE-SMOKING, PREMATURE RUPTURE OF MEMBRANES, AND VERTICAL TRANSMISSION OF HIV-1 AMONG WOMEN WITH LOW CD4+ LEVELS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV INFECTION; PREMATURE RUPTURE OF FETAL MEMBRANES; SMOKING ID EARLY DIAGNOSIS; CHILDBEARING WOMEN; FETAL MEMBRANES; RISK-FACTORS; INFECTION; VIRUS; ANTIBODIES; PREGNANCY; CELLS; AIDS AB To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4(+) level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4(+) lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4(+) level was <20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004). Among mothers who developed premature rupture of membranes, those with a low CD4(+) level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4(+) level on transmission. Among all mothers without regard to CD4(+) level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03). These findings suggest that it may be possible to decrease the risk of vertical transmission of HIV-1 among women with low CD4(+) levels by discontinuation of smoking during pregnancy and other interventions that reduce the risk of premature rupture of membranes. C1 SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. WESTAT CORP,BRONX,NY. NCI,VIRAL EPIDEMIOL SECT,BRONX,NY. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. RP BURNS, DN (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,6100 EXECUT BLVD,SUITE 4B11,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N0-1-CP-61013]; NICHD NIH HHS [N0-1-HD-82913, R0-1-HD-25714] NR 51 TC 94 Z9 96 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUL PY 1994 VL 7 IS 7 BP 718 EP 726 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NT688 UT WOS:A1994NT68800012 PM 7911527 ER PT J AU HAVERKOS, HW JONES, TS AF HAVERKOS, HW JONES, TS TI HIV, DRUG-USE PARAPHERNALIA, AND BLEACH SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Editorial Material CT NIDA/CSAT/CDC Workshop on the Use of Bleach for the Decontamination of Drug Injection Equipment CY FEB 09-AUG 10, 1994 CL JOHNS HOPKINS SCH HYGIENE & PUBLIC HLTH, BALTIMORE, MD SP NIDA, CTR DIS CONTROL & PREVENT, CTR SUBST ABUSE TREATMENT HO JOHNS HOPKINS SCH HYGIENE & PUBLIC HLTH ID INACTIVATION; DISINFECTION; VIRUS C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. RP HAVERKOS, HW (reprint author), NIDA,ROOM 10A-38,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 9 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUL PY 1994 VL 7 IS 7 BP 741 EP 742 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NT688 UT WOS:A1994NT68800020 PM 8207656 ER PT J AU CASPER, RC KATZ, MM BOWDEN, CL DAVIS, JM KOSLOW, SH HANIN, I AF CASPER, RC KATZ, MM BOWDEN, CL DAVIS, JM KOSLOW, SH HANIN, I TI THE PATTERN OF PHYSICAL SYMPTOM CHANGES IN MAJOR DEPRESSIVE DISORDER FOLLOWING TREATMENT WITH AMITRIPTYLINE OR IMIPRAMINE SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE MAJOR DEPRESSIVE DISORDER; PHYSICAL SYMPTOM; IMIPRAMINE; AMITRIPTYLINE ID BRANCH COLLABORATIVE PROGRAM; BIOLOGICAL COMPONENT; CLINICAL-RESPONSE; PLASMA-LEVELS; PSYCHOBIOLOGY; NORTRIPTYLINE; METHODOLOGY; RATIONALE; DRUGS; SLEEP AB The study describes a sequential analysis of depression-related physical symptoms and their relationship to imipramine and amitriptyline plasma levels over 4 weeks of treatment in 79 unipolar and bipolar patients hospitalized for major depressive disorder. Insomnia diminished in all patients after 2 weeks of drug administration. After 4 weeks, the sleep of patients whose depressive disorder had significantly improved was nearly normal, whereas patients who remained depressed showed continued sleep impairment. Reductions in loss of appetite, weight and sexual interest paralleled mood improvement. Tricyclic plasma levels significantly correlated with improved sleep. The findings suggest a close link between depressed mood and physical symptoms during recovery from major depressive disorder. C1 ALBERT EINSTEIN COLL MED,DEPT PSYCHIAT,NEW YORK,NY. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. ILLINOIS STATE PSYCHIAT INST,CHICAGO,IL 60612. NIMH,ROCKVILLE,MD 20857. LOYOLA UNIV,CHICAGO,IL 60611. RP CASPER, RC (reprint author), STANFORD UNIV,SCH MED,DEPT PSYCHIAT,ROOM 2365,STANFORD,CA 94305, USA. FU NIMH NIH HHS [U01 MH26976, U01 MH26977, U01 MH26979] NR 48 TC 40 Z9 40 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 JUL PY 1994 VL 31 IS 3 BP 151 EP 164 DI 10.1016/0165-0327(94)90024-8 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NX891 UT WOS:A1994NX89100001 PM 7963067 ER PT J AU CORYELL, W WINOKUR, G MASER, JD AKISKAL, HS KELLER, MB ENDICOTT, J AF CORYELL, W WINOKUR, G MASER, JD AKISKAL, HS KELLER, MB ENDICOTT, J TI RECURRENTLY SITUATIONAL (REACTIVE) DEPRESSION - A STUDY OF COURSE, PHENOMENOLOGY AND FAMILIAL PSYCHOPATHOLOGY SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE MAJOR DEPRESSION; SITUATIONAL; FAMILIAL; FOLLOW-UP ID DEXAMETHASONE SUPPRESSION TEST; III AXIS-IV; ENDOGENOUS-DEPRESSION; LIFE EVENTS; VALIDITY; SUBTYPES; VALIDATION; DISORDER AB Probands with non-bipolar major depressive disorder (MDD) were grouped according to the consistency across episodes with which depression appeared to arise from situational factors. Situational depression showed significant diagnostic stability across the second and third recurrences in a 10-year follow-up. The relatives of recurrently situational probands had higher neuroticism scores, higher lifetime rates of MDD and, when depressed, fewer endogenous symptoms than did the relatives of non-situational probands. This study joins two others in finding an association between stress-related depression and high familial loadings for MDD. It also illustrates the value of diagnostic consistency across episodes as a means of refining groups for the study of diagnostic subtypes. C1 NIMH,ROCKVILLE,MD 20857. BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI 02912. COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,NEW YORK,NY 10032. RP CORYELL, W (reprint author), UNIV IOWA,COLL MED,PSYCHIATRY ADM,200 HAWKINS DR 2887 JPP,IOWA CITY,IA, USA. FU NIMH NIH HHS [R01 MH025478] NR 30 TC 16 Z9 16 U1 1 U2 2 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 JUL PY 1994 VL 31 IS 3 BP 203 EP 210 DI 10.1016/0165-0327(94)90030-2 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NX891 UT WOS:A1994NX89100007 PM 7963073 ER PT J AU WUNDER, DE AARONSON, W HAYES, SF BLISS, JM SILVER, RP AF WUNDER, DE AARONSON, W HAYES, SF BLISS, JM SILVER, RP TI NUCLEOTIDE-SEQUENCE AND MUTATIONAL ANALYSIS OF THE GENE ENCODING KPSD, A PERIPLASMIC PROTEIN INVOLVED IN TRANSPORT OF POLYSIALIC ACID IN ESCHERICHIA-COLI K1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CAPSULAR POLYSACCHARIDE; MOLECULAR ANALYSIS; MEMBRANE-PROTEINS; SUICIDE VECTOR; RNA-POLYMERASE; GROUP-B; EXPRESSION; CONSTRUCTION; BACTERIA; CLUSTER AB The 17-kb kps gene cluster encodes proteins necessary for the synthesis, assembly, and translocation of the polysialic acid capsule of Escherichia coli K1. We previously reported that one of these genes, kpsD, encodes a 60-kDa periplasmic protein that is involved in the translocation of the polymer to the cell surface. The nucleotide sequence of the 2.4-kb BamHI-PstI fragment accommodating the kpsD gene was determined. Sequence analysis showed an open reading frame for a 558-amino-acid protein,vith a typical N-terminal prokaryotic signal sequence corresponding to the first 20 amino acids. KpsD was overexpressed, partially purified, and used to prepare polyclonal antiserum. A chromosomal insertion mutation was generated in the kpsD gene and results in loss of surface expression of the polysialic acid capsule. Immunodiffusion analysis and electron microscopy indicated that polysaccharide accumulates in the periplasmic space of mutant cells. A wild-type copy of kpsD supplied in trans complemented the chromosomal mutation, restoring extracellular expression of the K1 capsule. However, a kpsD deletion derivative (kpsD Delta C11), which results in production of a truncated KpsD protein lacking its 11 C-terminal amino acids, was nonfunctional. Western blot (immunoblot) data from cell fractions expressing KpsD Delta C11 suggest that the truncated protein was inefficiently exported into the periplasm and localized primarily to the cytoplasmic membrane. C1 UNIV ROCHESTER, MED CTR, DEPT MICROBIOL & IMMUNOL, ROCHESTER, NY 14642 USA. CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. NIAID, ROCKY MT LABS, VECTORS & PATHOGENS LAB, HAMILTON, MT 59840 USA. RI Bliss, Joseph/C-7446-2013 FU NIAID NIH HHS [AI26655] NR 60 TC 34 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1994 VL 176 IS 13 BP 4025 EP 4033 PG 9 WC Microbiology SC Microbiology GA NU758 UT WOS:A1994NU75800024 PM 8021185 ER PT J AU RIVEROLEZCANO, OM SAMESHIMA, JH MARCILLA, A ROBBINS, KC AF RIVEROLEZCANO, OM SAMESHIMA, JH MARCILLA, A ROBBINS, KC TI PHYSICAL ASSOCIATION BETWEEN SRC HOMOLOGY-3 ELEMENTS AND THE PROTEIN PRODUCT OF THE C-CBL PROTOONCOGENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID V-CBL; CYTOPLASMIC PROTEIN; TYROSINE KINASES; SH3 DOMAIN; CELLS; BINDING; GROWTH; RAS; NCK; SIMILARITY AB To investigate the nature of proteins recognized by Src homology 3 (SH3) domains, a cDNA expression library was prepared from macrophages and screened with a probe representing the three SH3 domains of p47(nck). Two clones were isolated, and one, designated SAKAP I (for Src A box Nck-associated protein I), contained the carboxyl-terminal half of the cbl proto-oncogene product. Studies in vitro demonstrated reactivity between SAKAP I and SH3 domains derived from a variety of molecules. Wide variations in this assay suggested a high degree of specificity inherent in SAKAP I binding. Moreover, it was possible to demonstrate an in vivo association between p47(nck) and p120(c-cbl) in HL60 cells. These findings suggest that proteins containing SH3 elements regulate Cbl function. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI marcilla, antonio/F-9996-2010; Rivero-Lezcano, Octavio/J-9089-2015 OI marcilla, antonio/0000-0003-0004-0531; Rivero-Lezcano, Octavio/0000-0002-8793-0731 NR 27 TC 163 Z9 163 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 1994 VL 269 IS 26 BP 17363 EP 17366 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU128 UT WOS:A1994NU12800002 PM 7517397 ER PT J AU HOLMAN, GD LEGGIO, LL CUSHMAN, SW AF HOLMAN, GD LEGGIO, LL CUSHMAN, SW TI INSULIN-STIMULATED GLUT4 GLUCOSE-TRANSPORTER RECYCLING - A PROBLEM IN MEMBRANE-PROTEIN SUBCELLULAR TRAFFICKING THROUGH MULTIPLE POOLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT ADIPOSE-CELLS; RECEPTOR-MEDIATED ENDOCYTOSIS; EPIDERMAL GROWTH-FACTOR; 3T3-L1 ADIPOCYTES; TRANSFERRIN RECEPTORS; PLASMA-MEMBRANE; PHORBOL ESTER; SURFACE; TRANSLOCATION; VESICLES AB The subcellular trafficking of GLUT4 in isolated rat adipose cells and 3T3-L1 adipocytes exhibits many of the properties observed in regulated secretory processes and neurosecretion. GLUT4 is sorted and sequestered from endosomes into a specialized secretory compartment in the basal state and the initial stimulation of its exocytosis by insulin is more rapid than its recycling through the endosomes and secretory compartment during the steady-state response to insulin. We present a mathematical analysis which shows that this behavior is inconsistent with a simple 2-pool model with one plasma membrane and one intracellular compartment, but that a 3-pool model, with two intracellular compartments, can simulate these properties. We extend this model to include the presence of occluded pools in the plasma membrane. Our analysis compares the behavior expected when these occluded pools are precursors in stimulation and/or clathrin-associated-like intermediates in endocytosis. The presence of a precursor occluded pool can account for a lag between the appearance of GLUT4 in the membrane and before the full stimulation of glucose transport activity. The analysis also shows that since the pool size of the occluded GLUT4 is relatively small, the formation of endocytic occluded intermediates such as GLUT4 in clathrin-coated pits is likely to be slow compared with the rate of endocytosis of the coated vesicles. C1 UNIV BATH,DEPT BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. NIDDK,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. RI Lo Leggio, Leila/B-4287-2015 OI Lo Leggio, Leila/0000-0002-5135-0882 NR 44 TC 143 Z9 144 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 1994 VL 269 IS 26 BP 17516 EP 17524 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU128 UT WOS:A1994NU12800030 PM 8021259 ER PT J AU DUESCHER, RJ LAWTON, MP PHILPOT, RM ELFARRA, AA AF DUESCHER, RJ LAWTON, MP PHILPOT, RM ELFARRA, AA TI FLAVIN-CONTAINING MONOOXYGENASE (FMO)-DEPENDENT METABOLISM OF METHIONINE AND EVIDENCE FOR FMO3 BEING THE MAJOR FMO INVOLVED IN METHIONINE SULFOXIDATION IN RABBIT LIVER AND KIDNEY MICROSOMES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADULT HUMAN LIVER; MULTIPLE FORMS; RAT-LIVER; COVALENT STRUCTURE; ESCHERICHIA-COLI; S-OXIDASE; PURIFICATION; LUNG; EXPRESSION; PATHWAY AB Methionine was a substrate for cDNA-expressed rabbit flavin containing monooxygenase (FMO) 1, FMO2, and FMO3, while incubations with membrane fractions containing cDNA-expressed FMO5 did not lead to the detection of methionine sulfoxide; K-m values with FMO1, FMO2, and FMO3 were about 48.0, 30.0, and 6.5 mM, respectively. With FMO3 methionine d-sulfoxide was formed in nearly 8-fold higher concentrations than the l-diastereomer, whereas with FMO1 and FMO2, the d:l diastereomeric ratios were approximately 1.5:1 and 0.7:1, respectively. These results provide evidence for methionine being the first identified endogenous compound metabolized to diastereomeric sulfoxides by flavin-containing monooxygenases. The K-m values for methionine sulfoxidation in rabbit liver and kidney microsomes (3.7 and 6.0 man, respectively) were more comparable to the K-m value obtained with FMO3 than with FMO1 or FMO2. This result provides evidence that FMO3 is the major FMO isoform involved in methionine sulfoxidation in rabbit liver and kidney microsomes. Further evidence for this hypothesis is provided by the finding that methionine d-sulfoxide was also the preferred product in rabbit liver and kidney microsomes by nearly 8:1 and 6:1 over the l-diastereomer, respectively. C1 UNIV WISCONSIN,SCH VET SCI,DEPT COMPARAT BIOSCI,MADISON,WI 53706. UNIV WISCONSIN,CTR ENVIRONM TOXICOL,MADISON,WI 53706. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FU NIDDK NIH HHS [DK44295] NR 31 TC 48 Z9 48 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 1994 VL 269 IS 26 BP 17525 EP 17530 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU128 UT WOS:A1994NU12800031 PM 8021260 ER PT J AU OHMORI, Y TEBO, J NEDOSPASOV, S HAMILTON, TA AF OHMORI, Y TEBO, J NEDOSPASOV, S HAMILTON, TA TI KAPPA-B BINDING-ACTIVITY IN A MURINE MACROPHAGE-LIKE CELL-LINE - SEQUENCE-SPECIFIC DIFFERENCES IN KAPPA-B BINDING AND TRANSCRIPTIONAL ACTIVATION FUNCTIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; DNA-BINDING; NUCLEAR FACTOR; C-REL; P65 SUBUNIT; COOPERATIVE INTERACTION; PERITONEAL-MACROPHAGES; SIGNAL TRANSDUCTION; INTERLEUKIN-6 GENE AB The role of two distinct kappa B sequence motifs found in the promoter of the murine IP-10 gene was studied in the transcriptional response of macrophages to lipopolysaccharides (LPS). When the murine macrophage cell line RAW 264.7 was stimulated with LPS, at least three different kappa B sequence specific complex-forming activities were observed in nuclear extracts as assayed by electrophoretic mobility shift assay (EMSA). These three complexes were distinguished from one another in terms of time of appearance following stimulation and selectivity for one of the two different kappa B sequence motifs. The participation of individual members of the Rel homology family of kappa B sequence binding factors was assessed by use of specific antibodies in combination with either EMSA or UV-cross-linking to radiolabeled, BrdUrd-substituted oligonucleotide probes. The C1 complex contained predominantly NF kappa B1 (p50). The C2 complex contained NF kappa B1, RelA (p65), and perhaps other factors. The C3 complex contained predominantly c-Rel. Both kappa B sequences were able to mediate reporter gene transcription in LPS-stimulated macrophages, but the sites behaved differentially in cells co-transfected with expression vectors encoding different members of the Rel homology family. The results indicate that LPS activates several different forms of kappa B binding activity in murine macrophages which are composed of at least three different members of the Rel homology family. These binding activities exhibit differential recognition of and functional activation through the two distinct kappa B sequence motifs. C1 VA ENGELHARDT MOLEC BIOL INST,CYTOKINE MOLEC BIOL UNIT,MOSCOW 117984,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP OHMORI, Y (reprint author), CLEVELAND CLIN FDN,DEPT IMMUNOL,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU NCI NIH HHS [CA 39621, CA 48919]; NHLBI NIH HHS [HL 29582] NR 73 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 1994 VL 269 IS 26 BP 17684 EP 17690 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU128 UT WOS:A1994NU12800054 PM 8021280 ER PT J AU CLEGHON, V MORRISON, DK AF CLEGHON, V MORRISON, DK TI RAF-1 INTERACTS WITH FYN AND SRC IN A NON-PHOSPHOTYROSINE-DEPENDENT MANNER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE-THREONINE KINASE; PROTEIN-TYROSINE KINASES; GROWTH-FACTOR RECEPTORS; SIGNAL TRANSDUCTION; SH2 DOMAINS; PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY DOMAIN; PHOSPHORYLATION; BINDING; ASSOCIATION AB To identify novel proteins capable of associating with the Raf-1 serine/threonine kinase, we investigated whether Raf-1 could interact with the Src homology 2 (SH2) domains of various signal-transducing molecules. In this report, we demonstrate that Raf-1 associated with the SH2 domain of Fyn (a member of the Src tyrosine kinase family) but not with the SH2 domains of phospholipase C-gamma 1, the p85 alpha subunit of phosphatidylinositol 3-kinase, and SH2 containing protein tyrosine phosphatase 2. Unlike most SH2 domain interactions that require tyrosine-phosphorylated residues, the Raf-1/Fyn SH2 domain association was dependent on the serine phosphorylation of Raf-1. Our results also demonstrate that Raf-1 interacted with the SH2 domain of Src and that this interaction was destabilized by mutation of Arg(175) found within the conserved SH2 domain FLVRES sequence. In addition, we show that inclusion of additional Src sequences containing the SH3 domain increased the association of Raf-1 with the Src SH2 domain. Finally, using the baculovirus/Sf9 cell system, we show that coexpression of Raf-1 with full-length Fyn/Src resulted in the coimmunoprecipitation of Raf-1 with Fyn/Src, the tyrosine phosphorylation of Raf-1, and the stimulation of Raf-1 kinase activity. These results suggest that Raf-1 may form a functional complex with Fyn/Src mediated in part by SH2 domains and the serine phosphorylation of Raf-1. RP CLEGHON, V (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC MECHANISMS CAREINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 51 TC 85 Z9 86 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 1994 VL 269 IS 26 BP 17749 EP 17755 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU128 UT WOS:A1994NU12800063 PM 7517401 ER PT J AU DAVIS, VL COUSE, JF GRAY, TK KORACH, KS AF DAVIS, VL COUSE, JF GRAY, TK KORACH, KS TI CORRELATION BETWEEN LOW-LEVELS OF ESTROGEN-RECEPTORS AND ESTROGEN RESPONSIVENESS IN 2 RAT OSTEOBLAST-LIKE CELL-LINES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID OSTEOGENIC-SARCOMA CELLS; PARATHYROID-HORMONE; MOUSE UTERUS; NUCLEAR ESTROGEN; ROS 17/2.8; ESTRADIOL; BINDING; UMR106; BONE; 17-BETA-ESTRADIOL AB With the knowledge that estrogen replacement therapy can circumvent postmenopausal osteoporosis and with the discovery of estrogen receptors (ER) in cultures of normal osteoblast-like cells, extensive investigations have been directed toward understanding the role of the ER in normal bone homeostasis. ROS 17/2.8 and UMR-106-01, two established osteoblast-like cell lines derived from rat osteosarcomas, have been shown to have estrogen-regulated biologic responses. Only the ROS 17/2.8 cell line has been reported to contain ER. In this study, high-affinity, saturable binding sites characteristic of the ER were detected in UMR-106-01 cells by binding assays with the high-affinity ligand, [I-125]17 beta-estradiol, An initial immunoconcentrtion step before western blot analysis also allowed detection of the full-length ER protein. In addition, northern blot analysis indicated that the entire ER transcript was expressed and that the half-life of the ER message was increased following cycloheximide treatment. Message levels were also regulated by removal of serum and treatment with estradiol. An estrogen-regulated reporter vector, ERET81CAT, was transfected into the UMR-106-01 cells to determine whether the detected level of ER was transcriptionally functional. Using this assay, estrogen responsiveness was evident; however, the response was inconsistent. Multiple factors, such as serum, estradiol, and cell density, influence the ER levels in these cells and probably cause fluctuations in the abundance of receptors available to induce the CAT response. When the cells are responsive, the ICI 164,384 antagonist could block the estrogen-induced activation of CAT. The ROS 17/2.8 cells were also analyzed in parallel with the UMR-106-01 cells to allow comparisons between these two osteoblast-like cell lines because they exhibit phenotypes for two unique stages of differentiation. ROS 17/2.8 cells were found to contain more receptor sites/cell by the I-125-E(2) (estradiol) binding assays, as well as higher levels of ER-specific transcripts, than UMR-106-01 cells (two- to threefold). This level of ER was consistently able to modulate estrogen-induced stimulation of the reporter CAT vector. Therefore, functional ER is expressed in both cell types, but the higher level of receptors found in the ROS 17/2.8 cell line improves the estrogen responsiveness of these osteoblast-like cells. These data also indicate that levels of ER that are low or undetectable by conventional methods are able to mediate biologic responses through direct interactions of the ER with the specific DNA response element. C1 NIEHS,RECEPTOR BIOL SECT,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC. NR 40 TC 53 Z9 55 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 1994 VL 9 IS 7 BP 983 EP 991 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NR378 UT WOS:A1994NR37800004 PM 7942167 ER PT J AU KAMEYAMA, S KAWAMATA, H PASTAN, I OYASU, R AF KAMEYAMA, S KAWAMATA, H PASTAN, I OYASU, R TI CYTOTOXIC EFFECT OF A FUSION PROTEIN FROM TRANSFORMING GROWTH-FACTOR-ALPHA AND PSEUDOMONAS EXOTOXIN ON RAT AND HUMAN BLADDER-CARCINOMA CELLS IN-VITRO SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE PSEUDOMONAS EXOTOXIN; TGF-ALPHA; RAT BLADDER CARCINOMA; HUMAN BLADDER CARCINOMA ID URINARY-BLADDER; FACTOR RECEPTOR; CANCER; MODEL; LINE; METASTASIS; EXPRESSION; INVASION AB A protein formed by fusion of transforming growth factor alpha with Pseudomonas exotoxin (TGFalpha-PE40) has been shown to have the ability to kill or inhibit the growth of several carcinoma cell lines. This study was designed to evaluate the in vitro cytotoxic effects of TGFalpha-PE40 on rat and human bladder carcinoma cell lines with different biological potential, and normal rat urothelial cells. The rat cell lines used were D44c, LMC19, and MYU3L, which were established in our laboratory. Human cell lines used were RT4, T24, and 253J. As a normal control, we used the first-passage culture of normal rat bladder urothelium (RU-P1). We examined the number and affinity of epidermal growth factor receptors (EGFR) in these cells, the ability of TGFalpha-PE40 to bind EGFR, and the cytotoxic effect of TGFalpha-PE40 and PE40. Rat cell lines, D44c, LMC19, and MYU3L (EGFR = 4.9 x 10(3)-11.4 x 10(3)/cell) had ED50 values (the concentration of TGFalpha-PE40 needed to reduce the viable cell population by 50%) of 180 pM, 540 pM and 6000 pM respectively; for c(I) (the concentration required to achieve complete inhibition of growth under continuous serum stimulation) TGFalpha-PE40 concentrations of 10(4) pM, 10(4) pM and higher than 10(4) pM respectively were required. Human cell lines, RT4, T24, and 253J (EGFR = 32 x 10(3) 126 x 10(3)/cell) had ED50 values of 20 pM, 66 pM, and 330 pM respectively and T24 showed c(I) values of 10(3) pM. RU-P1 (EGFR = 92.6 x 10(3)/cell) had the highest ED50 value of 8000 pM. These data indicate that the susceptibility to TGFalpha-PE40 does not always depend on the number of EGFR, that cells having a relatively small number of EGFR respond well to TGFalpha-PE40, and that normal urothelial cells are more resistant to TGFalpha-PE40 than are cancer cells. The differential effect of TGFalpha-PE40 on normal and neoplastic cells provides a rational basis for its use in vivo to control tumor growth. C1 NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,303 E CHICAGO AVE,CHICAGO,IL 60611. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA14649] NR 28 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD JUL PY 1994 VL 120 IS 9 BP 507 EP 512 DI 10.1007/BF01221026 PG 6 WC Oncology SC Oncology GA PA307 UT WOS:A1994PA30700001 PM 8045915 ER PT J AU NAGY, P BISGAARD, HC THORGEIRSSON, SS AF NAGY, P BISGAARD, HC THORGEIRSSON, SS TI EXPRESSION OF HEPATIC TRANSCRIPTION FACTORS DURING LIVER DEVELOPMENT AND OVAL CELL-DIFFERENTIATION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NUCLEAR FACTOR-I; DNA-BINDING-DOMAIN; TISSUE-SPECIFIC EXPRESSION; RAT-LIVER; GENE-EXPRESSION; MESSENGER-RNA; ACTIVATOR PROTEIN; ALPHA-FETOPROTEIN; LEUCINE ZIPPER; CHEMICAL HEPATOCARCINOGENESIS AB The oval cells are thought to be the progeny of a liver stem cell compartment and strong evidence now exists indicating that these cells can participate in liver regeneration by differentiating into different hepatic lineages. To better understand the regulation of this process we have studied the expression of liver-enriched transcriptional factors (HNF1 alpha and HNF1 beta, HNF3 alpha, HNF3 beta, and HNF3 gamma, HNF4, C/EBP, C/EBP beta, and DBP) in an experimental model of oval cell proliferation and differentiation and compared the expression of these factors to that observed during late stages of hepatic ontogenesis. The steady-state mRNA levels of four (HNF1 alpha, HNF3 alpha, HNF4, and C/EBP beta) ''liver-enriched'' transcriptional factors gradually decrease during the late period of embryonic liver development while three factors (HNF1 beta, HNF3 beta, and DBP) increase. In the normal adult rat liver the expression of all the transcription factors are restricted to the hepatocytes. However, during early stages of oval cell proliferation both small and large bile ducts start to express HNF1 alpha and HNF1 beta, HNF3 gamma, C/EBP, and DBP but not HNF4. At the later stages all of these factors are also highly expressed in the proliferating oval cells. Expression of HNF4 is first observed when the oval cells differentiate morphologically and functionally into hepatocytes and form basophilic foci. At that time the expression of some of the other factors is also further increased. Based on these data we suggest that the upregulation of the ''establishment'' factors (HNF1 and -3) may be an important step in oval cell activation. The high levels of these factors in the oval cells and embryonic hepatoblasts further substantiates the similarity between the two cell compartments. Furthermore, the data suggest that HNF4 may be responsible for the final commitment of a small portion of the oval cells to differentiate into hepatocytes which form the basophilic foci and eventually regenerate the liver parenchyma. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 68 TC 179 Z9 187 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1994 VL 126 IS 1 BP 223 EP 233 DI 10.1083/jcb.126.1.223 PG 11 WC Cell Biology SC Cell Biology GA NU489 UT WOS:A1994NU48900020 PM 8027180 ER PT J AU JUNG, W CASTREN, E ODENTHAL, M VANDEWOUDE, GF ISHII, T DIENES, HP LINDHOLM, D SCHIRMACHER, P AF JUNG, W CASTREN, E ODENTHAL, M VANDEWOUDE, GF ISHII, T DIENES, HP LINDHOLM, D SCHIRMACHER, P TI EXPRESSION AND FUNCTIONAL INTERACTION OF HEPATOCYTE GROWTH FACTOR-SCATTER FACTOR AND ITS RECEPTOR C-MET IN MAMMALIAN BRAIN SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; TYROSINE KINASE; MESSENGER-RNA; HEPATOPOIETIN-A; NEUROTROPHIC FACTOR; MOLECULAR-CLONING; MOUSE DEVELOPMENT; RAT HIPPOCAMPUS; IDENTIFICATION; TISSUES AB Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic cytokine with mito-, morpho-, and motogenic effects on a variety of epithelial and endothelial cells. HGE-SF activity is mediated by the c-met protooncogene, a membrane-bound tyrosine kinase. Here, we demonstrate that both genes are expressed in developing and adult mammalian brains. HGF-SF mRNA is localized in neurons, primarily in the hippocampus, the cortex, and the granule cell layer of the cerebellum, and it is also present at high levels in ependymal cells, the chorioid plexus, and the pineal body. c-met is expressed in neurons, preferentially in the CA-1 area of the hippocampus, the cortex, and the septum, as well as in the pons. In the embryonic mouse, brain HGF-SF and c-met are expressed as early as days 12 and 13, respectively. Neuronal expression of HGF-SF is evolutionary highly conserved and detectable beyond the mammalian class. Incubation of septal neurons in culture with HGF-SF leads to a rapid increase of c-fos mRNA levels. The results demonstrate the presence of a novel growth factor-tyrosine kinase signaling system in the brain, and they suggest that HGF-SF induces a functional response in a neuronal subpopulation of developing and adult CNS. C1 UNIV HOSP MAINZ,INST PATHOL,D-55101 MAINZ,GERMANY. MAX PLANCK INST PSYCHIAT,DEPT NEUROCHEM,D-82152 MARTINSRIED,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. MITSUBISHI KASEI CORP,RES CTR,YOKOHAMA 227,JAPAN. RI Castren, Eero/A-4618-2010; Lindholm, Dan/B-3777-2014 FU NCI NIH HHS [N01-CO-74101] NR 48 TC 164 Z9 169 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1994 VL 126 IS 2 BP 485 EP 494 DI 10.1083/jcb.126.2.485 PG 10 WC Cell Biology SC Cell Biology GA NX547 UT WOS:A1994NX54700019 PM 8034747 ER PT J AU MAJUMDAR, A KERBY, S STENBERG, PE MULLIKIN, B BECKSTEAD, JH COONEY, DA SEIDMAN, MM AF MAJUMDAR, A KERBY, S STENBERG, PE MULLIKIN, B BECKSTEAD, JH COONEY, DA SEIDMAN, MM TI I1-3 AND RIBAVIRIN INDUCE HIGH-LEVEL EXPRESSION OF MEGAKARYOCYTIC MARKERS AND MESSAGES DURING LONG-TERM TREATMENT OF A MEGAKARYOCYTIC LEUKEMIA-CELL LINE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PLATELET PROTEINS; MEGAKARYOBLASTIC LEUKEMIA; VONWILLEBRAND-FACTOR; ANTIVIRAL ACTIVITY; GROWTH-FACTORS; DIFFERENTIATION; MATURATION; TIAZOFURIN; INVITRO; CMK AB Megakaryocyte differentiation is a lengthy process with cells moving through a continuum delineated by the sequential expression of specific gene products. The limited number of primary cells available from marrow for analysis has brought attention to some leukemic cell lines which show enhanced megakaryocyte marker expression following incubation with inducing agents, the most common of which is phorbol myristate acetate (PMA). We developed an alternative induction protocol for the megakaryocytic leukemic cell line CMK, which involved incubation of the cells with IL-3 and the nucleoside analog, ribavirin, for 1-2 weeks. This treatment was neither toxic nor cytostatic and yielded increased levels of the surface glycoproteins GPIIb/IIIA and GPIb-IX. Levels of some megakaryocytic messages (GPIIIa, GPIX) showed a marked rise by 12 days of incubation in the inducer combination. This was due to a synergistic interaction between IL-3 and ribavirin which influenced both transcriptional and posttranscriptional events. Light and electron microscopy demonstrated the presence of large polyploid cells, with morphological features similar to those of megakaryocytes, in the induced cultures. Analysis of the heterogeneity or response in the cell population to the induction regimen after several days of treatment suggested that cells which failed to display surface markers had been stimulated by the inducers but did not have sufficient time to complete expression of that marker. The results were consistent with the view that the cells in the starting population were distributed along a temporal expression pathway, and those which were first to express the earliest marker would also lead in the expression of a later marker. The order of expression was the same as that during normal megakaryocyte development. (C) 1994 Wiley-Liss, Inc. C1 OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD 20850. OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201. NCI,BETHESDA,MD 20892. NR 44 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1994 VL 160 IS 1 BP 29 EP 39 DI 10.1002/jcp.1041600105 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NU586 UT WOS:A1994NU58600004 PM 8021297 ER PT J AU KIBBEY, MC CORCORAN, ML WAHL, LM KLEINMAN, HK AF KIBBEY, MC CORCORAN, ML WAHL, LM KLEINMAN, HK TI LAMININ SIKVAV PEPTIDE-INDUCED ANGIOGENESIS IN-VIVO IS POTENTIATED BY NEUTROPHILS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; BASEMENT-MEMBRANE; A-CHAIN; SYNTHETIC PEPTIDE; ENDOTHELIAL-CELLS; TUMOR-GROWTH; IDENTIFICATION; ATTACHMENT; ACTIVATION; INDUCTION AB Angiogenesis has been investigated in vivo using subcutaneously injected reconstituted basement membrane (Matrigel) supplemented with angiogenic factors. Previously we found that the laminin-derived synthetic peptide containing SIKVAV (ser-ile-lys-val-ala-val) promoted angiogenesis in vivo. In parallel studies, it was observed that new vessel formation in response to this peptide occurred several days after basic fibroblast growth factor-induced angiogenesis. Since this delay suggested that SIKVAV-induced angiogenesis may be secondary to other events, we investigated here earlier time points to determine if both indirect and direct mechanisms of angiogenesis are involved. We found that neutrophils are continuously recruited to the SIKVAV-containing plugs between 4 hours to 3 days following the initial injection. By day 7, columns of endothelial cells begin to migrate into the plug and form small blood vessels. In contrast, neutropenic mice had a 62% reduction in SIKVAV-induced angiogenesis when compared to control mice. Freshly isolated neutrophils also degraded laminin, the major component of the basement membrane Matrigel. These cells also produced factors in response to SIKVAV peptide which induced proliferation of human umbilical vein endothelial cells relative to a control peptide. In vitro experiments utilizing human neutrophils demonstrated that these cells migrate to the SIKVAV peptide and possess a specific cell surface SIKVAV binding protein of similar to 56 kD. These data suggest that neutrophils are induced to migrate to the Matrigel plugs, at least in part, by SIKVAV peptide, where they may release their own angiogenic factors and degrade the matrix, thus physically facilitating cell migration and liberating additional angiogenic matrix fragments and/or cytokines. (C) 1994 Wiley-Liss, Inc.** C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP KIBBEY, MC (reprint author), NIDR,DEV BIOL LAB,BLDG 30,BETHESDA,MD 20892, USA. NR 31 TC 35 Z9 36 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1994 VL 160 IS 1 BP 185 EP 193 DI 10.1002/jcp.1041600121 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NU586 UT WOS:A1994NU58600020 PM 7517404 ER PT J AU PEKAR, J LIGETI, L SINNWELL, T MOONEN, CTW FRANK, JA MCLAUGHLIN, AC AF PEKAR, J LIGETI, L SINNWELL, T MOONEN, CTW FRANK, JA MCLAUGHLIN, AC TI F-19 MAGNETIC-RESONANCE-IMAGING OF CEREBRAL BLOOD-FLOW WITH 0.4-CC RESOLUTION SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE MR; CBF; F-19; IMAGING; TRACER KINETICS; CAT ID NMR-SPECTROSCOPY AB F-19 magnetic resonance imaging techniques were used to determine ''wash-in'' and ''wash-out'' curves of the inert, diffusible gas CHF3 from 0.4-cc voxels in the cat brain, and mass spectrometer gas detection was used to determine the CH3 concentration in expired air. These two sets of data were used to calculate cerebral blood flow values in the 0.4-cc voxels, and the blood flow images were registered with high-resolution H-1 magnetic resonance images. Data were collected both during the wash-in and wash-out phases of the experiment, but the two sets of data were analyzed separately to obtain independent estimates of the blood flow during the two phases, i.e., Q(in) and Q(out). Repeated determinations of cerebral blood flow images were performed in individual animals, and the entire protocol was repeated on five different animals. The average values of Q(in) and Q(out) for a typical 0.4-cc voxel in the parietal cortex were 83 ml 100 g(-1) min(-1) and 72 ml 100 g(-1) min(-1), respectively. Monte Carlo calculations utilizing the noise in the F-19 NMR signal from this voxel predict an average standard deviation for Q(in) and Q(out) of +/- 10%. The average standard deviation for repeated measurements (in the same animal) of Q(in), and Q(out) in this voxel was +/-14%. We conclude that F-19 magnetic resonance imaging approaches have the potential to image cerebral blood flow in humans. C1 NIAAA,DIAGNOST RADIOL LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. SEMMELWEIS UNIV MED,H-1085 BUDAPEST,HUNGARY. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 9 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1994 VL 14 IS 4 BP 656 EP 663 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA NT499 UT WOS:A1994NT49900016 PM 8014213 ER PT J AU MATHEW, M TAKAGI, S FOWLER, BO MARKOVIC, M AF MATHEW, M TAKAGI, S FOWLER, BO MARKOVIC, M TI THE CRYSTAL-STRUCTURE OF CALCIUM SUCCINATE MONOHYDRATE SO JOURNAL OF CHEMICAL CRYSTALLOGRAPHY LA English DT Article DE CA(C4H4O4)CENTER-DOT-H2O; PENTAGONAL PYRAMID; CALCIUM SUCCINATE; CRYSTAL STRUCTURE ID OCTACALCIUM AB The crystal structure of calcium succinate monohydrate, Ca(C4H4O4).H2O, has been determined by single crystal X ray diffraction. The crystals are monoclinic with a = 11.952(2), b = 9.691(2), c = 11.606(2) Angstrom, beta = 108.81(1)degrees, space group C2/c, Z = 8, V = 1272.49 Angstrom(3), d, = 1.80, and d(c) = 1.818 Mg m(-3). The structure was refined by full-matrix least-squares techniques to R = 0.027, R(w) = 0.040, for 829 reflections with I greater than or equal to 3 sigma(I). Ca is coordinated to seven oxygen atoms, and the coordination polyhedron is best described as a pentagonal bipyramid. One carboxylate group in the succinate ion is bonded to three different Ca ions, forming a four-membered chelate ring with one Ca ion and unidentate bridge bonds to two other Ca ions. The other carboxylate group is bonded to two Ca ions through unidentate bonds. The structure is highly polymeric. The general structural features are nearly identical to those of calcium adipate monohydrate. C1 NIST,NIDR,BONE RES BRANCH,RES PROGRAM,GAITHERSBURG,MD 20899. RP MATHEW, M (reprint author), NIST,AMER DENT ASSOC HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899, USA. RI G, Neela/H-3016-2014 NR 14 TC 9 Z9 9 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 1074-1542 J9 J CHEM CRYSTALLOGR JI J. Chem. Crystallogr. PD JUL PY 1994 VL 24 IS 7 BP 437 EP 440 DI 10.1007/BF01666091 PG 4 WC Crystallography; Spectroscopy SC Crystallography; Spectroscopy GA PK361 UT WOS:A1994PK36100006 ER PT J AU KLING, MA DEBELLIS, MD OROURKE, DK LISTWAK, SJ GERACIOTI, TD MCCUTCHEON, IE KALOGERAS, KT OLDFIELD, EH GOLD, PW AF KLING, MA DEBELLIS, MD OROURKE, DK LISTWAK, SJ GERACIOTI, TD MCCUTCHEON, IE KALOGERAS, KT OLDFIELD, EH GOLD, PW TI DIURNAL-VARIATION OF CEREBROSPINAL-FLUID IMMUNOREACTIVE CORTICOTROPIN-RELEASING HORMONE LEVELS IN HEALTHY-VOLUNTEERS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BIOCHEMICAL MANIFESTATIONS; FACTOR CRF; DEPRESSION; BRAIN; STRESS; HUMANS; NEUROBIOLOGY; SECRETION; INCREASES; SEIZURES AB CRH is not only secreted into hypophyseal portal blood where it is believed to regulate the circadian rhythm of pituitary-adrenal activity, but is also measurable in cerebrospinal fluid (CSF). Altered CSF immunoreactive CRH (IR-CRH) levels have been found in patients with a number of neuropsychiatric disorders and have been implicated in some of the symptoms of these disorders. To further study the potential functional relevance of CRH in human CSF, we examined whether a nonuniform temporal pattern of IR-CRH levels existed in CSF using hourly sampling over a 30-h period in six healthy volunteers. CSF was withdrawn continuously at 6 mL/h through a catheter placed in the lumbar subarachnoid space and connected to a miniroller pump and fraction collector. A significant diurnal variation in CSF IR-CRH levels was observed (P < 0.001), with highest levels between 1830-2330 h and lowest levels around 0730 h. This pattern was nearly opposite that of plasma cortisol levels, which showed the expected peak around 0800 h and nadir around 2000-2200 h. In addition, CSF IR-CRH levels in three of the six volunteers showed significant negative correlations with simultaneous plasma cortisol levels. These data suggest that CSF IR-CRH concentrations are negatively modulated by peripheral cortisol secretion, which may be one factor involved in the entrainment of this rhythm. Although the functional significance of this diurnal variation in CSF IR-CRH levels is unknown, the presence of a distinct temporal organization of CRH release into the CSF in humans is compatible with the idea that CSF may play a functional role in or otherwise reflect nonsynaptic information processing in the central nervous system. Diurnal factors should be taken into account in future studies of CRH concentrations in human CSF. C1 NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. RP KLING, MA (reprint author), NIMH, INTRAMURAL RES PROGRAM, CLIN NEUROENDOCRINOL BRANCH,BLDG 10,ROOM 3S-231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 31 TC 42 Z9 42 U1 0 U2 1 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 JUL PY 1994 VL 79 IS 1 BP 233 EP 239 DI 10.1210/jc.79.1.233 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NW509 UT WOS:A1994NW50900043 PM 8027234 ER PT J AU SLATTERY, ML DYER, A JACOBS, DR HILNER, JE CAAN, BJ BILD, DE LIU, K MCDONALD, A VANHORN, L HARDIN, M AF SLATTERY, ML DYER, A JACOBS, DR HILNER, JE CAAN, BJ BILD, DE LIU, K MCDONALD, A VANHORN, L HARDIN, M TI PRESENTATION - A COMPARISON OF 2 METHODS TO ASCERTAIN DIETARY-INTAKE - THE CARDIA STUDY SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE DIETARY INTAKE; PHYSICAL ACTIVITY; EPIDEMIOLOGIC METHODS; KEYS SCORE; NUTRITION; PLASMA CHOLESTEROL ID DENSITY-LIPOPROTEIN CHOLESTEROL; FOOD FREQUENCY QUESTIONNAIRE; PHYSICAL-ACTIVITY; YOUNG-ADULTS; ASSESSMENT INSTRUMENTS; REPRODUCIBILITY; VALIDITY; HISTORY; DESIGN; RELIABILITY AB Data on dietary intake were collected in the Coronary Artery Risk Development in Young Adults (CARDIA) Study at the baseline examination in 1985-86 and again at the second examination 2 years later. At baseline, a diet history questionnaire developed for the CARDIA study was used; at the second exam the NCI (Block) food frequency questionnaire was used. The purpose of the present report is to compare the estimated nutrient intakes obtained with the two instruments; to compare correlations of nutrient intakes obtained at the two exams with those observed for other lifestyle and physiological variables also measured 2 years apart; and to assess ability to test hypotheses relating a-year changes in risk factors to between-exam differences in reported nutrient intakes. Mean levels of reported intake were generally greater for both blacks and whites on the CARDIA diet history than on the Block food frequency. Rank order correlations of reported nutrient intakes between the two questionnaires indicated greater consistency between instruments for whites (r's ranging between 0.35 and 0.52) than for blacks (r's ranging between 0.29 and 0.45). Correlations over time for nutrients were smaller than those observed for body size measures and lipid levels but were similar in magnitude to those for blood pressure, physical activity, and life events. At both exams, total caloric intake was positively associated with physical activity (range of r's for CARDIA were 0.07 for white women to 0.23 for black men, the range of r's for Block were 0.06 for women to 0.11 for white men). Using data from the two examinations, 2-year changes in total plasma cholesterol were significantly related to 2 year changes in Keys scores. The results of this comparison are useful in that they show similarities and differences between two instruments developed to gather dietary intake data. The study also illustrates the need to monitor young adults during a time when rapid changes occur in many lifestyle and physiologic factors. C1 NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV ALABAMA,COORDINATING CTR,CARDIA,BIRMINGHAM,AL. KAISER PERMANENTE MED CARE PROGRAM,DIV RES,OAKLAND,CA 94611. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP SLATTERY, ML (reprint author), UNIV UTAH,MED CTR,DEPT FAMILY & PREVENT MED,50 N MED DR,SALT LAKE CITY,UT 84112, USA. FU NHLBI NIH HHS [N01-HC-48049, N01-HC-48047, N01-HC-48048] NR 24 TC 13 Z9 13 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 1994 VL 47 IS 7 BP 701 EP 711 DI 10.1016/0895-4356(94)90166-X PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA PA987 UT WOS:A1994PA98700001 PM 7722583 ER PT J AU SLATTERY, ML DYER, A JACOBS, DR HILNER, JE CAAN, BJ BILD, DE LIU, KA MCDONALD, A VANHORN, L HARDIN, M AF SLATTERY, ML DYER, A JACOBS, DR HILNER, JE CAAN, BJ BILD, DE LIU, KA MCDONALD, A VANHORN, L HARDIN, M TI DISSENT - HOW SHOULD NUTRIENT INTAKE BE MEASURED IN EPIDEMIOLOGIC RESEARCH - RESPONSE SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article C1 NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV ALABAMA,COORDINATING CTR,CARDIA,BIRMINGHAM,AL. KAISER PERMANENTE MED CARE PROGRAM,DIV RES,OAKLAND,CA 94611. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP SLATTERY, ML (reprint author), UNIV UTAH,MED CTR,DEPT FAMILY & PREVENT MED,50 N MED DR,SALT LAKE CITY,UT 84112, USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 1994 VL 47 IS 7 BP 715 EP 717 DI 10.1016/0895-4356(94)90168-6 PG 3 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA PA987 UT WOS:A1994PA98700003 ER PT J AU SHIMAKAWA, T BILD, DE AF SHIMAKAWA, T BILD, DE TI RELATIONSHIP BETWEEN HEMOGLOBIN AND SERUM-ALBUMIN - RESPONSE SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter RP SHIMAKAWA, T (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 1994 VL 47 IS 7 BP 824 EP 824 DI 10.1016/0895-4356(94)90183-X PG 1 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA PA987 UT WOS:A1994PA98700018 ER PT J AU TAGA, K CHRETIEN, J CHERNEY, B DIAZ, L BROWN, M TOSATO, G AF TAGA, K CHRETIEN, J CHERNEY, B DIAZ, L BROWN, M TOSATO, G TI INTERLEUKIN-10 INHIBITS APOPTOTIC CELL-DEATH IN INFECTIOUS-MONONUCLEOSIS T-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EPSTEIN-BARR VIRUS; PROGRAMMED CELL DEATH; BCRF-1; CELL SURVIVAL; DNA FRAGMENTATION ID EPSTEIN-BARR-VIRUS; AUTOCRINE GROWTH-FACTOR; CYTOKINE SYNTHESIS; LYMPHOCYTES-T; B-CELLS; DIFFERENTIATION FACTOR; STIMULATORY FACTOR; INTERFERON-GAMMA; FLOW-CYTOMETRY; IL-10 AB T lymphocytes from patients with acute EBV-induced infectious mononucleosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a variety of functions on human T cells, we examined IL-10 effects on infectious mononucleosis T cell death. After 12 h of incubation in medium alone, only 35.6 (+/-8.2%) of the originally seeded infectious mononucleosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cell cultures significantly improved recovery of viable cells (71.3+/-6.2%, P = 0.0156). Viral IL-10 had comparable effects to human IL-10 in this system. Protection from death by human and viral IL-10 (100 U/ml) was dose dependent and continued over a 6-d culture period. The human IL-10 effect was neutralized by the anti-human IL-10 mAb 19F1. Morphology and analysis of DNA after separation on agarose gels showed that IL-10 inhibits loss of cell volume, chromatin condensation, and DNA fragmentation, characteristics of death by apoptosis. As assessed by [H-3]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T cells protected from death by IL-10 proliferated to IL-2 and spontaneously killed sensitive targets as effectively as medium-precultured T cells. Thus, IL-10 promotes the survival of infectious mononucleosis T cells otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. NIH,BETHESDA,MD 20892. RP TAGA, K (reprint author), US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BLDG 29A,ROOM 2D06,ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 60 TC 69 Z9 69 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1994 VL 94 IS 1 BP 251 EP 260 DI 10.1172/JCI117315 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600033 PM 8040267 ER PT J AU SELDIN, MF MOTT, D BHAT, D PETRO, A KUHN, CM KINGSMORE, SF BOGARDUS, C FEINGLOS, MN SURWIT, RS OPARA, E AF SELDIN, MF MOTT, D BHAT, D PETRO, A KUHN, CM KINGSMORE, SF BOGARDUS, C FEINGLOS, MN SURWIT, RS OPARA, E TI GLYCOGEN-SYNTHASE - A PUTATIVE LOCUS FOR DIET-INDUCED HYPERGLYCEMIA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GENETICS; MOUSE; NON-INSULIN DEPENDENT DIABETES MELLITUS; GLYCOGEN SYNTHASE; DIET ID DEPENDENT DIABETES-MELLITUS; RECOMBINANT INBRED STRAINS; LINKAGE ANALYSIS; SKELETAL-MUSCLE; C57BL/6J MICE; MOUSE STRAINS; BAYES THEOREM; TUBBY TUB; INSULIN; PROTEIN AB Inbred mouse strains fed a diabetogenic diet have different propensities to develop features analogous to type 2 diabetes mellitus. To define chromosomal locations that control these characteristics, recombinant inbred strains from diabetes-prone C57BL/6J (B/6J) and diabetes-resistant A/J strains were studied. Insulin levels and hyperglgcemia correlated with two different regions of mouse chromosome 7 (two point LOD scores > 3.0). For insulin levels, 15 of 16 recombinant inbred strains were concordant with a region that contains the tubby mutation that results in hyperinsulinemia. For hyperglycemia, 19 of 23 strains were concordant with the D7Mit25 marker and 20 of 23 strains with the Gpi-1 locus on proximal mouse chromosome 7. Using more stringent criteria for hyperglycemia, 10 of 11 strains characterized as A/J or B/6J like were concordant with D7Mit25. This putative susceptibility locus is consistent with that of the glycogen synthase gene (Gys) recently suggested as a candidate locus by analyses of type 2 diabetes patients. Fractional glycogen synthase activity in isolated muscle was significantly lower in normal B/6J diabetic-prone mice compared with normal diabetic-resistant A/J mice, a finding similar to that reported in relatives of human patients with type 2 diabetes. These data, taken together, raise the possibility that defects in the Gys gene may in part be responsible for the propensity to develop type 2 diabetes. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PSYCHOL,DURHAM,NC 27710. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. FU NIDDK NIH HHS [R01DK-42923]; NIMH NIH HHS [NIMH K05MA-00303] NR 52 TC 29 Z9 29 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1994 VL 94 IS 1 BP 269 EP 276 DI 10.1172/JCI117317 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600035 PM 8040269 ER PT J AU TAUB, DD TSARFATY, G LLOYD, AR DURUM, SK LONGO, DL MURPHY, WJ AF TAUB, DD TSARFATY, G LLOYD, AR DURUM, SK LONGO, DL MURPHY, WJ TI GROWTH-HORMONE PROMOTES HUMAN T-CELL ADHESION AND MIGRATION TO BOTH HUMAN AND MURINE MATRIX PROTEINS IN-VITRO AND DIRECTLY PROMOTES XENOGENEIC ENGRAFTMENT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CHEMOKINES; HUMAN SEVERE COMBINED IMMUNODEFICIENCY CHIMERAS; TRAFFICKING; LYMPHOCYTE MIGRATION; NEUROENDOCRINE IMMUNE EFFECTS ID IMMUNODEFICIENT MICE; LYMPHOCYTES AB Recombinant human growth hormone(rhGH) promotes human T cell engraftment in mice with severe combined immunodeficiency, suggesting that rhGH may have effects on T cell adhesion and migration in vivo. The ability of rhGH to directly affect the adhesion capacity of human T cells to a variety of human or murine adhesion molecules and extracellular matrix proteins was examined. rhGH induced significant human T cell adherence to both human and murine substrates via either beta 1 or beta 2 integrin molecules. rhGH was capable of inducing significant migration of resting and activated human T cells and their subsets. Most of the migratory response to rhGH was chemokinetic rather than chemotactic. In vivo engraftment studies in severe combined immunodeficiency mice receiving human T cells revealed that treatment with rhGH resulted in improved thymic engraftment, whereas treatment with non-human-reactive ovine GH demonstrated no significant effects. These data demonstrate that rhGH directly augments human T cell trafficking to peripheral murine lymphoid tissues. rhGH appears to be capable of directly altering the adhesive and migratory capacity of human T cells to molecules of either murine or human origin. Therefore, GH may, under either isogeneic or xenogeneic conditions, play a role in normal lymphocyte recirculation. C1 PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. PRINCE HENRY HOSP,DEPT INFECT DIS,LITTLE BAY,NSW 2036,AUSTRALIA. RP TAUB, DD (reprint author), NCI,FCRDC,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,BLDG 560,ROOM 31-19,FREDERICK,MD 21702, USA. NR 13 TC 83 Z9 84 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1994 VL 94 IS 1 BP 293 EP 300 DI 10.1172/JCI117320 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600038 PM 7518833 ER PT J AU MARUYAMA, M HAY, JG YOSHIMURA, K CHU, CS CRYSTAL, RG AF MARUYAMA, M HAY, JG YOSHIMURA, K CHU, CS CRYSTAL, RG TI MODULATION OF SECRETORY LEUKOPROTEASE INHIBITOR GENE-EXPRESSION IN HUMAN BRONCHIAL EPITHELIAL-CELLS BY PHORBOL EATER SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE PROTEASE INHIBITOR; TRANSCRIPTION; 5' FLANKING REGION; NEUTROPHIL ELASTASE; MESSENGER-RNA ID LEUKOCYTE PROTEASE INHIBITOR; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; CYSTIC-FIBROSIS; INTERLEUKIN-8 GENE; MESSENGER-RNA; MYRISTATE ACETATE; HUMAN-LUNG; NEUTROPHIL ELASTASE; POTENT INHIBITOR AB Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease, helps to protect the epithelial surface of the airways from the destructive capacity of neutrophil elastase. Based on the recognition that SLPI levels can increase in the presence of airway inflammation, we hypothesized that inflammatory stimuli should modulate the expression of the SLPI gene in airway epithelial cells. To evaluate this, the modulation of SLPI gene expression with various inflammatory stimuli was evaluated in the HS-24 human bronchial epithelial cell line. After preliminary studies showed that several inflammatory mediators enhanced SLPI messenger RNA (mRNA) levels, PMA was used as a model inflammatory stimulus. PMA significantly increased the level of 0.7-kb SLPI mRNA transcripts in HS-24 cells in a dose- and time-dependent fashion and increased the amount of SLPI protein in the culture supernatant. Nuclear run-on analyses showed that the SLPI gene transcription rate increased approximately twofold after PMA stimulation. Transfection studies using fusion genes composed of fragments of up to 1.2 kb of the 5' flanking sequence of the SLPI gene and a luciferase reporter gene demonstrated potent promoter activity in the 131-bp segment (-115 to +16 relative to the transcription start site), and all longer segments up to 1.2 kb, whereas smaller segments showed low promoter activity. An 18-bp element (-98 to -115), in a region with homology to PMA-responsive regions in the Moloney murine leukemia virus enhancer and the IL-8 gene, was shown to be of importance in the level of transcription of the SLPI gene. However, this element was not responsible for the upregulation of SLPI gene expression by PMA. Evaluation of HS-24 cells in the presence of actinomycin D demonstrated that SLPI mRNA transcripts were very stable and became more so in the presence of PMA. Thus, SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels. These mechanisms of SLPI upregulation likely play a role in defending the epithelial surface in the local milieu of inflammatory lung disease. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NR 65 TC 43 Z9 44 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1994 VL 94 IS 1 BP 368 EP 375 DI 10.1172/JCI117331 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600047 PM 7913712 ER PT J AU ZHAN, SL SHAPIRO, DN HELMAN, LJ AF ZHAN, SL SHAPIRO, DN HELMAN, LJ TI ACTIVATION OF AN IMPRINTED ALLELE OF THE INSULIN-LIKE GROWTH-FACTOR-II GENE IMPLICATED IN RHABDOMYOSARCOMA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE IGF2; RHABDOMYOSARCOMA; ALLELES; HUMAN; NEOPLASM ID ALVEOLAR RHABDOMYOSARCOMA; DETERMINES METHYLATION; TRANSCRIPTION FACTORS; TRANSGENIC MICE; CANCER; EXPRESSION; DISOMY; TUMOR; PAX3 AB The insulin-like growth factor II (IGF2) gene is exclusively silent at the maternal allele in the mouse as well as in normal human tissues and is expressed at a high level in rhabdomyosarcoma (RMS). We report here that the normally imprinted allele of the IGF2 gene is activated in RMS tumors as well as in one RMS cell line. Since overexpression of IGF2 has been shown to be important in the pathogenesis of RMS, our data suggest that loss of imprinting (LOI) may lead to overexpression of IGF2 and play an important role in the onset of RMS. Furthermore, embryonal RMS usually has loss of heterozygosity (LOH) with paternal disomy of the IGF2 locus. One informative embryonal RMS tumor evaluated in this study was heterozygous at the IGF2 allele and had LOI, raising the possibility that LOI may be the functional equivalent of LOH in this tumor with both events leading to overespression of IGF2. C1 NCI, PEDIAT BRANCH, MOLEC ONCOL SECT, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA-21765, CA-23099] NR 26 TC 178 Z9 184 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1994 VL 94 IS 1 BP 445 EP 448 DI 10.1172/JCI117344 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600058 PM 8040287 ER PT J AU CARTWRIGHT, CP NELSON, NA GILL, VJ AF CARTWRIGHT, CP NELSON, NA GILL, VJ TI DEVELOPMENT AND EVALUATION OF A RAPID AND SIMPLE PROCEDURE FOR DETECTION OF PNEUMOCYSTIS-CARINII BP PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE; MONOCLONAL-ANTIBODIES; DIAGNOSIS; PNEUMONIA; SPUTUM; STAIN AB We report the development of a simplified PCR-based assay for the detection of Pneumocystis carinii DNA in clinical specimens. The adoption of a rapid DNA extraction procedure and the introduction of a type of enzyme-linked immunosorbent assay for PCR product detection enabled this procedure to be carried out in a single working day in a clinical microbiology laboratory. The PCR assay was prospectively compared with an immunofluorescent antibody (FA) staining method for the detection of P. carinii in induced sputum and bronchoalveolar lavage (BAL) specimens. The results of the study showed that, for induced sputum specimens, FA staining had a sensitivity of 78% (32 of 41 specimens) and a specificity of 100% (166 of 166 specimens); PCR was 100% (41 of 41 specimens) sensitive and 98% (162 of 166 specimens) specific. For BAL specimens, FA staining was 100% sensitive (21 of 21 specimens) and 100% specific (133 of 133 specimens), and PCR had a sensitivity of 100% (21 of 21 specimens) and a specificity of 99% (132 of 133 specimens). These results strongly suggest that use of our PCR-based assay could effect clinically useful improvements in the sensitivity of induced sputum specimens for the detection of P. carinii. RP CARTWRIGHT, CP (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892, USA. NR 17 TC 37 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1994 VL 32 IS 7 BP 1634 EP 1638 PG 5 WC Microbiology SC Microbiology GA NR924 UT WOS:A1994NR92400003 PM 7929749 ER PT J AU CARTWRIGHT, CP STOCK, F GILL, VJ AF CARTWRIGHT, CP STOCK, F GILL, VJ TI IMPROVED ENRICHMENT BROTH FOR CULTIVATION OF FASTIDIOUS ORGANISMS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note AB An enrichment broth developed in our laboratory, fastidious broth (FB), was compared with two commercially available broth media, supplemented thioglycolate broth and enriched eugenic broth. FB supported the growth of a number of organisms that were not cultivatable in either of the other two media, including Corynebacterium jeikeium, Haemophilus influenzae, Neisseria gonorrhoeae, and Streptococcus pneumoniae. In addition, for several organisms that were able to grow in all three broths, including Neisseria meningitidis, Nocardia asteroides, and Actinomyces spp., both the time of incubation and the starting inoculum necessary to enable detection of growth were decreased significantly by using FB. RP CARTWRIGHT, CP (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892, USA. NR 3 TC 15 Z9 15 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1994 VL 32 IS 7 BP 1825 EP 1826 PG 2 WC Microbiology SC Microbiology GA NR924 UT WOS:A1994NR92400042 PM 7929784 ER PT J AU SCHWARTZENTRUBER, DJ HOM, SS DADMARZ, R WHITE, DE YANNELLI, JR STEINBERG, SM ROSENBERG, SA TOPALIAN, SL AF SCHWARTZENTRUBER, DJ HOM, SS DADMARZ, R WHITE, DE YANNELLI, JR STEINBERG, SM ROSENBERG, SA TOPALIAN, SL TI IN-VITRO PREDICTORS OF THERAPEUTIC RESPONSE IN MELANOMA PATIENTS RECEIVING TUMOR-INFILTRATING LYMPHOCYTES AND INTERLEUKIN-2 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; ADVANCED CANCER; NECROSIS-FACTOR; METASTATIC MELANOMA; CLINICAL-RESPONSE; SECRETION; INDUCTION C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP SCHWARTZENTRUBER, DJ (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B04,BETHESDA,MD 20892, USA. NR 25 TC 119 Z9 121 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1994 VL 12 IS 7 BP 1475 EP 1483 PG 9 WC Oncology SC Oncology GA NW075 UT WOS:A1994NW07500020 PM 8021739 ER PT J AU FIGG, WD STEVENS, JA COOPER, MR AF FIGG, WD STEVENS, JA COOPER, MR TI ADAPTIVE-CONTROL WITH FEEDBACK OF SURAMIN USING INTERMITTENT INFUSIONS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP FIGG, WD (reprint author), NCI,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 3 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1994 VL 12 IS 7 BP 1523 EP 1524 PG 2 WC Oncology SC Oncology GA NW075 UT WOS:A1994NW07500028 PM 8021743 ER PT J AU STEINBACH, PJ BROOKS, BR AF STEINBACH, PJ BROOKS, BR TI NEW SPHERICAL-CUTOFF METHODS FOR LONG-RANGE FORCES IN MACROMOLECULAR SIMULATION SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; NEUTRON-SCATTERING; PROTEIN DYNAMICS; LIQUID WATER; TEMPERATURE-DEPENDENCE; IONIC-SOLUTIONS; MYOGLOBIN; HYDRATION; THERMODYNAMICS; ALGORITHM AB New atom- and group-based spherical-cutoff methods have been developed for the treatment of nonbonded interactions in molecular dynamics (MD) simulation. A new atom-based method, force switching, leaves short-range forces unaltered by adding a constant to the potential energy, switching forces smoothly to zero over a specified range. A simple improvement to group-based cutoffs is presented: Switched group-shifting shifts the group-group potential energy by a constant before being switched smoothly to zero. Also introduced are generalizations of atom-based force shifting, which adds a constant to the Coulomb force between two charges. These new approaches are compared to existing methods by evaluating the energy of a model hydrogen-bonding system consisting of two N-methyl acetamide molecules and by full MD simulation. Thirty-five 150 ps simulations of carboxymyoglobin (MbCO) hydrated by 350 water molecules indicate that the new methods and atom-based shifting are each able to approximate no-cutoff results when a cutoff at or beyond 12 Angstrom is used. However, atom-based potential-energy switching and truncation unacceptably contaminate group-group electrostatic interactions. Group-based potential truncation should not be used in the presence of explicit water or other mobile electrostatic dipoles because energy is not a state function with this method, resulting in severe heating (about 4 K/ps in the simulations of hydrated MbCO). The distance-dependent dielectric (epsilon alpha gamma) is found to alter the temperature dependence of protein dynamics, suppressing anharmonic motion at high temperatures. Force switching and force shifting are the best atom-based spherical cutoffs, whereas switched group-shifting is the preferred group-based method. To achieve realistic simulations, increasing the cutoff distance from 7.5 12 Angstrom or beyond is much more important than the differences among the three best cutoff methods. (c) 1994 by John Wiley and Sons, RP NIH, DIV COMP RES & TECHNOL, STRUCT BIOL LAB, BETHESDA, MD 20892 USA. NR 32 TC 640 Z9 644 U1 3 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0192-8651 EI 1096-987X J9 J COMPUT CHEM JI J. Comput. Chem. PD JUL PY 1994 VL 15 IS 7 BP 667 EP 683 DI 10.1002/jcc.540150702 PG 17 WC Chemistry, Multidisciplinary SC Chemistry GA NU174 UT WOS:A1994NU17400001 ER PT J AU JONES, BD GHORI, N FALKOW, S AF JONES, BD GHORI, N FALKOW, S TI SALMONELLA-TYPHIMURIUM INITIATES MURINE INFECTION BY PENETRATING AND DESTROYING THE SPECIALIZED EPITHELIAL M-CELLS OF THE PEYERS-PATCHES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GROWTH-FACTOR-RECEPTOR; MOLECULAR CHARACTERIZATION; LYMPHOID FOLLICLES; MAMMALIAN-CELLS; ANTIGEN UPTAKE; INVASION; RABBIT; TRANSPORT; MICE; MECHANISM AB Salmonella species are known to initiate infection of mammalian hosts by penetrating the intestinal epithelium of the small bowel. These bacteria preferentially interact with Peyer's patches which are collections of lymphoid follicles making up the gut-associated lymphoid tissue. We infected murine ligated intestinal loops with invasive and noninvasive Salmonella typhimurium strains for 30, 60, 120, and 180 min and examined the infected tissue by transmission electron microscopy. Within 30 min, we found that invasive S. typhimurium exclusively entered M cells found within the follicle-associated epithelium (FAE) of the Peyer's patches. Initially, interactions between invasive bacteria and enterocytes adjacent to the M cells were not found. Invasion of M cells was associated with the ability of the bacteria to invade tissue culture cells. S. typhimurium mutants, which were noninvasive for tissue culture cells, could not be found in ligated loops associated with M cells or enterocytes after incubations of 30, 60, 120, or 180 min. At 60 min, internalized invasive S. typhimurium were cytotoxic for the M cells. Destruction of an M cell formed a gap in the FAE which allowed organisms to invade enterocytes adjacent to the dead cell. Later in the infection process (120 and 180 min), the presence of bacteria beneath the FAE correlated with changes in the cytoarchitecture of the lymphoid follicle. In addition, replicating Salmonella began to enter both the apical and basolateral surfaces of enterocytes adjacent to infected M cells. C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RP JONES, BD (reprint author), STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,SHERMAN FAIRCHILD BLDG D312,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI-08404, AI-26195]; NIDDK NIH HHS [DK38707] NR 34 TC 567 Z9 575 U1 1 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1994 VL 180 IS 1 BP 15 EP 23 DI 10.1084/jem.180.1.15 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900005 PM 8006579 ER PT J AU KOZHICH, AT KAWANO, YI EGWUAGU, CE CASPI, RR MATURI, RK BERZOFSKY, JA GERY, I AF KOZHICH, AT KAWANO, YI EGWUAGU, CE CASPI, RR MATURI, RK BERZOFSKY, JA GERY, I TI A PATHOGENIC AUTOIMMUNE PROCESS TARGETED AT A SURROGATE EPITOPE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RETINOID-BINDING PROTEIN; UVEORETINITIS; IDENTIFICATION; DETERMINANT; SEQUENCE; ANTIGEN; RATS; IRBP; GENE; IMMUNODOMINANT AB Immunization with the retinal interphotoreceptor retinoid-binding protein (IRBP) induces in a variety of animals an inflammatory eye disease, experimental autoimmune uveoretinitis (EAU). We have previously shown that sequence 1181-1191 of bovine IRBP (BOV 1181-1191) is immunodominant and highly uveitogenic and immunogenic in Lewis rats. Sequence 1181-1191 of the rat IRBP (RAT 1181-1191) differs from BOV 1181-1191 by two residues, at positions 1188 and 1190, that are pivotal for the immunological activity of the bovine epitope. Here we show that, unlike its bovine homologue, RAT 1181-1191 did not induce EAU or an immune response in Lewis rats. The immunological inactivity of RAT 1181-1191 in Lewis rats is due at least in part to its poor affinity toward the antigen-presenting cells of these rats, as shown by its failure to compete with binding of BOV 1181-1191 to Lewis adherent spleen cells. Moreover, unlike all other known autologous homologues of immunopathogenic epitopes, RAT 1181-1191 was not recognized by lymphocytes sensitized against BOV 1181-1191 and failed to stimulate proliferation, uveitogenic capacity or signal transduction in these cells. These findings thus suggest that RAT 1181-1191 is not a likely target for lymphocytes sensitized against BOV 1181-1191 in the process in which these cells recognize IRBP in the rat eye and trigger the inflammatory reaction of EAU. Our data further suggest that the target for the disease-inducing lymphocytes is sequence 273-283 of the rat IRBP: (a) sequence 273-283 is highly conserved and is identical in the bovine and rat proteins; (b) determinant 273-283 is a ''repeat'' of 1181-1191 in the fourfold structure of IRBP and shares seven residues with BOV 1181-1191; (c) rat peptide 273-283 is recognized by lymphocytes sensitized against BOV 1181-1191 and stimulates them for proliferation and for acquisition of uveitogenicity; and (d) moreover, sequence 273-283 is superior to BOV 1181-1191 in its capacity to generate uveitogenicity in lymphocytes sensitized against this bovine peptide. The present study thus describes for the first time a system in which an autologous homologue of an immunopathogenic epitope is inactive and a ''surrogate'' determinant apparently serves as the target for lymphocytes sensitized against the immunopathogenic peptide. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. RP KOZHICH, AT (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N208,BETHESDA,MD 20892, USA. NR 26 TC 10 Z9 11 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1994 VL 180 IS 1 BP 133 EP 140 DI 10.1084/jem.180.1.133 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900016 PM 7516403 ER PT J AU BADOLATO, R WANG, JM MURPHY, WJ LLOYD, AR MICHIEL, DF BAUSSERMAN, LL KELVIN, DJ OPPENHEIM, JJ AF BADOLATO, R WANG, JM MURPHY, WJ LLOYD, AR MICHIEL, DF BAUSSERMAN, LL KELVIN, DJ OPPENHEIM, JJ TI SERUM AMYLOID-A IS A CHEMOATTRACTANT - INDUCTION OF MIGRATION, ADHESION, AND TISSUE INFILTRATION OF MONOCYTES AND POLYMORPHONUCLEAR LEUKOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-BLOOD MONOCYTES; C-REACTIVE PROTEIN; DEGRADATION; ELASTASE; SURFACE; DENSITY; COMMON; SAA AB Serum amyloid A (SAA) is an acute phase protein that in the blood is bound to high density lipoproteins; SAA is secreted mainly by hepatocytes, and its concentration increases in the blood up to 1000 times during an inflammatory response. At present, its biological function is unclear. Since some forms of secondary amyloidosis are caused by deposition in tissues of peptides derived from the SAA and leukocytes seem to be involved in this process, we investigated the effect of human SAA on human monocytes and polymorphonuclear cells (PMN). When recombinant human SAA (rSAA) was used at concentrations corresponding to those found during the acute phase (>0.8 mu M), it induced directional migration of monocytes and polymorphonuclear leukocytes. Preincubation of rSAA with high density lipoproteins blocked this chemoattractant activity for both monocytes and PMN. rSAA also regulated the expression of the adhesion proteins CD11b and leukocyte cell adhesion molecule 1 and induced the adhesion of PMN and monocytes to umbilical cord vein endothelial cell monolayers. When subcutaneously injected into mice, rSAA recruited PMN and monocytes at the injection site. On the basis of these data, we suggest that SAA may participate in enhancing the migration of monocytes and PMN to inflamed tissues during an acute phase response. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. BROWN UNIV,MIRIAM HOSP,LIPID RES LAB,PROVIDENCE,RI 02906. RP BADOLATO, R (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. RI Badolato, Raffaele/A-8081-2010 OI Badolato, Raffaele/0000-0001-7375-5410 NR 23 TC 333 Z9 339 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1994 VL 180 IS 1 BP 203 EP 209 DI 10.1084/jem.180.1.203 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900023 PM 7516407 ER PT J AU KAWAKAMI, Y ELIYAHU, S SAKAGUCHI, K ROBBINS, PF RIVOLTINI, L YANNELLI, JR APPELLA, E ROSENBERG, SA AF KAWAKAMI, Y ELIYAHU, S SAKAGUCHI, K ROBBINS, PF RIVOLTINI, L YANNELLI, JR APPELLA, E ROSENBERG, SA TI IDENTIFICATION OF THE IMMUNODOMINANT PEPTIDES OF THE MART-1 HUMAN-MELANOMA ANTIGEN RECOGNIZED BY THE MAJORITY OF HLA-A2-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID T-CELL CLONES; IMMUNOTHERAPY; RESTRICTION; HLA-A2.1; CANCER AB Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein-1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL, when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP KAWAKAMI, Y (reprint author), NCI,SURG BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 2B42,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini, Licia/0000-0002-2409-6225 NR 27 TC 696 Z9 698 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1994 VL 180 IS 1 BP 347 EP 352 DI 10.1084/jem.180.1.347 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900037 PM 7516411 ER PT J AU SCHNITZLER, P SONNTAG, KC MULLER, M JANSSEN, W BUGERT, JJ KOONIN, EV DARAI, G AF SCHNITZLER, P SONNTAG, KC MULLER, M JANSSEN, W BUGERT, JJ KOONIN, EV DARAI, G TI INSECT IRIDESCENT VIRUS TYPE-6 ENCODES A POLYPEPTIDE RELATED TO THE LARGEST SUBUNIT OF EUKARYOTIC RNA-POLYMERASE-II SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CIRCULAR PERMUTATION; DNA-REPLICATION; GENOME; EVOLUTION; IDENTIFICATION; SEQUENCE; GENES; ARCHAEBACTERIA; HOMOLOGY AB Cytoplasmic DNA viruses encode a DNA-dependent RNA polymerase (DdRP) that is essential for transcription of viral genes. The amino acid sequences of known large subunits of DdRPs contain highly conserved regions. Oligonucleotide primers, deduced from two conserved domains [RQP(T/S)LH and NADFDG-DE] were used in PCR experiments for the detection of the corresponding gene of the genome of insect iridescent virus type 6, also known as Chilo iridescent virus (CIV). A specific DNA product of about 150 bp could be amplified and was used as a hybridization probe against the CIV gene library to identify the corresponding gene. The gene encoding the DdRP was identified within the EcoRI fragments M (7099 bp) and L (7400 bp) of CIV DNA, between map units 0.310 and 0.347 (7990 bp). The DNA nucleotide sequence (3153 bp) of the gene encoding the largest subunit of DdRP (RPO1) was determined. Northern blot hybridization revealed the presence of a 3.4 kb RNA transcript in CIV-infected cells that hybridized to the CIV DdRP gene. This predicted viral protein consists of 1051 amino acid residues (120K) and showed considerably higher similarity to the largest subunit of eukaryotic RNA polymerase II than to the homologous proteins of vaccinia virus and African swine fever virus. Phylogenetic analysis suggested that the putative RPO1 of CIV could have evolved from RNA polymerase II after the divergence of the three types of eukaryotic RNA polymerases. The putative RPO1 of CIV lacked the C-terminal domain that is conserved in eukaryotic, eubacterial and other viral RNA polymerases and in this respect was analogous to the RNA polymerases of Archaea. It is hypothesized that the equivalent of the C-terminal domain may reside in another subunit of CIV DdRP encoded by an unidentified viral gene. C1 UNIV HEIDELBERG, INST MED VIROL, D-69120 HEIDELBERG, GERMANY. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RI Bugert, Joachim/D-1705-2012 OI Bugert, Joachim/0000-0002-0556-3211 NR 39 TC 22 Z9 24 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 1994 VL 75 BP 1557 EP 1567 DI 10.1099/0022-1317-75-7-1557 PN 7 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA NV175 UT WOS:A1994NV17500006 PM 8021587 ER PT J AU GERNA, G STEELE, AD HOSHINO, Y SERENO, M GARCIA, D SARASINI, A FLORES, J AF GERNA, G STEELE, AD HOSHINO, Y SERENO, M GARCIA, D SARASINI, A FLORES, J TI A COMPARISON OF THE VP7 GENE-SEQUENCES OF HUMAN AND BOVINE ROTAVIRUSES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID SEROTYPE-SPECIFIC GLYCOPROTEIN; NUCLEOTIDE-SEQUENCE; NEUTRALIZATION EPITOPES; GENOMIC CHARACTERIZATION; RHESUS-ROTAVIRUS; SUBGROUP-I; STRAINS; SITES AB The sequences of the gene encoding VP7 (the major outer capsid protein) from one bovine and three human rotavirus strains were determined because of their unusual VP7 specificities. Two of the human strains (PA 169 and PA 151) had VP7 serotype 6 specificity whereas the two other strains, recovered from a child (HAL 1166) and a calf (678) belonged to VP7 serotype 8. The serotype 8 strains exhibited a high degree of sequence conservation when compared with each other and with other serotype 8 strains previously sequenced. The serotype 6 human strains shared a greater degree of sequence similarity with previously reported serotype 6 bovine strains than with other rotavirus serotypes; however the degree of sequence similarity among PA 169, PA 151 and the bovine strains was lower than had been previously reported for strains belonging to the same serotype. The demonstration of rotavirus serotypes that are shared between human and animal species supports the concept that interspecies transmission occurs and may play a role in rotavirus evolution. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NEW YORK MED COLL,VALHALLA,NY 10595. RP GERNA, G (reprint author), UNIV PAVIA,IRCCS,POLICLIN SAN MATTEO,INST INFECT DIS,VIRUS LAB,I-27100 PAVIA,ITALY. NR 27 TC 20 Z9 20 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 1994 VL 75 BP 1781 EP 1784 DI 10.1099/0022-1317-75-7-1781 PN 7 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA NV175 UT WOS:A1994NV17500029 PM 8021607 ER PT J AU SAMBUNARIS, A HYDE, TM AF SAMBUNARIS, A HYDE, TM TI STROKE-RELATED APHASIAS MISTAKEN FOR PSYCHOTIC SPEECH - 2 CASE-REPORTS SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article AB A large portion of the human central nervous system is dedicated to and specialized for language function. Aphasias, disorders of language, can be seen in many psychiatric and neurologic conditions. On occasion, it is difficult to differentiate between language abnormalities secondary to a patient's psychiatric illness and those secondary to a superimposed neurologic condition. In particular, in the evaluation of a patient with a history of a psychotic illness, it is easy to misinterpret the presentation of ''abnormal'' speech as an exacerbation of the patient's pre-existing psychiatric illness. To show this psychoneurologic comorbidity, two case reports are presented. C1 NIMH,HOSP NEUROPSYCHIAT RES,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIMH,HOSP NEUROPSYCHIAT RES,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 10 TC 6 Z9 6 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUL-SEP PY 1994 VL 7 IS 3 BP 144 EP 147 PG 4 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA PK903 UT WOS:A1994PK90300003 PM 7916937 ER PT J AU VUKICEVIC, S HELDER, MN LUYTEN, FP AF VUKICEVIC, S HELDER, MN LUYTEN, FP TI DEVELOPING HUMAN LUNG AND KIDNEY ARE MAJOR SITES FOR SYNTHESIS OF BONE MORPHOGENETIC PROTEIN-3 (OSTEOGENIN) SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE BONE MORPHOGENETIC PROTEIN-3; TGFP SUPERFAMILY; HUMAN DEVELOPMENT; LUNG DEVELOPMENT; KIDNEY DEVELOPMENT; IN SITU HYBRIDIZATION; IMMUNOHISTOCHEMISTRY; NORTHERN HYBRIDIZATION; HUMAN EMBRYOS ID FACTOR-BETA SUPERFAMILY; INSITU HYBRIDIZATION; CHROMOSOMAL LOCALIZATION; EMBRYONIC-DEVELOPMENT; HUMAN GENES; RNA; EXPRESSION; MOUSE; BMP-2A; OP-1 AB Bone morphogenetic protein-3 (BMP-3; osteogenin) is a member of the transforming growth factor-beta superfamily. We used human BMP-3 cDNA probes and a specific BMP-3 polyclonal peptide antibody to analyze BMP-3 expression and synthesis in human fetal and adult tissues. Northern blot hybridization revealed two mRNA species of 7 and 3 KB. High levels of BMP-3 mRNA were found in fetal lungs. By in situ hybridization, the BMP-3 transcripts were found in lung bronchial epithelium, straight collecting kidney tubules, intestinal mucosa, perichondrium, periosteum, and osteoblasts of human embryos of 6-14 weeks' gestation. Cellular BMP-3 immunostaining co-localized with the distribution of RNA. In addition, bone matrix showed intensive BMP-3 staining. These data suggest that although BMP-3 has been isolated from bone matrix, it may have additional regulatory roles in the morphogenesis and/or function of human lung, kidney, and intestine. C1 FREE UNIV AMSTERDAM,ACTA,DEPT ORAL CELL BIOL,AMSTERDAM,NETHERLANDS. RP VUKICEVIC, S (reprint author), NIDR,BONE RES BRANCH,BLDG 10,RM 1N108,BETHESDA,MD 20892, USA. NR 29 TC 58 Z9 59 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 1994 VL 42 IS 7 BP 869 EP 875 PG 7 WC Cell Biology SC Cell Biology GA NT934 UT WOS:A1994NT93400005 PM 8014470 ER PT J AU SHARROW, SO BARDEN, LA SINGER, A KATZ, SI AF SHARROW, SO BARDEN, LA SINGER, A KATZ, SI TI QUANTITATIVE DIFFERENCES IN CELL-SURFACE EXPRESSION OF CLASS-I MHC ANTIGENS ON MURINE EPIDERMAL LANGERHANS CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MONOCLONAL-ANTIBODIES; T-CELLS; RECOGNITION; PRODUCTS; THYMUS AB Epidermal Langerhans cells are derived from cells of bone marrow origin and, as the primary APC population in the skin, are responsible for initiation of many immune responses. Consequently, cell surface expression of MHC Ags by Langerhans cells is central to their function. Although murine Langerhans cells express class II MHC Ags at high levels, their level of expression of class I MHC has been controversial. In this study, cell surface expression of multiple individual class I MHC Ags on murine epidermal Langerhans cells was analyzed using quantitative immunofluorescence. It was found that Langerhans cells differentially express products of distinct class I genes. Langerhans cells expressed low cell surface amounts of H-2K and Qa-2, whereas expression of surface H-2D and H-2L by the same cells was high. Murine epidermal Langerhans cells therefore express low cell surface amounts of some but not all class I MHC Ags. Differential surface expression of products of distinct class I MHC genes by Langerhans cells may have a profound effect on cutaneous immune responses. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. RP SHARROW, SO (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. NR 25 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1994 VL 153 IS 1 BP 110 EP 116 PG 7 WC Immunology SC Immunology GA NV228 UT WOS:A1994NV22800011 PM 8207229 ER PT J AU OH, CK METCALFE, DD AF OH, CK METCALFE, DD TI TRANSCRIPTIONAL REGULATION OF THE TCA3 GENE IN MAST-CELLS AFTER FC-EPSILON-RI CROSS-LINKING SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; INFLAMMATORY CYTOKINES; INTERLEUKIN-2 GENE; EXPRESSION; PROMOTER; ENHANCER; PROTEIN; ACTIVATION; BINDING AB TCA3 is a pro-inflammatory cytokine expressed in mast cells after activation. To examine how this gene is reg TCA3 mRNA levels were examined and nuclear run-on experiments and promoter analysis were performed. Northern blot analysis showed that TCA3 message appeared in mast cells within 2 h after induction, with a t(1/2) of 30 min. Nuclear run-on experiments revealed that the appearance of TCA3 mRNA occurred in large part because of an increase in the level of de novo transcription. Analysis of the promoter region demonstrated that inducible gene expression was directed by a region extending between 1.324 kb and 0.082 kb upstream from the transcription start site. There was a 60- to 80-fold induction with TCA3 CAT constructs extending between 1.324 kb and 0.324 kb upstream from the transcription start site after treatment with PMA/A23187 and a 30- to 40-fold induction with Fc epsilon RI cross-linking. There was a seven- to eightfold induction with the region extending between 0.136 kb and 0.082 kb upstream from the transcription start site. TCA3 CAT constructs containing regions encompassing either the 0.042 kb or 2.0 kb sequence from the transcription start site were not able to direct CAT-protein synthesis. The TCA3 5' flanking sequence contained negative regulatory activity. Electrophoretic mobility shift assays revealed that protein in nuclear extracts of activated mast cells bound to an NF-kappa B element of the TCA3 gene. These findings demonstrate that the TCA3 gene is regulated transcriptionally in mast cells, with minimal promoter sequences contained within the 0.082 kb upstream region of the TCA3 gene; a putative enhancer NF-kappa B element is contained between 0.324 kb and 0.136 kb and a putative inhibitory element is contained between 1.324 kb and 2.0 kb upstream from the transcription start site. RP OH, CK (reprint author), NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BLDG 10,ROOM 11C-212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1994 VL 153 IS 1 BP 325 EP 332 PG 8 WC Immunology SC Immunology GA NV228 UT WOS:A1994NV22800034 PM 8207245 ER PT J AU PILARO, AM TAUB, DD MCCORMICK, KL WILLIAMS, HM SAYERS, TJ FOGLER, WE WILTROUT, RH AF PILARO, AM TAUB, DD MCCORMICK, KL WILLIAMS, HM SAYERS, TJ FOGLER, WE WILTROUT, RH TI TNF-ALPHA IS A PRINCIPAL CYTOKINE INVOLVED IN THE RECRUITMENT OF NK CELLS TO LIVER PARENCHYMA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; MIDDLE-T-ONCOGENE; ADOPTIVELY TRANSFERRED ADHERENT; ENDOTHELIAL-CELLS; VASCULAR ENDOTHELIUM; ADHESION MOLECULE-1; RESPONSE MODIFIERS; AUGMENTATION AB Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four- to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL THERAPEUT SECT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Sayers, Thomas/G-4859-2015 NR 44 TC 40 Z9 40 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1994 VL 153 IS 1 BP 333 EP 342 PG 10 WC Immunology SC Immunology GA NV228 UT WOS:A1994NV22800035 PM 8207246 ER PT J AU MARINCOLA, FM SHAMAMIAN, P SIMONIS, TB ABATI, A HACKETT, J ODEA, T FETSCH, P YANNELLI, J RESTIFO, NP MULE, JJ ROSENBERG, SA AF MARINCOLA, FM SHAMAMIAN, P SIMONIS, TB ABATI, A HACKETT, J ODEA, T FETSCH, P YANNELLI, J RESTIFO, NP MULE, JJ ROSENBERG, SA TI LOCUS-SPECIFIC ANALYSIS OF HUMAN-LEUKOCYTE ANTIGEN CLASS-I EXPRESSION IN MELANOMA CELL-LINES SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE MELANOMA; HUMAN LEUKOCYTE ANTIGEN CLASS I; IMMUNOTHERAPY ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN-MALIGNANT MELANOMA; MONOCLONAL-ANTIBODY; HLA-A; BETA-2-MICROGLOBULIN; DETERMINANTS; RESTRICTION; GENE; IDENTIFICATION; RECOGNITION AB Surface expression of human leukocyte antigen (HLA) class I antigens on melanoma lines was evaluated by locus-specific monoclonal antibodies (mAbs) with three different techniques: Fluorescence-activated cell sorting (FACS), immunohistochemistry with cytospin preparation (ICP), and complement-mediated cytotoxicity (CMC). Eleven HLA class I-expressing cell lines developed from metastases were used. Specific expression of HLA loci was examined under routine culture conditions and after 48-h incubation in interferon-gamma (IFN-gamma; 500 U/ml). Loss of allelic expression was seen in one line (586-MEL): Products of genes coding for HLA-A29 and -B44, in strong linkage disequilibrium, were not detectable. HLA-A antigens were consistently detected by all methodologies and minimally affected by pretreatment with IFN-gamma. HLA-B antigens were detectable in 8 of 11 lines by ICP and 3 of 11 lines by CMC. By FACS the supratypic specificity HLA-Bw6 was expressed at low levels in most lines (mean fluorescence 47.2 +/- 13.4 and rose to 259.8 +/- 45.9 after incubation with IFN-gamma; p < 0.001). HLA-Cw antigen detection by CMC correlated with HLA-B (p < 0.01), suggesting that down-regulation and sensitivity to IFN-gamma are shared by the two loci. This low expression of the HLA-B antigens may play a role in the evasion of the host immune response and its up-regulation may be useful in allowing tumor antigen recognition. C1 NCI,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,CYTOPATHOL SECT,BETHESDA,MD 20892. RP MARINCOLA, FM (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BLDG 10,RM 2B42,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 46 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1994 VL 16 IS 1 BP 13 EP 23 DI 10.1097/00002371-199407000-00002 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA NT514 UT WOS:A1994NT51400002 PM 8081556 ER PT J AU KIM, H ROSENBERG, SA STEINBERG, SM COLE, DJ WEBER, JS AF KIM, H ROSENBERG, SA STEINBERG, SM COLE, DJ WEBER, JS TI A RANDOMIZED DOUBLE-BLINDED COMPARISON OF THE ANTIEMETIC EFFICACY OF ONDANSETRON AND DROPERIDOL IN PATIENTS RECEIVING HIGH-DOSE INTERLEUKIN-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE ANTIEMESIS; ANTINAUSEA; HIGH-DOSE INTERLEUKIN-2; ONDANSETRON; DROPERIDOL ID SEROTONIN ANTAGONIST; METOCLOPRAMIDE; CHEMOTHERAPY; CANCER; NAUSEA AB Emesis and nausea are common toxicities seen during high-dose interleukin-2 (IL-2) therapy (720,000 IU/kg i.v. every 8 h). A growing list of randomized studies have documented the efficacy of ondansetron, a potent antagonist of the 5-hydroxytryptamine, receptor, in preventing acute chemotherapy-induced emesis and nausea. However, no study has evaluated the efficacy of ondansetron in preventing IL-2-induced emesis and nausea. This double-blinded, randomized trial was performed to compare the antiemetic and antinausea efficacy of ondansetron with that of droperidol, a butyrophenone, in patients receiving high-dose IL-2 on protocols at the National Cancer Institute. Ondansetron or droperidol was given intravenously, 30 min prior to the first dose of IL-2 and then every 8 h for the duration of IL-2 treatment. No significant differences were seen between the two agents in complete freedom from emesis (p2 = 0.51), level of nausea (p2 = 0.17), antiemetic treatment failure (p2 = 0.89), and time to first emetic episode (p2 = 0.44). Equivalent doses of IL-2 were administered on each arm of the study, with a similar incidence of liver dysfunction (p2 = 0.15) and diarrhea (p2 = 0.64). Finally, there was no significant difference in the response rates to metastatic disease in either arm of the antiemetic study (p2 = 0.67), and these response rates were similar to those in other patients treated under immunotherapy protocols in the Surgery Branch of the National Cancer Institute with high-dose IL-2. We conclude that droperidol is equally effective in preventing emesis and controlling nausea when compared with ondansetron for patients receiving high-dose IL-2. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP KIM, H (reprint author), NCI,SURG BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 2B42,BETHESDA,MD 20892, USA. NR 11 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1994 VL 16 IS 1 BP 60 EP 65 DI 10.1097/00002371-199407000-00006 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA NT514 UT WOS:A1994NT51400006 PM 8081560 ER PT J AU STRAUS, SE KOMAROFF, AL WEDNER, HJ AF STRAUS, SE KOMAROFF, AL WEDNER, HJ TI CHRONIC FATIGUE SYNDROME - POINT AND COUNTERPOINT SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POSTVIRAL FATIGUE; IMMUNOLOGICAL ABNORMALITIES; INFECTION; DEFINITION; ACTIVATION; BIOMARKERS; DISORDERS; EXPOSURE; ALLERGY; DISEASE AB Two clinical investigators with divergent views on chronic fatigue syndrome (CFS) were invited to debate their positions at the 1993 annual meeting of The Infectious Disease Society of America. Major points of the discourse focused on the value of the US Centers for Disease Control and Prevention case definition of CFS, the potential roles of infectious and allergic problems in the syndrome, the confounding problem of concurrent psychiatric problems, and the utility of diagnostic tests. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED & PRIMARY CARE,BOSTON,MA 02115. HARVARD UNIV,BOSTON,MA. WASHINGTON UNIV,DEPT MED,DIV CLIN ALLERGY & IMMUNOL,ST LOUIS,MO. RP STRAUS, SE (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,RM 11N228,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 17 Z9 18 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1994 VL 170 IS 1 BP 1 EP 6 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NR965 UT WOS:A1994NR96500001 PM 8014482 ER PT J AU HIRSCH, VM GOLDSTEIN, S HYNES, NA ELKINS, WR LONDON, WT ZACK, PM MONTEFIORI, D JOHNSON, PR AF HIRSCH, VM GOLDSTEIN, S HYNES, NA ELKINS, WR LONDON, WT ZACK, PM MONTEFIORI, D JOHNSON, PR TI PROLONGED CLINICAL LATENCY AND SURVIVAL OF MACAQUES GIVEN A WHOLE INACTIVATED SIMIAN IMMUNODEFICIENCY VIRUS-VACCINE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIBODY-DEPENDENT ENHANCEMENT; RHESUS-MONKEYS; CONFERS PROTECTION; SIV INFECTION; SUBUNIT VACCINES; HOMOSEXUAL MEN; CHALLENGE; DISEASE; CHIMPANZEES; HIV-1 AB Simian immunodeficiency virus (SIV) infection of macaques is a useful and relevant model for evaluating candidate human immunodeficiency virus (HIV) vaccines. One important feature of this model is that SIV vaccines can be evaluated for their ability to prevent infection as well as to prevent or delay the onset of AIDS. In the present study, a group of macaques was vaccinated with whole inactivated SIV and challenged with peripheral blood mononuclear cells from an SIV-infected macaque. This challenge represented a rigorous and realistic test of the immunization protocol. All macaques became infected after challenge; however, immunized animals survived significantly longer (P < .03) than naive controls. These data suggest that similar vaccines administered to humans at risk for HIV-1 infection might delay or prevent AIDS even if the vaccine failed to prevent infection. C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. WALTER REED ARMY INST PATHOL,BETHESDA,MD. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. OHIO STATE UNIV,CHILDRENS HOSP RES FDN,DEPT PEDIAT,COLUMBUS,OH 43210. RP HIRSCH, VM (reprint author), NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,TWINBROOK 2 FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 NR 56 TC 38 Z9 39 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1994 VL 170 IS 1 BP 51 EP 59 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NR965 UT WOS:A1994NR96500008 PM 8014520 ER PT J AU SATTLER, FR FRAME, P DAVIS, R NICHOLS, L SHELTON, B AKIL, B BAUGHMAN, R HUGHLETT, C WEISS, W BOYLEN, CT VANDERHORST, C BLACK, J POWDERLY, W STEIGBIGEL, RT LEEDOM, JM MASUR, H FEINBERG, J BENOIT, S EYSTER, E GOCKE, D BECK, K LEDERMAN, M PHAIR, J REICHMAN, R SACKS, HS SOIERO, R AF SATTLER, FR FRAME, P DAVIS, R NICHOLS, L SHELTON, B AKIL, B BAUGHMAN, R HUGHLETT, C WEISS, W BOYLEN, CT VANDERHORST, C BLACK, J POWDERLY, W STEIGBIGEL, RT LEEDOM, JM MASUR, H FEINBERG, J BENOIT, S EYSTER, E GOCKE, D BECK, K LEDERMAN, M PHAIR, J REICHMAN, R SACKS, HS SOIERO, R TI TRIMETREXATE WITH LEUCOVORIN VERSUS TRIMETHOPRIM-SULFAMETHOXAZOLE FOR MODERATE TO SEVERE EPISODES OF PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH AIDS - A PROSPECTIVE, CONTROLLED MULTICENTER INVESTIGATION OF THE AIDS-CLINICAL-TRIALS-GROUP PROTOCOL-029/031 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; DIHYDROFOLATE-REDUCTASE; ADJUNCTIVE THERAPY; CORTICOSTEROIDS; PENTAMIDINE; 566C80 AB Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P =.064), and the PAO(2) - Pao(2) improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P =.008), with respective mortality rates of 12% and 20% (P =.088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ. C1 UNIV CINCINNATI,COLL MED,CINCINNATI,OH. HARVARD UNIV,CTR STAT & DATA ANAL,AIDS CLIN TRIALS GRP,BOSTON,MA. RES TRIANGLE INST,RES TRIANGLE PK,NC. UNIV N CAROLINA,SCH MED,DEPT MED,DURHAM,NC. INDIANA UNIV,COLL MED,DEPT MED,INDIANAPOLIS,IN. WASHINGTON UNIV,DEPT MED,ST LOUIS,MO. SUNY STONY BROOK,HLTH SCI CTR,STONY BROOK,NY 11794. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY. NIAID,DIV AIDS,BETHESDA,MD. NIAID,CTR CLIN,BETHESDA,MD 20892. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,HERSHEY,PA. ROBERT WOOD JOHNSON MED CTR,NEW BRUNSWICK,NJ. CASE WESTERN RESERVE UNIV,CLEVELAND,OH. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. CUNY MT SINAI SCH MED,NEW YORK,NY. YESHIVA UNIV,YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX MUNICIPAL HOSP CTR,NEW YORK,NY. RP SATTLER, FR (reprint author), UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT MED,RAND SCHRADER CLIN,RM 349,1175 N CUMMINGS ST,LOS ANGELES,CA 90033, USA. FU NIAID NIH HHS [AI-6540] NR 27 TC 64 Z9 65 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1994 VL 170 IS 1 BP 165 EP 172 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NR965 UT WOS:A1994NR96500024 PM 8014493 ER PT J AU JACOBSON, MA KRAMER, F BASSIAKOS, Y HOOTON, T POLSKY, B GEHEB, H ODONNELL, JJ WALKER, JD KORVICK, JA VANDERHORST, C AF JACOBSON, MA KRAMER, F BASSIAKOS, Y HOOTON, T POLSKY, B GEHEB, H ODONNELL, JJ WALKER, JD KORVICK, JA VANDERHORST, C TI RANDOMIZED PHASE-I TRIAL OF 2 DIFFERENT COMBINATION FOSCARNET AND GANCICLOVIR CHRONIC MAINTENANCE THERAPY REGIMENS FOR AIDS PATIENTS WITH CYTOMEGALOVIRUS RETINITIS - AIDS-CLINICAL-TRIALS-GROUP PROTOCOL-151 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; INVITRO AB AIDS patients with newly diagnosed cytomegalovirus (CMV) retinitis who had just completed a 14-day course of ganciclovir induction therapy were randomly assigned to an alternating or concurrent combination regimen of chronic ganciclovir-foscarnet therapy for CMV retinitis. Each regimen used lower weekly cumulative doses of each drug than standard monotherapy maintenance treatment regimens. Dose-limiting toxicity attributable to foscarnet occurred in only 2 (7%) of 29 evaluatable patients, and no patients experienced dose-limiting nephrotoxicity. Although absolute neutrophil counts <500 cells/mu L occurred in 11 (38%) of 29 patients, all who subsequently used adjunctive granulocyte colony-stimulating factor had severe neutropenia prevented. Severe toxicity of any type and neutropenia, in particular, occurred significantly more frequently in patients assigned to the concurrent treatment regimen. CMV was isolated from none of 21 patients who had urine cultured and from only 1 of 24 who had blood cultured while being treated during the study (median evaluation, 12 weeks). This suggests that combination therapy provides better in vivo antiviral activity in suppressing CMV replication than previously reported with monotherapy regimens. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT MED,LOS ANGELES,CA 90089. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DOHENY EYE INST,DEPT OPHTHALMOL,LOS ANGELES,CA 90089. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. FRONTIER SCI & TECHNOL RES FDN INC,BOSTON,MA. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,NEW YORK,NY. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. FU NIAID NIH HHS [AI-25868, AI-25917, AI-27663] NR 12 TC 37 Z9 38 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1994 VL 170 IS 1 BP 189 EP 193 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NR965 UT WOS:A1994NR96500027 PM 8014496 ER PT J AU CLARK, SJ KELEN, GD HENRARD, DR DAAR, ES CRAIG, S SHAW, GM QUINN, TC AF CLARK, SJ KELEN, GD HENRARD, DR DAAR, ES CRAIG, S SHAW, GM QUINN, TC TI UNSUSPECTED PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN SERONEGATIVE EMERGENCY DEPARTMENT PATIENTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ANTIBODY; BLOOD; HIV; TRANSMISSION; INTERVENTION; TRANSFUSION; ANTIGEN; PLASMA; RISK AB To estimate the number of recently infected patients in the window period before human immunodeficiency virus type 1 (HIV-1) seroconversion among patients seeking medical care, randomly selected adults presenting to an inner city emergency department were tested for HIV-1 antibody and p24 antigen. Of 2300 patients enrolled, 180 (7.8%; 95% confidence interval [CI]: 6.7%-8.9%) were Western blot (WB)-positive for HIV-1 antibodies. Of 2120 antibody-negative or WB-indeterminate patients, none of whom were identified on clinical grounds as having primary HIV-1 infection, 6 (0.28%; CI, 0.07%-0.51%) were p24 antigen-positive with serologies consistent with primary HIV-1 infection. Of these 6, 3 were seronegative even with third-generation antibody ELISA. HIV-1 infection in these 6 patients was further confirmed by polymerase chain reaction amplification of virion-associated RNA in serum demonstrating 10(4)-10(5) virions/mL. With 40,000 new HIV-1 infections in the United States annually, similar to 750 persons with undiagnosed primary HIV-1 infections may seek primary health care in any given week in the United States. Testing for viral antibodies alone will fail to detect a large proportion of these persons. Thus, early identification by p24 antigen testing may be important to diagnose and treat symptomatic illness, implement public health and counseling measures, and arrange appropriate medical follow-up. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. UNIV ALABAMA,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,DIV HEMATOL ONCOL,BIRMINGHAM,AL 35294. ABBOTT LABS,DIV RETROVIRUS DIAGNOST,ABBOTT PK,IL 60064. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. JOHNS HOPKINS UNIV,SCH MED,DIV EMERGENCY MED,BALTIMORE,MD. NIAID,BETHESDA,MD 20892. OI Kelen, Gabor/0000-0002-3236-8286 FU NIAID NIH HHS [AI-27767, AI-27290] NR 15 TC 27 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1994 VL 170 IS 1 BP 194 EP 197 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NR965 UT WOS:A1994NR96500028 PM 8014497 ER PT J AU MORIWAKI, SI TARONE, RE KRAEMER, KH AF MORIWAKI, SI TARONE, RE KRAEMER, KH TI A POTENTIAL LABORATORY TEST FOR DYSPLASTIC NEVUS SYNDROME - ULTRAVIOLET HYPERMUTABILITY OF A SHUTTLE VECTOR PLASMID SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE MELANOMA; DNA REPAIR; TRANSFECTION; LYMPHOBLASTOID CELLS ID CUTANEOUS MALIGNANT-MELANOMA; XERODERMA-PIGMENTOSUM-CELLS; SISTER CHROMATID EXCHANGES; FAMILIAL MELANOMA; VARIANT CELLS; 4-NITROQUINOLINE 1-OXIDE; MUTATIONAL SPECTRUM; POINT MUTATIONS; MAMMALIAN-CELLS; FIBROBLASTS AB The diagnosis of the melanoma-prone disorder dysplastic nevus syndrome (DNS) is based currently on a combination of clinical and histopathologic examinations of patients. To develop a potential laboratory test for DNS, we utilized the observation that an ultraviolet light (UV)-treated mutagenesis plasmid shuttle vector has an abnormally increased frequency of mutations after transfection into lymphoblastoid cells from a patient with familial DNS. pSP189 (containing the bacterial suppressor tRNA gene supF as a marker for mutations and a gene for ampicillin resistance for selection) was treated with UV and transfected into familial DNS, xeroderma pigmentosum complementation group A (XP-A), and normal lymphoblastoid cells by electroporation or diethylaminoethyl (DEAE) dextran. Untreated plasmid pZ189K (containing a gene for kanamycin resistance) was co-transfected as an internal standard to reduce the variability of plasmid survival measurements. After 2 d, plasmids were extracted, used to transform an indicator strain of Escherichia coli, and assayed on plates containing ampicillin of kanamycin. Counting light blue or white colonies (containing mutate supF in the plasmid) and blue colonies (with wild type supF) permitted measurement of the plasmid survival and mutation frequency. Transfection by electroporation or DEAE dextran resulted in abnormally reduced survival of UV treated plasmid after passage through the XP-A but normal survival in the three DNS lines. Transfection of UV-treated plasmid by DEAE dextran yielded a greater hypermutability with the familial DNS lines than by electroporation. These results suggest that pSP189 UV hypermutability with normal UV survival using DEAE dextran transfection may form the basis of a potential laboratory assay for familial C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. FU Intramural NIH HHS [Z01 BC004517-31] NR 55 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1994 VL 103 IS 1 BP 7 EP 12 DI 10.1111/1523-1747.ep12388847 PG 6 WC Dermatology SC Dermatology GA NW533 UT WOS:A1994NW53300002 PM 8027583 ER PT J AU MUSSO, T BOSCO, MC LONGO, DL ESPINOZADELGADO, I SICA, A COX, GW GUSELLA, GL FORNI, G VARESIO, L AF MUSSO, T BOSCO, MC LONGO, DL ESPINOZADELGADO, I SICA, A COX, GW GUSELLA, GL FORNI, G VARESIO, L TI LPS-INDUCIBLE NUCLEAR FACTOR IN HUMAN MONOCYTES THAT BINDS THE NEGATIVE REGULATORY ELEMENT OF THE HIV LTR SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE LIPOPOLYSACCHARIDE; HIV; HUMAN MONOCYTES; NUCLEAR FACTOR ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; MONONUCLEAR PHAGOCYTES; TRANSCRIPTION FACTOR; HTLV-III; TYPE-1; REPLICATION; EXPRESSION; INFECTION; PROTEIN AB We studied the constitutive and lipopolysaccharide (LPS)-induced expression of nuclear protein binding to the negative regulatory element (NRE) of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in fresh human monocytes. We demonstrated the existence of a constitutive factor binding to the NRE 73-bp HpaII/HpaII fragment (-216 to -143) whose expression is up-regulated bp LPS treatment. Competition experiments with overlapping oligonucleotides covering the HpaII/HpaII fragment and with mutated oligonucleotides mapped the binding within the TTTCATCAC region (-171 to -163). This binding pattern is unique to human monocytes. C1 PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV TURIN,INST MICROBIOL,I-10124 TURIN,ITALY. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. CNR,CTR IMMUNOGENET & HISTOCOMPATIBIL,I-10126 TURIN,ITALY. RP MUSSO, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 FU NCI NIH HHS [N01-CO-74102] NR 33 TC 8 Z9 8 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 1994 VL 56 IS 1 BP 21 EP 26 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA NV803 UT WOS:A1994NV80300004 PM 8027666 ER PT J AU KNAPP, HR HULLIN, F SALEM, N AF KNAPP, HR HULLIN, F SALEM, N TI ASYMMETRIC INCORPORATION OF DIETARY N-3 FATTY-ACIDS INTO MEMBRANE AMINOPHOSPHOLIPIDS OF HUMAN ERYTHROCYTES SO JOURNAL OF LIPID RESEARCH LA English DT Article DE FIS OILS; OMEGA-3 FATTY ACIDS; TRINITROBENZENESULFONIC ACID; PHOSPHATIDYLETHANOLAMINE; PHOSPHATIDYLSERINE; PHOSPHOLIPID MOLECULAR SPECIES; MEMBRANE LIPID ASYMMETRY ID RED-CELL MEMBRANE; FISH-OIL; EICOSAPENTAENOIC ACID; PLASMA-MEMBRANE; HUMAN-PLATELETS; PHOSPHOLIPIDS; RAT; SUPPLEMENTATION; PROTEINS; PHOSPHATIDYLETHANOLAMINE AB Dietary supplementation with different classes of polyunsaturate fatty acids is known to result in their incorporation into cell membranes, but the effects of this on eicosanoid formation and other cell functions frequently does not correspond to the degree of alteration in total membrane fatty acids. This phenomenon may be related to the compartmentalization of polyunsaturate fatty acids both within the organelles and within membranes. Aminophospholipids are asymmetrically distributed across the membrane bilayers of most human cells. These phospholipids are highly enriched in polyunsaturated fatty acids, and are known to have specific interactions with a number of membrane proteins. To determine whether dietary n-3 fatty acids are preferentially incorporated into membrane lipids in a particular spatial pattern, we have utilized the nonpermeant aminophospholipid probe, trinitrobenzenesulfonic acid, to study the transmembrane molecular species distribution of human erythrocyte ethanolamine phospholipids and phosphatidylserines before and at the end of 4 weeks of dietary supplementation with n-3 fatty acids. Selective incorporation of n-3 fatty acids occurred in the inner membrane leaflet ethanolamine phospholipids, particularly into the alkenyl-acyl species. The n-3 species in phosphatidylserines, particularly 18:0 and 22:6 n-3 (sn-1 and sn-2, respectively), replaced n-6 and n-9 species. These data may provide a basis for different cell responses to n-3 fatty acid enrichment, and for different degrees of diet-induced alteration in responses involving inner and outer membrane leaflet functions. C1 NIAAA,MEMBRANE BIOCHEM & BIOPHYS LAB,BETHESDA,MD. RP KNAPP, HR (reprint author), UNIV IOWA,DEPT INTERNAL MED,DIV CLIN PHARMACOL,IOWA CITY,IA 52242, USA. FU NHLBI NIH HHS [HL-49264, HL-48877] NR 52 TC 33 Z9 33 U1 1 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1994 VL 35 IS 7 BP 1283 EP 1291 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW335 UT WOS:A1994NW33500015 PM 7964189 ER PT J AU DAVIS, DG PERLMAN, ME LONDON, RE AF DAVIS, DG PERLMAN, ME LONDON, RE TI DIRECT MEASUREMENTS OF THE DISSOCIATION-RATE CONSTANT FOR INHIBITOR-ENZYME COMPLEXES VIA THE T-1-RHO AND T-2 (CPMG) METHODS SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID RELAXATION-MATRIX ANALYSIS; SPIN-LATTICE RELAXATION; CHEMICAL EXCHANGE; ROTATING FRAME; NUCLEAR; CONFORMATIONS; PROTEINS; T2 AB The unimolecular dissociation rate constant, k(-1), for the inhibitor-enzyme complex tubercidin-Escherichia coli purine nucleoside phosphorylase (PNPase) has been determined directly via two related H-1 NMR methods for studying exchange-mediated transverse relaxation. One method involves measurements of the decay rate, 1/T-1 rho, of spin-locked magnetization in the rotating frame as a function of the strength of the spin-locking field, omega(SL) The second method involves measurements of the Carr-Purcell-Meiboom-Gill (CPMG) spin-echo decay rate, 1/T-2(CPMG) as a function of the repetition rate, 1/t(cp), of the refocusing pulses. Expressions describing the dependence of T-2(CPMG) as a function of 1/t(cp) and k(-1) have been previously derived with sufficient generality to include the two-site inhibitor-enzyme exchange case. Existing expressions for T-1 rho as a function of k(ex) and omega(SL), however, had to be reformulated to take into account differences between T-2(b) and T-1(b) for the bound form of the inhibitor as well as offset corrections important at low values of omega(SL) A new expression for exchange-mediated T-1 rho has been derived to take these factors into account and is shown to provide a more accurate description of observed T-1 rho data than previous models. Numerical analysis of relaxation rates, measured independently by either the rotating-frame or the spin-echo method for the H-1 and H-2 protons of tubercidin at different inhibitor:enzyme ratios, yields comparable values for k(-1) of 2400 (+/-350) and 900 (+/-80) s(-1) at 20 and 10 degrees C, respectively. The merits of both methods are compared and suggestions for optimizing the experiments are discussed. (C) 1994 Academic Press, Inc. RP DAVIS, DG (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 223 Z9 226 U1 2 U2 39 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUL PY 1994 VL 104 IS 3 BP 266 EP 275 DI 10.1006/jmrb.1994.1084 PG 10 WC Physics, Atomic, Molecular & Chemical SC Physics GA NX809 UT WOS:A1994NX80900008 PM 8069484 ER PT J AU TABOR, E HSIA, CC MUCHMORE, E AF TABOR, E HSIA, CC MUCHMORE, E TI HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL SIMILARITIES BETWEEN HEPATIC-TUMORS IN 2 CHIMPANZEES AND MAN SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE ALPHA-FETOPROTEIN; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HEPATOCELLULAR CARCINOMA; NON-A NON-B HEPATITIS; OVAL CELL; P53; STEM CELL; TRANSFORMING GROWTH FACTOR ALPHA; TUMOR SUPPRESSOR GENE ID GROWTH FACTOR-ALPHA; NON-B-HEPATITIS; HEPATOCELLULAR-CARCINOMA; P53 GENE; NON-A; LIVER; VIRUS; CELLS AB A well-differentiated trabecular hepatocellular carcinoma (HCC) and a well-differentiated tumor resembling HCC from each of two chimpanzees were found to have histochemical and immunohistochemical staining characteristics similar to those in human HCCs. Transforming growth factor alpha was overexpressed in both tumors. Oval cells, thought to be liver stem cell progeny with a possible role in hepatocarcinogenesis, were observed among nontumorous hepatocytes, particularly near the tumors. Hepatic tumors are rare in chimpanzees but their similarities to human HCC provides a useful research model. C1 NYU, MED CTR, EXPTL MED & SURG PRIMATES LAB, TUXEDO PK, NY USA. RP TABOR, E (reprint author), NCI, BETHESDA, MD 20892 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUL PY 1994 VL 23 IS 5 BP 271 EP 279 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA PR002 UT WOS:A1994PR00200001 PM 7869355 ER PT J AU RASOOL, NBG HAMZAH, M JEGATHESAN, M WONG, YH QIAN, Y GREEN, KY AF RASOOL, NBG HAMZAH, M JEGATHESAN, M WONG, YH QIAN, Y GREEN, KY TI IDENTIFICATION OF A HUMAN GROUP-C ROTAVIRUS IN MALAYSIA SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE DIARRHEA; G147; DS RNA ID GROUP-A ROTAVIRUSES; HUMAN PARAROTAVIRUS; BLOT HYBRIDIZATION; DIARRHEA; OUTBREAK; PIGS; NORTHERN; VIRUS; GENE; VP7 AB Stool specimens from 334 infants and young children hospitalized with diarrhea in the General Hospital, Kuala Lumpur, Malaysia between August and November, 1987 were analyzed for the presence of rotavirus double-stranded (ds) RNA by polyacrylamide gel electrophoresis. Of the 334 specimens analyzed, 32 (9.6%) were positive for rotavirus RNA. One specimen (designated G147) exhibited a ds RNA electropherotype profile characteristic of Group C rotavirus and was selected for further characterization. In Northern blot hybridization studies, the gene 5 segment of strain G147 hybridized with a cDNA probe generated from the cloned gene 5 (which encodes the VP6 inner capsid protein that is group specific) of porcine Group C rotavirus strain Cowden, confirming the classification of strain G147 in Group C. The association of Group C rotavirus with diarrheal illness in Malaysia is consistent with earlier studies that suggest a global distribution of this virus and supports the need for additional epidemiologic studies. (C) 1994 Wiley-Liss, Inc. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. UNIV MALAYA,DEPT GENET & CELLULAR BIOL,KUALA LUMPUR,MALAYSIA. KUALA LUMPUR GEN HOSP,INST MED RES,KUALA LUMPUR,MALAYSIA. KUALA LUMPUR GEN HOSP,DEPT LAB SERV,KUALA LUMPUR,MALAYSIA. NR 33 TC 16 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 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUL PY 1994 VL 43 IS 3 BP 209 EP 211 DI 10.1002/jmv.1890430302 PG 3 WC Virology SC Virology GA NT500 UT WOS:A1994NT50000001 PM 7931180 ER PT J AU HSIA, CC THORGEIRSSON, SS TABOR, E AF HSIA, CC THORGEIRSSON, SS TABOR, E TI EXPRESSION OF HEPATITIS-B SURFACE AND CORE ANTIGENS AND TRANSFORMING GROWTH-FACTOR-ALPHA IN OVAL CELLS OF THE LIVER IN PATIENTS WITH HEPATOCELLULAR-CARCINOMA SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE OVAL CELL; HEPATITIS B SURFACE ANTIGEN; HEPATITIS B VIRUS; STEM CELL; TRANSFORMING GROWTH FACTOR-ALPHA; HEPATOCELLULAR CARCINOMA ID HEPATOCARCINOGENESIS; VIRUS; RAT AB Recent studies have identified epithelial cell populations in human livers that are similar to the ''oval cells'' and ''transitional cells'' seen in rat livers during the early stages of chemical carcinogenesis. It has been suggested that these cells might be precursors of hepatocytes and theoretically could be involved in hepatocarcinogenesis. The hepatitis B virus (HBV) also is believed to play a role in the etiology of hepatocellular carcinoma (HCC). Therefore, a study was conducted in nontumorous livers adjacent to HCCs obtained from 26 patients from China to determine whether HBV antigens could be identified in oval cells and transitional cells using an immunohistochemical technique. Hepatitis B surface antigen (HBsAg) was detected in the nontumorous livers of 22/26 (85%) patients. HBsAg was detected in oval cells in 18/26 (69%), in transitional cells in 21/26 (81%), and in mature hepatocytes in 22/26 (85%), but not in bile duct or ductule cells. Transforming growth factor-alpha (TGF-alpha) was expressed in oval cells, transitional cells, and bile duct cells in 24/26 (92%) patients, an in mature hepatocytes in 25/26 (96%). Coexpression of HBsAg and TGF-alpha was identified in the same cells in populations of oval cells and transitional cells of selected patients. Because of the possibility that oval cells could be a source of evolving HCC, these findings suggest that expression of TGF-alpha associated with HBV infection of oval cells could be a mechanism of human hepatocarcinogenesis. Thus, oval cells could be a site (or one of the sites) where HBV participates in the development of HCC. (C) 1994 Wiley-Liss, Inc. C1 NCI,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NR 18 TC 63 Z9 65 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUL PY 1994 VL 43 IS 3 BP 216 EP 221 DI 10.1002/jmv.1890430304 PG 6 WC Virology SC Virology GA NT500 UT WOS:A1994NT50000003 PM 7523580 ER PT J AU LEEHUANG, S KUNG, HF CHEN, HC HUANG, PL RYBAK, SM HUANG, PL BOURINBAIAR, AS MUSAYEV, F LIAW, YC AF LEEHUANG, S KUNG, HF CHEN, HC HUANG, PL RYBAK, SM HUANG, PL BOURINBAIAR, AS MUSAYEV, F LIAW, YC TI CRYSTALLIZATION AND PRELIMINARY-X-RAY ANALYSIS OF GAP-31 - A PROTEIN WHICH INHIBITS THE LIFE-CYCLE OF HIV-1 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE ANTIVIRAL/ANTI-TUMOR AGENT; DNA/RNA BINDING; RIBOSOME INACTIVATION PROTEIN; CRYSTALLIZATION; X-RAY ANALYSIS ID SEQUENCE; DNA C1 ACAD SINICA,INST MOLEC BIOL,TAIPEI 11529,TAIWAN. NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016. NCI,FREDERICK CANC RES & DEV CTR,DCT,BRMP,BIOCHEM PATHOL LAB,FREDERICK,MD 21701. NICHHD,BETHESDA,MD 20892. AMER BIOSCI,NEW YORK,NY 10021. OI Lee-Huang, Sylvia/0000-0003-3302-241X FU NIAID NIH HHS [R01 AI31334] NR 12 TC 9 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 1 PY 1994 VL 240 IS 1 BP 92 EP 94 DI 10.1006/jmbi.1994.1421 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU952 UT WOS:A1994NU95200010 PM 8021945 ER PT J AU YUHKI, N OBRIEN, SJ AF YUHKI, N OBRIEN, SJ TI EXCHANGES OF SHORT POLYMORPHIC DNA SEGMENTS PREDATING SPECIATION IN FELINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE FELINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I GENES; MOLECULAR EVOLUTION ID ANTIGEN-BINDING SITE; T-CELL RECOGNITION; DOMESTIC CAT; EVOLUTION; DIVERSITY; RECOMBINATION; PREVALENCE; MOLECULES; PEPTIDES; GORILLA AB Sequence comparisons of 14 distinct MHC class I cDNA clones isolated from species representing the three major taxonomic lineages of Felidae (domestic cat lineage, ocelot lineage, and pantherine lineage) revealed that feline MHC class I alleles have highly mosaic structures with short polymorphic sequence motifs that are rearranged between alleles of individual MHC loci, between MHC class I genes within cat species, and between homologous MHC loci in different species. The pattern of sequence variation in felids supports the role of the following factors in production and maintenance of MHC variation: (1) gradual spontaneous mutation; (2) selective pressure to conserve certain residues but also to vary in hypervariable regions, notably residues that functionally participate in antigen recognition and presentation; and (3) recombination-mediated gene exchange between alleles and between related genes. The overall amount of genetic variation observed among MHC class I genes in the Felidae family is no greater than the amount of variation within any outbred cat species (i.e., domestic cat, ocelot). The occurrence of equivalent levels of polymorphism plus the simultaneous persistence of the same sequence motifs in divergent feline species suggest that most MHC class I nucleotide site polymorphism predated species divergences. Ancient polymorphisms have been transmitted through the speciation events and modern feline MHC class I alleles were derived by recombinational exchange of polymorphic sequence motifs. Moreover, some of these sequence motifs were found in other mammalian MHC class I genes, such as classical human KLA-BS, nonclassical human HLA-E class I genes, and bovine class I genes. These results raise the prospect of an ancient origin for some motifs, although the possibility of convergence in parallel mammalian radiations cannot be excluded. RP YUHKI, N (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 33 TC 19 Z9 19 U1 2 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD JUL PY 1994 VL 39 IS 1 BP 22 EP 33 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA NQ008 UT WOS:A1994NQ00800004 PM 8064870 ER PT J AU GEORGE, MS KELLNER, CH BERNSTEIN, H GOUST, JM AF GEORGE, MS KELLNER, CH BERNSTEIN, H GOUST, JM TI A MAGNETIC-RESONANCE-IMAGING INVESTIGATION INTO MOOD DISORDERS IN MULTIPLE-SCLEROSIS - A PILOT-STUDY SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Note ID CEREBRAL BLOOD-FLOW; DEPRESSED-PATIENTS; MAJOR DEPRESSION; HYPOMETABOLISM; ABNORMALITIES; DISEASE; SERIAL; LOBE C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT IMMUNOL,CHARLESTON,SC 29425. OI Kellner, Charles/0000-0001-9663-3571 NR 26 TC 14 Z9 14 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1994 VL 182 IS 7 BP 410 EP 412 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NV308 UT WOS:A1994NV30800008 PM 8021642 ER PT J AU HAUSER, P AF HAUSER, P TI THE THYROID AXIS AND PSYCHIATRIC-ILLNESS - JOFFE,RT, LEVITT,AJ SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP HAUSER, P (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1994 VL 182 IS 7 BP 420 EP 420 DI 10.1097/00005053-199407000-00025 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NV308 UT WOS:A1994NV30800025 ER PT J AU PENNYPACKER, KR THAI, L HONG, JS MCMILLIAN, MK AF PENNYPACKER, KR THAI, L HONG, JS MCMILLIAN, MK TI PROLONGED EXPRESSION OF AP-1 TRANSCRIPTION FACTORS IN THE RAT HIPPOCAMPUS AFTER SYSTEMIC KAINATE TREATMENT SO JOURNAL OF NEUROSCIENCE LA English DT Article DE FOS-RELATED ANTIGEN; JUN; CELL DEATH; GLIOSIS; REACTIVE ASTROCYTE; DNA BINDING ACTIVITY ID C-FOS EXPRESSION; PROGRAMMED CELL-DEATH; IMMEDIATE EARLY GENES; DNA-BINDING ACTIVITY; STATUS EPILEPTICUS; NERVOUS-SYSTEM; BRAIN; SEIZURES; ISCHEMIA; JUN AB Systemic administration of kainate, a glutamate receptor agonist, caused neuronal death in the CA1 and CA3 fields of the rat hippocampus. In the areas of cell loss, reactive astrocytes increased their expression of an astrocyte-specific protein, glial fibrillary acidic protein (GFAP). AP-1 DNA binding activity and the expression of a 35 kDa fos-related antigen (fra) remained elevated in the rat hippocampus for at least 2 weeks after a single systemic injection of kainate, which correlated with changes in gene expression during reactive gliosis. Immunoreactivity for fras was detected in the nuclei of neurons in the dentate gyrus, but relatively few cells in CA1 and CA3 were immunoreactive 1 week after kainate treatment. However, elevated AP-1 DNA binding activity was observed in the CA1 and CA3 regions as well as in the dentate gyrus, suggesting that proteins other than the fras were involved in the astrocytic AP-1 complex. The AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promotor region of the GFAP gene, suggesting that GFAP is a potential target gene. Thus, a single systemic injection of kainate causes long-term activation of AP-1 DNA binding activity in the rat hippocampus and may be important for long-term changes in gene expression in hippocampal cells. RP PENNYPACKER, KR (reprint author), NIEHS,NEUROPHARMACOL SECT,MD 14-06,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 28 TC 124 Z9 128 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1994 VL 14 IS 7 BP 3998 EP 4006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NZ620 UT WOS:A1994NZ62000002 PM 8027758 ER PT J AU SHAMIAN, J HAGEN, B HU, TW FOGARTY, TE AF SHAMIAN, J HAGEN, B HU, TW FOGARTY, TE TI THE RELATIONSHIP BETWEEN LENGTH OF STAY AND REQUIRED NURSING-CARE HOURS SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PROSPECTIVE PAYMENT SYSTEM; DRG; DISCHARGE; OUTCOMES; COSTS AB The average length of stay (LOS) of patients in hospitals has declined rapidly since the introduction of the prospective payment system. It has been argued by nurses that reduced LOS is associated with increased nursing resource consumption, but there has been little empirical evidence to support the argument. The authors offer evidence of a relationship between LOS and hours per patient day in eleven clinical specialty areas. These findings have major implications for budgeting and the delivery of nursing care services. C1 GRASP SYST NURSE CONSULTING LTD, LONGMONT, CO USA. UNIV CALIF BERKELEY, NATL INST AGING, HLTH SERV & POLICY ANAL GRP, BERKELEY, CA 94720 USA. RP SHAMIAN, J (reprint author), MT SINAI HOSP, TORONTO M5G 1X5, ONTARIO, CANADA. NR 26 TC 22 Z9 23 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUL-AUG PY 1994 VL 24 IS 7-8 BP 52 EP 58 PG 7 WC Nursing SC Nursing GA PB531 UT WOS:A1994PB53100012 PM 8057174 ER PT J AU STRECKFUS, CF MARCUS, S WELSH, S BROWN, RH CHERRYPEPPERS, G AF STRECKFUS, CF MARCUS, S WELSH, S BROWN, RH CHERRYPEPPERS, G TI PAROTID FUNCTION AND COMPOSITION OF PAROTID-SALIVA AMONG ELDERLY EDENTULOUS AFRICAN-AMERICAN DIABETICS SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE AFRICAN-AMERICAN; ELDERLY; IGA; PAROTID; SALIVA ID FLOW-RATE; DISEASES; MELLITUS AB This study examined parotid salivary flow rate and composition in three groups of differently treated diabetics and a control group of non-diabetics. The study population was composed of edentulous African-Americans at least 65 years of age. Group A was the control, Group B insulin-dependent (Regular Iletin, U-100 qd.), Group C controlled by oral medication (Tolbutamide, 500 mg qd.), and Group D was diet controlled. All diabetic patients had serum glucose values under 250 mg/dl. Salivary flow rates, secretory IgA, electrolytes (Na+, Cl-, K+, Ca++) and total protein concentrations were evaluated. The results showed no significant differences between groups with respect to salivary flow rates, electrolytes and IgA concentrations. Additionally, all diabetic groups demonstrated a significantly lower salivary total protein concentration when compared to the controls. There appears to be no evident decrease in salivary flow rate in these three differently controlled diabetic groups compared with healthy non-diabetics. C1 UNIV TEXAS,HLTH SCI CTR,DEPT ORAL DIAGNOST SERV,DALLAS,TX. RP STRECKFUS, CF (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,ROOM 718C,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 20 TC 16 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD JUL PY 1994 VL 23 IS 6 BP 277 EP 279 DI 10.1111/j.1600-0714.1994.tb00059.x PG 3 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA NX412 UT WOS:A1994NX41200008 PM 7932247 ER PT J AU STRECKFUS, CF WU, AJ SHIP, JA BROWN, LJ AF STRECKFUS, CF WU, AJ SHIP, JA BROWN, LJ TI STIMULATED PAROTID SALIVARY FLOW-RATES IN NORMOTENSIVE, HYPERTENSIVE, AND HYDROCHLOROTHIAZIDE-MEDICATED AFRICAN-AMERICANS SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE AFRICAN-AMERICAN; ELDERLY; HYPERTENSION; PAROTID; SALIVA AB Stimulated parotid salivary now rates were compared in elderly normotensive, hypertensive, and controlled hypertensive African-Americans, the latter group taking hydrochlorothiazide (HCTZ). The normotensive group consisted of 15 healthy unmedicated subjects with systolic blood pressures of less than 150 mm Hg and diastolic pressures less than 90 mm Hg. The hypertensive group consisted of 10 unmedicated subjects with systolic pressures greater than 160 mm Hg and diastolic pressures greater than 100 mm Hg. The controlled hypertensive group consisted of 20 subjects taking HCTZ (50 mg, daily) with controlled blood pressures similar to the normotensive control group. Stimulated parotid salivary samples were collected from each subject. A 2% citrate solution applied to the dorsum of the tongue was used for stimulation. The results showed no significant differences in stimulated parotid flow rates between normotensive and uncontrolled hypertensive subjects. However, the medicated, controlled hypertensive subjects had a significant reduction of stimulated parotid salivary flow rates compared to both the normotensive and hypertensive groups. C1 NIDR,EODPP,BETHESDA,MD 20892. NIDR,CIPCB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH DENT,ANN ARBOR,MI 48109. NR 31 TC 11 Z9 13 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD JUL PY 1994 VL 23 IS 6 BP 280 EP 283 DI 10.1111/j.1600-0714.1994.tb00060.x PG 4 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA NX412 UT WOS:A1994NX41200009 PM 7932248 ER PT J AU MUELLER, BU PIZZO, PA FARLEY, M HUSSON, RN GOLDSMITH, J KOVACS, A WOODS, L ONO, J CHURCH, JA BROUWERS, P JAROSINSKI, P VENZON, D BALIS, FM AF MUELLER, BU PIZZO, PA FARLEY, M HUSSON, RN GOLDSMITH, J KOVACS, A WOODS, L ONO, J CHURCH, JA BROUWERS, P JAROSINSKI, P VENZON, D BALIS, FM TI PHARMACOKINETIC EVALUATION OF THE COMBINATION OF ZIDOVUDINE AND DIDANOSINE IN CHILDREN WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF PEDIATRICS LA English DT Article ID AIDS; 2',3'-DIDEOXYINOSINE; RESISTANCE; THERAPY; PLASMA AB As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m(2) per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m(2) per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mu mol . hr per liter at 60 mg/m(2) to 11.0 mu mol . hr per liter at the 180 mg/m(2) level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mu mol . hr per liter (60 mg/m(2)) to 8.0 mu mol hr per liter (180 mg/m(2)), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications far the future utility of therapeutic drug monitoring with these agents. C1 NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT PHARM, BETHESDA, MD 20892 USA. CHILDRENS HOSP LOS ANGELES, DIV HEMATOL ONCOL, LOS ANGELES, CA 90027 USA. UNIV SO CALIF, LOS ANGELES CTY MED CTR, LOS ANGELES, CA 90033 USA. RP MUELLER, BU (reprint author), NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 18 TC 17 Z9 17 U1 0 U2 1 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 JUL PY 1994 VL 125 IS 1 BP 142 EP 146 DI 10.1016/S0022-3476(94)70141-5 PG 5 WC Pediatrics SC Pediatrics GA NW317 UT WOS:A1994NW31700028 PM 8021765 ER PT J AU BIESECKER, LG KLETTER, G TOPF, K AF BIESECKER, LG KLETTER, G TOPF, K TI FAMILIAL PALLISTER-HALL SYNDROME - REPLY SO JOURNAL OF PEDIATRICS LA English DT Letter C1 UNIV MICHIGAN, MED CTR, DEPT PEDIAT, ENDOCRINOL SECT, ANN ARBOR, MI 48109 USA. PERMANENTE MED GRP INC, SACRAMENTO, CA 95825 USA. RP BIESECKER, LG (reprint author), NIH, NATL CTR HUMAN GENOME RES, GENET DIS RES LAB, BLDG 49, ROOM 4A80, BETHESDA, MD 20892 USA. NR 5 TC 0 Z9 0 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 JUL PY 1994 VL 125 IS 1 BP 171 EP 171 PG 1 WC Pediatrics SC Pediatrics GA NW317 UT WOS:A1994NW31700039 ER PT J AU IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO AF IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO TI RECOMMENDED REVISIONS TO AMERICAN-DENTAL-ASSOCIATION GUIDELINES FOR ACCEPTANCE OF CHEMOTHERAPEUTIC PRODUCTS FOR GINGIVITIS CONTROL SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE GINGIVITIS; AMERICAN DENTAL ASSOCIATION; EFFICACY; CLINICAL TRIALS ID CHLORHEXIDINE AB This paper presents suggested revisions to the American Dental Association's 1985 guidelines for acceptance of anti-gingivitis chemotherapeutic agents. The areas of study design, choice and quality control of clinical gins measurements, statistical analysis, and minimum strength of effect, are addressed. The revisions articulate certain aspects of study design which were implicit in the 1985 guidelines, clarify language on cross-over designs and independence of studies, and recommend use of a United States population in at least one trial supporting a product. Separate recording and analysis of a product's effect on gingival bleeding is proposed, and quality control of clinical measurements receives enhanced emphasis. Modestly elaborated statistical reporting guidelines and strengthened approval criteria, based on size of estimated effect as well as statistical significance, are advocated. C1 UNIV ILLINOIS,DEPT MED INFORMAT SCI,URBANA,IL 61801. UNIV ILLINOIS,DEPT COMMUNITY HLTH STAT,URBANA,IL 61801. UNIV ILLINOIS,CTR RES ORAL MOLEC BIOL,URBANA,IL 61801. COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY. COLUMBIA UNIV,DIV BIOSTAT,NEW YORK,NY. UNIV MINNESOTA,MINNESOTA CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. EASTMAN DENT CTR,DIV BIOSTAT,ROCHESTER,NY. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. UNIV PENN,EPIDEMIOL SECT,PHILADELPHIA,PA 19104. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. SUNY BUFFALO,DEPT PERIODONTOL,BUFFALO,NY. SUNY BUFFALO,DEPT ORAL MED,BUFFALO,NY. USN,DENT RES INST,GREAT LAKES,IL. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. VIRGINIA COMMONWEALTH UNIV,DEPT PERIODONT,RICHMOND,VA. FORSYTH DENT CTR,BOSTON,MA 02115. UNIV MISSOURI,DEPT PERIODONT,KANSAS CITY,MO 64110. UNIV FLORIDA,DEPT STAT,DIV BIOSTAT,GAINESVILLE,FL 32611. SUNY STONY BROOK,DEPT PREVENT MED,STONY BROOK,NY 11794. UNIV PENN,DEPT PERIODONT,PHILADELPHIA,PA 19104. RP IMREY, PB (reprint author), UNIV ILLINOIS,TASK FORCE DESIGN & ANAL DENT & ORAL RES,190 MED SCI BLDG,506 S MATHEWS AVE,URBANA,IL 61801, USA. OI Imrey, Peter/0000-0002-0533-4603 NR 11 TC 23 Z9 24 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUL PY 1994 VL 29 IS 4 BP 299 EP 304 DI 10.1111/j.1600-0765.1994.tb01225.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PA409 UT WOS:A1994PA40900010 PM 7932024 ER PT J AU MIYAMOTO, Y BOWEN, WD PORTOGHESE, PS TAKEMORI, AE AF MIYAMOTO, Y BOWEN, WD PORTOGHESE, PS TAKEMORI, AE TI LACK OF INVOLVEMENT OF DELTA-1 OPIOID RECEPTORS IN THE DEVELOPMENT OF PHYSICAL-DEPENDENCE ON MORPHINE IN MICE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DIFFERENTIAL ANTAGONISM; TOLERANCE; SUBTYPES; ENKEPHALIN; NALTRINDOLE AB Previously, we have shown that the development of physical dependence on morphine in mice is inhibited substantially by treatment of mice with the highly selective, nonequilibrium delta-2 opioid receptor antagonist, naltrindole-5'-isothiocyanate. With the availability of the highly selective, nonequilibrium delta-1 opioid receptor antagonist, [D-Ala(2),Leu(5),Cys(6)]enkephalin, it was possible, in the present report, to examine the possible involvement of delta-1 opioid receptors in the development of opiate dependence. Mice were made physically dependent on morphine by s.c. implantation of morphine pellets (75-mg free base) for 3 days. The degree of dependence was quantified by determining the ED(50) values of naloxone to precipitate withdrawal jumping and diarrhea. Neither sign of opiate withdrawal was affected by chronic treatment of animals with [D-Ala(2),Leu(5),Cys(6)]enkephalin during the morphine implant period. The data suggest that delta-1, as opposed to delta-2, opioid receptors are not involved in the development of physical dependence on morphine. This fact takes on added significance because the recently cloned delta opioid receptors appear to be the delta-2 subtype and the present data together with previous findings suggest that the cloned receptors may be proper models for the study of opiate dependence. C1 UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,COLL PHARM,DEPT MED CHEM,MINNEAPOLIS,MN 55455. NIDDKD,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BETHESDA,MD 20892. NR 15 TC 20 Z9 20 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 37 EP 39 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500006 PM 8035333 ER PT J AU AGUAYO, LG PANCETTI, FC AF AGUAYO, LG PANCETTI, FC TI ETHANOL MODULATION OF THE GAMMA-AMINOBUTYRIC ACID(A)-ACTIVATED AND GLYCINE-ACTIVATED CL- CURRENT IN CULTURED MOUSE NEURONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CEREBRAL CORTICAL-NEURONS; GABAA RECEPTOR CHANNEL; SPINAL-CORD NEURONS; PROTEIN-KINASE-C; CHLORIDE CURRENTS; XENOPUS OOCYTES; BENZODIAZEPINE RECEPTOR; KINETIC-PROPERTIES; PYRAMIDAL CELLS; RAT AB The effects of ethanol on the GABA (gamma-aminobutyric acid)(A)-activated Cl- current were studied in cultured mouse hippocampal and cortical neurons using whole-cell techniques. Ethanol (0.25-200 mM) reversibly potentiated the current in 68 of the 131 hippocampal neurons examined. Ethanol also potentiated a strychnine-sensitive glycine-activated Cl- current in hippocampal and spinal neurons. Ethanol (40 mM) enhanced the maximal response to GABA without changing the Hill coefficient (1.2) or the affinity of the receptor for GABA (EC(50) = 15 vs. 14 mu M). We found neurons with distinct sensitivities to ethanol, and even concentrations of 425 and 850 mM further potentiated the response induced by GABA and glycine. Ethanol was able to potentiate the GABA(A) current even after removing Ca++ from the external solution. The protein kinase C activator phorbol, 12 myristate, 13 acetate inhibited the amplitude of the GABA current by 73 +/- 7% of control; however, 4-alpha-phorbol, 12 myristate, 13 acetate, its inactive analog, had no effects. In addition, 2 min of preapplication of 1 mu M phorbol, 12 myristate, 13 acetate reduced the ethanol-potentiation from 140 +/- 8 to 122 +/- 6%. Recordings of GABA- and glycine-activated Cl- currents showed that low concentrations of ethanol can differentially affect these receptors in a single neuron. This suggests that the GABAergic effect of ethanol is not mediated by a nonspecific change and that different mechanisms might account for the potentiation of these two ligand-activated Cl- channels by ethanol. In addition, the absence of saturation with high concentrations suggests that ethanol modulates these receptor-ion channel complexes by acting in several sites, one of which might control the state of receptor phosphorylation. C1 NIAAA, PHYSIOL & PHARMACOL STUDIES LAB, ELECTROPHYSIOL SECT, ROCKVILLE, MD 20852 USA. RP AGUAYO, LG (reprint author), PONTIFICIA UNIV CATOLICA VALPARAISO, INST CHEM, NEUROPHARMACOL LAB, POB 4095, VALPARAISO, CHILE. RI Pancetti, Floria/A-2491-2013 FU NIAAA NIH HHS [AA08857] NR 49 TC 122 Z9 122 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 61 EP 69 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500010 PM 8035343 ER PT J AU AULAKH, CS MAZZOLAPOMIETTO, P WOZNIAK, KM HILL, JL MURPHY, DL AF AULAKH, CS MAZZOLAPOMIETTO, P WOZNIAK, KM HILL, JL MURPHY, DL TI EVIDENCE THAT 1-(2,5-DIMETHOXY-4-METHYLPHENYL)-2-AMINOPROPANE-INDUCED HYPOPHAGIA AND HYPERTHERMIA IN RATS IS MEDIATED BY SEROTONIN-2A RECEPTORS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE DOI; 5-HT1C RECEPTORS; ANTAGONISTS; AGONIST; RADIOLIGAND; BINDING; BRAIN; INVOLVEMENT; TEMPERATURE; AXIS AB The administration of various doses of the phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) to rats produced dose-related decreases in 1-hr food intake in a food-restricted paradigm and in locomotor activity. DOM also produced dose-related increases in temperature. Pretreatment with propranolol [a beta adrenoceptor antagonist that also has high binding affinity for serotonin (5-HT) 5-HT1A, 5-HT1B and 5-HT2C sites], bemesetron or ondansetron (5-HT3 antagonists) did not attenuate either DOM-induced hypophagia or hyperthermia. In contrast, pretreatment with metergoline (a 5-HT1/5-HT2 antagonist) and ritanserin (a 5-HT2A/5-HT2C antagonist) significantly attenuated both DOM-induced hypophagia and hyperthermia. However, pretreatment with mesulergine (a 5-HT2c/5-HT2A antagonist) significantly attenuated DOM-induced hyperthermia but not hypophagia. On the other hand, spiperone (5-HT1A/5-HT2A/D-2 antagonist) pretreatment significantly attenuated DOM-induced hyperthermia but accentuated DOM-induced hypophagia. Daily administration of DOM (1.0 mg kg(-1) day(-1)) produced complete tolerance to its hypophagic effect by day 4 but did not produce cross-tolerance to m-chlorophenylpiperazine-induced hypophagia. In contrast, daily administration of DOM for 7 days did not produce either tolerance to its hyperthermic effect or modify m-chlorophenylpiperazine-induced hyperthermia in rats. These findings suggest that DOM-induced hypophagia and hyperthermia in rats are mediated by stimulation of 5-HT2A receptors. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,WINSTON SALEM,NC 27103. RP AULAKH, CS (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 32 TC 21 Z9 21 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 127 EP 132 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500018 PM 8035308 ER PT J AU MASSERANO, JM VENABLE, D WYATT, RJ AF MASSERANO, JM VENABLE, D WYATT, RJ TI EFFECTS OF CHRONIC COCAINE ADMINISTRATION ON [H-3] DOPAMINE UPTAKE IN THE NUCLEUS-ACCUMBENS, STRIATUM AND FRONTAL-CORTEX OF RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TYROSINE-HYDROXYLASE IMMUNOREACTIVITY; DOPAMINE TRANSPORTER BINDING; MEDIAL PREFRONTAL CORTEX; EXTRACELLULAR DOPAMINE; AMPHETAMINE PSYCHOSIS; BIOGENIC-AMINES; UPTAKE COMPLEX; BRAIN; SCHIZOPHRENIA; SENSITIZATION AB The uptake of [H-3]dopamine into synaptosomes obtained from the nucleus accumbens, striatum and frontal cortex was evaluated after chronic treatment with cocaine. Cocaine was administered in a concentration of 10 mg/kg, twice a day for 7 days. Fourteen days after the last injection, locomotor activity and [H-3] dopamine uptake were evaluated. Base-line locomotor activity was significantly lower (29%) in rats treated chronically with cocaine compared with saline-treated rats. A challenge dose of cocaine (2.5 mg/kg or 5.0 mg/kg) or d-amphetamine (1 mg/kg) produced similar increases in locomotor activity above the corresponding base-line values in both saline- and cocaine-treated rats, indicating that behavioral sensitization had not occurred. Chronic cocaine administration produced a significant decrease in the uptake of [H-3]dopamine into the frontal cortex (49%) with no significant differences in the nucleus accumbens or striatum. The decrease in [H-3]dopamine uptake in the frontal cortex was due to a decrease in the V-max with no change in the affinity of [H-3]dopamine for the dopamine transporter. No differences were produced in the IC50 values of GBR 12909 or cocaine for [H-3] dopamine uptake after chronic cocaine treatment. However, in all three brain regions, the IC50 values for cocaine were significantly greater than the values for GBR 12909. In addition, the IC50 values for GBR 12909 and cocaine in the frontal cortex were significantly greater than values for either compound in the nucleus accumbens or striatum. The administration of methamphetamine, using a similar treatment schedule, produced no changes in [H-3]dopamine uptake in any of the three brain areas. These data indicate an inhibitory effect of repeated cocaine administration on [H-3]dopamine uptake in the frontal cortex of rats. RP MASSERANO, JM (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 65 TC 33 Z9 33 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 133 EP 141 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500019 PM 8035309 ER PT J AU ROTHMAN, RB CADET, JL AKUNNE, HC SILVERTHORN, ML BAUMANN, MH CARROLL, FI RICE, KC DECOSTA, BR PARTILLA, JS WANG, JB UHL, G GLOWA, JR DERSCH, CM AF ROTHMAN, RB CADET, JL AKUNNE, HC SILVERTHORN, ML BAUMANN, MH CARROLL, FI RICE, KC DECOSTA, BR PARTILLA, JS WANG, JB UHL, G GLOWA, JR DERSCH, CM TI STUDIES OF THE BIOGENIC-AMINE TRANSPORTERS .4. DEMONSTRATION OF A MULTIPLICITY OF BINDING-SITES IN RAT CAUDATE MEMBRANES FOR THE COCAINE ANALOG [I-125] RTI-55 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; NOREPINEPHRINE UPTAKE SITES; DOPAMINE UPTAKE COMPLEX; H-3 GBR-12935 BINDING; HIGH-AFFINITY BINDING; NONHUMAN-PRIMATES; MOUSE-BRAIN; SEROTONIN TRANSPORTER; STRIATAL MEMBRANES; NEURONAL DOPAMINE AB The drug 3 beta-[4'-iodophenyl]tropan-2 beta-carboxylic acid methyl ester (RTI-55) is a cocaine congener with high affinity for the dopamine transporter (K-d < 1 nM). The present study characterized [I-125]RTI-55 binding to membranes prepared from rat, monkey and human caudates and COS cells transiently expressing the cloned rat dopamine (DA) transporter. Using the method of binding surface analysis, two binding sites were resolved in rat caudate: a high-capacity binding site (site 1, B-max = 11,900 fmol/mg of protein) and a low-capacity site (site 2, B-max = 846 fmol/mg of protein). The Kd (or Ki) values of selected drugs at the two sites were as follows: (K-i for high-capacity site and K-i for low-capacity site, respectively): RTI-55 (0.76 and 0.21 nM), 1-[2(diphenyl-methoxy)ethyl]-4-(3-phenylpropyl)piperazine (0.79 and 358 nM), mazindol (37.6 and 631 nM), 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (45.0 and 540 nM) and cocaine (341 and 129 nM). Nisoxetine, a selective noradrenergic uptake blocker, had low affinity for both sites. Serotonergic uptake blockers had a high degree of selectivity and high affinity for the low-capacity binding site (K-i of citalopram = 0.38 nM; K-i of paroxetine = 0.033 nM). The i.c.v. administration of 5,7-dihydroxytryptamine to rats pretreated with nomifensine (to protect dopaminergic and noradrenergic nerve terminals) selectively decreased the B-max of site 2, strongly supporting the idea that site 2 is a binding site on the serotonin (5-HT) transporter. This serotonergic lesion also increased the affinity of [I-125]RTI-55 for the DA transporter by 10-fold. The ligand selectivity of the caudate 5-HT transporter was different from the [I-125]RTI-55 binding site on the 5-HT transporter present in membranes prepared from whole rat brain minus caudate. The [I-125]RTI-55 binding to the DA transporter was further resolved into two components, termed sites 1a and 1b, by using human and monkey (Macaca mulatta) caudate membranes but not the membranes prepared from rat caudate or COS cells that transiently expressed the cloned cocaine-sensitive DA transporter complementary DNA. Similar experiments also resolved two components of the caudate 5-HT transporter. Viewed collectively, these data provide evidence that [I-125]RTI-55 labels multiple binding sites associated with the DA and 5-HT transporters. C1 NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 86 TC 69 Z9 69 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 296 EP 309 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500038 PM 8035327 ER PT J AU NIMS, RW MCCLAIN, RM MANCHAND, PS BELICA, PS THOMAS, PE MELLINI, DW UTERMAHLEN, WE LUBET, RA AF NIMS, RW MCCLAIN, RM MANCHAND, PS BELICA, PS THOMAS, PE MELLINI, DW UTERMAHLEN, WE LUBET, RA TI COMPARATIVE PHARMACODYNAMICS OF HEPATIC CYTOCHROME-P450-2B INDUCTION BY 5,5-DIPHENYL-SUBSTITUTED AND 5,5-DIETHYL-SUBSTITUTED BARBITURATES AND HYDANTOINS IN THE MALE F344/NCR RAT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PHENOBARBITAL-LIKE INDUCER; MONO-OXYGENASE ACTIVITY; PLEIOTROPIC RESPONSE; SPECIES-DIFFERENCES; MICROSOMAL-ENZYMES; GENE-EXPRESSION; LIVER; HEPATOCYTES; SERIES; 5-ETHYL-5-PHENYLHYDANTOIN AB To explore further the structural requirements for ligand interaction with the putative phenobarbital receptor, the pharmacodynamics of CYP2B induction by 5,5-diphenylbarbituric acid, phenytoin (5,5-diphenylhydantoin), barbital (5,5-diethylbarbituric acid) and 5,5-diethylhydantoin were investigated in the male F344/NCr rat. Steady-state total (free plus protein-bound) serum drug concentration, measured after 14 days of administration of the compounds in the diet, was used as an approximation of intrahepatocellular drug concentration. The serum concentrations associated with half-maximal hepatic CYP2B induction (EC(50) values) were 6 to 11 mu M and 15 to 18 mu M for the diphenyl-substituted barbiturate and hydantoin, respectively, based on measurement of pentoxy- or benzyloxyresorufin O-dealkylation activities, or immunoreactive CYP2B1 protein. The corresponding potency values for the diethyl-substituted barbiturate and hydantoin were 16 to 20 mu M and greater than or equal to 500 mu M, respectively. The magnitudes of the maximal CYP2B induction responses elicited by the diphenyl-substituted congeners and by barbital were 94 to 122% of the responses resulting from phenobarbital itself. In contrast, the maximum induction responses elicited by 5,5-diethylhydantoin were only 24% as great as those elicited by phenobarbital. The finding of a CYP2B inducer with a potency value 2 to 3 orders of magnitude lower than those for certain other prototype CYP2B inducers is suggestive but not proof of receptor mediation in the induction process. C1 HOFFMANN LA ROCHE INC,DEPT TOXICOL & PATHOL,NUTLEY,NJ 07110. HOFFMANN LA ROCHE INC,DEPT SYNTHET CHEM,NUTLEY,NJ 07110. RUTGERS STATE UNIV,COLL PHARM,DEPT BIOL CHEM,PISCATAWAY,NJ. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 46 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 348 EP 355 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500044 PM 8035330 ER PT J AU KNICKLE, LC PHILPOT, RM BEND, JR AF KNICKLE, LC PHILPOT, RM BEND, JR TI N-ARALKYLATED DERIVATIVES OF 1-AMINOBENZOTRIAZOLE ARE POTENT ISOZYME-SELECTIVE AND LUNG-SELECTIVE MECHANISM-BASED INHIBITORS OF GUINEA-PIG CYTOCHROME-P-450 IN-VIVO SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SPECIES-DEPENDENT EXPRESSION; RAT-LIVER; MICROSOMAL CYTOCHROME-P-450; PULMONARY CYTOCHROME-P-450; DIFFERENTIAL INDUCTION; BETA-NAPHTHOFLAVONE; RABBIT; INACTIVATION; METABOLISM; MONOOXYGENASES AB 1-Aminobenzotriazole (ABT) and its N-benzyl-1-aminobenzotriazole (BBT) and N-alpha-methylbenzyl (alpha-MB) derivatives were compared as isozyme-selective, lung-selective (vs. liver) mechanism-based inhibitors of cytochrome P-450 (P450) in noninduced, beta-naphthoflavone-induced and phenobarbital-induced guinea pigs 4 hr after i.v. administration. Isozyme-selective monooxygenase activities for lung P450 1A1, 2B4 and 4B1 orthologues (7-thoxyresorufin O-deethylation for guinea pig P450 1A1, 7-pentoxyresorufin O-depentylation for P450 2Bx and 4-aminobiphenyl N-hydroxylation for P450 4Bx, respectively) were determined in pulmonary and hepatic microsomes. BBT and alpha-MB inactivated pulmonary P450 in an isozyme-selective manner; in non- and phenobarbital-induced animals the order of inactivation was 2Bx > 1A1 >>> 4Bx. In beta-naphthoflavone-induced animals, alpha-MB specifically inhibited 2Bx in the lung (>90% inactivation at 0.075 mu mol/kg, whereas a 100-fold higher dose did not inhibit 4Bx or 1A1). BBT and alpha-MB also were highly selective for the inactivation of pulmonary vs. hepatic P450. In each case at least one of the doses administered caused marked inactivation of pulmonary 2Bx (>80% with alpha-MB and 50-70% with BBT) without inhibiting the hepatic monooxygenase activities. In contrast, ABT displayed little isozyme-selectively and little tissue-selectivity. The differences in tissue-selectivity of the inhibitors are due to BBT and alpha-MB being much more potent (100- to 1000-fold) inactivators of pulmonary P450 2Bx than ABT consistent with BBT and alpha-MB, but not ABT, serving as substrates for the lipophilic aromatic amine uptake system in the lung. In summary, BBT and alpha-MB, at appropriate doses, are isozyme-selective/specific (P450 2Bx), lung-specific inhibitors of P450 in guinea pig in vivo. C1 UNIV WESTERN ONTARIO,DEPT PHARMACOL & TOXICOL,LONDON N6A 5C1,ON,CANADA. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 40 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 377 EP 385 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500048 PM 8035335 ER PT J AU MCCARTHY, GR GUCKES, AD AF MCCARTHY, GR GUCKES, AD TI ADDITION OF AN IMPLANT PILLAR TO AN EXISTING IMPLANT PROSTHESIS SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article AB When an implant is lost, it is sometimes desirable to replace it to ensure adequate support of the prosthesis. Such an addition may necessitate a costly and time-consuming remake procedure. A technique is offered that, in some circumstances, may allow incorporation of the newly placed implant into the existing restoration. RP MCCARTHY, GR (reprint author), NIDR,BLDG 10,ROOM 1N113,BETHESDA,MD 20892, USA. NR 5 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 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUL PY 1994 VL 72 IS 1 BP 26 EP 28 DI 10.1016/0022-3913(94)90212-7 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NV464 UT WOS:A1994NV46400007 PM 7916053 ER PT J AU CLORE, GM GRONENBORN, AM AF CLORE, GM GRONENBORN, AM TI STRUCTURES OF LARGER PROTEINS AND PROTEIN-LIGAND AND PROTEIN-DNA COMPLEXES BY HETERONUCLEAR MULTIDIMENSIONAL NMR SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article; Proceedings Paper CT 10th International Conference on Methods in Protein Structure Analysis CY SEP 08-13, 1994 CL SNOWBIRD, UT SP Int Symp Immunobiol Protein & Peptides Inc ID 3-DIMENSIONAL STRUCTURE; SPECTROSCOPY RP CLORE, GM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 6 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 1994 VL 13 IS 5 BP 441 EP 442 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD448 UT WOS:A1994PD44800004 ER PT J AU APPELLA, E FISCELLA, M ZAMBRANO, N ULLRICH, SJ SAKAGUCHI, K SAKAMOTO, H LEWIS, MS LIN, D MERCER, WE ANDERSON, CW AF APPELLA, E FISCELLA, M ZAMBRANO, N ULLRICH, SJ SAKAGUCHI, K SAKAMOTO, H LEWIS, MS LIN, D MERCER, WE ANDERSON, CW TI STRUCTURE AND POSTTRANSLATIONAL MODIFICATION OF THE HUMAN P53 PROTEIN SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article; Proceedings Paper CT 10th International Conference on Methods in Protein Structure Analysis CY SEP 08-13, 1994 CL SNOWBIRD, UT SP Int Symp Immunobiol Protein & Peptides Inc ID PHOSPHORYLATION C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RP APPELLA, E (reprint author), NIH,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Zambrano, Nicola/B-9352-2014 OI Zambrano, Nicola/0000-0001-9395-3481 NR 9 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 1994 VL 13 IS 5 BP 499 EP 500 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD448 UT WOS:A1994PD44800051 ER PT J AU ANDERSON, CW CONNELLY, MA ZHANG, H SIPLEY, JD LEESMILLER, SP SAKAGUCHI, K ULLRICH, SJ JACKSON, SP APPELLA, E AF ANDERSON, CW CONNELLY, MA ZHANG, H SIPLEY, JD LEESMILLER, SP SAKAGUCHI, K ULLRICH, SJ JACKSON, SP APPELLA, E TI THE HUMAN DNA-ACTIVATED PROTEIN-KINASE, DNA-PK, IS ACTIVATED BY DNA BREAKS AND PHOSPHORYLATES NUCLEAR DNA-BINDING PROTEIN SUBSTRATES ON SERINES AND THREONINES FOLLOWING BY GLUTAMINE SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article; Proceedings Paper CT 10th International Conference on Methods in Protein Structure Analysis CY SEP 08-13, 1994 CL SNOWBIRD, UT SP Int Symp Immunobiol Protein & Peptides Inc ID KU-AUTOANTIGEN; ANTIGEN; P53 C1 NIH,CELL BIOL LAB,BETHESDA,MD 20892. JCRC WELLCOME RES INST,CAMBRIDGE CB2 1QR,ENGLAND. RP ANDERSON, CW (reprint author), BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973, USA. RI Dry, Kate/I-2328-2014 NR 10 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 1994 VL 13 IS 5 BP 500 EP 501 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD448 UT WOS:A1994PD44800052 ER PT J AU BEG, ZH STONIK, JA HOEG, JM BREWER, HB AF BEG, ZH STONIK, JA HOEG, JM BREWER, HB TI POSTTRANSLATIONAL MODIFICATION BY COVALENT PHOSPHORYLATION OF HUMAN APOLIPOPROTEIN B-100 - PROTEIN-KINASE C-MEDIATED REGULATION OF SECRETED APO B-100 IN HEP G-2 CELLS SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article; Proceedings Paper CT 10th International Conference on Methods in Protein Structure Analysis CY SEP 08-13, 1994 CL SNOWBIRD, UT SP Int Symp Immunobiol Protein & Peptides Inc ID POST-TRANSLATIONAL MODIFICATION; LOW-DENSITY LIPOPROTEINS; A-I; DISEASE C1 ALIGARH MUSLIM UNIV,JN MED COLL,DEPT BIOCHEM,ALIGARH,UTTAR PRADESH,INDIA. RP BEG, ZH (reprint author), NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 1994 VL 13 IS 5 BP 509 EP 511 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD448 UT WOS:A1994PD44800061 ER PT J AU MAAS, JW KATZ, MM KOSLOW, SH SWANN, A DAVIS, JM BERMAN, N BOWDEN, CL STOKES, PE LANDIS, H AF MAAS, JW KATZ, MM KOSLOW, SH SWANN, A DAVIS, JM BERMAN, N BOWDEN, CL STOKES, PE LANDIS, H TI ADRENOMEDULLARY FUNCTION IN DEPRESSED-PATIENTS SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID BRANCH COLLABORATIVE PROGRAM; SYMPATHETIC NERVOUS-SYSTEM; URINARY BIOGENIC-AMINES; ADRENAL-MEDULLARY; ADRENOCORTICAL FUNCTION; BIOLOGICAL COMPONENT; CEREBROSPINAL-FLUID; VIDEO METHODOLOGY; HEALTHY; PSYCHOPATHOLOGY AB In this paper from the Collaborative Depression Study (CDS)-Biological, a set of data analyses are presented which indicate that depressed states and perhaps depressed mood are associated with a greater activation of the adrenomedullary system than the sympathetic nervous system [as measured by norepinephrine (NE) and normetanephrine excretion]. For the most part this finding of predominant activation of the adrenomedullary system is seen in unipolar and not bipolar patients. C1 NIMH,BETHESDA,MD. ALBERT EINSTEIN COLL MED,BRONX,NY. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. ILLINOIS STATE PSYCHIAT INST,CHICAGO,IL. CORNELL UNIV MED COLL,NEW YORK,NY. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. RP MAAS, JW (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIMH NIH HHS [UO1 MH26977, UO1 MH26975, UO1 MH38084] NR 30 TC 16 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUL-AUG PY 1994 VL 28 IS 4 BP 357 EP 367 DI 10.1016/0022-3956(94)90018-3 PG 11 WC Psychiatry SC Psychiatry GA PX480 UT WOS:A1994PX48000003 PM 7877115 ER PT J AU JACOBSSON, LTH PILLEMER, SR AF JACOBSSON, LTH PILLEMER, SR TI WHAT CAN WE LEARN ABOUT RHEUMATIC DISEASES BY STUDYING PIMA-INDIANS SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID SHARED EPITOPE HYPOTHESIS; ARTHRITIS; PREVALENCE; MORTALITY; POPULATION; ROCHESTER; MINNESOTA C1 NIAMSD,BETHESDA,MD 20892. NR 31 TC 11 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1994 VL 21 IS 7 BP 1179 EP 1182 PG 4 WC Rheumatology SC Rheumatology GA NW809 UT WOS:A1994NW80900002 PM 7966054 ER PT J AU GLASS, DN NEPOM, BS WHITE, PH SHULMAN, LE AF GLASS, DN NEPOM, BS WHITE, PH SHULMAN, LE TI RESEARCH IN PEDIATRIC RHEUMATOLOGY SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material C1 VIRGINIA MASON RES CTR,SEATTLE,WA. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIH,BETHESDA,MD. RP GLASS, DN (reprint author), UNIV CINCINNATI,COLL MED,CHILDRENS HOSP,MED CTR,CINCINNATI,OH 45229, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1994 VL 21 IS 7 BP 1347 EP 1351 PG 5 WC Rheumatology SC Rheumatology GA NW809 UT WOS:A1994NW80900034 PM 7966083 ER PT J AU MCKENNA, K GORDON, CT RAPOPORT, JL AF MCKENNA, K GORDON, CT RAPOPORT, JL TI CHILDHOOD-ONSET SCHIZOPHRENIA - TIMELY NEUROBIOLOGICAL RESEARCH SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE SCHIZOPHRENIA; BRAIN IMAGING; GENETICS ID DORSOLATERAL PREFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; CEREBROSPINAL-FLUID; PHYSIOLOGIC DYSFUNCTION; DEVELOPMENTAL DISORDER; MONOAMINE METABOLITES; NEUROLEPTIC TREATMENT; DISTURBED-CHILDREN; AUTISTIC-CHILDREN; CORPUS-CALLOSUM AB Objective: To review timely research on childhood-onset schizophrenia in view of advances in biological research on, and neurodevelopmental theories of, the later-onset disorder. Method: Research issues are outlined including further clarification of ICD- and DSM-defined childhood schizophrenia, and differentiation from autism ''spectrum'' and other subtle, chronic developmental disorders. Key neurobiological advances are reviewed for which child studies are relevant and feasible. Conclusion: It is anticipated that narrowly defined childhood-onset schizophrenics will constitute a predominately male population. A high rate of family illness or chromosomal and/or brain developmental abnormalities, which will be instructive regarding the pathophysiology of later-onset schizophrenia, is expected. RP MCKENNA, K (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 133 TC 54 Z9 55 U1 2 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL-AUG PY 1994 VL 33 IS 6 BP 771 EP 781 DI 10.1097/00004583-199407000-00001 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NU824 UT WOS:A1994NU82400001 PM 7521867 ER PT J AU LEONARD, HL TOPOL, D BUKSTEIN, O HINDMARSH, D ALLEN, AJ SWEDO, SE AF LEONARD, HL TOPOL, D BUKSTEIN, O HINDMARSH, D ALLEN, AJ SWEDO, SE TI CLONAZEPAM AS AN AUGMENTING AGENT IN THE TREATMENT OF CHILDHOOD-ONSET OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE OBSESSIVE-COMPULSIVE DISORDER; CLONAZEPAM; FLUOXETINE; SEROTONIN REUPTAKE INHIBITORS AB This case study is of a young man with childhood onset of severe obsessive-compulsive disorder (OCD). The patient had no clinical improvement during therapeutic trials of clomipramine, fluoxetine, and fluvoxamine, including buspirone augmentation. The patient consumed 50 tablets of fluoxetine in a suicide attempt and experienced a total remission of his OCD symptoms for the first time in his life. This remission lasted approximately 1 month and raises interesting questions about the mechanism of action of the serotonin reuptake inhibitors. Subsequently, the patient was able to achieve a 75% improvement in symptomatology when treated with a combination of fluoxetine and clonazepam. This open report suggests that clonazepam may be an effective augmentation agent to a serotonin reuptake inhibitor in the treatment of OCD. C1 MED COLL PENN,OAKDALE,PA. ALLEGHENY NEUROPSYCHIATR INST,OAKDALE,PA. UNIV PITTSBURGH,WESTERN PSYCHIAT INST CTR,PITTSBURGH,PA 15260. RP LEONARD, HL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 50 Z9 51 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL-AUG PY 1994 VL 33 IS 6 BP 792 EP 794 DI 10.1097/00004583-199407000-00003 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NU824 UT WOS:A1994NU82400003 PM 8083135 ER PT J AU ERNST, M LIEBENAUER, LL KING, AC FITZGERALD, GA COHEN, RM ZAMETKIN, AJ AF ERNST, M LIEBENAUER, LL KING, AC FITZGERALD, GA COHEN, RM ZAMETKIN, AJ TI REDUCED BRAIN METABOLISM IN HYPERACTIVE GIRLS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; GLUCOSE METABOLISM; ATTENTION-DEFICIT HYPERACTIVITY DISORDER; GENDER; ADOLESCENT ID ATTENTION DEFICIT DISORDER; CEREBRAL GLUCOSE-METABOLISM; CHILD PSYCHOPATHOLOGY; PSYCHIATRIC STATUS; BOYS; GENDER; SEX; TRANSMISSION; DYSFUNCTION; BEHAVIOR AB Objective: This study assesses the effect of attention-deficit hyperactivity disorder (ADHD) and gender on cerebral glucose metabolism (CMRglu), using positron emission tomography and F-18-fluorodeoxyglucose. Method: Nineteen normal (6 females; 14.3 +/- 1.3 years old) and 20 ADHD adolescents (5 females; 14.7 +/- 1.6 years old) participated in the study. An auditory continuous performance task was used during the 30-minute uptake of F-18-fluorodeoxyglucose. Results: There were no statistically significant differences in global or regional CMRglu between ADHD (N = 20) and normal (N = 19) adolescents. However, the global CMRglu in ADHD girls (N = 5) was 15.0% lower than in normal girls (N = 6) (p = .04), while global CMRglu in ADHD boys was not different than in normal boys. Furthermore, global CMRglu in ADHD girls was 19.6% lower than in ADHD boys (p = .02) and was not different between normal girls and normal boys. Clinical rating scales did not differentiate ADHD girls from ADHD boys, nor normal girls from normal boys. Conclusions: The greater brain metabolism abnormalities in females than males strongly stress that more attention be given to the study of girls with ADHD. RP ERNST, M (reprint author), NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,ROOM 4N317,BETHESDA,MD 20892, USA. NR 56 TC 142 Z9 146 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL-AUG PY 1994 VL 33 IS 6 BP 858 EP 868 DI 10.1097/00004583-199407000-00012 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NU824 UT WOS:A1994NU82400012 PM 8083143 ER PT J AU ROSS, RG HOMMER, D BREIGER, D VARLEY, C RADANT, A AF ROSS, RG HOMMER, D BREIGER, D VARLEY, C RADANT, A TI EYE-MOVEMENT TASK-RELATED TO FRONTAL-LOBE FUNCTIONING IN CHILDREN WITH ATTENTION-DEFICIT DISORDER SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE EYE MOVEMENTS; CHILDREN; SACCADES; ATTENTION-DEFICIT HYPERACTIVITY DISORDER; VISUOSPATIAL WORKING MEMORY ID DORSOLATERAL PREFRONTAL CORTEX; HYPERACTIVITY DISORDER; CORTICAL CONTROL; GUIDED SACCADES; BEHAVIOR; INJURY AB Objective: Attention-deficit hyperactivity disorder (ADHD) has been postulated to be related to dysfunction of the prefrontal cortex. In the oculomotor delayed response task, a subject is cued as to where he or she should look (shift visual gaze to) but must delay a short period and then shift gaze to the location where the cue previously existed but no longer exists (a memory-guided saccade). Dependent measures from this task provide information on three functions tentatively tied to prefrontal cortex functioning: the ability to inhibit response (during the delay period), preparation of motor response (inversely tied to the latency of shifting visual gaze), and accuracy of working visuospatial memory (accuracy of the memory-guided saccade). Method: Thirteen children with ADHD and 10 normal controls, aged 9 to 12 years, were tested using an 800-msec delay period. Results: Children with ADHD showed, relative to normal controls, deficits on inhibiting response during the delay period but no differences in latency (preparation of motor response) or accuracy of visuospatial memory. Conclusions: These results support the hypothesis that the primary deficit in ADHD is difficulty in inhibition of response. This deficit may be associated with pathology located outside the dorsolateral prefrontal cortex. C1 UNIV WASHINGTON,SEATTLE,WA 98195. NIAAA,ROCKVILLE,MD 20852. NR 23 TC 90 Z9 92 U1 0 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL-AUG PY 1994 VL 33 IS 6 BP 869 EP 874 DI 10.1097/00004583-199407000-00013 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NU824 UT WOS:A1994NU82400013 PM 8083144 ER PT J AU QUYYUMI, AA EPSTEIN, SE AF QUYYUMI, AA EPSTEIN, SE TI ANGIOGENESIS AND LOW-MOLECULAR-WEIGHT HEPARIN - REPLY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID CORONARY RP QUYYUMI, AA (reprint author), NIH,CARDIOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 7B15,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1994 VL 24 IS 1 BP 273 EP 274 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH375 UT WOS:A1994PH37500046 ER PT J AU BEEKMANN, SE HENDERSON, DK AF BEEKMANN, SE HENDERSON, DK TI MANAGING OCCUPATIONAL RISKS IN THE DENTAL OFFICE - HIV AND THE DENTAL PROFESSIONAL SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE WORKERS; UNIVERSAL PRECAUTIONS; NEEDLESTICK INJURIES; EDUCATIONAL-PROGRAM; INFECTION; EXPOSURES; ZIDOVUDINE; DENTISTS; BLOOD AB Despite universal precautions, work behavior modifications and technological advances, health care workers continue to experience occupational exposures to HIV and other bloodborne pathogens. Although the risk for infection is low when compared with other bloodborne Pathogens, 39 documented cases of HIV seroconversion have been recorded. Recent attention has focused on secondary prevention of HIV infection through post-exposure chemoprophylaxis. RP BEEKMANN, SE (reprint author), NIH,HOSP EPIDEMIOL SERV,CTR CLIN,ROOM 4A21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 4 Z9 4 U1 2 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 1994 VL 125 IS 7 BP 847 EP 852 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NV794 UT WOS:A1994NV79400013 PM 8040535 ER PT J AU KUTNER, NG SCHECHTMAN, KB ORY, MG BAKER, DI MILLER, JP PROVINCE, MA ARFKEN, CL ROSSITER, J HORNBROOK, MC STEVENS, VJ WINGFIELD, DJ GREENLICK, MR TINETTI, ME CLAUS, EB HORWITZ, RI BUCHNER, DM WAGNER, EH DELATEUR, BJ CRESS, ME PRICE, R ABRASS, IB ESSELMAN, P MARGUERITA, T MULROW, CD GERETY, MB CORNELL, JE SATTIN, RW DENINO, LA KANTEN, D WOLF, SL GREEN, RC MCNEELY, E COOGLER, C FIATARONE, MA ONEILL, EF RYAN, ND CLEMENTS, KM LIPSITZ, LA KEHAYIAS, JJ ROBERTS, SB EVANS, WJ WALLACE, R ROSS, JE HUSTON, JC KUNDEL, CJ SELLBERG, MS WOLFSON, LI WHIPPLE, RH AMERMAN, PM JUDGE, JO DERBY, CA KING, MB HADLEY, EC TAMBOLI, A WEISS, S AF KUTNER, NG SCHECHTMAN, KB ORY, MG BAKER, DI MILLER, JP PROVINCE, MA ARFKEN, CL ROSSITER, J HORNBROOK, MC STEVENS, VJ WINGFIELD, DJ GREENLICK, MR TINETTI, ME CLAUS, EB HORWITZ, RI BUCHNER, DM WAGNER, EH DELATEUR, BJ CRESS, ME PRICE, R ABRASS, IB ESSELMAN, P MARGUERITA, T MULROW, CD GERETY, MB CORNELL, JE SATTIN, RW DENINO, LA KANTEN, D WOLF, SL GREEN, RC MCNEELY, E COOGLER, C FIATARONE, MA ONEILL, EF RYAN, ND CLEMENTS, KM LIPSITZ, LA KEHAYIAS, JJ ROBERTS, SB EVANS, WJ WALLACE, R ROSS, JE HUSTON, JC KUNDEL, CJ SELLBERG, MS WOLFSON, LI WHIPPLE, RH AMERMAN, PM JUDGE, JO DERBY, CA KING, MB HADLEY, EC TAMBOLI, A WEISS, S TI OLDER ADULTS PERCEPTIONS OF THEIR HEALTH AND FUNCTIONING IN RELATION TO SLEEP DISTURBANCE, FALLING, AND URINARY-INCONTINENCE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the Gerontological-Society-of-America CY NOV 20, 1992 CL WASHINGTON, DC SP GERONTOL SOC AMER ID FICSIT TRIALS; INTERVENTIONS; DISORDERS; FRAILTY; ELDERS AB OBJECTIVE: To investigate variation in older adults' perceived health and functioning that is associated with self-reported sleep disturbance, falling, and urinary incontinence, controlling for self-reported depression, ambulation difficulty, number of chronic conditions, and subjects' sociodemographic characteristics. DESIGN: Multicenter prospective study (FICSIT). SETTING: Persons age 70 and older living in the community evaluated at baseline. PARTICIPANTS: 239 women, 113 men; mean age = 77. MEASUREMENTS: Sleep disturbance score based on EPESE questions, recent falls history (Y/N), incontinent episodes (Y/N), CES-D score, SIP Ambulation score, and 4 MOS SF-36 scale scores. RESULTS: Women were significantly more likely than men to report multiple conditions (sleep disturbance, falling, incontinence) and to report lower levels of functioning as measured by 3 of 4 SF-36 scales. In regression analyses, sleep disturbance and urinary incontinence were significant predictors of perceived limitation in usual role activities because of physical health problems. Depression and ambulation measures significantly predicted scores on all 4 SF-36 scales. CONCLUSIONS: Our analysis suggests that it is important to address depressive symptomatology and ambulation difficulty-which in turn are related to sleep disturbance, falling, and urinary incontinence-in efforts to enhance older adults' perceived health and functioning. C1 WASHINGTON UNIV,DIV BIOSTAT,ST LOUIS,MO. NIA,BETHESDA,MD 20892. YALE UNIV,SCH NURSING,NEW HAVEN,CT 06536. WASHINGTON UNIV,SCH MED,DIV BIOSTAT,ST LOUIS,MO 63130. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. YALE UNIV,SCH MED,PROGRAM AGING,NEW HAVEN,CT 06520. WASHINGTON UNIV,DEPT HLTH SCI,ST LOUIS,MO 63130. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX. CTR DIS CONTROL & PREVENT,ATLANTA,GA. UNIV CONNECTICUT,CTR HLTH,DEPT NEUROL,STORRS,CT 06269. NIA,NCNR,BETHESDA,MD. HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,USDA HUMAN NUTR RES CTR AGING,CAMBRIDGE,MA. UNIV IOWA,IOWA CITY,IA 52242. UNIV IOWA,IOWA STATE UNIV SCI & TECHNOL,IOWA CITY,IA. RP KUTNER, NG (reprint author), EMORY UNIV,SCH MED,DEPT REHABIL MED,1441 CLIFTON RD NE,ATLANTA,GA 30322, USA. RI Wolf, Steven/F-6588-2010; OI Wolf, Steven/0000-0002-9446-8995; Miller, J Philip/0000-0003-4568-6846 FU NIA NIH HHS [U01-AG09089] NR 27 TC 42 Z9 44 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1994 VL 42 IS 7 BP 757 EP 762 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NW339 UT WOS:A1994NW33900012 PM 8014352 ER PT J AU FLESSNER, MF DEDRICK, RL AF FLESSNER, MF DEDRICK, RL TI ROLE OF THE LIVER IN SMALL-SOLUTE TRANSPORT DURING PERITONEAL-DIALYSIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Note DE PERITONEUM; CAPILLARY TRANSPORT; MASS TRANSFER; MATHEMATICAL MODEL ID DISTRIBUTED MODEL; PLASMA TRANSPORT; RAT AB Peritoneal dialysis (PD) is dependent on the transport of water and solutes from the blood capillaries within the tissues that surround the peritoneal cavity. Because of their large blood supply and surface area, the viscera have been considered the most important tissues for PD transport. In animals, however, removal of the gastrointestinal tract decreases PD small-solute mass transfer by only 10 to 27% (9,10). To investigate the theoretical basis for these observations, a distributed model of peritoneal transport was extended to take into account the transport characteristics of four tissue groups that surround the cavity: the liver, the hollow viscera, the abdominal wall, and the diaphragm. The mass transfer-area coefficient (MTAC) of sucrose for each tissue was calculated from the following: MTAC = {(D(pa))0.5}A, where D is the effective solute interstitial diffusivity, pa is the solute transcapillary permeability-area per unit tissue volume, and A is the apparent peritoneal surface area of the tissue. Our results for the adult human predict that the MTAC for the liver is comparable to that of all of the other viscera and makes up 43% of the total MTAC for the peritoneal cavity. The predicted MTAC is 4 cm3/min (plasma) or 6 cm3/min (blood), in good agreement with published values. It is concluded that the liver is responsible for a major portion of the small-solute MTAC. This also explains the earlier observations in eviscerated animals whose PD transport was likely preserved by intact livers. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP FLESSNER, MF (reprint author), UNIV ROCHESTER,MED CTR,SCH MED,DEPT MED,NEPHROL UNIT,BOX 675,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. NR 19 TC 10 Z9 10 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1994 VL 5 IS 1 BP 116 EP 120 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA NX377 UT WOS:A1994NX37700015 PM 7948778 ER PT J AU SEPULVEDA, W ROMERO, R QURESHI, F GREB, AE COTTON, DB AF SEPULVEDA, W ROMERO, R QURESHI, F GREB, AE COTTON, DB TI PRENATAL-DIAGNOSIS OF ENTEROLITHIASIS - A SIGN OF FETAL LARGE-BOWEL OBSTRUCTION SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID IMPERFORATE ANUS; CALCIFICATIONS; ATRESIAS; PENIS; TWINS C1 WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT PATHOL,DETROIT,MI 48202. WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48202. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. NR 25 TC 8 Z9 9 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 1994 VL 13 IS 7 BP 581 EP 585 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA NX401 UT WOS:A1994NX40100014 PM 7933024 ER PT J AU ALEXANDER, RB THOMPSON, N POCKAJ, BA CHANG, R AF ALEXANDER, RB THOMPSON, N POCKAJ, BA CHANG, R TI DILATION OF LOWER URETERAL STRICTURES WITH VANANDEL CATHETERS SO JOURNAL OF UROLOGY LA English DT Article DE URETER; URETERAL OBSTRUCTION; BALLOON DILATATION; DILATATION; CATHETERIZATION ID MANAGEMENT; DILATATION AB We present a simple method to dilate ureteral strictures, which was performed in 7 patients with metastatic cancer (1 breast, 1 lymphoma, 2 ovarian and 3 colorectal tumors) who presented with newly discovered obstruction in the distal ureter. The obstruction was due to tumor in the pelvis in 5 patients and to pelvic radiotherapy in 2. A 0.035-inch guide wire was passed beyond the stricture cystoscopically. In each case a double pigtail stent could not be passed beyond the stricture over the guide wire. The strictures were then dilated with progressively larger Van Andel catheters passed over the guide wire through the cystoscope. Following dilation a 7.5F to 8.5F soft double pigtail catheter was easily advanced. All patients had good drainage on followup radiographic studies. The method is presented as an alternative to balloon dilation of lower ureteral strictures when the goal is placement of an adequate diameter indwelling ureteral stent. C1 NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. RP ALEXANDER, RB (reprint author), NCI,SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1994 VL 152 IS 1 BP 68 EP 69 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA NQ770 UT WOS:A1994NQ77000017 PM 8201691 ER PT J AU MYERS, RB MEREDITH, RF SCHLOM, J LOBUGLIO, AF BUESCHEN, AJ WHEELER, RH STOCKARD, CR GRIZZLE, WE AF MYERS, RB MEREDITH, RF SCHLOM, J LOBUGLIO, AF BUESCHEN, AJ WHEELER, RH STOCKARD, CR GRIZZLE, WE TI TUMOR-ASSOCIATED GLYCOPROTEIN-72 IS HIGHLY EXPRESSED IN PROSTATIC ADENOCARCINOMAS SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATIC NEOPLASMS; CARCINOEMBRYONIC ANTIGEN; TUMOR MARKERS, BIOLOGICAL ID MONOCLONAL-ANTIBODY B72.3; ANTIGEN; CANCER; CARCINOMAS; TISSUES AB We examined the expression of two well-characterized oncofetal antigens, the tumor associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA), in malignant prostatic tissues. Three specific monoclonal antibodies, B72.3, CC49 and CC83, were used to examine the expression of TAG-72. Immunoreactivity was detected in 63% of the malignant specimens using B72.3. CC49 and CC83 were more sensitive than B72.3 in detecting TAG-72 expression. Immunoreactivity was detected in approximately 80% of prostatic adenocarcinomas with CC49 or CC83. The pattern and localization of TAG-72 immunoreactivity were similar for the three antibodies with most immunoreactivity observed within the cytoplasm of malignant cells and within the lumens of malignant glands. TAG-72 immunoreactivity was not detected within benign epithelium or stroma, with the exception of focal epithelial expression in areas of acute prostatitis. The COL-1 antibody to CEA did not detect CEA in benign glands, stroma, or malignant cells of prostate specimens resected for prostatic adenocarcinoma. These results demonstrate that TAG-72, but not CEA, is frequently expressed in prostatic adenocarcinomas. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. NR 20 TC 32 Z9 32 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1994 VL 152 IS 1 BP 243 EP 246 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA NQ770 UT WOS:A1994NQ77000076 PM 8201675 ER PT J AU SUTTER, G RAMSEYEWING, A ROSALES, R MOSS, B AF SUTTER, G RAMSEYEWING, A ROSALES, R MOSS, B TI STABLE EXPRESSION OF THE VACCINIA VIRUS K1L GENE IN RABBIT-CELLS COMPLEMENTS THE HOST-RANGE DEFECT OF A VACCINIA VIRUS MUTANT SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-REPLICATION; DELETION; MULTIPLICATION; PROTEINS; VECTOR; MVA AB Modified vaccinia virus Ankara (MVA), having acquired genomic deletions during passage in chicken embryo fibroblasts, is highly attenuated and unable to productively infect most mammalian cell lines. Multiplication in rabbit kidney-derived RK13 cells, but not other nonpermissive cells, can be restored by insertion of the vaccinia virus K1L gene into the MVA genome. During nonproductive infection of RK13 cells by MVA, transcription of representative viral early genes was revealed by Northern (RNA) blotting, whereas synthesis of an intermediate mRNA and replication of viral DNA could not be detected. Despite the persistence of viral early mRNA for at least several hours, synthesis of virus-induced polypeptides occurred only during the first hour and was followed by abrupt inhibition of all protein synthesis. Transfection of RK13 cells with a eukaryotic expression plasmid that contained the K1L gene allowed h PVA infection to proceed to late stages of viral protein synthesis. Moreover, RK13 cell lines that stably expressed the K1L gene were permissive for MVA as well as a K1L deletion mutant of the WR strain of vaccinia virus. This is the first description of the complementation of a poxvirus mutant by cells that stably express a viral gene. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 30 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4109 EP 4116 PG 8 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300001 PM 8207789 ER PT J AU GHADGE, GD MALHOTRA, P FURTADO, MR DHAR, R THIMMAPAYA, B AF GHADGE, GD MALHOTRA, P FURTADO, MR DHAR, R THIMMAPAYA, B TI IN-VITRO ANALYSIS OF VIRUS-ASSOCIATED RNA-I (VAI RNA) - INHIBITION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN-KINASE PKR BY VAI RNA MUTANTS CORRELATES WITH THE IN-VIVO PHENOTYPE AND THE STRUCTURAL INTEGRITY OF THE CENTRAL DOMAIN SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; RESPONSIVE REGION RNA; VIRAL MESSENGER-RNAS; TRANSLATIONAL CONTROL; MOUSE FIBROBLASTS; HELA-CELLS; ADENOVIRUS; INITIATION; BINDING; DAI AB Adenoviruses use the virus-encoded virus-associated RNA (VAI RNA) as a defense against cellular antiviral response by blocking the activation of the interferon-induced, double-stranded RNA-activated protein kinase PKR. The structure of VAI RNA consists of two long, imperfectly base-paired duplex regions connected by a complex short stem-loop at the center, referred to as the central domain, By using a series of adenovirus mutants with linker-scan mutations in the VAI RNA gene, we recently showed that the critical elements required for function in the VAI RNA molecule are in the central domain and that these same elements of the central domain are also involved in binding to PKR. In virus-infected cells, VAM RNA interacts with latent kinase, which is bound to ribosomes; this interaction takes place in a complex milieu. To more fully understand the relationship between structure and function and to determine whether the in vivo phenotype of these mutants can be reproduced in vitro, we have now analyzed these mutant VAI alleles for their ability to block the activation of a partially purified PKR from HeLa cells. We have also derived the structure of these mutants experimentally and correlated the structure with function. Without exception, when the structure of the short stem-loop of the central domain was perturbed, the mutants failed to inhibit PKR. Structural disruptions elsewhere in the central domain or in the long duplex regions of the molecule were not deleterious for in vitro function. Thus, these results support our previous findings and underscore the importance of the elements present in the central domain of the VAI RNA for its function. Our results also suggest that the interaction between PKR and VAI RNA involves a precise secondary (and tertiary) structure in the central domain. It has been suggested that VAI RNA does not activate PKR in virus-infected cells because of mismatches in the imperfectly base-paired long duplex regions. We constructed mutant VAI genes in which the imperfectly base-paired duplex regions were converted to perfectly base-paired regions and assayed in vitro for the activation of PKR. As with the wild-type VAI RNA, these mutants failed to activate PKR in vitro, while they were able to block the activation of PKR better than did the wild type. These results suggest that the failure of VAI RNA to activate PKR is not the result of mismatches in the long duplex regions. Thus, the role of the long duplex regions of VAI RNA is probably to hold the nucleotide sequences of the central domain in a conformation optimal for function. C1 NORTHWESTERN UNIV,SCH MED,ROBERT H LURIE CANC CTR,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,CHICAGO,IL 60611. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI18029, AI20156] NR 58 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4137 EP 4151 PG 15 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300004 PM 7911532 ER PT J AU VANIN, EF KALOSS, M BROSCIUS, C NIENHUIS, AW AF VANIN, EF KALOSS, M BROSCIUS, C NIENHUIS, AW TI CHARACTERIZATION OF REPLICATION-COMPETENT RETROVIRUSES FROM NONHUMAN-PRIMATES WITH VIRUS-INDUCED T-CELL LYMPHOMAS AND OBSERVATIONS REGARDING THE MECHANISM OF ONCOGENESIS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; NUCLEOTIDE-SEQUENCE; GENE-TRANSFER; ENVELOPE GENE; BONE-MARROW; ENV GENE; VECTORS; FRIEND; EXPRESSION AB Rapidly progressive T-cell lymphomas were observed in 3 of 10 rhesus monkeys several months after autologous transplantation of enriched bone marrow stem cells that had been transduced with a retroviral vector preparation containing replication-competent virus (R. E. Donahue, S. W. Kessler, D. Bodice, K. McDonagh, C. Dunbar, S. Goodman, B. Agricola, E. Byrne, M. Raffeld, R. Moen, J. Bacher, K. M. Zsebo, and A. W. Nienhuis, J. Exp. Med. 176:1124-1135, 1992). The animals with lymphoma appeared to be tolerant to retroviral antigens in that their sera lacked antibodies reactive with viral proteins and contained 10(4) to 10(5) infectious virus particles per mi. By molecular cloning and DNA sequencing, we have now demonstrated that the serum from one of the monkeys contained a replication-competent retrovirus that arose by recombination between vector and packaging encoding sequences (vector/helper [V/H] recombinant) in the producer clone used for transduction of bone marrow stem cells. Southern blot analysis demonstrated 14 or 25 copies of this genome per cell where present in two animals. The genome of a second replication-competent virus was also recovered by molecular cloning; it arose by recombination involving the genome of the V/H recombinant and endogenous murine retroviral genomes in the producer clone. Twelve copies of this amphotropic virus/mink cell focus-forming virus genome were present in tumor DNA of one animal, but it was not found in tumor DNA of the other two animals with lymphoma. Southern blot analysis of DNA from various tissues demonstrated common insertion site bands in several samples of tumor DNA from one animal, suggesting clonal origin of the lymphoma. Our data are most consistent with a pathogenic mechanism in which chronic productive retroviral infection allowed insertional mutagenesis of critical growth control genes, leading to cell transformation and clonal tumor evolution. C1 GENET THERAPY INC,GAITHERSBURG,MD 20878. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 45 TC 86 Z9 89 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4241 EP 4250 PG 10 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300014 PM 8207799 ER PT J AU WILLEY, RL THEODORE, TS MARTIN, MA AF WILLEY, RL THEODORE, TS MARTIN, MA TI AMINO-ACID SUBSTITUTIONS IN THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 V3 LOOP THAT CHANGE VIRAL TROPISM ALSO ALTER PHYSICAL AND FUNCTIONAL-PROPERTIES OF THE VIRION ENVELOPE SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-LINE; INFECTIOUS MOLECULAR CLONES; SOLUBLE CD4; MONONUCLEAR PHAGOCYTES; MACROPHAGE TROPISM; FUSION DOMAIN; HOST-RANGE; HIV-1; GLYCOPROTEIN; BINDING AB The third variable (V3) region within the gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) has been reported to be an important determinant of viral tropism, In this study a series of isogenic recombinant HIV-1 viruses, containing V3 regions from fresh isolates, were examined to ascertain if a relationship exists between viral tropism and specific properties of the virion-associated envelope. All of the viruses were able to infect CD4(+) primary lymphocytes, although with different infection kinetics. Several recombinants, however, were unable to infect a continuous CD4(+) T-cell line permissive for the parental virus and exhibited a marked decrease in the kinetics of virion-associated gp120 binding to a soluble form of CD4. A known macrophage-tropic HIV-1 isolate, also unable to infect the T-cell line, bound CD4 with similarly slow reaction kinetics. Although the inability to infect T-cell lines is a commonly observed property of macrophagetropic isolates of HIV-1, the loss of T-cell line tropism by the V3 recombinants was not accompanied by a substantial infectivity for monocyte-derived macrophages, as monitored by reverse transcriptase production, Additional analyses of the recombinant virion gp120s indicated that most of the V3 substitutions increased the inherent stability of the virion gp120-gp41 envelope complex. These results indicate that V3-induced alterations in viral tropism are associated with changes in physical and functional properties of the virion envelope. RP WILLEY, RL (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 61 TC 60 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4409 EP 4419 PG 11 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300032 PM 7515973 ER PT J AU GOLDSTEIN, DJ LI, WQ WANG, LM HEIDARAN, MA AARONSON, S SHINN, R SCHLEGEL, R PIERCE, JH AF GOLDSTEIN, DJ LI, WQ WANG, LM HEIDARAN, MA AARONSON, S SHINN, R SCHLEGEL, R PIERCE, JH TI THE BOVINE PAPILLOMAVIRUS TYPE-1 E5 TRANSFORMING PROTEIN SPECIFICALLY BINDS AND ACTIVATES THE BETA-TYPE RECEPTOR FOR THE PLATELET-DERIVED GROWTH-FACTOR BUT NOT OTHER RELATED TYROSINE KINASE-CONTAINING RECEPTORS TO INDUCE CELLULAR-TRANSFORMATION SO JOURNAL OF VIROLOGY LA English DT Article ID VACUOLAR H+-ATPASE; OPEN READING FRAME; PDGF RECEPTOR; TUMORIGENIC TRANSFORMATION; SIGNAL TRANSDUCTION; CELLS; ONCOPROTEIN; DOMAIN; GENES; CDNA AB The 44-amino-acid E5 protein of bovine papillomavirus type 1 is a highly hydrophobic protein which appears to transform cells through the activation of growth factor receptors. To investigate the specificity of E5-growth factor receptor interactions required for mitogenic signaling, we utilized a nontumorigenic, murine myeloid cell line (32D) which is strictly dependent on interleukin-3 (IL-3) for sustained proliferation in culture. This IL-3 dependence can be functionally substituted by the expression of a variety of surrogate growth factor receptors and the addition of the corresponding ligand. Several receptor cDNAs for the alpha- and beta-type platelet-derived growth factor receptors [alpha PDGFR and beta PDGFR], the epidermal growth factor receptor, and the colony-stimulating factor 1 receptor) were transfected into 32D cells constitutively expressing the E5 protein to test for IL-3-independent growth. Only beta PDGFR war capable of abrogating the IL-3 dependence of 32D cells. The proliferative signal induced by the coexpression of beta PDGFR and E5 was accompanied by stable complex formation between these proteins, constitutive tyrosine phosphorylation of the receptor, and tumorigenicity in nude mice. The lack of cooperative interaction between E5 and the epidermal growth factor receptor, the colony-stimulating factor 1 receptor, and the highly related a PDGFR was paralleled by the inability of E5 to bind to these receptors and failure to increase receptor tyrosine phosphorylation. Thus, these data indicate that the ability of ES to induce sustained proliferation and transformation of 32D cells is a direct consequence of specific interaction between the E5 protein and the beta PDGFR signaling complex and the subsequent stimulation of receptor tyrosine phosphorylation. C1 GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP GOLDSTEIN, DJ (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007, USA. FU NCI NIH HHS [R01CA53371-03] NR 40 TC 67 Z9 69 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4432 EP 4441 PG 10 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300035 PM 8207816 ER PT J AU POWER, C MCARTHUR, JC JOHNSON, RT GRIFFIN, DE GLASS, JD PERRYMAN, S CHESEBRO, B AF POWER, C MCARTHUR, JC JOHNSON, RT GRIFFIN, DE GLASS, JD PERRYMAN, S CHESEBRO, B TI DEMENTED AND NONDEMENTED PATIENTS WITH AIDS DIFFER IN BRAIN-DERIVED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE SEQUENCES SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; IMMUNE-DEFICIENCY SYNDROME; CENTRAL NERVOUS-SYSTEM; MOLECULAR CHARACTERIZATION; NEUROLOGIC MANIFESTATIONS; PRODUCTIVE INFECTION; CEREBROSPINAL-FLUID; VIRAL DETERMINANTS; MACROPHAGE TROPISM; MICROGLIAL CELLS AB Human immunodeficiency virus (HIV) dementia is a common clinical syndrome of uncertain pathogenesis in patients with AIDS. In several animal models of retrovirus-induced brain disease, specific viral envelope sequences have been found to influence the occurrence of central nervous system disease. Therefore, to search for unique envelope sequences correlated with HIV dementia, we studied 22 HIV-infected patients who were neurologically assessed premortem and classified into demented (HIVD) (n = 14) and nondemented (ND) (n = 8) groups. Using DNA from autopsied brain and spleen, we amplified, cloned, and sequenced a 430-nucleotide region including the V3 loop and flanking regions. All brain-derived clones in both clinical groups showed marked homology to the macrophage-tropic consensus sequence within the V3 loop. Two amino acid positions within (position 305) and outside (position 329) the V3 region showed significant divergence between the two clinical groups. At position 305, a histidine was predominant in the HIVD group and was not observed in the ND group, but a proline was predominant in the ND group and was not observed in the HIVD group. Similarly, at position 329, a leucine was predominant in the HIVD group but rarely observed in the ND group,whereas an isoleucine,vas predominant in the ND group at this position. In addition, the HIVD group had 21 amino acid residues at specific positions that were unique relative to the ND group, whereas only 2 residues at specific positions were unique to the ND group. These data suggest that distinct HIV envelope sequences are associated with the clinical expression of HIV dementia. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD 21287. RI Power, Christopher/C-7181-2013; OI Power, Christopher/0000-0002-5131-9711 FU NCRR NIH HHS [RR 00722]; NIAID NIH HHS [AI 767234]; NINDS NIH HHS [NS 26643] NR 60 TC 232 Z9 235 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4643 EP 4649 PG 7 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300059 PM 8207838 ER PT J AU WONG, S MOMOEDA, M FIELD, A KAJIGAYA, S YOUNG, NS AF WONG, S MOMOEDA, M FIELD, A KAJIGAYA, S YOUNG, NS TI FORMATION OF EMPTY B19 PARVOVIRUS CAPSIDS BY THE TRUNCATED MINOR CAPSID PROTEIN SO JOURNAL OF VIROLOGY LA English DT Note ID STRUCTURAL PROTEINS; MINUTE VIRUS; UNIQUE; REGION; MICE; VP1 AB We previously reported that empty capsids of B19 parvovirus were formed by the major capsid protein (VP2) alone expressed in a baculovirus system, but the minor capsid protein (VP1), longer by 227 amino acids, alone did not form empty capsids. We report here further investigations of the constraints on capsid formation by truncated versions of VP1. Studies were performed with recombinant baculoviruses expressed in Sf9 cells. Severely shortened VP1, extended beyond the VP2 core sequence by about 70 amino acids of the unique region, formed capsids normal in appearance; longer versions of VPI also formed capsids but did so progressively less efficiently and produced capsids of more markedly dysmorphic appearance as the VP1-unique region was lengthened. C1 NHLBI,BETHESDA,MD 20892. CENT PUBL HLTH LAB,VIRUS REFERENCE LAB,LONDON NW9 5HT,ENGLAND. NR 19 TC 13 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4690 EP 4694 PG 5 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300067 PM 8207846 ER PT J AU PORTIS, JL SPANGRUDE, GJ MCATEE, FJ AF PORTIS, JL SPANGRUDE, GJ MCATEE, FJ TI IDENTIFICATION OF A SEQUENCE IN THE UNIQUE 5' OPEN READING FRAME OF THE GENE ENCODING GLYCOSYLATED GAG WHICH INFLUENCES THE INCUBATION PERIOD OF NEURODEGENERATIVE DISEASE INDUCED BY A MURINE RETROVIRUS (VOL 68, PG 3881, 1994) SO JOURNAL OF VIROLOGY LA English DT Correction, Addition RP PORTIS, JL (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1994 VL 68 IS 7 BP 4706 EP 4706 PG 1 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300072 ER PT J AU CARRARO, R LI, ZH GREGERMAN, RI AF CARRARO, R LI, ZH GREGERMAN, RI TI CATECHOLAMINE-SENSITIVE LIPOLYSIS IN THE RAT - DIFFERENT LOCI FOR EFFECT OF AGE ON THE LIPOLYTIC CASCADE IN EPIDIDYMAL VS PERIRENAL FAT-CELLS SO JOURNALS OF GERONTOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; STIMULATED LIPOLYSIS; ADIPOSE-TISSUE; AGING RABBITS; ADIPOCYTES; INHIBITION; ADENOSINE AB The biochemical locus of the decrease of lipolytic responsiveness to catecholamines in the aging rat has not heretofore been completely identified. Although increased sensitivity to the inhibitory action of adenosine is the likely explanation for the decrease during maturation, the nature of the age effect during senescence has been unclear. In order to determine whether the proximal or distal portion of the lipolytic pathway is involved, we have studied the lipolytic effect of the distally acting cyclic AMP analogue, 8-(4-chlorophenylthioadenosine) 3'5'-monophosphate (cyclic) (Cl-cAMP) on rat fat cells from both the epididymal and perirenal fat pads of mature (6 mo) and senescent (24 mo) Fischer 344 rats. Using an adenosine (N-6-l-2-phenylisopropyl-adenosine; PIA) regulated system, the lipolytic response to epinephrine (glycerol release) was measured simultaneously with that to Cl-cAMP. The effects of age on lipolysis are greatly influenced by the anatomic site of origin of the fat cells. The epididymal cells of the old rats showed no decreased responsiveness to either epinephrine or Cl-cAMP. However, the perirenal cells of the old rats showed a grossly impaired maximal response to both epinephrine (60% decrease relative to young; p < .005) and Cl-cAMP (42% and 58% decrease in 2 sets of experiments; p <. 05 and. 04, respectively). Although decreased lipolytic response to epinephrine in epididymal cells was not seen in these studies, this has been clearly shown in earlier work, suggesting that diminished response to epinephrine is demonstrable only when the system is not already maximally inhibited by PIA. The distal defect in perirenal cells is in agreement with recent studies of the site of the age effect on lipolysis in human subcutaneous fat. C1 NIA,GERONTOL RES CTR,JOHNS HOPKINS BAYVIEW RES CAMPUS,BALTIMORE,MD 21224. NR 15 TC 5 Z9 5 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1994 VL 49 IS 4 BP B140 EP B143 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NV799 UT WOS:A1994NV79900002 PM 8014385 ER PT J AU FOZARD, JL VERCRUYSSEN, M REYNOLDS, SL HANCOCK, PA QUILTER, RE AF FOZARD, JL VERCRUYSSEN, M REYNOLDS, SL HANCOCK, PA QUILTER, RE TI AGE-DIFFERENCES AND CHANGES IN REACTION-TIME - THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO JOURNALS OF GERONTOLOGY LA English DT Article ID CHOICE-REACTION-TIME; ELDERLY SUBJECTS; MOVEMENT TIME; POPULATION AB This study analyzed auditory reaction time (RT) data from 1,265 community-dwelling volunteers (833 males and 432 females) who ranged in age from 17 to 96. Cross-sectional analyses revealed slowing of simple (SRT) and relatively greater slowing of disjunctive (DRT; aka ''go-no-go'') reaction time across decades for both males and females. Repeated testing within participants (longitudinal analyses) over eight gears showed consistent slowing and increased variability with age. Males were faster than females across age groups, RT tasks, and visits. Beginning at about age 20, RTs increased at a rate of approximately 0.5 msec/yr for SRT and 1.6 msec/yr for DRT. Errors also increased, making unlikely a tradeoff of accuracy for faster responses. The findings are consistent with the hypotheses that slowing of behavior is: (a) a continuous process over the adult life span; (6) characterized by age-associated increases in within-participant variability; (c) a direct function of task complexity and, presumably, the degree of mediation by higher regions in the central nervous system; and (d) greater in women than men. C1 EINDHOVEN UNIV TECHNOL,INST GERONTECHNOL,5600 MB EINDHOVEN,NETHERLANDS. UNIV HAWAII,CTR AGING,HONOLULU,HI 96822. UNIV HAWAII,DEPT PSYCHOL,HONOLULU,HI 96822. PSY MED ASSOCIATES,HONOLULU,HI. UNIV MINNESOTA,HUMAN FACTORS RES LAB,MINNEAPOLIS,MN 55455. RP FOZARD, JL (reprint author), NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Fozard, James Leonard/B-3660-2009 NR 50 TC 61 Z9 63 U1 1 U2 11 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1994 VL 49 IS 4 BP P179 EP P189 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NV799 UT WOS:A1994NV79900017 PM 8014399 ER PT J AU RAPPAPORT, J KOPP, JB KLOTMAN, PE AF RAPPAPORT, J KOPP, JB KLOTMAN, PE TI HOST VIRUS INTERACTIONS AND THE MOLECULAR REGULATION OF HIV-1 - ROLE IN THE PATHOGENESIS OF HIV-ASSOCIATED NEPHROPATHY SO KIDNEY INTERNATIONAL LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REV PROTEIN; TAR-INDEPENDENT TRANSACTIVATION; LYMPHOBLASTOID CELL-LINE; TRANS-ACTIVATOR GENE; VIRAL MESSENGER-RNA; GROWTH-FACTOR-BETA; NF-KAPPA-B; BASIC DOMAIN; BINDING-PROTEIN RP RAPPAPORT, J (reprint author), NIDR,LDB,BLDG 30,RM 433,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 165 TC 44 Z9 44 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1994 VL 46 IS 1 BP 16 EP 27 DI 10.1038/ki.1994.240 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA NT128 UT WOS:A1994NT12800003 PM 7933833 ER PT J AU SEMINOMORA, MC LEONMONZON, ME DALAKAS, MC AF SEMINOMORA, MC LEONMONZON, ME DALAKAS, MC TI EFFECT OF L-CARNITINE ON THE ZIDOVUDINE-INDUCED DESTRUCTION OF HUMAN MYOTUBES .1. L-CARNITINE PREVENTS THE MYOTOXICITY OF AZT IN-VITRO SO LABORATORY INVESTIGATION LA English DT Article DE MUSCLE MITOCHONDRIA; L-CARNITINE; LIPID DROPLETS ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; MITOCHONDRIAL MYOPATHY; ULTRASTRUCTURAL-CHANGES; MUSCLE MITOCHONDRIA; DNA; SKELETAL; CELLS; 3'-AZIDO-3'-DEOXYTHYMIDINE; REPLICATION AB BACKGROUND: Zidovudine (AZT) as used in the treatment of AIDS, causes a mitochondrial myopathy characterized by depletion of mitochondrial DNA, enzymatic defects in the respiratory chain system, and accumulation of lipid droplets. Most of these changes are also seen in normal human myotubes treated with AZT. Because L-carnitine plays a major role in the transport of long chain fatty acids across the inner mitochondrial membrane and facilitates the P-oxidation of fatty acids, we examined the effect of L-carnitine in preventing the destructive effect of AZT on the mitochondria and the myotubes of human muscle in tissue culture. EXPERIMENTAL DESIGN: Myotubes, prepared from human muscle biopsies, were exposed to various concentrations of AZT for up to 3 weeks. One-third of the flasks were treated with AZT alone, another third with AZT plus L-carnitine and another third were untreated. The cultures were evaluated with: (a) immunocytochemistry counting the number of myotubes stained with antibodies to Leu-19; (b) enzyme histochemistry for NADH reaction and oil-red-O stain to assess mitochondrial enzymatic activity and lipid droplet accumulation; and (c) electron microscopy counting all the organelles within representative sections of the myotubes, at x 24,000, and calculating the volumetric density of each organelle/unit volume of tissue. RESULTS: AZT, at concentrations 250 mu M and above, caused depopulation of the Leu-19-positive myotubes, destructive changes in the mitochondria consisting of swelling, lamellar inclusions and multiple concentric cristae, accumulation of lipid droplets, and increase lysosomes. L-Carnitine increased the number of Leu-19-positive myotubes from 3.4 +/- 0.6 to 9.4 +/- 1.2, preserved the morphology of the mitochondria, increased their volumetric density from 2.5 +/- 0.4 to 6.0 +/- 0.7, and reduced the volumetric density of the lipid droplets from 12.2 +/- 4.9 to 1.4 +/- 0.7 and of the lysosomes from 15.6 +/- 3.6 to 3.9 +/- 1.4 (p < 0.001). CONCLUSIONS: L-Carnitine, used concurrently with AZT, prevents the human myotubes from the AZT-associated destruction, preserves the structure and volume of mitochondria and prevents the accumulation of lipids. The findings may have potential clinical implications in preventing the myotoxicity of AZT in patients with AIDS. C1 NINCDS,NEUROMUSCULAR DIS SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 33 TC 36 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 1994 VL 71 IS 1 BP 102 EP 112 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PA454 UT WOS:A1994PA45400013 PM 7518879 ER PT J AU DUYN, JH MATTAY, VS SEXTON, RH SOBERING, GS BARRIOS, FA LIU, GY FRANK, JA WEINBERGER, DR MOONEN, CTW AF DUYN, JH MATTAY, VS SEXTON, RH SOBERING, GS BARRIOS, FA LIU, GY FRANK, JA WEINBERGER, DR MOONEN, CTW TI 3-DIMENSIONAL FUNCTIONAL IMAGING OF HUMAN BRAIN USING ECHO-SHIFTED FLASH MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE BRAIN, FUNCTION; BRAIN, MR; MR, RAPID IMAGING; FUNCTIONAL MRI ID GRADIENT-RECALLED MRI; HUMAN VISUAL-CORTEX; SENSORY STIMULATION; PHOTIC-STIMULATION; SIGNAL CHANGES; MOTOR CORTEX; CONTRAST; OXYGENATION; TIME; ACTIVATION AB A 3-dimensional MRI method has been developed for functional mapping of the human brain, based on brood oxygenation level dependent (BOLD) contrast mechanisms. The method uses recently introduced principles of echo-shifted FLASH to acquire a single 3D data set in 20 s. The technique was tested on a conventional 1.5 Tesla clinical scanner with a standard head coil using visual stimulation with a 8 Hz flashing white light, or a varying checkerboard pattern. Areas of increased signal intensity were identified in the visual cortex, consistent with the known functional organization. C1 NIH,NCRR,BEIP,IN VIVO NMR RES CTR,BETHESDA,MD 20892. NIH,OIR,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC. COMPUTAT PHYS INC,FAIRFAX,VA. RI Liu, Guang Yu/A-8802-2008; Duyn, Jozef/F-2483-2010; Barrios, Fernando/B-4295-2012; Barrios, Fernando/D-1591-2016; Moonen, Chrit/K-4434-2016 OI Barrios, Fernando/0000-0002-5699-4222; Moonen, Chrit/0000-0001-5593-3121 NR 30 TC 49 Z9 53 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUL PY 1994 VL 32 IS 1 BP 150 EP 155 DI 10.1002/mrm.1910320123 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NT738 UT WOS:A1994NT73800022 PM 8084232 ER PT J AU DOSIK, JK BARTON, CH HOLIDAY, DL KRALL, MM BLACKWELL, JM MOCK, BA AF DOSIK, JK BARTON, CH HOLIDAY, DL KRALL, MM BLACKWELL, JM MOCK, BA TI AN NRAMP-RELATED SEQUENCE MAPS TO MOUSE CHROMOSOME-17 SO MAMMALIAN GENOME LA English DT Note ID LEISHMANIA-MAJOR INFECTION; NATURAL-RESISTANCE; GENETIC-CONTROL; MICE; LOCUS; BCG; LSH C1 NCI,GENET LAB,BETHESDA,MD 20892. UNIV CAMBRIDGE,ADDENBROOKES HOSP,SCH CLIN,DEPT MED,CAMBRIDGE CB2 2Q,CAMBS,ENGLAND. RI Blackwell, Jenefer/H-3015-2015 FU NCI NIH HHS [N01-CB-21075]; Wellcome Trust NR 20 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1994 VL 5 IS 7 BP 458 EP 460 DI 10.1007/BF00357010 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA NV037 UT WOS:A1994NV03700012 PM 7919662 ER PT J AU DEUTSCH, D PALMON, A YOUNG, MF SELIG, S KEARNS, WG FISHER, LW AF DEUTSCH, D PALMON, A YOUNG, MF SELIG, S KEARNS, WG FISHER, LW TI MAPPING OF THE HUMAN TUFTELIN (TUFT1) GENE TO CHROMOSOME-1 BY FLUORESCENCE IN-SITU HYBRIDIZATION SO MAMMALIAN GENOME LA English DT Note ID ENAMEL; LOCALIZATION; PROTEIN C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT CELLULAR BIOCHEM,IL-91010 JERUSALEM,ISRAEL. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. RP DEUTSCH, D (reprint author), HEBREW UNIV JERUSALEM,HADASSAH SCH DENT MED,DENT RES UNIT,POB 1172,IL-91010 JERUSALEM,ISRAEL. FU NIDCR NIH HHS [R01-DEO-5780] NR 9 TC 25 Z9 29 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1994 VL 5 IS 7 BP 461 EP 462 DI 10.1007/BF00357011 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA NV037 UT WOS:A1994NV03700013 PM 7919663 ER PT J AU ZHENG, T AF ZHENG, T TI DNA-DAMAGE AND THE PROLIFERATION AND AGING OF CELLS IN CULTURE - A MATHEMATICAL-MODEL WITH TIME-LAG SO MATHEMATICAL BIOSCIENCES LA English DT Article ID CELLULAR SENESCENCE; FIBROBLASTS; GROWTH AB This paper is an extension of an earlier one by the same author in which a mathematical model was presented to describe the proliferation and aging of cells in culture. The model consists of a group of ordinary differential equations with a time lag. In the previous paper, the time lag was omitted for simplicity and the resulting differential equations were resolved analytically. It was shown that the model explains the behavior of a cell culture reasonably well. In this paper, the analytical solution of the original differential equations is presented without omitting the time lag. An analytical description of the variations in doubling capability between sister cells that was only simulated numerically in the earlier paper is given. RP ZHENG, T (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JUL PY 1994 VL 122 IS 1 BP 67 EP 88 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA NV693 UT WOS:A1994NV69300003 ER PT J AU NATH, R BIGGS, PJ BOVA, FJ LING, CC PURDY, JA VANDEGEIJN, J WEINHOUS, MS AF NATH, R BIGGS, PJ BOVA, FJ LING, CC PURDY, JA VANDEGEIJN, J WEINHOUS, MS TI AAPM CODE OF PRACTICE FOR RADIOTHERAPY ACCELERATORS - REPORT OF AAPM RADIATION-THERAPY TASK GROUP NO-45 SO MEDICAL PHYSICS LA English DT Review ID ELECTRON ARC THERAPY; DYNAMIC STEREOTACTIC RADIOSURGERY; LINEAR-ACCELERATOR; X-RAYS; APPLICATOR SYSTEM; DOSIMETRIC PROPERTIES; DOSE DISTRIBUTIONS; FILM DOSIMETRY; OUTPUT FACTORS; PHOTON BEAMS C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT MED,BOSTON,MA 02114. UNIV FLORIDA,J HILLIS MILLER HLTH CTR,DEPT RADIAT THERAPY,GAINESVILLE,FL 32610. MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY 10021. EDWARD MALLINCKRODT INST RADIOL,DIV RADIAT ONCOL,ST LOUIS,MO 63110. NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RP NATH, R (reprint author), YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,NEW HAVEN,CT 06510, USA. NR 139 TC 103 Z9 104 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 1994 VL 21 IS 7 BP 1093 EP 1121 DI 10.1118/1.597398 PG 29 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NY972 UT WOS:A1994NY97200011 PM 7968843 ER PT J AU ANDRADE, SG KLOETZEL, JK BORGES, MM FERRANS, VJ AF ANDRADE, SG KLOETZEL, JK BORGES, MM FERRANS, VJ TI MORPHOLOGICAL ASPECTS OF THE MYOCARDITIS AND MYOSITIS IN CALOMYS CALLOSUS EXPERIMENTALLY INFECTED WITH TRYPANOSOMA-CRUZI - FIBROGENESIS AND SPONTANEOUS REGRESSION OF FIBROSIS SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article DE TRYPANOSOMA CRUZI; CALOMYS CALLOSUS; MYOCARDITIS; MYOSITIS; FIBROGENESIS; FIBROCLASIA; ULTRASTRUCTURE; COLLAGEN ID CHAGAS-DISEASE; MICE; STRAINS; CELLS AB Calomys callosus a wild rodent, is a natural host of Trypanosoma cruzi. Twelve C. callosus were infected with 10(5) trypomastigotes of the F strain (a myotropic strain) of T. cruzi. Parasitemia decreased on the 21st day becoming negative around the 40th day of infection. All animals survived but had positive parasitological rests, until the end of the experiment The infected animals developed severe inflammation in the myocardium and skeletal muscle. This process was pronounced from the 26th to the 30th day and gradually subsided from the 50th day becoming absent or residual on the 64th day after infection. Collagen was identfied by the picro Sirius red method. Fibrogenesis developed early, but regression of fibrosis occurred between the 50th and 64th day. Ultrastructural study disclosed a predominance of macrophages and fibroblasts in the inflammatory infiltrates, with small numbers of lymphocytes. Macrophages had active phagocytosis and showed points C1 UNIV SAO PAULO,ICB,INST MED TROP SAO PAULO,BR-05403000 SAO PAULO,BRAZIL. UNIV SAO PAULO,ICB,DEPT PARASITOL,BR-05403000 SAO PAULO,BRAZIL. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP ANDRADE, SG (reprint author), UFBA,FIOCRUZ,CTR PESQUISAS GONCALO MONIZ,RUA VALDEMAR FALCAO 121,BR-40295001 SALVADOR,BA,BRAZIL. RI Borges, Monamaris/E-2702-2013 NR 20 TC 13 Z9 14 U1 0 U2 0 PU MEM INST OSWALDO CRUZ PI RIO DE JANEIRO PA SECRETARY CAIXA POSTAL 926, 20001 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD JUL-SEP PY 1994 VL 89 IS 3 BP 379 EP 393 PG 15 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA QD873 UT WOS:A1994QD87300016 PM 7476222 ER PT J AU WEISS, DJ CHARLES, MA DUNAIF, A PRIOR, DE LILLIOJA, S KNOWLER, WC HERMAN, WH AF WEISS, DJ CHARLES, MA DUNAIF, A PRIOR, DE LILLIOJA, S KNOWLER, WC HERMAN, WH TI HYPERINSULINEMIA IS ASSOCIATED WITH MENSTRUAL IRREGULARITY AND ALTERED SERUM ANDROGENS IN PIMA INDIAN WOMEN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID POLYCYSTIC OVARY SYNDROME; GLUCOSE-TOLERANCE TEST; INVIVO INSULIN ACTION; GONADOTROPIN-SECRETION; HYPERANDROGENIC WOMEN; ACANTHOSIS NIGRICANS; RESISTANCE; SUPPRESSION; DISEASE; POPULATION C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV ENDOCRINOL & METAB,ANN ARBOR,MI 48109. NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ. PENN STATE UNIV,COLL MED,DIV ENDOCRINOL DIABET & METAB,HERSHEY,PA. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 FU NCRR NIH HHS [RR-00071]; NIDDK NIH HHS [DK40605] NR 35 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 1994 VL 43 IS 7 BP 803 EP 807 DI 10.1016/0026-0495(94)90257-7 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NV984 UT WOS:A1994NV98400002 PM 8028500 ER PT J AU DENGEL, DR HAGBERG, JM COON, PJ DRINKWATER, DT GOLDBERG, AP AF DENGEL, DR HAGBERG, JM COON, PJ DRINKWATER, DT GOLDBERG, AP TI EFFECTS OF WEIGHT-LOSS BY DIET ALONE OR COMBINED WITH AEROBIC EXERCISE ON BODY-COMPOSITION IN OLDER OBESE MEN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PHYSICAL-ACTIVITY; REDUCTION; REGIMENS C1 UNIV MARYLAND, SCH MED, DIV GERONTOL, BALTIMORE, MD 21201 USA. UNIV MARYLAND, CTR AGING, COLL PK, MD 20742 USA. NIA, GERONTOL RES CTR, CLIN PHYSIOL LAB, METAB SECT, BALTIMORE, MD USA. RP VET ADM MED CTR, GERIATR SERV 18, 10 N GREEN ST, BALTIMORE, MD 21201 USA. FU NIA NIH HHS [P01 AG-04402, KO8 AG-00347, F32AG-05555] NR 26 TC 46 Z9 46 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 1994 VL 43 IS 7 BP 867 EP 871 DI 10.1016/0026-0495(94)90268-2 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NV984 UT WOS:A1994NV98400013 PM 8028510 ER PT J AU GREENWALD, P AF GREENWALD, P TI CHEMOPREVENTION RESEARCH AT THE UNITED-STATES NATIONAL-CANCER-INSTITUTE SO MILITARY MEDICINE LA English DT Article AB The use of specific chemicals to prevent the development or retard the progression of carcinogenesis-known as chemoprevention-is a rapidly growing area in cancer research. Developed through the integration of strong laboratory and epidemiologic evidence, chemoprevention research has moved successfully into the clinical research setting, with diverse agents being tested for their efficacy in individuals at high risk of developing certain cancers. The public health potential for reducing cancer incidence and mortality through chemical intervention provides a unique and promising opportunity, and continued support of this multidisciplinary approach to cancer prevention remains a high priority for the U.S. National Cancer Institute. RP GREENWALD, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 1994 VL 159 IS 7 BP 505 EP 512 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PL885 UT WOS:A1994PL88500010 PM 7816223 ER PT J AU CLARK, CG PUNG, OJ AF CLARK, CG PUNG, OJ TI HOST-SPECIFICITY OF RIBOSOMAL DNA VARIATION IN SYLVATIC TRYPANOSOMA-CRUZI FROM NORTH-AMERICA SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE TRIATOMA SANGUISUGA; TRYPANOSOMA CRUZI; RIBOPRINTING; RIBOSOMAL RNA GENE; OPOSSUM; POLYMORPHISM; RACCOON ID CHAGAS-DISEASE C1 GEORGIA SO UNIV,DEPT BIOL,STATESBORO,GA 30460. GEORGIA SO UNIV,INST ARTHROPODOL & PARASITOL,STATESBORO,GA 30460. RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 13 TC 69 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 1994 VL 66 IS 1 BP 175 EP 179 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA PB578 UT WOS:A1994PB57800023 PM 7984184 ER PT J AU YAMAMOTO, K QUELLE, FW THIERFELDER, WE KREIDER, BL GILBERT, DJ JENKINS, NA COPELAND, NG SILVENNOINEN, O IHLE, JN AF YAMAMOTO, K QUELLE, FW THIERFELDER, WE KREIDER, BL GILBERT, DJ JENKINS, NA COPELAND, NG SILVENNOINEN, O IHLE, JN TI STAT4, A NOVEL GAMMA-INTERFERON ACTIVATION SITE-BINDING PROTEIN EXPRESSED IN EARLY MYELOID DIFFERENTIATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SPERMATOGONIAL DEPLETION JSD; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; ERYTHROPOIETIN RECEPTOR; MURINE; CELL; GENE; KINASE; DOMAIN; JAK2 AB Interferon regulation of gene expression is dependent on the tyrosine phosphorylation and activation of the DNA-binding activity of two related proteins of 91 kDa (STAT1) and/or 113 kDa (STAT2). Recent studies have suggested that these proteins are substrates of Janus kinases and that proteins related to STAT1 are involved in a number of signalling pathways, including those activated in myeloid cells by erythropoietin and interleukin-3 (IL-3). To clone STAT-related proteins from myeloid cells, degenerate oligonucleotides were used in PCRs to identify novel family members expressed in myeloid cells. This approach allowed the identification and cloning of the Stat4 gene, which is 52% identical to STAT1. Unlike STAT1, Stat4 expression is restricted but includes myeloid cells and spermatogonia. In the erythroid lineage, Stat4 expression is differentially regulated during differentiation. Functionally, Stat4 has the properties of other STAT family genes. In particular, cotransfection of expression constructs for Stat4 and Jak1 or Jak2 results in the tyrosine phosphorylation of Stat4 and the acquisition of the ability to bind to the gamma interferon (IFN-gamma)-activated sequence of the interferon regulatory factor 1 (IRF-1) gene. Stat4 is located on mouse chromosome 1 and is tightly linked to the Stat1 gene, suggesting that the genes arose by gene duplication. Unlike Stat1, neither IFN-alpha nor IFN-gamma activates Stat4. Nor is Stat4 activated in myeloid cells by a number of cytokines, including erythropoietin, IL-3, granulocyte colony-stimulating factor, stem cell factor, colony-stimulating factor 1, hepatocyte growth factor, IL-2, IL-4, and IL-6. C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. UNIV TENNESSEE, CTR HLTH SCI, SCH MED, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. FU NCI NIH HHS [P30 CA21765, N01 CO-74101]; NIDDK NIH HHS [R01 DK42932] NR 39 TC 211 Z9 215 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4342 EP 4349 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600002 PM 8007943 ER PT J AU MATTEN, W DAAR, I WOUDE, GFV AF MATTEN, W DAAR, I WOUDE, GFV TI PROTEIN-KINASE A ACTS AT MULTIPLE POINTS TO INHIBIT XENOPUS-OOCYTE MATURATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED MAP KINASE; MEIOTIC MATURATION; CDC25 PROTEIN; CELL-CYCLE; TYROSINE PHOSPHORYLATION; REGULATORY SUBUNIT; ONCOGENE PRODUCT; FROG OOCYTES; IN-VITRO; II-BETA AB In Xenopus oocytes, initiation of maturation is dependent on reduction of cyclic AMP-dependent protein kinase (PKA) activity and the synthesis of the mos proto-oncogene product. Mos is required during meiosis I for the activation of both maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK). Here we show that injection of the catalytic subunit of PKA (PKA(c)) prevented progesterone-induced synthesis of endogenous Mos as well as downstream MPF and MAPK activation. However, PKA(c) did not prevent injected soluble Mos product from activating MAPK. While MAPK is activated during Mos-PKA(c) coinjection, attendant MPF activation is blocked. Additionally, PKA(c) caused a potent block in the electrophoretic mobility shift of cdc25 that is associated with phosphatase activation. This inhibition of cdc25 activity was not reversed by progesterone, Mos, or MPF. We conclude that PKA(c) acts as a negative regulator at several points in meiotic maturation by preventing both Mos translation and MPF activation. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-74101] NR 63 TC 98 Z9 99 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4419 EP 4426 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600010 PM 8007949 ER PT J AU PRIEBE, SD WESTMORELAND, J NILSSONTILLGREN, T RESNICK, MA AF PRIEBE, SD WESTMORELAND, J NILSSONTILLGREN, T RESNICK, MA TI INDUCTION OF RECOMBINATION BETWEEN HOMOLOGOUS AND DIVERGED DNAS BY DOUBLE-STRAND GAPS AND BREAKS AND ROLE OF MISMATCH REPAIR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MEIOTIC GENE CONVERSION; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; INITIATION SITE; ECTOPIC RECOMBINATION; NUCLEOTIDE-SEQUENCE; SUBSTRATE LENGTH; SHUTTLE VECTORS; RECA-PROTEIN; YEAST AB Sequence homology is expected to influence recombination. To further understand mechanisms of recombination and the impact of reduced homology, we examined recombination during transformation between plasmid-borne DNA flanking a double-strand break (DSB) or gap and its chromosomal homolog. Previous reports have concentrated on spontaneous recombination or initiation by undefined lesions. Sequence divergence of approximately 16% reduced transformation frequencies by at least 10-fold. Gene conversion patterns associated with double-strand gap repair of episomal plasmids or with plasmid integration were analyzed by restriction endonuclease mapping and DNA sequencing. For episomal plasmids carrying homeologous DNA, at least one input end was always preserved beyond 10 bp, whereas for plasmids carrying homologous DNA, both input ends were converted beyond 80 bp in 60% of the transformants. The system allowed the recovery of transformants carrying mixtures of recombinant molecules that might arise if heteroduplex DNA-a presumed recombination intermediate-escapes mismatch repair. Gene conversion involving homologous DNAs frequently involved DNA mismatch repair, directed to a broken strand. A mutation in the PMS1 mismatch repair gene significantly increased the fraction of transformants carrying a mixture of plasmids for homologous DNAs, indicating that PMS1 can participate in DSB-initiated recombination. Since nearly all transformants involving homeologous DNAs carried a single recombinant plasmid in both Pms(+) and Pms(-) strains, stable heteroduplex DNA appears Less likely than for homologous DNAs. Regardless of homology, gene conversion does not appear to occur by nucleolytic expansion of a DSB to a gap prior to recombination. The results with homeologous DNAs are consistent with a recombinational repair model that we propose does not require the formation of stable heteroduplex DNA but instead involves other homology-dependent interactions that allow recombination-dependent DNA synthesis. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. UNIV COPENHAGEN,INST MOLEC BIOL,DK-1353 COPENHAGEN K,DENMARK. NR 59 TC 54 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4802 EP 4814 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600050 PM 8007979 ER PT J AU CHANG, YC KWONCHUNG, KJ AF CHANG, YC KWONCHUNG, KJ TI COMPLEMENTATION OF A CAPSULE-DEFICIENT MUTATION OF CRYPTOCOCCUS-NEOFORMANS RESTORES ITS VIRULENCE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SEROTYPE-A; POLYSACCHARIDE; MUTANTS; URA5; TRANSFORMATION; VARIANT; GENE; DNA AB Capsule formation plays a significant role in the pathogenicity of Cryptococcus neoformans. To study the molecular basis of capsule synthesis, the capsule-deficient phenotype of a mutant strain was complemented by transformation. A plasmid rescued from the resulting Cap(+) transformant complemented a cap59 mutation which was mapped previously by classical recombination analysis. Gene deletion by homologous integration resulted in an acapsular phenotype, indicating that we have identified the CAP59 gene. The CAP59 gene was assigned to chromosome I by Southern blot analysis of contour-clamped homogeneous electric field gel electrophoresis-resolved chromosomes of C. neoformans var. neoformans. Sequence comparison of genomic and cDNA clones indicated the presence of six introns CAP59 encoded a 1.9-kb transcript and a deduced protein of 458 amino acids. Analysis of the nucleotide sequence revealed little similarity to existing sequences in the data bank. When the capsule-deficient phenotype was complemented, the originally avirulent C. neoformans strain became virulent for mice. In addition, the acapsular strain created by gene deletion of CAP59 lost its virulence. This work demonstrates the molecular basis for capsule-related virulence and that the CAP59 gene is required for capsule formation. C1 NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. NR 30 TC 319 Z9 336 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4912 EP 4919 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600060 PM 8007987 ER PT J AU PATCHEV, VK BRADY, LS KARL, M CHROUSOS, GP AF PATCHEV, VK BRADY, LS KARL, M CHROUSOS, GP TI REGULATION OF HSP90 AND CORTICOSTEROID RECEPTOR MESSENGER-RNA BY CORTICOSTERONE LEVELS IN-VIVO SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE HEAT SHOCK PROTEIN 90; GLUCOCORTICOID RECEPTOR; HIPPOCAMPUS; HYPOTHALAMUS; THYMUS ID ADRENAL-STEROID RECEPTORS; HEAT-SHOCK PROTEINS; GLUCOCORTICOID RECEPTOR; MINERALOCORTICOID RECEPTOR; MESSENGER-RNA; RAT-BRAIN; NERVOUS-SYSTEM; EXPRESSION; ACTIVATION; PITUITARY AB The non-activated 9S forms of several steroid hormone receptors are heterooligomeric complexes consisting of the aporeceptor and three heat shock proteins, hsp90, hsp70 and hsp56. Hsp90 appears to play a facilitatory role in high-affinity steroid binding and to promote the efficacy of steroid actions on target tissues. Circulating glucocorticoid levels have a major regulatory impact on the binding capacity of hippocampal and hypothalamic corticosteroid receptors, a phenomenon that affects the activity of the hypothalamic-pituitary-adrenal axis and neuronal excitability in general. This study demonstrates that hsp90 mRNA is present in substantial amounts in hippocampal and hypothalamic areas characterized by high densities of corticosteroid receptors, and in the thymus. Steady-state levels of hsp90 mRNA in these regions were altered by chronic changes of circulating glucocorticoid concentrations in a site-specific fashion. In the hippocampus, mRNAs coding for hsp90 and both types of corticosteroid receptors (type I, MR and type II, GR) displayed a coordinate increase following adrenalectomy and castration (ADX/GX); in the hypothalamus only hsp90 mRNA levels were elevated, and none of the parameters studied was affected in the thymus by steroid hormone deprivation. Supplementation of ADX/GX rats with various doses of corticosterone in vivo elicited differential responses. Moderate elevation of circulating corticosterone levels normalized ADX/GX-increased hsp90 mRNA concentrations in the hippocampus and the hypothalamic paraventricular nucleus (PVN); this was associated with similar changes in GR and MR mRNA levels in the hippocampus, while GR mRNA concentrations in the PVN were not altered. Administration of high doses of corticosterone decreased hippocampal MR mRNA levels below those measured in controls, whereas a significant upregulation of GR mRNA and a trend towards increase in hsp90 mRNA were observed in this structure. In the PVN, hsp90 mRNA was markedly decreased in parallel with significantly decreased GR mRNA levels. In the thymus, hsp90 and GR mRNA concentrations were simultaneously decreased by any of the employed doses of corticosterone. These data suggest that, in addition to changes in the transcription of their own receptors, glucocorticoids can also influence the expression of hsp90, an important modifier of their cellular activity. The effects of altered glucocorticoid levels in vivo on these parameters appear to be site-specific, the characteristics of the response probably being dependent on the corticosteroid receptor composition (relative abundance of MR versus GR) in the tissue studied. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 29 TC 30 Z9 30 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL PY 1994 VL 103 IS 1-2 BP 57 EP 64 DI 10.1016/0303-7207(94)90069-8 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NU198 UT WOS:A1994NU19800007 PM 7958398 ER PT J AU DOMENE, HM MARIN, G SZTEIN, J YU, YM BARON, J CASSORLA, FG AF DOMENE, HM MARIN, G SZTEIN, J YU, YM BARON, J CASSORLA, FG TI ESTRADIOL INHIBITS GROWTH-HORMONE RECEPTOR GENE-EXPRESSION IN RABBIT LIVER SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE GROWTH HORMONE RECEPTOR; DEVELOPMENT; ESTRADIOL ID SERUM BINDING-PROTEIN; MESSENGER-RNA; FACTOR-I; TISSUE DISTRIBUTION; RAT SERUM; IGF-I; ESTROGEN; INSULIN; PURIFICATION; PROLACTIN AB We studied the ontogeny of GH receptor mRNA levels and the effect of exogenous estradiol administration on GH receptor mRNA levels in rabbit liver. A solution hybridization-RNase protection assay revealed a predominant 370-base long protected band corresponding to the mRNA encoding the transmembrane GH receptor, and a 241-base long protected band, representing about 9.0%, with the predicted size for the truncated form of the GH receptor. To study the developmental profile of GH receptor expression, we studied 12 female rabbits, at ages 1, 3, 5 and 7 months. Maximal GH receptor mRNA levels were observed in 3-month-old animals and decreased in 7-month-old animals. To investigate the effect of estradiol, 8-week-old immature female rabbits were randomly divided into five groups, and received subcutaneous pellets containing either placebo or estradiol at doses of 0.1, 0.5, 1.5 and 5.0 mg for 3 weeks. Exogenous administration of estradiol, at doses that resulted in physiological circulating levels, induced a reduction in GH receptor expression, measured both by GH binding (36 and 46%), and GH receptor mRNA levels (38 and 87%), in animals receiving pellets containing 1.5 and 5.0 mg of estradiol, respectively. We conclude that estradiol decreases GH receptor expression in rabbit liver. The results of our study suggest that there is an inverse relationship between circulating estrogen concentrations and liver GH receptor expression. C1 NEI,VET RES & RESOURCES SECT,BETHESDA,MD 20892. RP DOMENE, HM (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. RI Sztein, Jorge/B-7165-2012; OI Sztein, Jorge Mario/0000-0001-7047-2634 NR 32 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL PY 1994 VL 103 IS 1-2 BP 81 EP 87 DI 10.1016/0303-7207(94)90072-8 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NU198 UT WOS:A1994NU19800010 PM 7958400 ER PT J AU GU, J REN, K DUBNER, R IADAROLA, MJ AF GU, J REN, K DUBNER, R IADAROLA, MJ TI CLONING OF A DNA-BINDING PROTEIN THAT IS A TYROSINE KINASE SUBSTRATE AND RECOGNIZES AN UPSTREAM INITIATOR-LIKE SEQUENCE IN THE PROMOTER OF THE PREPRODYNORPHIN GENE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE TRANSCRIPTION FACTOR; PROTOONCOGENES; TYROSINE KINASE; PHOSPHOTYROSINE; DYNORPHIN ID TRANSCRIPTION FACTOR USF; CHRONIC ARTHRITIC RATS; SPINAL-CORD DYNORPHIN; AMINO-ACID-SEQUENCE; PRODYNORPHIN GENE; MESSENGER-RNAS; OPIOID RECEPTOR; POLYMERASE-II; NEO-ENDORPHIN; EXPRESSION AB A 90 bp fragment prepared from the promoter region of the rat preprodynorphin gene formed a complex with rat brain nuclear extracts as assessed by gel mobility shift assays. An 8 base pair sequence, CACTCTCC, termed upstream regulatory element (URE), was identified within this fragment as a binding site by DNase 1 footprint analysis and gel mobility shift assays with synthetic oligonucleotides. The URE is a consensus sequence for a transcription initiator (Inr) element although in the preprodynorphin promoter it is located upstream at -208 and overlaps a region conserved between rat and human promoters. A unique 310 amino acid protein (UreB1) that specifically bound the URE was cloned from a rat brain cDNA library using the URE-containing oligonucleotide. Recombinantly expressed, affinity purified UreB1 protein retains specific binding to the URE oligonucleotide. UreB1 contains a tyrosine kinase phosphorylation consensus and binding is enhanced following phosphorylation with the p43(v-abl) tyrosine kinase. The UreB1 tyrosine phosphoprotein increases transcription in vitro, consistent with a positive transcriptional regulatory function. UreB1 transcripts are well expressed in subsets of neurons in multiple brain areas suggesting that, in addition to regulation of the preprodynorphin gene, it may have a more generalized role in gene transcription. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 59 TC 23 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1994 VL 24 IS 1-4 BP 77 EP 88 DI 10.1016/0169-328X(94)90120-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA NU579 UT WOS:A1994NU57900010 ER PT J AU CHANDRASEKARAN, K GIORDANO, T BRADY, DR STOLL, J MARTIN, LJ RAPOPORT, SI AF CHANDRASEKARAN, K GIORDANO, T BRADY, DR STOLL, J MARTIN, LJ RAPOPORT, SI TI IMPAIRMENT IN MITOCHONDRIAL CYTOCHROME-OXIDASE GENE-EXPRESSION IN ALZHEIMER-DISEASE SO MOLECULAR BRAIN RESEARCH LA English DT Note DE HUMAN BRAIN; TEMPORAL CORTEX; PRIMARY MOTOR CORTEX; NORTHERN BLOT; OXIDATIVE METABOLISM; ALZHEIMERS DISEASE; SYNAPTIC LOSS ID MESSENGER-RNA; MONKEY BRAIN; TRANSCRIPTION; MUTATIONS; DEMENTIA; DEFECTS; ATP AB Brains from 5 patients with Alzheimer's disease (AD) showed a 50%-65% decrease in mRNA levels of the mitochondrial-encoded cytochrome oxidase (COX, a marker of oxidative metabolism) subunits I and III in the middle temporal association neocortex, but not in the primary motor cortex, as compared to 5 control brains. The amount of mitochondrial-encoded 12S rRNA was not altered, nor was the amount of nuclear-encoded lactate dehydrogenase B mRNA (a marker of glycolytic metabolism). These data suggest that the decrease in COX I and III subunits mRNA in affected brain regions may contribute to reduced brain oxidative metabolism in AD. C1 ABBOTT LABS,DEPT 47-W,ABBOTT PK,IL 60064. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. RP CHANDRASEKARAN, K (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 30 TC 145 Z9 146 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1994 VL 24 IS 1-4 BP 336 EP 340 DI 10.1016/0169-328X(94)90147-3 PG 5 WC Neurosciences SC Neurosciences & Neurology GA NU579 UT WOS:A1994NU57900037 ER PT J AU TENNANT, RW PRESCOTT, DM PUCK, TT SLAGA, TJ SAFFIOTTI, U WOGAN, GN NESNOW, S MCCLAIN, RM AF TENNANT, RW PRESCOTT, DM PUCK, TT SLAGA, TJ SAFFIOTTI, U WOGAN, GN NESNOW, S MCCLAIN, RM TI 8TH ASPEN CANCER CONFERENCE - MOLECULAR MECHANISMS OF TOXICITY IN RELATION TO THE GENETICS OF ANIMAL AND HUMAN NEOPLASIA SO MOLECULAR CARCINOGENESIS LA English DT Editorial Material C1 UNIV COLORADO,DEPT MOLEC CELLULAR & DEV BIOL,BOULDER,CO 80309. UNIV COLORADO,HLTH SCI CTR,ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80206. UNIV TEXAS,MD ANDERSON CANC CTR,SCI PK RES DIV,SMITHVILLE,TX 78957. NCI,DIV CANC ETIOL,EXPTL PATHOL LAB,BETHESDA,MD 20892. MIT,WHITAKER COLL,DIV TOXICOL,CAMBRIDGE,MA 02139. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. US EPA,HLTH EFFECTS RES LAB,CARCINOGENESIS & METAB BRANCH,RES TRIANGLE PK,NC 27711. HOFFMANN LA ROCHE INC,DEPT TOXICOL & PATHOL,NUTLEY,NJ 07110. RP TENNANT, RW (reprint author), NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,MD B3-09,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 1994 VL 10 IS 3 BP 117 EP 124 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA NZ797 UT WOS:A1994NZ79700001 PM 8043194 ER PT J AU SHOU, MG KORZEKWA, KR CRESPI, CL GONZALEZ, FJ GELBOIN, HV AF SHOU, MG KORZEKWA, KR CRESPI, CL GONZALEZ, FJ GELBOIN, HV TI THE ROLE OF 12-CDNA-EXPRESSED HUMAN, RODENT, AND RABBIT CYTOCHROMES-P450 IN THE METABOLISM OF BENZO[A]PYRENE AND BENZO[A]PYRENE TRANS-7,8-DIHYDRODIOL SO MOLECULAR CARCINOGENESIS LA English DT Article DE BENZO[A]PYRENE; BENZO[A]PYRENE TRANS-7,8-DIHYDRODIOL; HUMAN; CYTOCHROME P450; CDNA EXPRESSION ID POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN CELL-LINE; HUMAN-LIVER; VACCINIA VIRUS; ENZYMES; BENZO(A)PYRENE; AFLATOXIN-B1; ACTIVATION; 7,8-DIOL-9,10-EPOXIDES; CARCINOGENESIS AB The potent carcinogen benzo[a]pyrene (B[a]P) and its metabolite B[a]P trans-7,8-dihydrodiol (7,8-diol) require metabolic activation by the microsomal cytochrome P450s (P450s) to exert several adverse biological effects, including binding to DNA, toxicity, mutagenicity, and carcinogenicity. in the study reported here, we defined the role of each of 12 individual cDNA-expressed cytochrome P450s in the metabolism of B[a]P and 7,8-diol. Human P450s 1A1 and 1A2 were expressed in the absence or presence of epoxide hydrolase (EH) in a human lymphoblastoid cell line, and six human and five rodent and rabbit P450s were expressed from cDNA with vaccinia virus vectors in the hepatoma cell line Hep G2. B[a]P metabolism resulted in nine metabolites (three diols, three quinones, and three phenols), which were separated, identified, and quantitated by high-pressure liquid chromatography. In the human lymphoblastoid cells, human 1A1 metabolized B[a]P at a rate 4.5 times greater than that for 1A2. EH was shown to be directly involved in B[a]P activation, since increasing the amount of EH resulted in less 7-hydroxybenzo[a]pyrene and more 7,8-diol formation. Of the human P450s expressed with the vaccinia virus vectors in Hep G2 cells, 1A2 and 2C9 showed the highest activity and 2B6 showed moderate activity for B[a]P metabolism. Mouse 1A1 had activity 40 times higher than any human, rabbit, or rodent P450s, indicating the potential pitfalls of extrapolating P450 activity across species, Metabolism of the 7,8-diol resulted in six metabolites (four tetrols and two triols). In the lymphoblastoid cells, human 1A1 was shown to be 4.2 times more active than 1A2 for 7,8-diol metabolism. Among human P450s expressed from vaccinia virus, 1A2, 2E1, and 2C9 gave the highest activity, and 2C8 and 3A4 showed moderate activity for 7,8-diol metabolism to the diol epoxides. Again, mouse 1A1 was much more active than any other P450. These studies, in which we determined the capacity of individual P450 in the metabolism and activation of B[a]P and 7,8-diol, may thus lead to a better understanding of how P450s control the detoxification and activation of polycyclic aromatic hydrocarbons. (C) 1994 Wiley-Liss, Inc. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. GENTEST CORP,WOBURN,MA. NR 42 TC 153 Z9 156 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 1994 VL 10 IS 3 BP 159 EP 168 DI 10.1002/mc.2940100307 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA NZ797 UT WOS:A1994NZ79700006 PM 8043197 ER PT J AU BEI, R KANTOR, J KASHMIRI, SVS SCHLOM, J AF BEI, R KANTOR, J KASHMIRI, SVS SCHLOM, J TI SEROLOGICAL AND BIOCHEMICAL-CHARACTERIZATION OF RECOMBINANT BACULOVIRUS CARCINOEMBRYONIC ANTIGEN SO MOLECULAR IMMUNOLOGY LA English DT Article DE RECOMBINANT HUMAN CEA; HUMAN CARCINOMAS; BACULOVIRUS; EPITOPE MAPPING; GLYCOSYLATION; IMMUNOGENICITY ID DISTINCT MONOCLONAL-ANTIBODIES; VACCINIA VIRUS-VACCINE; STRUCTURAL DETERMINANTS; IMMOBILIZED LECTINS; HUMAN MAMMARY; OLIGOSACCHARIDES; GENE; EXPRESSION; EPITOPES; TUMORS AB Carcinoembryonic antigen (CEA), a glycosylated protein of M, 180 kDa, is one of the most widely used human tumor markers. A majority of gastrointestinal cancers as well as breast and nonsmall cell lung carcinomas express CEA. We have previously described a recombinant baculovirus BVCEA-140 expressing the full-length human CEA and a variant, BVCEA-16, that encodes only the NH2-terminal domain, as well as a recombinant (BVNCA) expressing the closely related molecule nonspecific cross-reactive antigen (NCA). We have now compared a panel of 24 anti-CEA and anti-NCA monoclonal antibodies (MAbs) for their ability to bind to these recombinant CEA and NCA proteins, as well as with a new 60 kDa subgenomic form designated BVCEA-60. The epitope mapping studies indicate that all the CEA specific MAbs can recognize BVCEA-140. We also compared the sugar composition of BVCEA-140 to native CEA, using a lectin-linked immunoradiometric assay. The results demonstrated that both the native and recombinant baculovirus CEA contain simple high-mannose carbohydrates as well as biantennary and biantennary hybrid complexes. However, native CEA also contains triantennary and tetraantennary complex sugars, while the recombinant CEA molecule does not. Immunogenicity of the recombinant CEA molecules was demonstrated in mice. ELISA and Western blot analyses were used to determine the cross-reactivity of the anti-CEA sera. Mice immunized with BVCEA-140 elicit antibodies that are reactive to native CEA. When the BVCEA-16 was used as an immunogen, the antisera failed to detect native CEA or BVCEA-140. These studies demonstrate that minor sugar differences exist between native and baculovirus-derived CEA. However, epitope mapping with a panel of 24 anti-CEA MAbs (recognizing at least 10 CEA epitopes) stowed virtual immunologic identity between these two molecules. Moreover, BVCEA-140 appears to be a more potent humoral immunogen in mice than native CEA. These purified recombinant proteins can thus serve as standards in CEA serum assays for the possible detection and characterization of cell-mediated immune responses to CEA and as a potential source of immunogen (primary or for boosting) for active specific immunotherapy protocols of human carcinomas. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 38 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 1994 VL 31 IS 10 BP 771 EP 780 DI 10.1016/0161-5890(94)90151-1 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA NZ054 UT WOS:A1994NZ05400008 PM 7518569 ER PT J AU BUSTAMANTE, JO LIEPINS, A HANOVER, JA AF BUSTAMANTE, JO LIEPINS, A HANOVER, JA TI NUCLEAR-PORE COMPLEX ION CHANNELS (REVIEW) SO MOLECULAR MEMBRANE BIOLOGY LA English DT Review DE NUCLEAR ENVELOPE; NUCLEAR PORE COMPLEX; NUCLEOCYTOPLASMIC TRANSPORT; ION CHANNELS; SIGNAL TRANSDUCTION; CONTROL OF GENE ACTIVITY ID SMOOTH-MUSCLE CELLS; RAT-LIVER NUCLEI; PERMEABILIZED MAMMALIAN-CELLS; SENSITIVE FLUORESCENT DYE; FIBROBLAST GROWTH-FACTOR; SALIVARY-GLAND CELLS; INTRACELLULAR CALCIUM; PROTEIN IMPORT; ENDOPLASMIC-RETICULUM; TEMPORAL RESOLUTION AB It is currently thought that nuclear pore complexes (NPCs) primarily govern nucleocytoplasmic interactions via selective recognition and active transport of macromolecules. However, in various nuclear preparations, patch-clamp and fluorescence luminiscence and ion microscopy support classical microelectrode measurements indicating that monoatomic ion flow across the nuclear envelope (NE) is strictly regulated. Gating of large conductance nuclear envelope ion channels (NICs) somewhat resembles that of gap junctional channels. In other respects, NICs are distinct in that they require cytosolic factors, are blocked by wheat germ agglutinin and are blocked and/or modified by antibodies to epitopes of NPC glycoproteins. Therefore, NIC activity, recorded as electrical current/conductance is likely to be intrinsic to NPCs. This observation suggests a potential use for the patch-clamp technique in establishing the mechanisms underlying nuclear pore gating in response to cytosolic and nucleosolic factors such as transcription and growth factors, oncogene and proto-oncogene products and receptors far retinoids, steroids and thyroid hormone. NIC activity may also be useful in evaluating the mechanisms of nuclear import of foreign nucleic acid material such as that contained in virons and viroids. Finally, in consideration to the electrophysiological data accumulated so far, the study of nuclear pore ion channel activity may help our understanding of other important issues such as cell suicide, programmed cell death or apoptosis. C1 UNIV MARYLAND,SCH MED,CTR HEART,DEPT PHYSIOL,DIV CARDIOL,BALTIMORE,MD 21021. MEM UNIV NEWFOUNDLAND,SCH MED,DIV BASIC MED SCI,ST JOHNS A1B 3V6,NF,CANADA. NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. RP BUSTAMANTE, JO (reprint author), UNIV MARYLAND,SCH MED,CTR HEART,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21021, USA. NR 147 TC 30 Z9 30 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JUL-SEP PY 1994 VL 11 IS 3 BP 141 EP 150 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH477 UT WOS:A1994PH47700001 PM 7538009 ER PT J AU ELSON, HF DIMITROV, DS BLUMENTHAL, R AF ELSON, HF DIMITROV, DS BLUMENTHAL, R TI A TRANSDOMINANT MUTATION IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) ENVELOPE GLYCOPROTEIN GP41 INHIBITS MEMBRANE-FUSION WHEN EXPRESSED IN TARGET-CELLS SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article DE FUSION; HIV-I; ENVELOPE GLYCOPROTEIN; CD4; VACCINIA VIRUS ID HTLV-III/LAV ENVELOPE; AIDS VIRUS; NUCLEOTIDE-SEQUENCE; SYNCYTIA FORMATION; PEPTIDE SEQUENCE; VACCINIA VIRUS; INITIAL-STAGES; T4 MOLECULE; I ENVELOPE; PROTEIN AB A recombinant vaccinia virus was used to express a mutation in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120-gp41. In this mutant protein, the second amino acid in the N-terminal region of gp41 has been converted from a hydrophobic valine residue to the polar glutamate. When recombinant vaccinia viruses encoding wild-type HIV-1 envelope glycoprotein infect a lymphocyte cell line lacking CD4, the cells express the HIV-1 envelope glycoprotein gp120-gp41 and are able to fuse with a CD4(4) T lymphocyte cell line. Cells expressing the mutant envelope glycoprotein are unable to fuse with CD4(4) T lymphocytes. When both viruses infect CD4(-) cells simultaneously, there is an inhibition of fusion to CD4(+) cells with an increasing fraction of the virus encoding the mutated envelope glycoprotein. Interestingly, when the opposing, or CD4(+) target cells are infected with the mutation-expressing virus, while CD4(-) cells are infected with wild-type envelope-expressing virus, a similar inhibition of fusion is observed. This suggests that the mutated envelope glycoprotein does not need to reside in the same membrane as the wild-type protein it inhibits. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 34 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JUL-SEP PY 1994 VL 11 IS 3 BP 165 EP 169 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH477 UT WOS:A1994PH47700004 PM 7742881 ER PT J AU ALTUVIA, S ALMIRON, M HUISMAN, G KOLTER, R STORZ, G AF ALTUVIA, S ALMIRON, M HUISMAN, G KOLTER, R STORZ, G TI THE DPS PROMOTER IS ACTIVATED BY OXYR DURING GROWTH AND BY IHF AND A SIGMA(S) IN STATIONARY-PHASE SO MOLECULAR MICROBIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; OXIDATIVE STRESS; SALMONELLA-TYPHIMURIUM; HYDROGEN-PEROXIDE; GENE-PRODUCT; PROTEIN; REGULON; RPOS; REGULATOR AB Dps is a non-specific DNA-binding protein abundant in starved Escherichia coli cells and is important for the defence against hydrogen peroxide. We found that dps mRNA levels are controlled by rpoS-encoded sigma(S), the transcriptional activator OxyR and the histonelike IHF protein. In exponentially growing cells, dps is induced by treatment with hydrogen peroxide in an OxyR-dependent manner. This OxyR-dependent induction occurs only during log phase, although the OxyR protein is present in stationary phase. In the stationary phase cells, dps is expressed in a sigma(S)- and IHF-dependent manner. The purified OxyR and IHF proteins are also shown to bind upstream of the dos promoter. Our results suggest that the dps promoter is recognized by both sigma(70)-holoenzyme and os-holoenzyme, since OxyR acts through sigma(70) and the starts of the OxyR- and sigma S-dependent transcripts are identical. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NR 26 TC 312 Z9 319 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 1994 VL 13 IS 2 BP 265 EP 272 DI 10.1111/j.1365-2958.1994.tb00421.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA NY272 UT WOS:A1994NY27200009 PM 7984106 ER PT J AU BENBARUCH, N REINHOLD, WC ALEXANDROVA, N ICHINOSE, I BLAKE, M TREPEL, JB ZAJAC-KAYE, M AF BENBARUCH, N REINHOLD, WC ALEXANDROVA, N ICHINOSE, I BLAKE, M TREPEL, JB ZAJAC-KAYE, M TI C-MYC DOWN-REGULATION IN SURAMIN-TREATED HL-60 CELLS PRECEDES GROWTH-INHIBITION BUT DOES NOT TRIGGER DIFFERENTIATION SO MOLECULAR PHARMACOLOGY LA English DT Article ID MOUSE ERYTHROLEUKEMIA-CELLS; PROMYELOCYTIC CELLS; MESSENGER-RNA; EXPRESSION; ONCOGENE; HL-60; PROLIFERATION; LINE; GENE; RESPONSIVENESS AB Down-regulation of c-myc mRNA expression is linked to growth arrest and the state of differentiation of hematopoietic cells. We showed that treatment of HL60 cells with suramin results in a rapid reduction of c-myc expression followed by an inhibition of cell growth. Both c-myc mRNA and protein levels decreased by day 1 of treatment, and, by day 4, only 10% of control c-myc protein levels were detected. In contrast to retinoic acid, dimethyl sulfoxide, and 12-O-tetradecanoylphorbol-13-acetate treatment, however, exposure of HL60 cells to suramin did not result in the induction of differentiation. These results demonstrate that suramin modulates c-myc levels in HL60 cells and that the down-regulation of c-myc is not sufficient to trigger differentiation toward either granulocytic or monocytic lineages. C1 NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. NCI, CLIN PHARMACOL BRANCH, BETHESDA, MD 20892 USA. RUSSIAN ACAD SCI, VA ENGELHARDT MOLEC BIOL INST, MOSCOW, RUSSIA. NR 43 TC 10 Z9 11 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1994 VL 46 IS 1 BP 73 EP 78 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ052 UT WOS:A1994NZ05200010 PM 8058059 ER PT J AU PARTIN, KM PATNEAU, DK MAYER, ML AF PARTIN, KM PATNEAU, DK MAYER, ML TI CYCLOTHIAZIDE DIFFERENTIALLY MODULATES DESENSITIZATION OF ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID RECEPTOR SPLICE VARIANTS SO MOLECULAR PHARMACOLOGY LA English DT Article ID GLUTAMATE-OPERATED CHANNELS; STRUCTURAL DETERMINANTS; FUNCTIONAL EXPRESSION; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING; CONCANAVALIN-A; NMDA RECEPTOR; SUBUNIT; PERMEABILITY; FAMILY AB Agonist responses for flip splice variants of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR-A, -C, and -D are more strongly potentiated by cyclothiazide than are those for the flop forms. Cyclothiazide shows both greater efficacy and higher apparent affinity for potentiation of GluR-A(flip) versus GluR-A(flop). Consistent with higher affinity for the Rip splice variant, recovery from potentiation by cyclothiazide proceeds 30 times more slowly for GluR-AR(flip) than for GluR-A(flop). In the presence of 300 mu M cyclothiazide a 6-fold leftward shift in the kainate dose-response curve for GluR-A(flip) but not GluR-A(flop) additionally contributes to a difference in potentiation for these splice variants. Although control responses to glutamate show strong desensitization for both splice variants of GluR-A, in the presence of 100 mu M cyclothiazide desensitization is strongly attenuated for GluR-A(flip), whereas for GluR-A(flop) desensitization remains pronounced but with a rate of onset slowed 50-fold, compared with control. In heteromeric AMPA receptors formed from GluR-A and GluR-B, the flip splice variants are dominant for controlling both recovery from potentiation of responses to kainate and block of desensitization of responses to glutamate. Our results suggest that the flip/flop module could directly contribute to the binding site for cyctothiazide, raising the possibility that this site is located in an extracellular receptor domain. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. RI Mayer, Mark/H-5500-2013; Partin, Kathryn/A-8706-2015 OI Partin, Kathryn/0000-0003-3801-3299 NR 31 TC 253 Z9 255 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1994 VL 46 IS 1 BP 129 EP 138 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ052 UT WOS:A1994NZ05200017 PM 8058047 ER PT J AU HAYDEN, PJ FREE, KE CHIGNELL, CF AF HAYDEN, PJ FREE, KE CHIGNELL, CF TI STRUCTURE-ACTIVITY-RELATIONSHIPS FOR THE FORMATION OF SECONDARY RADICALS AND INHIBITION OF KERATINOCYTE PROLIFERATION BY 9-ANTHRONES SO MOLECULAR PHARMACOLOGY LA English DT Article ID TUMOR-PROMOTING ACTIVITY; ORNITHINE DECARBOXYLASE INDUCTION; DITHRANOL ANTHRALIN; 10-ACYL ANALOGS; SENCAR MICE; MODEL SYSTEMS; HUMAN-SKIN; CHRYSAROBIN; IRRITATION; SUPEROXIDE AB The biological properties of tumor-promoting and antipsoriatic 9-anthrones have been hypothesized to be mediated by free radical products such as the corresponding 9-anthron-10-yl radicals or by O-2(radical-anion) (OH)-O-., and other persistent secondary radicals that are formed in the skin after topical treatment with 9-anthrones. To gain additional insights into the possible role of reactive oxygen or secondary radicals in mediating the biological effects of 9-anthrones, we have used EPR spectroscopy to investigate the formation of these species by a series of 9-anthrones or 9-anthrone dimers with known tumor-promoting and antipsoriatic activities. The effect of the 9-anthrones on keratinocyte proliferation in vitro was also investigated. 5,5-Dimethyl-1-pyrroline N-oxide was used as a spin trap to detect reactive oxygen-centered radicals in aqueous buffer/dimethylsulfoxide solutions. Superoxide was trapped during the autoxidation of most of the 9-anthrones. For 9-anthrones that generated no detectable superoxide, evidence of anthronyl-peroxyl radical formation was found instead. In the presence of Fe3+ complexed to EDTA, but not diethylenetriaminepentaacetic acid, the hydroxyl radical was produced by all of the 9-anthrones. 9-Anthrone dimers produced oxygen-centered radicals only weakly or not at all. Direct EPR was used to detect 9-anthrone-derived secondary radicals in keratinocyte suspensions or in dimethylsulfoxide solutions. These radicals were similar to those previously reported to occur in skin after topical treatment with the antipsoriatic drug anthralin (1,8-dihydroxy-9-anthrone). In contrast to the ubiquitous ability of the 9-anthrones to generate reactive oxygen radicals, only the hydroxy-substituted 9-anthrones or their dimers possessed significant secondary radical-forming ability. The ability of the 9-anthrones or dimers to form secondary radicals in keratinocytes was found to correlate with their in vitro inhibition of keratinocyte proliferation. The data suggest the possible importance of reactive dimeric intermediates in mediating the biological effects of the 9-anthrones. RP HAYDEN, PJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,MAIL DROP 17-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 54 TC 24 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1994 VL 46 IS 1 BP 186 EP 198 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ052 UT WOS:A1994NZ05200024 PM 8058052 ER PT J AU OHARA, BF DONOVAN, DM LINDBERG, I BRANNOCK, MT RICKER, DD MOFFATT, CA KLAUNBERG, BA SCHINDLER, C CHANG, TSK NELSON, RJ UHL, GR AF OHARA, BF DONOVAN, DM LINDBERG, I BRANNOCK, MT RICKER, DD MOFFATT, CA KLAUNBERG, BA SCHINDLER, C CHANG, TSK NELSON, RJ UHL, GR TI PROENKEPHALIN TRANSGENIC MICE - A SHORT PROMOTER CONFERS HIGH TESTIS EXPRESSION AND REDUCED FERTILITY SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE ENKEPHALIN GENE; REGULATION; SPERMATOGENESIS; INFERTILITY ID POSTMEIOTIC GERM-CELLS; MESSENGER-RNA; GENE-EXPRESSION; CHLORAMPHENICOL ACETYLTRANSFERASE; REPRODUCTIVE-SYSTEM; SERTOLI CELLS; SOMATIC-CELLS; CYCLIC AMP; RAT TESTIS; TRANSCRIPTION AB The regulation and possible function of the preproenkephalin gene in testis were studied in vivo in transgenic mice containing: (1) bases -193 to +210 of the human proenkephalin gene and an additional one kilobase of 3' proenkephalin flanking sequence driving expression of bacterial chloramphenicol acetyltransferase (CAT), and (2) the same promoter and flanking sequences driving expression of a rat proenkephalin cDNA. Five lines of mice, designated HEC1-5, expressed the first construct and 10, HER1-10, the second. Each HEC male and many HER males showed dramatic expression of the transgene in the testis, although much lower expression was observed in the brain and other enkephalin-producing tissues. High levels of expression in testis can thus be achieved with a very short promoter region and do not require intron A sequences previously considered necessary. Altered enkephalin expression may affect testicular function. One founder, HER8, displayed grossly abnormal testicular morphology and was completely infertile. A second founder, HER6, had low sperm motility. Two offspring from other lines also displayed subnormal fertility. These studies support a role for specific promoter sequences in testis expression and may further support a significant role for proenkephalin in testicular function. (C) 1994 Wiley-Liss, Inc.* C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT POPULAT DYNAM,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG,BALTIMORE,MD. JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. LOUISIANA STATE UNIV,SCH MED,DEPT BIOCHEM,NEW ORLEANS,LA. LOUISIANA STATE UNIV,SCH MED,DEPT MOLEC BIOL,NEW ORLEANS,LA. OI Nelson, Randy/0000-0002-8194-4016 FU NIDA NIH HHS [R01 DA005084] NR 36 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JUL PY 1994 VL 38 IS 3 BP 275 EP 284 DI 10.1002/mrd.1080380308 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA NV782 UT WOS:A1994NV78200007 PM 7917279 ER PT J AU BRASILNETO, JP COHEN, LG HALLETT, M AF BRASILNETO, JP COHEN, LG HALLETT, M TI CENTRAL FATIGUE AS REVEALED BY POSTEXERCISE DECREMENT OF MOTOR EVOKED-POTENTIALS SO MUSCLE & NERVE LA English DT Article DE TRANSCRANIAL MAGNETIC STIMULATION; MOTOR EVOKED POTENTIALS; EXERCISE; FATIGUE ID MAGNETIC STIMULATION; DEPRESSION; CORTEX AB We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement in amplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS delivered at the rates of 0.1, 0.15, 0.3, 1,3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue. (C) 1994 John Wiley and Sons, Inc. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORTICAL PHYSIOL UNIT,BETHESDA,MD 20892. RI Brasil-Neto, Joaquim/A-1171-2009 NR 13 TC 119 Z9 121 U1 2 U2 7 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 1994 VL 17 IS 7 BP 713 EP 719 DI 10.1002/mus.880170702 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NR499 UT WOS:A1994NR49900001 PM 8007995 ER PT J AU PASCUALLEONE, A VALLSSOLE, J TORO, C WASSERMANN, EM HALLETT, M AF PASCUALLEONE, A VALLSSOLE, J TORO, C WASSERMANN, EM HALLETT, M TI RESETTING OF ESSENTIAL TREMOR AND POSTURAL TREMOR IN PARKINSONS-DISEASE WITH TRANSCRANIAL MAGNETIC STIMULATION SO MUSCLE & NERVE LA English DT Article DE TREMOR; PARKINSONS DISEASE; ESSENTIAL TREMOR; TRANSCRANIAL MAGNETIC STIMULATION ID SUBJECTS MIMICKING TREMOR; MOTOR CORTEX; CORTICAL STIMULATION; ACTIVATION; WRIST; BRAIN; COIL AB We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease. (C) 1994 John Wiley and Sons, Inc. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORTICAL PHYSIOL UNIT,BETHESDA,MD 20892. NR 22 TC 66 Z9 67 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 1994 VL 17 IS 7 BP 800 EP 807 DI 10.1002/mus.880170716 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NR499 UT WOS:A1994NR49900015 PM 8008009 ER PT J AU DILLON, D COMBES, R ZEIGER, E AF DILLON, D COMBES, R ZEIGER, E TI ACTIVATION BY CECAL REDUCTION OF THE AZO-DYE-D-AND-C-RED-NO-9 TO A BACTERIAL MUTAGEN SO MUTAGENESIS LA English DT Article ID 300 CHEMICALS; SALMONELLA; DRUG; GENOTOXICITY; INVITRO; TESTS; CELLS; FOOD AB D and C Red No. 9 is a monoazo dye used for manufacturing printing inks, rubber and plastics, and as an additive in cosmetics and drugs. In an NTP carcinogenicity study in rats and mice it induced splenic sarcomas and liver nodules in male rats; no chemical-related tumours were induced in mice. On the basis of its contradictory responses in a range of in vitro tests and its inactivity in several bl vivo genotoxicity assays, it has been suggested that the dye may act as a non-genotoxic carcinogen. We tested the dye in the Salmonella mutagenicity assay using several different protocols. The dye was not mutagenic when tested using the standard (aerobic) preincubation protocol. Variable responses were seen when the flavin mononucleotide (FMN) reduction protocol was used. A third protocol was provided by incubating the test compound overnight with a rat caecal preparation under anoxic conditions to reduce the azo bond. Ethyl acetate extracts of this incubation mixture, when tested in the standard preincubation protocol using induced rat liver S9, yielded dose-related mutagenic responses in TA100, and a weak response in TA98. The presumed major reduction product, 1-amino-2-naphthol (1-A-2-N) was mutagenic to TA100, but not TA98, in standard protocols with S9. The results show that it is necessary to use a protocol in which D and C Red No. 9 is reduced in order to demonstrate the mutagenicity of this dye. The non-genotoxicity previously reported for D and C Red No. 9, may have been due to insufficient reductive cleavage. The carcinogenicity of this compound may, therefore, be a consequence of its genotoxicity, rather than a result of some non-genotoxic process. C1 NIEHS,RES TRIANGLE PK,NC 27709. INVERESK RES INT LTD,TRANENT EH33 2NE,SCOTLAND. FU NIEHS NIH HHS [NIEHS N01-ES-55127] NR 28 TC 17 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JUL PY 1994 VL 9 IS 4 BP 295 EP 299 DI 10.1093/mutage/9.4.295 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NY271 UT WOS:A1994NY27100003 PM 7968569 ER PT J AU NESNOW, S BECK, S ROSENBLUM, S LASLEY, J TIANO, HF HOSOKAWA, M CRESPI, CL LANGENBACH, R AF NESNOW, S BECK, S ROSENBLUM, S LASLEY, J TIANO, HF HOSOKAWA, M CRESPI, CL LANGENBACH, R TI N-NITROSODIETHYLAMINE AND 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE INDUCED MORPHOLOGICAL TRANSFORMATION OF C3H/10T1/2CL8 CELLS EXPRESSING HUMAN CYTOCHROME-P450 2A6 SO MUTATION RESEARCH LA English DT Article DE N-NITROSODIETHYLAMINE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; MORPHOLOGICAL TRANSFORMATION; 10T1/2 CELLS; CYP2A6 ID MOUSE EMBRYO FIBROBLASTS; HA-RAS ONCOGENE; RADIATION-INDUCED TRANSFORMATION; DNA ADDUCT FORMATION; C3H-10T1/2 CELLS; C3H10T1/2CL8 CELLS; POSTCONFLUENCE INHIBITION; CHEMICAL ONCOGENESIS; ACTIVATION SYSTEMS; LIVER-MICROSOMES AB Transfection of specific genes into cells capable of expressing chemically induced morphological cell transformation provides a valuable approach to study the mechanisms of action of carcinogens. A human cytochrome P450 isozyme, CYP2A6, has been successfully expressed from a retroviral vector in transformable C3H/10T1/2 (10T1/2) mouse embryo fibroblasts and these resulting 10T1/2 clones were evaluated for the cytotoxic and transforming activities of two nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosodiethylamine (DEN). 10T1/2 clone 29 cells, which expressed high levels of CYP2A6 activity, were responsive to the cytotoxic and morphological transforming effects of DEN or NNK on a concentration-related basis. In 10T1/2 clone 29 cells, DEN at 600 mu g/ml decreased cell survival to 67%, and induced 0.5 type II&III foci/dish. NNK at 400 mu g/ml administered to 10T1/2 clone 29 cells decreased survival to 57% and induced 0.43 type II&III foci/dish. Wild-type 10T1/2 cells and 10T1/2 clone 4 cells (infected with the vector but not expressing the CYP2A6 activity) were unresponsive. These results indicate that expression of a cDNA coding for cytochrome P450 in 10T1/2 cells can provide information about the role of the enzyme in the activities of chemical carcinogens and also increase the sensitivity of 10T1/2 cells to a larger number of classes of chemical carcinogens. C1 ENVIRONM HLTH RES & TESTING INC,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS BRANCH,RES TRIANGLE PK,NC 27709. GENTEST CORP,WOBURN,MA 01801. RP NESNOW, S (reprint author), US EPA,HLTH EFFECTS RES LAB,CARCINOGENESIS & METAB BRANCH,MD-86,RES TRIANGLE PK,NC 27711, USA. FU NIEHS NIH HHS [Y01-ES-00186] NR 51 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1994 VL 324 IS 3 BP 93 EP 102 DI 10.1016/0165-7992(94)90052-3 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NW488 UT WOS:A1994NW48800002 PM 8022436 ER PT J AU MONJAN, AA BARZILAI, D AF MONJAN, AA BARZILAI, D TI NEUROENDOCRINOLOGY AND AGING - PERSPECTIVES AND PROSPECTIVES SO NEUROBIOLOGY OF AGING LA English DT Editorial Material C1 TECHNION ISRAEL INST TECHNOL,DEPT MED & ENDOCRINOL,IL-31096 HAIFA,ISRAEL. RP MONJAN, AA (reprint author), NIA,NEUROSCI & NEUROPSYCHOL AGING PROGRAM,GATEWAY BLDG,SUITE 3C307,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 1 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 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1994 VL 15 IS 4 BP 477 EP 477 DI 10.1016/0197-4580(94)90082-5 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA NW475 UT WOS:A1994NW47500013 ER PT J AU ENDO, H KITTUR, S SABRI, MI AF ENDO, H KITTUR, S SABRI, MI TI ACRYLAMIDE ALTERS NEUROFILAMENT PROTEIN GENE-EXPRESSION IN RAT-BRAIN SO NEUROCHEMICAL RESEARCH LA English DT Article DE ACRYLAMIDE; NEUROFILAMENT; NEUROTOXICITY; CYTOSKELETON ID SLOW AXONAL-TRANSPORT; MOTOR-NEURON DISEASE; NEUROFIBRILLARY TANGLES; OPTIC AXONS; NF-L; NEUROPATHY; DEGENERATION; COMPONENTS; PERIKARYA; ANTIGENS AB Acrylamide, a prototype neurotoxin, alters neurofilament protein (NF) gene expression in rat brain. Levels of mRNA coding for neurofilament protein subunits NF-L, NF-M, and NF-H have been determined by Northern blot analysis using P-32-labeled cDNA probes. Acrylamide given acutely (100 mg/kg, single intraperitoneal injection) causes a selective increase in NF-M mRNA (approximately 50%) compared to controls. The expression of NF-L or NF-H mRNA is not affected by acrylamide. Tn contrast, chronic treatment with acrylamide [0.03% (w/v) in drinking water for 4 weeks] induces a modest but significant increase (approximately 22%) in NF-L mRNA compared to controls. Levels of NF-M, and NF-H mRNA are not altered by acrylamide treatment. The expression of beta-actin mRNA, an ubiquitous protein, is nor affected by either treatment regimen of acrylamide. The results of this study show that acrylamide increases the expression of mRNA for NF protein subunits in rat brain. The increase of specific mRNA for NF subunits depends on the dose, duration and route of acrylamide administration. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. OREGON HLTH SCI UNIV,CTR RES OCCUPAT & ENVIRONM TOXICOL,PORTLAND,OR 97201. FU NINDS NIH HHS [NS 19611] NR 45 TC 13 Z9 16 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUL PY 1994 VL 19 IS 7 BP 815 EP 820 DI 10.1007/BF00967449 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NX959 UT WOS:A1994NX95900005 PM 7969750 ER PT J AU PUCHALSKI, RB LOUIS, JC BROSE, N TRAYNELIS, SF EGEBJERG, J KUKEKOV, V WENTHOLD, RJ ROGERS, SW LIN, F MORAN, T MORRISON, JH HEINEMANN, SF AF PUCHALSKI, RB LOUIS, JC BROSE, N TRAYNELIS, SF EGEBJERG, J KUKEKOV, V WENTHOLD, RJ ROGERS, SW LIN, F MORAN, T MORRISON, JH HEINEMANN, SF TI SELECTIVE RNA EDITING AND SUBUNIT ASSEMBLY OF NATIVE GLUTAMATE RECEPTORS SO NEURON LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; HIGH-AFFINITY KAINATE; NICOTINIC ACETYLCHOLINE-RECEPTORS; RAT-BRAIN; FUNCTIONAL EXPRESSION; CA2+ PERMEABILITY; STRUCTURAL DETERMINANTS; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING AB RNA editing and subunit assembly of ionotropic glutamate receptors (GluRs) were examined in an oligodendrocyte progenitor cell line, CG4, which expresses GluR2-GluR4, GluR6, GluR7, KA1, and KA2. AMPA-evoked currents rapidly desensitize, whereas kainate-evoked currents contain a steady-state component with a nearly linear current-voltage relation and a fast desensitizing component that is inwardly rectifying. The Q/R site is edited >95% to the arginine codon in GluR2(Q607) mRNA, and <5% in GluR6(Q621) mRNA. Immunoprecipitation experiments demonstrate that GluR6 and/or GluR7 subunits assemble with KA2, but not with GluR2-GluR4. These results indicate that oligodendrocyte progenitor cells selectively edit and assemble glutamate receptors into at least two functionally and structurally distinct heteromeric channels. C1 SALK INST BIOL STUDIES, HOWARD HUGHES MED INST, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA. NIDOCD, NEUROCHEM LAB, BETHESDA, MD 20892 USA. UNIV COLORADO, HLTH SCI CTR, DEPT PHARMACOL, DENVER, CO 80262 USA. CUNY MT SINAI SCH MED, FISHBERG RES CTR NEUROBIOL, NEW YORK, NY 10029 USA. RP PUCHALSKI, RB (reprint author), SALK INST BIOL STUDIES, MOLEC NEUROBIOL LAB, LA JOLLA, CA 92037 USA. RI Morrison, John/F-9229-2012 FU NIA NIH HHS [AG06647]; NINDS NIH HHS [NS08549-03, NS09029-02] NR 64 TC 136 Z9 139 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1994 VL 13 IS 1 BP 131 EP 147 DI 10.1016/0896-6273(94)90464-2 PG 17 WC Neurosciences SC Neurosciences & Neurology GA NZ247 UT WOS:A1994NZ24700010 PM 7519023 ER PT J AU BRILEY, EM LOLAIT, SJ AXELROD, J FELDER, CC AF BRILEY, EM LOLAIT, SJ AXELROD, J FELDER, CC TI THE CLONED VASOPRESSIN V1A RECEPTOR STIMULATES PHOSPHOLIPASE A(2), PHOSPHOLIPASE-C, AND PHOSPHOLIPASE-D THROUGH ACTIVATION OF RECEPTOR-OPERATED CALCIUM CHANNELS SO NEUROPEPTIDES LA English DT Article ID SMOOTH-MUSCLE CELLS; ARACHIDONIC-ACID RELEASE; PROTEIN-KINASE-C; SIGNAL TRANSDUCTION; RAT; HYDROLYSIS; CA2+; MOBILIZATION; INHIBITOR; POTENT AB Arginine vasopressin mediates its effects through vasopressin receptor activation and second messenger production. Recent cloning of the V1a receptor provided the opportunity to investigate the possible signal transduction pathways associated with this single vasopressin receptor subtype. When stably expressed in CHO cells, vasopressin stimulated several signal transduction pathways simultaneously including calcium influx, phospholipase A(2), phospholipase C, and phospholipase D. Vasopressin-stimulated release of arachidonic acid, IP3 formation, and phosphatidylethanol formation (in the presence of 1% ethanol) were used as indexes of phospholipase A(2), phospholipase C, and phospholipase D activation, respectively. V1a receptor-activation stimulated a peak followed by a sustained plateau phase of intracellular calcium. The plateau phase was dependent on extracellular calcium, insensitive to blockers of voltage sensitive calcium channels, blocked by heavy metals, and quenched when MnCl2 was present in the extracellular media. Removal of extracellular calcium blunted the release of IP3, and blocked the release of arachidonic acid and phosphatidylethanol indicating that these responses were at least in part regulated by receptor-operated calcium influx. Vasopressin-stimulated release of arachidonic acid and phosphatidylethanol were augmented with the phorbol ester PMA, and this augmentation was blocked by inhibitors of protein kinase C and absent with long-term PMA treatment. Vasopressin-stimulated IP3 release was inhibited with PMA and the inhibition reversed with protein kinase C inhibitors. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 35 TC 42 Z9 42 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD JUL PY 1994 VL 27 IS 1 BP 63 EP 74 DI 10.1016/0143-4179(94)90017-5 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA NU949 UT WOS:A1994NU94900009 PM 7969820 ER PT J AU GEORGE, MS KETTER, TA PAREKH, P GILL, DS HUGGINS, T MARANGELL, L PAZZAGLIA, PJ POST, RM AF GEORGE, MS KETTER, TA PAREKH, P GILL, DS HUGGINS, T MARANGELL, L PAZZAGLIA, PJ POST, RM TI SPATIAL ABILITY IN AFFECTIVE-ILLNESS - DIFFERENCES IN REGIONAL BRAIN ACTIVATION DURING A SPATIAL MATCHING TASK (H2O)-O-15 PET) SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE SPATIAL; PET; REGIONAL CEREBRAL BLOOD FLOW; BRAIN METABOLISM; DEPRESSION; MOOD; BIPOLAR DISORDER ID CEREBRAL BLOOD-FLOW; PHOTON-EMISSION TOMOGRAPHY; MAJOR DEPRESSION; MOOD DISORDERS; SCHIZOPHRENIA; GLUCOSE; ABNORMALITIES; PATHWAYS; ANATOMY; CORTEX AB Previous studies have determined that mood disorder patients have decreased spatial analysis skills and report subjective deficits in spatial reasoning. We therefore wondered if regional cerebral blood flow (rCBF) activation patterns during a spatial matching task would differ in patients with recurrent mood disorders compared to controls. We imaged 10 mood-disorder patients and 10 age- and sex-matched healthy controls with (H2O)-O-15 PET, while subjects performed tasks involving matching for spatial relationships or, as a control, facial identity. In normal volunteer controls, spatial matching activated the temporoparietal cortex bilaterally as well as the left prefrontal cortex. Mood disorder patients activated a significantly broader area of the temporoparietal cortex during this task, while failing to activate the left dorsolateral prefrontal cortex. In the mood-disorder group, lower self-rated spatial skills significantly correlated with less activity in the left prefrontal cortex and more activity in the temporal lobes bilaterally during the spatial task. Compared to healthy controls, mood-disordered subjects activate a broader region of the temporoparietal lobes and do not activate the left prefrontal cortex while performing a spatial matching task. The more impaired the patients rated themselves in spatial/navigational skills, the less they used their left prefrontal cortex and the more they used the temporal lobes during a spatial task. These results provide a tentative functional neuroanatomic explanation of the abnormalities in subjective spatial reasoning and extend the existing literature on functional brain abnormalities in affective illness both at rest and during specific tasks. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,4000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 17 Z9 17 U1 3 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1994 VL 7 IS 3 BP 143 EP 153 PG 11 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA PC765 UT WOS:A1994PC76500001 ER PT J AU WEINSTEIN, EA FRIEDLAND, RP WAGNER, EE AF WEINSTEIN, EA FRIEDLAND, RP WAGNER, EE TI DENIAL UNAWARENESS OF IMPAIRMENT AND SYMBOLIC BEHAVIOR IN ALZHEIMERS-DISEASE SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE ALZHEIMERS DISEASE; DENIAL; DEMENTIA ID TRANSIENT GLOBAL AMNESIA; METABOLIC PATTERNS; DEMENTIA; ANOSOGNOSIA; DIAGNOSIS; CAPGRAS; ONSET AB Disease features in Alzheimer's disease patients with and without denial of their disease status, were contrasted in a three year longitudinal follow-up study, inpatient and outpatient departments, Clinical Center, and the NIH. Twenty-one patients with AD who denied or appeared unaware of impairment were compared to 20 who acknowledged deficits. The groups were not differentiated by severity or duration of disease, but denial/unawareness was significantly associated with confabulation, reduplicative delusions and misidentifications, and symbolic or delusional environmental disorientation. It also occurred significantly more often when the initial manifestations were of memory loss and behavioral disturbance suggestive of frontal and paralimbic involvement, than with deficits in reading, writing, calculations and visuospatial orientation indicative of predominant posterior brain involvement. We concluded denial/unawareness is distinguished from loss of insight by lack of correlation with severity of dementia, and by its adaptive symbolic features. C1 CASE WESTERN RESERVE UNIV,UNIV HOSP CLEVELAND,CTR ALZHEIMER,2074 ABINGTON RD,CLEVELAND,OH 44120. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RI Friedland, Robert/A-2834-2010 OI Friedland, Robert/0000-0001-5721-1843 NR 52 TC 57 Z9 57 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1994 VL 7 IS 3 BP 176 EP 184 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA PC765 UT WOS:A1994PC76500005 ER PT J AU ROTHMAN, RB AF ROTHMAN, RB TI PCP SITE-2 - A HIGH-AFFINITY MK-801-INSENSITIVE PHENCYCLIDINE BINDING-SITE SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE PCP; (+)-5-METHYL-10,11-DIHYDRO-5H-DIBENZO[A,D]CYCLOHEPTEN-5,10-IMINE; MALEATE; DOPAMINE TRANSPORTER; SEROTONIN TRANSPORTER; 1-[1-(2-THIENYL)CYCLOHEXYL]PIPERIDINE ID GUINEA-PIG BRAIN; DISCRIMINATIVE STIMULUS PROPERTIES; RAT HIPPOCAMPAL-NEURONS; AMINE REUPTAKE COMPLEX; DOPAMINE TRANSPORTER; NMDA RECEPTORS; PSEUDOALLOSTERIC MODULATION; TETRAETHYLAMMONIUM IONS; SEROTONIN TRANSPORTER; POTASSIUM CHANNELS AB Phencyclidine (PCP), a psychotomimetic drug with anticonvulsant and neuroprotective properties interacts with several central nervous system (CNS) macromolecules. These include cholinergic receptors, potassium channels, biogenic amine reuptake systems, the N-methyl-D-aspartate (NMDA) excitatory amino acid receptor, and sigma binding sites. The good correlation between the affinity of arylcycloalkylamines for high affinity PCP binding sites and their ED50 values for inhibition of [H-3]dopamine uptake supports the notion that a PCP binding site associated with the transporter for the biogenic amines should be detectable in ligand binding studies. This article reviews data primarily from the author's laboratory, which shows that the PCP analog, [H-3]1-[1-(2-thienyl)cyclohexyl]piperidine, binds to a second site, not associated with the NMDA receptor/ionophore complex, called PCP site 2. The ligand-selectivity of this binding site and the evidence that it is associated with the biogenic amine transporters are reviewed. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 64 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 1994 VL 16 IS 4 BP 343 EP 353 DI 10.1016/0892-0362(94)90022-1 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA PB306 UT WOS:A1994PB30600002 PM 7968938 ER PT J AU ECKELMAN, WC DICHIRO, G SALVATORE, M LARSON, SM AF ECKELMAN, WC DICHIRO, G SALVATORE, M LARSON, SM TI DIAGNOSTIC-IMAGING IN ONCOLOGY, 28-30-APRIL-1993, NAPLES, ITALY - INTRODUCTION SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Editorial Material RP ECKELMAN, WC (reprint author), NIH,CTR CLIN,DEPT PET,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JUL PY 1994 VL 21 IS 5 BP 681 EP 681 DI 10.1016/0969-8051(94)90037-X PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NU513 UT WOS:A1994NU51300001 ER PT J AU ECKELMAN, WC AF ECKELMAN, WC TI THE APPLICATION OF RECEPTOR THEORY TO RECEPTOR-BINDING AND ENZYME-BINDING ONCOLOGIC RADIOPHARMACEUTICALS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Conference on Diagnostic Imaging in Oncology CY APR 28-30, 1993 CL NAPLES, ITALY ID POSITRON EMISSION TOMOGRAPHY; CELL LUNG-CARCINOMA; MUSCARINIC ACETYLCHOLINE-RECEPTORS; PROTEIN-SYNTHESIS RATES; SOMATOSTATIN RECEPTORS; GROWTH-FACTOR; CANCER-CELLS; BENZODIAZEPINE BINDING; CHOLINERGIC RECEPTORS; COMPUTED-TOMOGRAPHY AB The successful imaging of tumor biochemistry using a receptor binding radiotracer is related to the affinity constant and the receptor concentration. The target to nontarget ratio can be predicted by steady state equations using in vitro data, although this is a necessary but not sufficient upper limit. The prediction of the sensitivity of the radiopharmaceutical to changes in the tumor biochemistry is not possible with this evaluation. RP ECKELMAN, WC (reprint author), NIH,CTR CLIN,DEPT PET,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 81 TC 41 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JUL PY 1994 VL 21 IS 5 BP 759 EP 769 DI 10.1016/0969-8051(94)90047-7 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NU513 UT WOS:A1994NU51300011 PM 9241652 ER PT J AU VARRICCHIO, C AF VARRICCHIO, C TI HUMAN AND INDIRECT COSTS OF HOME CARE SO NURSING OUTLOOK LA English DT Article ID CANCER-PATIENTS; FAMILY CAREGIVERS; NEEDS RP VARRICCHIO, C (reprint author), NCI,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD 20892, USA. NR 33 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JUL-AUG PY 1994 VL 42 IS 4 BP 151 EP 157 PG 7 WC Nursing SC Nursing GA PD102 UT WOS:A1994PD10200002 PM 7984445 ER PT J AU PALMER, MH AF PALMER, MH TI A HEALTH-PROMOTION PERSPECTIVE OF URINARY CONTINENCE SO NURSING OUTLOOK LA English DT Article ID NURSING-HOME PATIENTS; INCONTINENCE; MANAGEMENT; KNOWLEDGE; EXPERIENCE; DEMENTIA; BEHAVIOR; REDUCE; CARE RP PALMER, MH (reprint author), NINR,BETHESDA,MD, USA. NR 46 TC 11 Z9 11 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JUL-AUG PY 1994 VL 42 IS 4 BP 163 EP 169 PG 7 WC Nursing SC Nursing GA PD102 UT WOS:A1994PD10200004 PM 7984447 ER PT J AU LEIDY, NK AF LEIDY, NK TI FUNCTIONAL STATUS AND THE FORWARD PROGRESS OF MERRY-GO-ROUNDS - TOWARD A COHERENT ANALYTICAL FRAMEWORK SO NURSING RESEARCH LA English DT Article ID SICKNESS IMPACT PROFILE; CHRONIC PHYSICAL ILLNESS; BREAST-CANCER; HEALTH; EXPERIENCE; DISEASE; STRESS AB Functional status is frequently discussed as a key element of nursing practice and a critical outcome criterion, and yet this phenomenon is poorly understood. Many important questions have not been addressed, in part because terms such as functional status, functional ability, health status, and quality of life have been used interchangeably. Failure to clearly outline the terminology and refine the definitions has placed us on a functional status merry-go-round that inhibits scientific progress in this area. The purpose of this article is to introduce an analytical framework for the study of functional status. Four dimensions of functional status are proposed: functional capacity, performance, reserve, and capacity utilization. These terms are defined and clarified through a discussion emphasizing the consequences for measurement, intervention, and clinical trials. The article concludes by illustrating the utility of the framework in recognizing and appreciating functional status trajectory patterns in aging and chronic illness. RP LEIDY, NK (reprint author), NINR,STUDY HUMAN RESPONSES HLTH & ILLNESS,BETHESDA,MD, USA. NR 34 TC 118 Z9 120 U1 1 U2 52 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 SN 0044-7781 J9 NURS RES JI Nurs. Res. PD JUL-AUG PY 1994 VL 43 IS 4 BP 196 EP 202 PG 7 WC Nursing SC Nursing GA QY699 UT WOS:A1994QY69900002 PM 8047422 ER PT J AU GRIFFITH, P JAMES, B CROPP, A AF GRIFFITH, P JAMES, B CROPP, A TI EVALUATION OF THE SAFETY AND EFFICACY OF TOPICAL NITROGLYCERIN OINTMENT TO FACILITATE VENOUS CANNULATION SO NURSING RESEARCH LA English DT Article ID PLASMA; PAIN AB The purpose of this study was to determine the safety and efficacy of 2% nitroglycerin ointment to facilitate venous cannulation. In a double-blind experimental design, 80 adult subjects were randomly assigned to receive a 2% nitroglycerin ointment or a placebo ointment prior to cannulation. Variables measured before and after ointment application included heart rate, electrocardiogram, vein size, and presence of headache. No statistically significant differences were found in vein size or adverse effects following nitroglycerin ointment application. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. PFIZER INC,DIV CARDIOVASC CENT RES,GROTON,CT 06340. RP GRIFFITH, P (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CONTR,BETHESDA,MD 20892, USA. NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 SN 0044-7781 J9 NURS RES JI Nurs. Res. PD JUL-AUG PY 1994 VL 43 IS 4 BP 203 EP 206 PG 4 WC Nursing SC Nursing GA QY699 UT WOS:A1994QY69900003 PM 8047423 ER PT J AU MILLER, RC WOLF, EJ GOULD, M MACRI, CJ CHARNAS, LR AF MILLER, RC WOLF, EJ GOULD, M MACRI, CJ CHARNAS, LR TI FETAL OCULOCEREBRORENAL SYNDROME OF LOWE ASSOCIATED WITH ELEVATED MATERNAL SERUM AND AMNIOTIC-FLUID ALPHA-FETOPROTEIN LEVELS SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CONGENITAL NEPHROSIS; PROTEINURIA; DIAGNOSIS AB Objective: To report an association between fetal oculocerebrorenal syndrome of Lowe and elevations in maternal serum alpha-fetoprotein (MSAFP) and amniotic fluid alphafetoprotein (AFAFF). Methods: Case 1 was identified during routine MSAFP screening. Cases 2-5 were identified through review of a data base of individuals with oculocerebrorenal syndrome enrolled at the National Institutes of Health. To estimate the frequency of this association, only those whose mothers would have been in the early second trimester from February 1987 to August 1993 were enumerated. The MSAFP was assumed to be normal unless explicitly reported or unless information outside the data base confirmed that MSAFP was not determined. Results: An elevated MSAFP (2.5 multiples of the median [MoM] or greater) was detected in five of 20 pregnancies with a fetus affected by oculocerebrorenal syndrome. Maternal serum alpha-fetoprotein was greater than 5.0 MoM in three pregnancies undergoing amniocentesis, and all had an elevated AFAFP without significant acetylcholinesterase activity. No abnormalities were found by ultrasound, and there was no other cause of elevated AFP identified postnatally. Family history was positive in three of the five cases. The mothers were carriers in four of the five cases, whereas the fifth case appeared to be a spontaneous mutation. Conclusions: Elevated MSAFP and AFAFP appear to occur at a higher than expected frequency in pregnancies carrying an oculocerebrorenal syndrome fetus. The mechanism of elevation of AFP may be related to fetal renal tubular dysfunction. A directed interview, focusing on a maternal family history of male relatives with unexplained mental retardation, early institutionalization, or congenital rubella, is appropriate with unexplained MSAFP elevations and, particularly, with unexplained AFAFF elevations without acetylcholinesterase activity. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. RP MILLER, RC (reprint author), UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,DEPT OBSTET & GYNECOL,8901 WISCONSIN AVE,BETHESDA,MD 20889, USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 1994 VL 84 IS 1 BP 77 EP 80 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PH953 UT WOS:A1994PH95300017 PM 7516514 ER PT J AU MCVICAR, DW LAL, BK LLOYD, A KAWAMURA, M CHEN, YQ ZHANG, XY STAPLES, JE ORTALDO, JR OSHEA, JJ AF MCVICAR, DW LAL, BK LLOYD, A KAWAMURA, M CHEN, YQ ZHANG, XY STAPLES, JE ORTALDO, JR OSHEA, JJ TI MOLECULAR-CLONING OF LSK, A CARBOXYL-TERMINAL SRC KINASE (CSK) RELATED GENE, EXPRESSED IN LEUKOCYTES SO ONCOGENE LA English DT Article ID PROTEIN-TYROSINE KINASE; NATURAL-KILLER-CELLS; SH3 DOMAINS; SIGNAL TRANSDUCTION; LYMPHOCYTES-T; NK CELLS; PHOSPHORYLATES; RECEPTORS; P50(CSK); ENCODES AB Regulation of the activity of src-family kinases is thought to occur, in part, through the phosphorylation of conserved carboxyl-terminal tyrosine residues. Although the src-family includes several molecules with tissue or cell-type restricted expression, the only kinase implicated in the regulatory phosphorylation of these enzymes is p50(csk). Herein we report the molecular cloning of a tissue specific p50(csk)-related gene. Like p50(csk), the deduced protein sequence of this novel cDNA includes a tyrosine kinase catalytic domain, SH2 and SH3 domains, a short amino terminus, and no autophosphorylation or carboxyl-terminal tyrosine residues. Additionally, neither this novel kinase nor p50(csk) contain the amino-terminal myristoylation site characteristic of the src-family. However, whereas csk is ubiquitously expressed, mRNA corresponding to this novel gene is expressed in brain, natural killer (NK) cells, and activated T cells but not in a variety of other tissues and cell lines. In agreement with the mRNA expression pattern, antiserum reactive with the predicted carboxyl-terminus of the cDNA recognizes a 57 kDa polypeptide in immunoblots of NK cells and PHA-activated T cells, Because of its limited expression and high homology to p50(csk), we named this gene lsk; leukocyte carboxyl-terminal src kinase related gene. Identification of a molecule like lsk suggests the existence of tissue specific src-regulatory pathways that function in activated lymphocytes. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP MCVICAR, DW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE CELL BIOL SECT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015 NR 40 TC 51 Z9 51 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1994 VL 9 IS 7 BP 2037 EP 2044 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NR685 UT WOS:A1994NR68500028 PM 7516063 ER PT J AU VELASCO, JA CASTRO, R AVILA, MA LABORDA, J DIPAOLO, JA CANSADO, J NOTARIO, V AF VELASCO, JA CASTRO, R AVILA, MA LABORDA, J DIPAOLO, JA CANSADO, J NOTARIO, V TI CPH, A NOVEL ONCOGENE WHICH COOPERATES WITH H-RAS IN THE TRANSFORMATION OF NIH3T3 FIBROBLASTS SO ONCOGENE LA English DT Note ID BLADDER-CARCINOMA ONCOGENE; POINT MUTATION; PROTO-ONCOGENE; NEU ONCOGENE; ACTIVATION; CELLS; GENE; SEQUENCES; CANCER; ACQUISITION AB We have performed the molecular cloning of the non-ras transforming sequences previously detected in neoplastic Syrian hamster embryo fibroblasts initiated in vitro with 3-methylcholanthrene (MCA) (Notario et at, 1990). These sequences were isolated using cosmid-rescue techniques from a third-cycle NIH3T3 transformant obtained by sequential transfections of genomic DNA from MCA-initiated hamster fetal cells. Rescued (C-5) clones encompassed about 42.5 kbp of Syrian hamster genomic DNA containing hamster-specific repetitive elements (HRS). An internal 19 kbp BamHI fragment (B-1) was the only C-5 fragment which recognized specific transcripts in poly(A)(+) RNA from hamster embryo cells, The same mRNA species were present in both normal and MCA-initiated neoplastic cells: a major transcript of about 2.5 kb, and other less abundant ones, ranging from approximately 2.0 kb to 5.0 kb. These mRNA species were detected consistently by each of several B-1 DNA subfragments located at positions spanning almost the entire B-1 length. The nucleotide sequence of some transcript-positive (S5P2 and S-6) genomic B-1 fragments was determined. No significant homology exists between the nucleotide sequences of these B-1 subfragments and established DNA databases. Therefore, the C-5 cosmid clone contains novel genomic sequences. Transfection of C-5 DNA into mouse NIH3T3 cells resulted in the appearance of transformed foci (about five foci per mu g of DNA) within 25 days post-transfection, thus demonstrating the transforming activity of the C-5 clone, which was consequently renamed as the cph oncogene. Co-transfection of the cph oncogene with the human H-ras oncogene (T24), demonstrated a synergistic action between the two oncogenes in the transformation of murine fibroblasts. C1 GEORGETOWN UNIV,MED CTR,DEPT RADIAT MED,DIV EXPTL CARCINOGENESIS,WASHINGTON,DC 20007. NCI,BIOL LAB,BETHESDA,MD 20892. RI Cansado, Jose/K-5212-2014; Laborda, Jorge/L-5726-2014 OI Laborda, Jorge/0000-0002-9210-838X FU NCI NIH HHS [CA49858] NR 34 TC 29 Z9 29 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1994 VL 9 IS 7 BP 2065 EP 2069 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NR685 UT WOS:A1994NR68500032 PM 8208552 ER PT J AU CHAN, CC HIKITA, N DASTGHEIB, K WHITCUP, SM GERY, I NUSSENBLATT, RB AF CHAN, CC HIKITA, N DASTGHEIB, K WHITCUP, SM GERY, I NUSSENBLATT, RB TI EXPERIMENTAL MELANIN-PROTEIN-INDUCED UVEITIS IN THE LEWIS RAT - IMMUNOPATHOLOGIC PROCESSES SO OPHTHALMOLOGY LA English DT Article ID AUTOIMMUNE ANTERIOR UVEITIS; ENDOTOXIN-INDUCED UVEITIS; KOYANAGI-HARADA DISEASE; RETINAL-PIGMENT EPITHELIUM; INDUCTION; EAAU; LYMPHOCYTES AB Purpose: To study the immunopathology of experimental melanin-protein-induced uveitis in the Lewis rat. Methods: Rats were immunized with bovine ocular melanin protein. The kinetics of experimental melanin-protein-induced uveitis was studied by clinical examination and immunopathology. Cellular and humoral responses were evaluated by lymphocyte proliferation, delayed-type hypersensitivity, and agglutination. After clinical disease subsided, recurrent experimental uveitis was induced with a low-dose footpad injection of lipopolysaccharide. Results: Experimental melanin-protein-induced uveitis was characterized by bilateral uveal infiltration mainly with lymphocytes and monocytes. Delayed-type hypersensitivity, lymphocyte proliferation, and agglutination to bovine ocular melanin protein were positive. Expressions of major histocompatibility complex class IL and intercellular adhesion molecule-1 were observed before ocular infiltration. The predominantly infiltrating cells were CD4+ lymphocytes. Experimental melanin-protein-induced uveitis subsided within 1 month, spontaneously recurred within 1 week in approximately one quarter of the rats, and was inducible in most rats with 5 mu g of lipopolysaccharide confirmed by histopathology. Conclusions: Experimental melanin-protein-induced uveitis is a T-cell-mediated autoimmune uveitis, resembling noninfectious recurrent iridocyclitis and choroiditis in humans. RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,RN 10N103,BETHESDA,MD 20892, USA. NR 26 TC 59 Z9 61 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1994 VL 101 IS 7 BP 1275 EP 1280 PG 6 WC Ophthalmology SC Ophthalmology GA NY941 UT WOS:A1994NY94100027 PM 7913541 ER PT J AU KOBER, V YAROSLAVSKY, LP CAMPOS, J YZUEL, MJ AF KOBER, V YAROSLAVSKY, LP CAMPOS, J YZUEL, MJ TI OPTIMAL FILTER APPROXIMATION BY MEANS OF A PHASE-ONLY FILTER WITH QUANTIZATION SO OPTICS LETTERS LA English DT Article AB Approximate filters based on a phase-only filter for reliable recognition of objects are proposed. Good light efficiency and discrimination capability close to that of the optimal filter can be obtained. Computer simulation results are presented and discussed. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RUSSIAN ACAD SCI,INST INFORMAT TRANSMISS PROBLEMS,MOSCOW 101447,RUSSIA. RP KOBER, V (reprint author), AUTONOMOUS UNIV BARCELONA,DEPT PHYS,E-08193 BARCELONA,SPAIN. RI Campos, Juan/N-1211-2014; Yzuel, Maria/H-7158-2015; OI Campos, Juan/0000-0002-2479-4373; Yzuel, Maria/0000-0002-7235-5578; Kober, Vitaly/0000-0002-9374-9883 NR 8 TC 18 Z9 18 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUL 1 PY 1994 VL 19 IS 13 BP 978 EP 980 DI 10.1364/OL.19.000978 PG 3 WC Optics SC Optics GA NU437 UT WOS:A1994NU43700018 PM 19844507 ER PT J AU PATTON, LL BRAHIM, JS BAKER, AR AF PATTON, LL BRAHIM, JS BAKER, AR TI METASTATIC MALIGNANT-MELANOMA OF THE ORAL CAVITY - A RETROSPECTIVE STUDY SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CUTANEOUS MELANOMA; SURGICAL-TREATMENT; GENE-THERAPY; HEAD; NECK; IMMUNOTHERAPY; NEOPLASMS; CANCER; UPDATE AB Metastatic malignant melanoma of the oral cavity is rarely reported in the dental literature. This retrospective study identified metastatic oral lesions in 3.0% of 809 patients with melanoma treated at the National Institutes of Health between 1953 and 1989. Fifteen cases met established rigorous criteria for metastatic tumors and were reviewed for disease course and outcome. Nine white men and six white women, with an average age of 40.6 years, had cutaneous primary tumors predominantly of the trunk and head and neck region that commonly presented as moles that were enlarging, bleeding, or showing both of these signs. A mean of 4.2 years elapsed between primary tumor and oral metastasis diagnosis. Tongue, buccal mucosa, and parotid gland were the predominant oral sites. Enlarging oral masses, pigmented lesions, and nonhealing extraction sites with masses were common oral presentations. Surgery, chemotherapy, radiation therapy, and immunotherapy were used in various combinations for treatment of the primary lesion and oral metastasis. Prognosis, although poor, was highly variable. C1 NIH,BETHESDA,MD 20892. RP PATTON, LL (reprint author), UNIV N CAROLINA,SCH DENT,DEPT DENT ECOL,CB7450,CHAPEL HILL,NC 27599, USA. OI Patton, Lauren/0000-0002-8253-4588 NR 36 TC 25 Z9 29 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUL PY 1994 VL 78 IS 1 BP 51 EP 56 DI 10.1016/0030-4220(94)90117-1 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NX935 UT WOS:A1994NX93500012 PM 8078664 ER PT J AU NAHIN, RL REN, K DELEON, M RUDA, M AF NAHIN, RL REN, K DELEON, M RUDA, M TI PRIMARY SENSORY NEURONS EXHIBIT ALTERED GENE-EXPRESSION IN A RAT MODEL OF NEUROPATHIC PAIN SO PAIN LA English DT Article DE CALCITONIN GENE-RELATED PEPTIDE; GALANIN; GROWTH-ASSOCIATED PROTEIN-43; NEUROPEPTIDE Y; SUBSTANCE P; VASOACTIVE INTESTINAL POLYPEPTIDE; MESSENGER-RNA; IN-SITU HYBRIDIZATION; CHRONIC CONSTRICTION INJURY; DORSAL ROOT GANGLIA; AXOTOMY ID DORSAL-ROOT GANGLION; NERVE GROWTH-FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; PREPROTACHYKININ MESSENGER-RNA; PRIMARY AFFERENT NEURONS; EXPERIMENTAL PERIPHERAL NEUROPATHY; SPINAL-CORD; SCIATIC-NERVE; SUBSTANCE-P; NEUROPEPTIDE EXPRESSION AB Using a number of complementary anatomical and molecular techniques, we studied the effects of chronic constriction injury (CCI), a model of partial nerve injury that elicits behavioral hyperalgesia, on primary sensory neurons in the rat. Dorsal root ganglia taken from animals with CCI were analyzed for alterations in mRNA levels encoding growth-associated protein-43 (GAP-43), calcitonin gene-related peptide (CGRP), galanin (GAL), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal polypeptide (VIP). We found that GAP-43 expression increased 3-fold, peaking between 7 and 14 days after development of the CCI. However, within this same 7-14 day time frame, both CGRP and SP mRNAs fell to half their normally abundant constitutive levels of expression. The most dramatic change in expression occurred for GAL, NPY and VIP mRNAs which all rose rapidly (day 3) from non-detectable levels. Similar alterations in gene expression have been described after complete sciatic nerve transection or crush. RP NAHIN, RL (reprint author), NIDR, NEUROBIOL & ANESTHESIOL BRANCH, ROOM B-20, BLDG 30, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI De Leon, Marino/A-6922-2009 OI De Leon, Marino/0000-0001-6576-785X NR 83 TC 136 Z9 142 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUL PY 1994 VL 58 IS 1 BP 95 EP 108 DI 10.1016/0304-3959(94)90189-9 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA NX705 UT WOS:A1994NX70500010 PM 7526320 ER PT J AU CLARK, CG DIAMOND, LS AF CLARK, CG DIAMOND, LS TI PATHOGENICITY OR VIRULENCE - REPLY SO PARASITOLOGY TODAY LA English DT Letter RP CLARK, CG (reprint author), NIH,PARASIT DIS LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUL PY 1994 VL 10 IS 7 BP 263 EP 263 PG 1 WC Parasitology SC Parasitology GA NR837 UT WOS:A1994NR83700008 ER PT J AU REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HC SIMON, PR FALK, H MILLER, RW ROGAN, WJ AF REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HC SIMON, PR FALK, H MILLER, RW ROGAN, WJ TI PCBS IN BREAST-MILK SO PEDIATRICS LA English DT Editorial Material ID POLYCHLORINATED-BIPHENYLS; EXPOSURE C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA. NCI,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. RI Goldman, Lynn/D-5372-2012 NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1994 VL 94 IS 1 BP 122 EP 123 PG 2 WC Pediatrics SC Pediatrics GA NU544 UT WOS:A1994NU54400029 ER PT J AU KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR AF KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR MULINARE, J KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR TI CAMPHOR REVISITED - FOCUS ON TOXICITY SO PEDIATRICS LA English DT Editorial Material ID DATA-COLLECTION-SYSTEM C1 AMER MED ASSOC,CHICAGO,IL 60610. CTR DIS CONTROL & PREVENT,ATLANTA,GA. PHARMACEUT MANUFACTURERS ASSOC,WASHINGTON,DC. HLTH PROTECT BRANCH,OTTAWA,ON,CANADA. AMER COLL OBSTET GYNECOL,WASHINGTON,DC. US FDA,WASHINGTON,DC. NIH,BETHESDA,MD 20892. AMER ACAD PEDIAT,ANESTHESIOL SECT,ELK GROVE VILLAGE,IL. NR 11 TC 14 Z9 14 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1994 VL 94 IS 1 BP 127 EP 128 PG 2 WC Pediatrics SC Pediatrics GA NU544 UT WOS:A1994NU54400031 ER PT J AU BRYANT, SD ATTILA, M SALVADORI, S GUERRINI, R LAZARUS, LH AF BRYANT, SD ATTILA, M SALVADORI, S GUERRINI, R LAZARUS, LH TI MOLECULAR-DYNAMICS CONFORMATIONS OF DELTORPHIN ANALOGS ADVOCATE DELTA-OPIOID BINDING-SITE MODELS SO PEPTIDE RESEARCH LA English DT Article ID RAT-BRAIN; RECEPTOR SUBTYPES; HIGH-AFFINITY; TOPOGRAPHICAL REQUIREMENTS; DIFFERENTIAL ANTAGONISM; FUNCTIONAL EXPRESSION; OPIATE RECEPTORS; AMPHIBIAN SKIN; PEPTIDES; SELECTIVITY AB Multi-site binding models for the delta opioid receptor were studied in vitro with [H-3]DPDPE as the labeled ligand using anologues of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) altered at position 4. Modifications included a change in chirality (L- to D-Asp(4)), increased length of the anionic side-chain (Glu(4)), elimination of the charged group (Abu(4)) addition of an anionic group (Gla(4)), and change in backbone conformation (Pro(4)). All of the peptides had relatively high delta affinities (0.09 to 1.15 nM); the major variability in delta selectivity resided in changes in mu affinities (1.6 to 530 nM). Three analogues (Glu(4), D-Asp(4) and Pro(4)) revealed better fits to two-site binding models (Hill coefficients < 0.850 with narrow 95% confidence intervals and P <0.0001). Deltorphin C and analogues containing Gla(4) and Abu(4) (which were weakly delta selective), as well as deltorphin A (H-Tyr-D-Met-Phe- His-Leu-Met-Asp-NH2), fitted one-site binding models. Molecular dynamics simulations performed on deltorphin C and Abu(4) exhibited similarities in the tertiary structure of their low energy conformers while differing from the three-dimensional structures of the analogues containing Glu(4), D-Asp(4) and Pro(4) substitutions. The data provide support that the three-dimensional architecture of an opioid peptide is an important factor in the designation of delta opioid receptor subtypes. C1 UNIV FERRARA,FERRARA,ITALY. UNIV HELSINKI,HELSINKI,FINLAND. RP BRYANT, SD (reprint author), NIEHS,POB 12233,MD C3-04,RES TRIANGLE PK,NC 27709, USA. NR 64 TC 20 Z9 22 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 1040-5704 J9 PEPTIDE RES JI Peptide Res. PD JUL-AUG PY 1994 VL 7 IS 4 BP 175 EP 184 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA787 UT WOS:A1994PA78700002 PM 7696838 ER PT J AU ENOMOTO, K FURUYA, K YAMAGISHI, S OKA, T MAENO, T AF ENOMOTO, K FURUYA, K YAMAGISHI, S OKA, T MAENO, T TI THE INCREASE IN THE INTRACELLULAR CA2+ CONCENTRATION INDUCED BY MECHANICAL STIMULATION IS PROPAGATED VIA RELEASE OF PYROPHOSPHORYLATED NUCLEOTIDES IN MAMMARY EPITHELIAL-CELLS SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE INTRACELLULAR CALCIUM; FURA-2; MAMMARY EPITHELIAL CELLS; MECHANICAL STIMULATION; PURINOCEPTOR ID FIBROBLASTS L-CELLS; EXTRACELLULAR ATP; CALCIUM OSCILLATIONS; ENDOTHELIAL-CELLS; PHOSPHOLIPASE-C; HL60 CELLS; RECEPTOR; RESPONSES; CA-2+; HYPERPOLARIZATIONS AB Mechanical stimulation of one mammary tumor cell in culture induced an increase in its intracellular calcium concentration which spread to surrounding cells. The increase in calcium can also be induced by addition of a solution in which cultured mammary tumor cells were stimulated by repeated pipetting (solution after pipetting cells, SAPC). The activity of the SAPC was completely abolished by treatment with snake venom phosphodiesterase or pyrophosphatase. Uridine triphosphate (UTP), uridine diphosphate (UDP) and ATP (1 mu M each) were detected in the SAPC, whereas 5'-UMP and 5'-AMP were produced by phosphodiesterase digestion. A mixture of UTP, UDP and ATP (1 mu M each) elicited a calcium response which was comparable to that induced by SAPC, while UTP, UDP or ATP alone at 1 mu M elicited a small increase in calcium concentration in mammary tumor cells. Suramin, a competitive antagonist of P-2 purinoceptors, diminished the spreading of the calcium wave induced by mechanical stimulation, It also blocked the responses to SAPC, UTP, UDP and ATP. These findings suggest that the mechanical stimulation results in the release of UTP, UDP and ATP into the extracellular space which mediates induction of the spreading calcium response via P-2U-type purinoceptors. C1 NATL INST PHYSIOL SCI,DEPT CELL PHYSIOL,OKAZAKI,AICHI 444,JAPAN. NIH,MOLEC & CELL BIOL LAB,BETHESDA,MD 20892. RP ENOMOTO, K (reprint author), SHIMANE MED UNIV,DEPT PHYSIOL,IZUMO,SHIMANE 693,JAPAN. NR 43 TC 78 Z9 78 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JUL PY 1994 VL 427 IS 5-6 BP 533 EP 542 DI 10.1007/BF00374271 PG 10 WC Physiology SC Physiology GA NU221 UT WOS:A1994NU22100020 PM 7971152 ER PT J AU MCBAIN, CJ MAYER, ML AF MCBAIN, CJ MAYER, ML TI N-METHYL-D-ASPARTIC ACID RECEPTOR STRUCTURE AND FUNCTION SO PHYSIOLOGICAL REVIEWS LA English DT Review ID PROTEIN-KINASE-C; CULTURED HIPPOCAMPAL-NEURONS; EXCITATORY AMINO-ACIDS; LONG-TERM POTENTIATION; REDOX MODULATORY SITE; MOUSE CENTRAL NEURONS; RAT CORTICAL-NEURONS; SPINAL-CORD NEURONS; MEDIATED SYNAPTIC TRANSMISSION; SINGLE-CHANNEL CONDUCTANCES RP MCBAIN, CJ (reprint author), NICHHD, CELLULAR & MOLEC NEUROPHYSIOL LAB, BETHESDA, MD 20892 USA. RI Mayer, Mark/H-5500-2013 NR 256 TC 763 Z9 777 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JUL PY 1994 VL 74 IS 3 BP 723 EP 760 PG 38 WC Physiology SC Physiology GA NX900 UT WOS:A1994NX90000006 PM 8036251 ER PT J AU SPANGLER, EL HELLER, B HENGEMIHLE, J MUTH, NJ JONES, BE GAROFALO, P INGRAM, DK AF SPANGLER, EL HELLER, B HENGEMIHLE, J MUTH, NJ JONES, BE GAROFALO, P INGRAM, DK TI THROMBOSIS OF PARIETAL, BUT NOT STRIATE, CORTEX IMPAIRS ACQUISITION OF A 14-UNIT T-MAZE IN THE RAT SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE PARIETAL CORTEX; STRIATE CORTEX; LEARNING; MEMORY ID FIMBRIA-FORNIX LESIONS; RETENTION PERFORMANCE; RODENT MODELS; YOUNG-RATS; AGED RATS; MEMORY AB We evaluated parietal cortex (PCTX) involvement in learning a shock-motivated, 14-unit T-maze in young F344 rats. In Experiment 1, each rat was placed into a stereotaxic instrument, and the scalp was retracted before either the photosensitive dye, rose bengal, or saline (CON) was provided via a jugular catheter. After 60 s, halogen lamps were used to illuminate the cranium bilaterally over PCTX for 40 min to activate the dye and generate a thrombus in dye-injected rats. Active avoidance pretraining in a straight runway occurred 12 days after surgery. Each rat was provided acquisition (ACQ) trials in the 14-unit T-maze 24-h later. The PCTX rats were impaired relative to CON in errors, run time, alternation errors, and shock frequency measures in the 14-unit T-maze, but not in shock duration. The thrombosis extended to areas comprising anteromedial and posterior PCTX, and also into the striate cortex (SCTX). In Experiment 2, rats were divided into four groups: a PCTX group that received bilateral illumination; PCTX + SCTX and SCTX groups that were illuminated at midline; and a CON group that received the surgery and either dye or illumination. Only PCTX differed from CON, with maze performance similar to Experiment 1. The thrombosis for the PCTX group in Experiment 2 was confined to anteromedial and posterior PCTX. Thus, PCTX, but not SCTX, was implicated in ACQ of this maze task, suggesting that PCTX might be involved in the robust age-related impairments in ACQ previously observed. C1 ESSEX COMMUNITY COLL,ESSEX,MD 21237. SYMPHONY PHARMACEUT INC,MALVERN,PA 19355. RP SPANGLER, EL (reprint author), NIA,GERONTOL RES CTR,MOLEC & CELLULAR BIOL LAB,MOLEC PHYSIOL & GENET SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Jones, Barbara/A-8033-2017 NR 26 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUL PY 1994 VL 56 IS 1 BP 95 EP 101 DI 10.1016/0031-9384(94)90265-8 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA NP669 UT WOS:A1994NP66900012 PM 8084912 ER PT J AU PETROV, ES VARLINSKAYA, EI ROBINSON, SR SMOTHERMAN, WP DECOSTA, BR RICE, KC AF PETROV, ES VARLINSKAYA, EI ROBINSON, SR SMOTHERMAN, WP DECOSTA, BR RICE, KC TI KAPPA-OPIOID EFFECTS ON FETAL BEHAVIOR - CENTRAL ADMINISTRATION OF U50,488 SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE U50,488; NOR-BINALTORPHIMINE; KAPPA; OPIOID; RAT FETUS ID STRETCH RESPONSE; RAT FETUS; ONTOGENY; MILK; RECEPTORS; SYSTEMS AB The kappa opioid agonist U50,488 was administered to E21 rat fetuses via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of U50,488 promoted a threefold increase in motor activity, which was predominated by movements of caudal regions of the body (rearlimbs, body trunk, and tail). The agonist effect was reversed by IC administration of the selective kappa opioid antagonist nor-binaltorphimine. The IH injection of U50,488 had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including rearlimb, trunk and tail movements. The IT administration of nor-binaltorphimine blocked U50,488 effects, whereas IH injection of the antagonist had little influence on fetal behavior. These findings suggest that kappa opioid receptors located in the spinal cord may play a role in the regulation of fetal motor behavior. C1 SUNY BINGHAMTON,DEPT PSYCHOL,CTR DEV PSYCHOBIOL,PERINATAL NEUROETHOL LAB,BINGHAMTON,NY 13902. RUSSIAN ACAD MED SCI,INST EXPTL MED,DEPT PAVLOVIAN PHYSIOL,ST PETERSBURG,RUSSIA. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RI Robinson, Scott/J-6024-2012 FU NICHD NIH HHS [NICHD HD 16102, HD 28231, HD 28014] NR 20 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUL PY 1994 VL 56 IS 1 BP 175 EP 182 DI 10.1016/0031-9384(94)90276-3 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA NP669 UT WOS:A1994NP66900023 PM 8084898 ER PT J AU ERNST, ND OBARZANEK, E AF ERNST, ND OBARZANEK, E TI CHILD HEALTH AND NUTRITION - OBESITY AND HIGH BLOOD CHOLESTEROL SO PREVENTIVE MEDICINE LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; MUSCATINE PONDEROSITY FAMILY; CORONARY-ARTERY DISEASE; RISK FACTOR VARIABLES; EARLY LIFE EXPERIENCE; SCHOOL-AGE CHILDREN; BODY-MASS INDEX; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; UNITED-STATES AB Background. The epidemiology of obesity and high blood cholesterol in children is discussed, along with strategies for the prevention of these two disorders and mention of some nutrition and child health research and education programs supported by the National Heart, Lung, and Blood Institute (NHLBI). Conclusions. Available data confirm that both obesity and high blood cholesterol levels in U.S. children are higher than optimal and that the benefit of reducing the prevalence of these conditions in childhood will be realized in adulthood. Current NHLBI-supported research and education activities focus on unanswered questions about the childhood predictors of transition to the obese state, the feasibility, efficacy, and safety of long-term dietary intervention in children, and the effects of school-based intervention that include classroom curriculum and school environmental changes related to food intake, physical activity, and tobacco use and dissemination of materials that promote nutrition and cardiovascular health in children and adolescents. (C) 1994 Academic Press, Inc. RP ERNST, ND (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892, USA. NR 92 TC 26 Z9 26 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1994 VL 23 IS 4 BP 427 EP 436 DI 10.1006/pmed.1994.1058 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PB843 UT WOS:A1994PB84300003 PM 7971869 ER PT J AU SIMONSMORTON, BG TAYLOR, WC SNIDER, SA HUANG, IW FULTON, JE AF SIMONSMORTON, BG TAYLOR, WC SNIDER, SA HUANG, IW FULTON, JE TI OBSERVED LEVELS OF ELEMENTARY AND MIDDLE SCHOOL CHILDRENS PHYSICAL-ACTIVITY DURING PHYSICAL-EDUCATION CLASSES SO PREVENTIVE MEDICINE LA English DT Article ID HEALTHFUL DIET; PUBLIC-HEALTH; FITNESS; INTERVENTIONS; STUDENTS; YOUTH AB Background. The benefits of childhood physical activity include fitness, weight control, and exercise habits that may carry over into adulthood. School physical education is the primary program responsible for training the nation's youth to be physically active and national objectives call for students to be engaged in moderate-to-vigorous physical activity at least 50% of class time. The purpose of this study was to determine through systematic observation in a regional sample of elementary and middle schools the amount of moderate-to-vigorous physical activity students obtain during physical education classes. Methods. Twenty elementary schools and 7 middle schools were randomly sampled from the 355 elementary schools and 117 middle schools in the 20 school districts in Harris County, Texas. In addition, 9 elementary and 6 middle schools that were identified as having excellent physical education programs were sampled purposively to provide a comparison. Seven systematic observations of student's physical activity were conducted during physical education in each school. Results. The average moderate-to-vigorous physical activity in the randomly selected elementary schools was 8.6%, significantly less (P < 0.05) than for the randomly selected middle schools (16.1%) or for the comparison elementary schools (20.6%) and middle schools (24.0%). Conclusions. The average amount of physical activity observed in this regional sample of schools was less than the estimated national average of 27% and far less than the national recommendation calling for a minimum of 50%. (C) 1994 Academic Press, Inc. C1 UNIV TEXAS,SCH PUBL HLTH,CTR HLTH PROMOT RES & DEV,HOUSTON,TX 77225. RP SIMONSMORTON, BG (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 21 TC 58 Z9 60 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1994 VL 23 IS 4 BP 437 EP 441 DI 10.1006/pmed.1994.1059 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PB843 UT WOS:A1994PB84300004 PM 7971870 ER PT J AU NELSON, DL KURMAN, CC AF NELSON, DL KURMAN, CC TI TARGETING HUMAN IL-2 RECEPTORS FOR DIAGNOSIS AND THERAPY SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Workshop on the Superfamily of Receptors for Growth Hormone, Prolactin, Erythropoietin, and Cytokines CY NOV 07-11, 1993 CL HAIFA, ISRAEL SP GROWTH & GROWTH HORMONE FORUM ID T-CELL LEUKEMIA; SOLUBLE TAC PEPTIDE; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODY; BETA-CHAIN; ASSOCIATION; DISTINCT; COMPLEX; BINDS AB The high-affinity interleukin-2 receptor (IL-2R) is a multichain receptor with at least three IL-2 binding chains: IL-2R alpha (55 kDa) bound by the monoclonal antibody anti-Tac, IL-2R beta (75 kDa) and IL-2R gamma (64 kDa). The IL-2R alpha also exists as a naturally occurring soluble molecule (sIL-2R alpha). We target the IL-2R for immune intervention since resting normal cells do not express the high-affinity IL-2R, whereas this receptor is on some cells in certain lymphoid neoplasias, select autoimmune disorders, and in individuals rejecting organ allografts. Treatments have included unmodified murine anti-Tac and radioisotopes conjugated to murine anti-Tac. Our emerging understanding of the IL-2R system continues to open possibilities for more specific immune intervention. RP NELSON, DL (reprint author), NCI,METAB BRANCH,IMMUNOPHYSIOL SECT,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. NR 20 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1994 VL 206 IS 3 BP 309 EP 311 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PE178 UT WOS:A1994PE17800029 PM 8016170 ER PT J AU GREENBLATT, JM HUFFMAN, LC REISS, AL AF GREENBLATT, JM HUFFMAN, LC REISS, AL TI FOLIC-ACID IN NEURODEVELOPMENT AND CHILD-PSYCHIATRY SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE FOLIC ACID; FRAGILE-X SYNDROME; NEURODEVELOPMENT; NEUROTRANSMITTERS ID FRAGILE-X SYNDROME; FOLATE-DEFICIENCY; S-ADENOSYLMETHIONINE; BRAIN; DEPRESSION; TRIAL; MALES; RAT AB 1. Folic acid deficiency has been associated with diverse neuropsychiatric symptoms. 2. This paper discusses the impact of folate on brain development, maturation and function and reviews the role of folate in psychiatric disorders, particularly childhood 3. A brief case report examines the use of folate in the treatment of attentional problems in a child with fragile X syndrome. C1 KENNEDY KRIEGER INST,BEHAV GENET & NEUROIMAGING RES CTR,550 N BROADWAY,SUITE 507,BALTIMORE,MD 21205. NIMH,DIVNEUROSCI & BEHAV SCI PERSONAL & SOCIAL PROC RES BRANCH,ROCKVILLE,MD 20857. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,DIV CHILD PSYCHIAT,BALTIMORE,MD 21205. FU NICHD NIH HHS [HD24061]; NIMH NIH HHS [MH16744] NR 58 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL PY 1994 VL 18 IS 4 BP 647 EP 660 DI 10.1016/0278-5846(94)90074-4 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NX419 UT WOS:A1994NX41900002 PM 7938557 ER PT J AU CACHAU, RE ERICKSON, JW VILLAR, HO AF CACHAU, RE ERICKSON, JW VILLAR, HO TI NOVEL PROCEDURE FOR STRUCTURE REFINEMENT IN HOMOLOGY MODELING AND ITS APPLICATION TO THE HUMAN CLASS MU-GLUTATHIONE S-TRANSFERASES SO PROTEIN ENGINEERING LA English DT Article DE HOMOLOGY MODELING; HUMAN CLASS MU GLUTATHIONE S-TRANSFERASE; STRUCTURE REFINEMENT ID PROTEIN STRUCTURES; DESIGN AB Glutathione S-transferases (GST) are a major class of phase II detoxifying enzymes that conjugate glutathione to electrophiles. Their involvement in the degradation of chemotherapeutic agents, which contributes to drug resistance, makes this family of enzymes potential targets for therapeutic agents. This study generates, by homology modeling, a 3-D structure of three GST human isozymes of the Mu class, Mlb-lb, M2-2 and M3-3, using the Rat3-3 GST structure as a template. The high percentage of identity among these enzymes and the lack of insertions and deletions make the system ideally suited to the technique of homology modeling. A novel technique for the modeling of protein structures was applied. The structure of the template was used to generate a low-resolution crystallographic map in which the initial coordinates of the structure to be modeled were placed. The structure was then annealed within this envelope. In addition, a feedback-restrained molecular dynamics procedure was adopted to scale the template restraints during the simulations. Three independent validation procedures were applied. To assess the reliability of the methods, an identical series of simulation steps to those used in the refinement were applied to the template structure (self modeling). Further, a homology structure for the Rat3-3 template was generated, starting from the modeled Mlb-lb structure (reverse modeling). To assess the reasonableness of the modeled structures, two recently developed methodologies to verify protein structures based on statistics of the nonbonded interactions were applied. Overall, the structures appear to be consistent. C1 TERRAPIN TECHNOL INC,S SAN FRANCISCO,CA 94080. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PRI,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM,FREDERICK,MD 21702. FU NCI NIH HHS [1CO-74102] NR 30 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD JUL PY 1994 VL 7 IS 7 BP 831 EP 839 DI 10.1093/protein/7.7.831 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA NY260 UT WOS:A1994NY26000002 PM 7971945 ER PT J AU KIM, SJ TSUKIYAMA, T LEWIS, MS WU, C AF KIM, SJ TSUKIYAMA, T LEWIS, MS WU, C TI INTERACTION OF THE DNA-BINDING DOMAIN OF DROSOPHILA HEAT-SHOCK FACTOR WITH ITS COGNATE DNA SITE - A THERMODYNAMIC ANALYSIS USING ANALYTICAL ULTRACENTRIFUGATION SO PROTEIN SCIENCE LA English DT Article DE HSE; SHF; PROTEIN-DNA INTERACTIONS; ULTRACENTRIFUGAL ANALYSIS ID MOLECULAR-CLONING; PROTEIN; RECOGNITION; EXPRESSION; ACTIVATION; REPRESSOR; STABILITY; COMPLEXES; MOTIF; UNIT AB Heat shock transcription factor (HSF) mediates the activation of heat shock genes by binding to its cognate sites with high affinity and specificity. The high-affinity binding of HSF is dependent on the formation of an HSF homotrimer, which interacts specifically with the heat shock response element (HSE), comprised of 3 inverted repeats of the 5-bp sequence NGAAN. In order to investigate the thermodynamic basis of the interaction between HSF and HSE, we have overexpressed and purified a polypeptide (dHSF(33-163)) encompassing only the DNA-binding domain of HSF from Drosophila and analyzed its binding to DNA by equilibrium analytical ultracentrifugation using a multiwavelength scan technique. We demonstrate that dHSF(33-163) can bind as a monomer with 1:1 stoichiometry to a synthetic 13-bp DNA containing a single NGAAN sequence. The values of the thermodynamic parameters obtained from the temperature dependence of the equilibrium binding constants indicate that the changes of free energy for the binding of dHSF(33-163) to the wild-type site and a mutant DNA site are predominantly characterized by substantial negative changes of enthalpy. Binding to the wild-type DNA is characterized by a significant positive change of entropy, whereas binding to the mutant DNA is distinguished by a negative change of entropy of comparable magnitude. The binding to the mutant DNA was also highly sensitive to increasing salt concentrations, indicating a dominance of ionic interactions. The sequence-specific, 1:1 binding of dHSF(33-163) to the NGAAN sequence provides a basis for the analysis of higher order interactions between HSF trimers and the HSE. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 40 TC 44 Z9 44 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUL PY 1994 VL 3 IS 7 BP 1040 EP 1051 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU550 UT WOS:A1994NU55000006 PM 7920249 ER PT J AU MUSHEGIAN, AR KOONIN, EV AF MUSHEGIAN, AR KOONIN, EV TI UNEXPECTED SEQUENCE SIMILARITY BETWEEN NUCLEOSIDASES AND PHOSPHORIBOSYLTRANSFERASES OF DIFFERENT SPECIFICITY SO PROTEIN SCIENCE LA English DT Article DE NUCLEOSIDASES; PHOSPHORIBOSYLTRANSFERASES; SEQUENCE SIMILARITY ID ACID SUBSTITUTION MATRICES; ESCHERICHIA-COLI; THYMIDINE PHOSPHORYLASE; 3-DIMENSIONAL STRUCTURE; AMP NUCLEOSIDASE; STORAGE PROTEIN; ATP-BINDING; EXPRESSION; GENE; OPERON AB Amino acid sequences of enzymes that catalyze hydrolysis or phosphorolysis of the N-glycosidic bond in nucleosides and nucleotides (nucleosidases and phosphoribosyltransferases) were explored using computer methods for database similarity search and multiple alignment. Two new families, each including bacterial and eukaryotic enzymes, were identified. Family I consists of Escherichia coli AMP hydrolase (Amn), uridine phosphorylase (Udp), purine phosphorylase (DeoD), uncharacterized proteins from E. coli and Bacteroides uniformis, and, unexpectedly, a group of plant stress-inducible proteins. It is hypothesized that these plant proteins have evolved from nucleosidases and may possess nucleosidase activity. The proteins in this new family contain 3 conserved motifs, one of which was found also in eukaryotic purine nucleosidases, where it corresponds to the nucleoside-binding site. Family II is comprised of bacterial and eukaryotic thymidine phosphorylases and anthranilate phosphoribosyltransferases, the relationship between which has not been suspected previously. Based on the known tertiary structure of E. coli thymidine phosphorylase, structural interpretation was given to the sequence conservation in this family. The highest conservation is observed in the N-terminal alpha-helical domain, whose exact function is not known. Parts of the conserved active site of thymidine phosphorylases and anthranilate phosphoribosyltransferases were delineated. A motif in the putative phosphate-binding site is conserved in family II and in other phosphoribosyltransferases. Our analysis suggests that certain enzymes of very similar specificity, e.g., uridine and thymidine phosphorylases, could have evolved independently. In contrast, enzymes catalyzing such different reactions as AMP hydrolysis and uridine phosphorolysis or thymidine phosphorolysis and phosphoribosyl anthranilate synthesis are likely to have evolved from common ancestors. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. UNIV KENTUCKY,DEPT PLANT PATHOL,LEXINGTON,KY 40546. OI Mushegian, Arcady/0000-0002-6809-9225 NR 45 TC 24 Z9 24 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUL PY 1994 VL 3 IS 7 BP 1081 EP 1088 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU550 UT WOS:A1994NU55000011 PM 7920254 ER PT J AU MOLCHAN, SE ATACK, JR SUNDERLAND, T AF MOLCHAN, SE ATACK, JR SUNDERLAND, T TI DECREASED CSF INOSITOL MONOPHOSPHATASE ACTIVITY AFTER LITHIUM TREATMENT SO PSYCHIATRY RESEARCH LA English DT Note C1 MERCK SHARP & DOHME LTD,NEUROSCI RES CTR,RES LABS,HARLOW CM20 2QR,ESSEX,ENGLAND. RP MOLCHAN, SE (reprint author), NIMH,CLIN SCI LAB,CTR CLIN,GERIATR PSYCHIAT SECT,BLDG 10,RM 3D-41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL PY 1994 VL 53 IS 1 BP 103 EP 105 DI 10.1016/0165-1781(94)90099-X PG 3 WC Psychiatry SC Psychiatry GA PE502 UT WOS:A1994PE50200009 PM 7991727 ER PT J AU ZOCCHI, A PERT, A AF ZOCCHI, A PERT, A TI ALTERATIONS IN STRIATAL ACETYLCHOLINE OVERFLOW BY COCAINE, MORPHINE, AND MK-801 - RELATIONSHIP TO LOCOMOTOR OUTPUT SO PSYCHOPHARMACOLOGY LA English DT Article DE ACETYLCHOLINE; MICRODIALYSIS; STRIATUM; COCAINE; MORPHINE; MK-801; LOCOMOTOR ACTIVITY ID FREELY MOVING RATS; D-ASPARTATE RECEPTOR; EXCITATORY AMINO-ACIDS; ENDOGENOUS ACETYLCHOLINE; NUCLEUS-ACCUMBENS; BRAIN ACETYLCHOLINE; CEREBRAL-CORTEX; EXTRACELLULAR ACETYLCHOLINE; DOPAMINERGIC REGULATION; NEOSTRIATAL SLICES AB The activity of cholinergic interneurons in the striatum appears to be modulated by a variety of different systems including dopamine, opiate, and glutamate. The purpose of this study was to characterize the effects of drugs known to act on these three systems (i.e., cocaine, morphine, and MK-801) on striatal ACh overflow with microdialysis procedures, and to determine if alterations in ACh function induced by these agents are related to changes in locomotor activity. Cocaine was found to increase striatal ACh following intraperitoneal injections of 20 and 40 mg/kg, but not 10 mg/kg. The increases in locomotor activity induced by cocaine appeared to be dose dependent, while the effects on striatal ACh were not. Injections of 0.1 mg/kg MK-801 (a non-competitive NMDA receptor antagonist) produced dramatic increases in locomotor activity while decreasing striatal ACh overflow. A lower dose (0.03 mg/kg) of MK-801 failed to alter locomotor activity or striatal ACh. Morphine produced an apparent dose-dependent elevation in striatal ACh while only the lowest dose (5 mg/kg) increased locomotor activity. There appears to be no relationship between alterations in striatal ACh and locomotor output following systemic administration of these psychoactive agents. RP ZOCCHI, A (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 67 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1994 VL 115 IS 3 BP 297 EP 304 DI 10.1007/BF02245069 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NW248 UT WOS:A1994NW24800002 PM 7871068 ER PT J AU BROADBEAR, JH NEGUS, SS BUTELMAN, ER DECOSTA, BR WOODS, JH AF BROADBEAR, JH NEGUS, SS BUTELMAN, ER DECOSTA, BR WOODS, JH TI DIFFERENTIAL-EFFECTS OF SYSTEMICALLY ADMINISTERED NOR-BINALTORPHIMINE (NOR-BNI) ON KAPPA-OPIOID AGONISTS IN THE MOUSE WRITHING ASSAY SO PSYCHOPHARMACOLOGY LA English DT Article DE NOR-BINALTORPHIMINE; CI-977; U69,593; U50,488; BREMAZOCINE; ETHYLKETOCYCLAZOCINE; MR2034; MORPHINE; BW-373U86; BETA-FUNALTREXAMINE; KAPPA ANTAGONISTS; ACETIC ACID-INDUCED WRITHING; MICE ID GUINEA-PIG BRAIN; BETA-FUNALTREXAMINE; RECEPTOR SUBTYPES; OPIATE RECEPTORS; DELTA-RECEPTOR; BINDING-SITES; MORPHINE-LIKE; RAT-BRAIN; ANTAGONIST; ANTINOCICEPTION AB The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in mice. All eight agonists completely and dose-dependently inhibited writhing. Antagonism of CI-977 was apparent 1 h after administration of 32 mg/kg nor-BNI, peaking after 4 h and was maintained for at least 4 weeks; no antagonist effects of nor-BNI were apparent after 8 weeks. Nor-BNI (32 mg/kg) caused little or no antagonism of morphine or BW-373U86 at 1 h and none at 24 h after nor-BNI administration. Subsequently, dose-effect curves for CI-977, U50,488, U69,593, EKC, Mr2034 and bremazocine were determined 24 h after pretreatment with 3.2, 10 and 32 mg/kg nor-BNI. Pretreatment with 3.2 mg/kg nor-BNI produced significant antagonism of all six kappa agonists, suggesting that their antinociceptive effects were mediated at least in part by nor-BNI-sensitive kappa receptors. At higher doses, nor-BNI dose-dependently shifted the agonist dose-effect curves of CI-977, U50,488, U69,593 and bremazocine, but not those of EKC and Mr2034, suggesting that the latter compounds may be producing effects via nor-BNI-insensitive receptors. Mu receptor involvement was demonstrated following a 24 h pretreatment with 32 mg/kg beta-FNA in combination with nor-BNI, which significantly increased the degree of antagonism of Mr2034 and EKC from that seen with nor-BNI alone. Hence, SC administered nor-BNI selectively antagonized agonist activity mediated through kappa-opioid receptors without differentiating between kappa subtypes. Nor-BNI also enabled the mu agonist activity of proposed kappa agonists to be measured. C1 UNIV MICHIGAN,DEPT PSYCHOL,ANN ARBOR,MI 48109. NIDDK,BETHESDA,MD 20892. RP BROADBEAR, JH (reprint author), UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109, USA. RI Broadbear, Jillian/A-6864-2011 FU NIDA NIH HHS [DA 00254] NR 49 TC 101 Z9 103 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1994 VL 115 IS 3 BP 311 EP 319 DI 10.1007/BF02245071 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NW248 UT WOS:A1994NW24800004 PM 7871070 ER PT J AU DUNCAN, CC RUMSEY, JM WILKNISS, SM DENCKLA, MB HAMBURGER, SD ODOUPOTKIN, M AF DUNCAN, CC RUMSEY, JM WILKNISS, SM DENCKLA, MB HAMBURGER, SD ODOUPOTKIN, M TI DEVELOPMENTAL DYSLEXIA AND ATTENTION DYSFUNCTION IN ADULTS - BRAIN POTENTIAL INDEXES OF INFORMATION-PROCESSING SO PSYCHOPHYSIOLOGY LA English DT Article DE EVENT-RELATED POTENTIALS; P300; DYSLEXIA; ATTENTION-DEFICIT HYPERACTIVITY DISORDER; INFORMATION PROCESSING ID EVENT-RELATED POTENTIALS; READING-DISABILITY; LEARNING-DISABILITIES; EVOKED-RESPONSES; CHILDREN; P300; RETARDATION; PROBABILITY; GENERATORS; PREVALENCE AB Event-related brain potentials (ERPs) were recorded from a group of 13 men with severe developmental dyslexia and 15 matched normal controls. Auditory and visual stimuli, presented in separate reaction time tasks of graded difficulty, were used to elicit ERPs. No group differences in P300 were seen under relatively undemanding task conditions. However, as task demands increased, visual P300 was reduced in the dyslexic men as compared with the normal readers. An Abbreviated Conners Parent Rating Scale was used to assess retrospectively childhood symptoms of attention-deficit hyperactivity disorder (ADHD). Additional analyses revealed that the dyslexics with a history of many symptoms of ADHD in childhood (high ADHD) accounted for the group differences in P300; the dyslexics with a history of few or no such symptoms (low ADHD) were indistinguishable from the controls at all electrode sites. Furthermore, whereas the low-ADHD dyslexics showed the same hemispheric asymmetry in auditory P300 as did the controls (right > left), auditory P300 was more symmetrically distributed in the high-ADHD dyslexics. The results are interpreted as suggesting that a distinct brain organization may characterize dyslexic men with a history of concomitant deficits in attention. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. KENNEDY INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. RP DUNCAN, CC (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 68 TC 47 Z9 47 U1 4 U2 7 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JUL PY 1994 VL 31 IS 4 BP 386 EP 401 DI 10.1111/j.1469-8986.1994.tb02447.x PG 16 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA NR028 UT WOS:A1994NR02800008 PM 10690919 ER PT J AU KLEINERMAN, RA LITTLEFIELD, LG TARONE, RE SAYER, AM COOKFAIR, DL WACTAWSKIWENDE, J INSKIP, PD BLOCK, AMW RAMESH, KH BOICE, JD AF KLEINERMAN, RA LITTLEFIELD, LG TARONE, RE SAYER, AM COOKFAIR, DL WACTAWSKIWENDE, J INSKIP, PD BLOCK, AMW RAMESH, KH BOICE, JD TI CHROMOSOME-ABERRATIONS IN LYMPHOCYTES FROM WOMEN IRRADIATED FOR BENIGN AND MALIGNANT GYNECOLOGICAL DISEASE SO RADIATION RESEARCH LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; ACTIVE BONE-MARROW; CONTROL POPULATION; X-IRRADIATION; RADIATION; CANCER; RADIOTHERAPY; FREQUENCY; LEUKEMIA; CERVIX AB Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received. C1 OAK RIDGE INST SCI & EDUC, DIV MED SCI, OAK RIDGE, TN 37831 USA. NCI, BIOSTAT BRANCH, BETHESDA, MD 20892 USA. UNIV BUFFALO SUNY, DEPT NEUROL, BUFFALO, NY 14222 USA. UNIV BUFFALO SUNY, DEPT SOCIAL & PREVENT MED, BUFFALO, NY 14214 USA. SUNY BUFFALO, SCH MED & BIOMED SCI, DEPT GYNECOL & OBSTET, NEW YORK, NY 14219 USA. SUNY BUFFALO, SCH MED & BIOMED SCI, DEPT SOCIAL & PREVENT MED, NEW YORK, NY 14219 USA. ROSWELL PK CANC INST, CLIN CYTOGENET LAB, BUFFALO, NY 14263 USA. RP NCI, RADIAT EPIDEMIOL BRANCH, EPN 408, BETHESDA, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP9-5614, Y01-CP-80505, N01-CP8-5604] NR 30 TC 23 Z9 24 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1994 VL 139 IS 1 BP 40 EP 46 DI 10.2307/3578730 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA NU848 UT WOS:A1994NU84800006 PM 8016306 ER PT J AU MEUNIER, M BACHEVALIER, J MISHKIN, M AF MEUNIER, M BACHEVALIER, J MISHKIN, M TI THE ANATOMY OF MEMORY SO RECHERCHE LA French DT Article ID AMYGDALA; MONKEYS; LESIONS; CORTEX C1 UNIV BORDEAUX 1, NEUROSCI COMPORTEMENTALES & COGNIT LAB, CNRS, F-33405 TALENCE, FRANCE. UNIV TEXAS, DEPT NEUROBIOL & ANAT, HOUSTON, TX 77025 USA. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RI MEUNIER, Martine/C-2611-2015 OI MEUNIER, Martine/0000-0002-9380-9372 NR 17 TC 0 Z9 0 U1 0 U2 1 PU SOC ED SCIENTIFIQUES PI PARIS 06 PA 57 RUE DE SEINE, 75280 PARIS 06, FRANCE SN 0029-5671 J9 RECHERCHE JI Recherche PD JUL-AUG PY 1994 VL 25 IS 267 BP 760 EP 766 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NW412 UT WOS:A1994NW41200008 ER PT J AU LENFANT, C AF LENFANT, C TI INTERNATIONAL CONSENSUS REPORT ON DIAGNOSIS AND TREATMENT OF ASTHMA SO REVUE FRANCAISE D ALLERGOLOGIE ET D IMMUNOLOGIE CLINIQUE LA French DT Article RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0335-7457 J9 REV FR ALLERGOL JI Rev. Fr. Allergol. Immunol. Clin. PD JUL PY 1994 VL 34 IS 3 BP 243 EP 314 PG 72 WC Allergy SC Allergy GA PF575 UT WOS:A1994PF57500001 ER PT J AU KNEPPER, MA NIELSEN, S CHOU, CL DIGIOVANNI, SR AF KNEPPER, MA NIELSEN, S CHOU, CL DIGIOVANNI, SR TI MECHANISM OF VASOPRESSIN ACTION IN THE RENAL COLLECTING DUCT SO SEMINARS IN NEPHROLOGY LA English DT Review ID NEPHROGENIC DIABETES-INSIPIDUS; INTRAMEMBRANOUS PARTICLE CLUSTERS; CYCLIC ADENOSINE-MONOPHOSPHATE; REGULATED UREA TRANSPORTER; DOSE-RESPONSE RELATIONSHIP; INDUCED WATER-FLOW; ANTIDIURETIC-HORMONE; RAT-KIDNEY; TUBULE CELLS; ARGININE VASOPRESSIN C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 150 TC 73 Z9 76 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JUL PY 1994 VL 14 IS 4 BP 302 EP 321 PG 20 WC Urology & Nephrology SC Urology & Nephrology GA NV766 UT WOS:A1994NV76600002 PM 7938946 ER PT J AU CROUSE, JR GOLDBOURT, U EVANS, G PINSKY, J SHARRETT, AR SORLIE, P RILEY, W HEISS, G AF CROUSE, JR GOLDBOURT, U EVANS, G PINSKY, J SHARRETT, AR SORLIE, P RILEY, W HEISS, G TI ARTERIAL ENLARGEMENT IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) COHORT - IN-VIVO QUANTIFICATION OF CAROTID ARTERIAL ENLARGEMENT SO STROKE LA English DT Article DE AGING; ULTRASONICS; ARTERIAL OCCLUSIVE DISEASES; CAROTID ARTERIES; GENDER ID B-MODE ULTRASOUND; MYOCARDIAL-INFARCTION; DISEASE; CHOLESTEROL; DETERMINANTS; ASSOCIATIONS; PERSPECTIVES; POPULATIONS; PROGRESSION; PREVALENCE AB Background and Purpose The relation between arterial wall (intimal-medial) thickness and lumen narrowing is complex and has previously been studied predominantly at autopsy. B-mode ultrasound affords the opportunity to visualize both wall and lumen of the extracranial carotid arteries in vivo. Several studies have quantified the relation of various independent variables to wall thickness of carotid arteries in population-based samples, but the relation of age and wall thickness to interadventitial and lumen diameter has not previously been investigated in these samples. Methods We used B-mode ultrasound to quantify the relation of arterial lumen diameter to age, arterial wall thickness, and arterial size (interadventitial diameter) of the extracranial carotid artery in 13 711 members of the Atherosclerosis Risk in Communities (ARIC) cohort. Results Men had greater interadventitial diameters, thicker walls, and wider lumens than women. Wall thicknesses of the common carotid artery were greater by 21% in men and 22% in women aged 60 to 64 years compared with those aged 45 to 49 years (P<.001). However, lumen diameters were also greater in older individuals because interadventitial diameters were greater. Wall thickness of the internal carotid artery was also associated positively with age, but the lumen diameter of the internal carotid artery was smaller in older individuals. Diameters of the carotid artery segments also differed in their relation to arterial wall thickening. The lumen of the internal carotid artery was uniformly progressively narrower with increasing wall thickness. For the common carotid artery greater wall thickness bare only a small correlation with narrower lumen diameter for thickening of the arterial wall up to 1.2 mm, but the association was more marked for the range of thicknesses between 1.2 mm and 2.5 mm. Conclusions When arterial enlargement accompanies increased wall thickness, less lumen constriction results than expected. Quantification of these complex relations in vivo may provide new insight into the pathogenesis of symptoms related to vascular disease. Narrowing of the internal carotid artery lumen associated with thicker walls is consistent with the observation that stenosis develops in this region and often leads to symptoms. C1 NEUFELD CARDIAC RES INST,TEL HASHOMER,ISRAEL. NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC. RP CROUSE, JR (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [NHLBI NO1-HC-55016, NHLBI NO1-HC-55015, NHLBI NO1-HC-55018] NR 35 TC 99 Z9 99 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1994 VL 25 IS 7 BP 1354 EP 1359 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA NW212 UT WOS:A1994NW21200004 PM 8023349 ER PT J AU NEVILLE, RF BARTORELLI, AL SIDAWY, AN LEON, MB AF NEVILLE, RF BARTORELLI, AL SIDAWY, AN LEON, MB TI VASCULAR STENT DEPLOYMENT IN VEIN BYPASS GRAFTS - OBSERVATIONS IN AN ANIMAL-MODEL SO SURGERY LA English DT Article ID ANGIOPLASTY; REVISION; PATENCY; EXPERIENCE; STENOSIS; DILATION; FAILURE AB Background. An important cause of vein graft failure is anastomotic stenosis caused by myointimal hyperplasia. Intravascular stents may allow balloon dilation of these hyperplastic lesions, thereby increasing secondary graft patency. Methods. To evaluate intravascular stent deployment in vein grafts, we implanted 26 stents across the anastomotic sited of reversed vein grafts in 13 sheep. Stent deployment was evaulated immediately and at 3, 8, and 24 weeks by arteriography, light microscopy, and scanning electron microscopy. In a second animal cohort, stent-arterial wall contact after deployment was evaluated with intravascular ultrasonography (IVUS). Stents were imaged with IVUS after partial (n = 5) and complete (n = 5) expansion in 10 sheep carotid arteries. Results. Stents were deployed across vascular anastomoses without immediate thrombosis. Partial neointimal coverage occurred after 3 and 8 weeks, with complete coverage by 24 weeks. Complications included distal migration (n = 3), arteriographic stenosis (n = 2), and late graft occlusion (n = 2). Incomplete stent-vessel wall contact at deployment was observed in the stents with complications. IVUS accurately showed stent expansion and the degree of stent-vessel wall contact. Conclusions. Stents can be deployed in vein grafts with the expectation of neointimal coverage and maintenance of graft patency. IVUS may prove important in guiding optimal stent deployment by providing an assessment of stent-vessel wall contact. C1 NHLBI, BETHESDA, MD USA. RP NEVILLE, RF (reprint author), GEORGETOWN UNIV, MED CTR,DEPT SURG,PHC,4TH FLOOR, 3800 RESERVOIR RD, WASHINGTON, DC 20007 USA. NR 19 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 1994 VL 116 IS 1 BP 55 EP 61 PG 7 WC Surgery SC Surgery GA NV645 UT WOS:A1994NV64500009 PM 8023269 ER PT J AU COLE, DJ ETTINGHAUSEN, SE PASS, HI DANFORTH, DN LINEHAN, MW MYERS, CW COOPER, MR SINDELAR, WF AF COLE, DJ ETTINGHAUSEN, SE PASS, HI DANFORTH, DN LINEHAN, MW MYERS, CW COOPER, MR SINDELAR, WF TI POSTOPERATIVE COMPLICATIONS IN PATIENTS RECEIVING SURAMIN THERAPY SO SURGERY LA English DT Article ID RENAL-CELL CARCINOMA; INHIBITION; PHARMACOKINETICS AB Background. Suramin is an antiparasitic agent that is currently being evaluated for antineoplastic activity. Documented toxicities of suramin include adrenal and renal insufficiency, coagulation factor abnormalities, immunosuppression, and polyneuropathy. These adverse effects have potential for contributing to postoperative morbidity in surgical patients. Because no experience with suramin has been reported in the surgical literature, this 5-year retrospective review of postoperative complications in patients receiving suramin was performed. Methods. From a review of 171 charts, 14 patients were identified who had undergone a major surgical procedure either while receiving intravenous suramin or within 1 year after its administration. Primary diagnoses included prostate cancer (six), lymphoma (four), ovarian cancer (two), colon cancer (one), and glioblastoma (one). All patients received replacement dose hydrocortisone at the initiation of suramin therapy and thereafter. Results. Eighteen major surgical procedures were performed with 18 complications occurring in five patients. The predominant complications encountered were hemorrhage (five), impaired would healing (three), and bowel dysmotility (two). A highly significant relationship existed between the incidence of complications and interval from completion of suramin therapy to the time of operation (p < 0.0005), with 17 of the 18 morbidities occurring within the first month. The length of operation (p < 0.05) and amount of blood transfused during the procedure were related to postoperative morbidity (p < 0.5). No other factors evaluated were correlated to complications. Conclusions. This experience suggests the avoidance of elective procedures during the first month after suramin therapy and a heightened awareness of the potential for bleeding and would healing problems in patients receiving suramin who do require an emergent procedure. C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP COLE, DJ (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 24 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD JUL PY 1994 VL 116 IS 1 BP 90 EP 95 PG 6 WC Surgery SC Surgery GA NV645 UT WOS:A1994NV64500014 PM 8023275 ER PT J AU DEBARGE, LR CHAN, CC GREENBERG, SC MCLEAN, IW YANNUZZI, LA NUSSENBLATT, RB AF DEBARGE, LR CHAN, CC GREENBERG, SC MCLEAN, IW YANNUZZI, LA NUSSENBLATT, RB TI CHORIORETINAL, IRIS, AND CILIARY BODY INFILTRATION BY JUVENILE XANTHOGRANULOMA MASQUERADING AS UVEITIS SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE APOLIPOPROTEIN; DERMATOLOGICAL DISORDER; HISTIOCYTE; INFLAMMATORY DISORDER; JUVENILE XANTHOGRANULOMA; UVEITIS ID HISTIOCYTOSIS-X; PROTEIN AB Juvenile xanthogranuloma is a benign cutaneous disorder which occasionally involves the eye, orbit, and ocular adnexa in children. Iris and ciliary, body manifestations are commonly seen, but retinal and choroidal lesions are exceedingly rare. We report a unique case of retinal, choroidal, iris, and ciliary body infiltration in a 12-year-old patient diagnosed by excisional biopsy of the iris. The diagnosis was confirmed by routine histology and oil-red-o staining. Immunohistochemistry revealed predominantly macrophages, monocytes, and T-helper lymphocytes. Unusual features of this case include the late age at diagnosis, posterior pole involvement, and lack of cutaneous lesions. The presence of cellular adhesion molecules and T lymphocytes implicate a lymphocyte-driven inflammatory process. Apolipoprotein A was the predominant apolipoprotein present within the foamy histiocytes. We also present a critical review of the literature. C1 ARMED FORCES INST PATHOL,DEPT OPHTHALMOL,WASHINGTON,DC 20306. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. RP DEBARGE, LR (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N202,BETHESDA,MD 20892, USA. NR 26 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JUL-AUG PY 1994 VL 39 IS 1 BP 65 EP 71 DI 10.1016/S0039-6257(05)80046-3 PG 7 WC Ophthalmology SC Ophthalmology GA PA825 UT WOS:A1994PA82500007 PM 7974193 ER PT J AU MCCANN, DJ WEISSMAN, AD SU, TP AF MCCANN, DJ WEISSMAN, AD SU, TP TI SIGMA-1 AND SIGMA-2 SITES IN RAT-BRAIN - COMPARISON OF REGIONAL, ONTOGENIC, AND SUBCELLULAR PATTERNS SO SYNAPSE LA English DT Article DE SIGMA RECEPTORS; SIGMA SITES; HALOPERIDOL; PENTAZOCINE; (+)-3-PPP; DTG; SKF-10,047; N-ALLYLNORMETAZOCINE; BUTACLAMOL; DIZOCILPINE; MK-801; PROGESTERONE; TESTOSTERONE ID GUINEA-PIG BRAIN; INDUCED NEURONAL ACTIVATION; BINDING-SITES; RECEPTORS; AFFINITY; LIGANDS; SUGGEST; SYSTEMS; STATES; GERBIL AB Radioligand binding assay conditions were established for the selective labeling of sigma-1 and sigma-2 sites in membrane homogenates of rat brain. Selective sigma-1 assays were conducted using 5 nM (+)[H-3]SKF-10,047 in the presence of 300 nM dizocilpine (MK-801). Selective sigma-2 assays were conducted using 5 nM [H-3]DTG in the presence of 1 mu M (+)SKF-10,047. Distributions of sigma-1 and sigma-2 binding among brain regions were found to differ. While the brain stem yields the highest level of sigma-1 binding, it yields among the lowest levels of sigma-2 binding. The reverse is true in hippocampal membranes. Different ontogenetic patterns were also observed. Sigma-2 binding decreases substantially during brain development, whereas sigma-1 binding does not vary significantly. Patterns of distribution among subcellular fractions of rat brain homogenates were found to be similar. Both sigma-1 and sigma-2 sites are most enriched in microsomal fractions, and neither is enriched in synaptosomal or mitochondrial fractions. The present results suggest that sigma-1 and sigma-2 sites are distinct entities; they do not appear to be located on a common macromolecule, and they do not represent two different affinity states of a single type of binding site. While the precise subcellular locations of sigma-1 and sigma-2 sites remain to be determined, we conclude that localization of either type of binding site to synaptic regions of plasma membrane or to mitochondria is highly unlikely. (C) 1994 Wiley-Liss, Inc. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,NEUROCHEM UNIT,MOLEC PHARMACOL SECT,BALTIMORE,MD 21224. NR 42 TC 86 Z9 88 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 1994 VL 17 IS 3 BP 182 EP 189 DI 10.1002/syn.890170307 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NU319 UT WOS:A1994NU31900006 PM 7974201 ER PT J AU FUJITA, S PURI, R YU, ZX TRAVIS, W YAMAGUCHI, M FERRANS, VJ AF FUJITA, S PURI, R YU, ZX TRAVIS, W YAMAGUCHI, M FERRANS, VJ TI INTERLEUKIN-1-ALPHA REDUCES THE SEVERITY OF THE VASCULAR LEAK SYNDROME PRODUCED BY INTERLEUKIN-2 AND INTERLEUKIN-2 PLUS INTERFERON-ALPHA SO TOXICOLOGIC PATHOLOGY LA English DT Article DE MYOCARDIUM; LIVER; LUNG; ENDOTHELIUM; TOXICITY; ULTRASTRUCTURE; LYMPHOCYTE; MACROPHAGE AB Histological and ultrastructural changes were investigated in lung, liver, and heart of mice given interleukin-2 (IL-2), either alone or in combination with other cytokines. IL-2 induced a vascular leak syndrome (VLS) of a moderate degree with infiltration of lymphoid cells, moderate endothelial damage, mild hepatic parenchymal damage, and minimal myocardial alterations. Interferon-alpha (IFN-alpha) produced infiltration mainly of monocytes/macrophages in liver and heart; endothelial cell damage was absent in lung and heart and minimal in liver. Interleukin-1 alpha (IL-1 alpha) caused an increased number of neutrophils in liver and lung; VLS and parenchymal cell and endothelial damage were not found. The VLS and the cellular damage caused by the combination of IL-2 and IFN were much more severe than those produced by IL-2 alone. In animals treated with IL-2, IFN-alpha, and IL-1 alpha, VLS was minimal and parenchymal and endothelial cell damage were less severe than after IL-2 alone or IL-2 plus IFN-alpha. Taken together, these observations show that IL-1 alpha reduces ultrastructural changes produced by IL-2 and IFN-alpha. This reduction may be clinically useful in the treatment of neoplasms. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1994 VL 22 IS 4 BP 381 EP 397 PG 17 WC Pathology; Toxicology SC Pathology; Toxicology GA PK265 UT WOS:A1994PK26500004 PM 7817127 ER PT J AU DIWAN, BA WARD, JM KURATA, Y RICE, JM AF DIWAN, BA WARD, JM KURATA, Y RICE, JM TI DISSIMILAR FREQUENCY OF HEPATOBLASTOMAS AND HEPATIC CYSTADENOMAS AND ADENOCARCINOMAS ARISING IN HEPATOCELLULAR NEOPLASMS OF D2B6F1 MICE INITIATED WITH N-NITROSODIETHYLAMINE AND SUBSEQUENTLY GIVEN AROCLOR-1254, DICHLORODIPHENYLTRICHLOROETHANE, OR PHENOBARBITAL SO TOXICOLOGIC PATHOLOGY LA English DT Article DE DIFFERENTIATION; DEDIFFERENTIATION; HYPERPLASIA; INTESTINAL METAPLASIA; PROMOTION; PROGRESSION AB Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to phenobarbital (PB) for their ability to promote hepatocellular proliferative lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular neoplasms developed in all mice given NDEA and were more numerous in mice fed promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB was the most effective of the 3 agents in stimulating the evolution of hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast, lesions resembling benign and malignant cholangiocellular neoplasms were frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal metaplasia/cholangiocellular tumor morphology appear to constitute different patterns of genetic programming induced by certain promoters in expanding clones of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1 male mice. RP DIWAN, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 538,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 0 TC 10 Z9 10 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1994 VL 22 IS 4 BP 430 EP 439 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA PK265 UT WOS:A1994PK26500009 PM 7817132 ER PT J AU CHAN, P CARDY, R HASEMAN, J MOE, J HUFF, J AF CHAN, P CARDY, R HASEMAN, J MOE, J HUFF, J TI LEUKEMIA INDUCED IN RATS BUT NOT MICE BY DIMETHYL MORPHOLINOPHOSPHORAMIDATE, A SIMULANT ANTICHOLINESTERASE AGENT SO TOXICOLOGY LA English DT Article DE DIMETHYL MORPHOLINOPHOSPHORAMIDATE; LEUKEMIA IN RATS; CARCINOGENESIS BIOASSAY; ORGANOPHOSPHATE ID NATIONAL TOXICOLOGY PROGRAM; MONONUCLEAR CELL LEUKEMIA; FISCHER RATS; F344 RATS; CHEMICALS; CARCINOGENICITY; PATHOLOGY; TESTS AB Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (females only) mg/kg body weight under the same schedule. DMMPA induced a dose-related enhancement in the incidence of mononuclear cell leukemia in rats - males: controls = 14/50, 150 mg group 21/50; 300 mg group = 19/50; 600 mg group = 25/50; females: controls = 9/50, 150 mg group = 13/50; 300 mg group = 12/49; 600 mg group = 18/50. Survival-adjusted rates strengthen the DMMPA effect: males - 31%, 50%, 47%, and 63%; females - 20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. C1 LITTON BIONET INC,ROCKVILLE,MD 20850. RP CHAN, P (reprint author), NIEHS,DIV INTRAMURAL RES,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 1 PY 1994 VL 91 IS 2 BP 127 EP 137 DI 10.1016/0300-483X(94)90139-2 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PD513 UT WOS:A1994PD51300002 PM 8059437 ER PT J AU WEISS, SRB POST, RM AF WEISS, SRB POST, RM TI CAVEATS IN THE USE OF THE KINDLING MODEL OF AFFECTIVE-DISORDERS SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT Conference on Low-Level Exposure to Chemicals and Neurobiologic Sensitivity CY APR 06-07, 1994 CL BALTIMORE, MD SP US DEP HLTH & HUMAN SERV, PUBLIC HLTH SERV, AGCY TOX SUBST & DIS REGISTRY ID AMPHETAMINE-ELICITED PERSEVERATION; FOS MESSENGER-RNA; ELECTRICAL-STIMULATION; SPONTANEOUS SEIZURES; CONVULSIVE SEIZURES; LOCOMOTOR RESPONSE; FOOTSHOCK STRESS; BETA-ENDORPHIN; COCAINE; BRAIN RP WEISS, SRB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 82 TC 28 Z9 28 U1 0 U2 1 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 421 EP 447 PG 27 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300014 PM 7778106 ER PT J AU NEWLIN, DB AF NEWLIN, DB TI DRUG SENSITIZATION, SUBSTANCE-ABUSE, AND CHEMICAL-SENSITIVITY SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT Conference on Low-Level Exposure to Chemicals and Neurobiologic Sensitivity CY APR 06-07, 1994 CL BALTIMORE, MD SP US DEP HLTH & HUMAN SERV, PUBLIC HLTH SERV, AGCY TOX SUBST & DIS REGISTRY DE ALCOHOL; COCAINE; COMMON FACTORS; MESOLIMBIC DOPAMINE; MULTIPLE CHEMICAL SENSITIVITY; NICOTINE; SENSITIZATION; SUBSTANCE ABUSE; TOBACCO SMOKE ID MORPHINE-TOLERANCE; COCAINE; ALCOHOL; CHALLENGE; RATS; SONS AB Substance abuse, involving drugs such as cocaine, heroin, alcohol, marijuana, nicotine, barbiturates, etc., is by far by the most prevalent psychiatric disorder. March has been learned about the abuse of these substances that may be useful to consider in designing and analyzing research concerning multiple chemical sensitivities (MCS). We review the central role of sensitization in this literature, including its definition, measurement, and expression in animals and human volunteers. Common factors among abused drugs, including sensitization, are discussed. Finally, empirical studies are delineated or proposed to test some of the notions presented in this paper. RP NEWLIN, DB (reprint author), NIDA,ADDICT RES CTR,POB 5180,4949 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 43 TC 13 Z9 13 U1 2 U2 2 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 463 EP 480 PG 18 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300016 PM 7778108 ER PT J AU KIPEN, H BELL, I MILLER, C LETZ, R ROSENTHAL, N AF KIPEN, H BELL, I MILLER, C LETZ, R ROSENTHAL, N TI PROCEEDINGS OF THE CONFERENCE ON LOW-LEVEL EXPOSURE TO CHEMICALS AND NEUROBIOLOGICAL SENSITIVITY, 6-7-APRIL-1994, BALTIMORE, MARYLAND - RESPONSE PANEL-2 SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Discussion C1 TUCSON VET AFFAIRS MED CTR,TUCSON,AZ 85723. UNIV ARIZONA,HLTH SCI CTR,DEPT PSYCHIAT,TUCSON,AZ. UNIV TEXAS,HLTH SCI CTR,DEPT FAMILY PRACTICE,SAN ANTONIO,TX 78284. EMORY UNIV,ATLANTA,GA 30322. NIMH,PSYCHOBIOL BRANCH,OUTPATIENT PSYCHIAT SECT,BETHESDA,MD 20892. RP KIPEN, H (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED CTR,PISCATAWAY,NJ 08854, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 481 EP 486 PG 6 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300017 ER PT J AU KIPEN, H BELL, I MILLER, C LETZ, R ROSENTHAL, N AF KIPEN, H BELL, I MILLER, C LETZ, R ROSENTHAL, N TI PROCEEDINGS OF THE CONFERENCE ON LOW-LEVEL EXPOSURE TO CHEMICALS AND NEUROBIOLOGICAL SENSITIVITY 6-7 APRIL, 1994 BALTIMORE, MARYLAND - RESPONSE PANEL-3 SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Discussion C1 TUCSON VET AFFAIRS MED CTR,TUCSON,AZ 85723. UNIV TEXAS,HLTH SCI CTR,DEPT FAMILY PRACTICE,SAN ANTONIO,TX. EMORY UNIV,ATLANTA,GA 30322. NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT PSYCHIAT SECT,BETHESDA,MD 20892. RP KIPEN, H (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED CTR,PISCATAWAY,NJ 08854, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 555 EP 560 PG 6 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300024 ER PT J AU MAYBERG, H KIPEN, H BELL, I MILLER, C LETZ, R ROSENTHAL, N AF MAYBERG, H KIPEN, H BELL, I MILLER, C LETZ, R ROSENTHAL, N TI PROCEEDINGS OF THE CONFERENCE ON LOW-LEVEL EXPOSURE TO CHEMICALS AND NEUROBIOLOGICAL SENSITIVITY 6-7 APRIL, 1994 BALTIMORE, MARYLAND - RESPONSE PANEL-4 SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Discussion C1 TUCSON VET AFFAIRS MED CTR,TUCSON,AZ. UNIV ARIZONA,HLTH SCI CTR,DEPT PSYCHIAT,TUCSON,AZ. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED CTR,PISCATAWAY,NJ 08854. EMORY UNIV,ATLANTA,GA 30322. NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT PSYCHIAT SECT,BETHESDA,MD 20892. WESTERN MICHIGAN UNIV,KALAMAZOO,MI 49008. UNIV MARYLAND,ENVIRONM RES FACIL,BALTIMORE,MD 21201. RP MAYBERG, H (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT FAMILY PRACTICE,7703 FLOYD DR,SAN ANTONIO,TX 78284, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 597 EP 603 PG 7 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300029 ER PT J AU LAMIELLE, M ROSENTHAL MILLER BELL BERKSON, J HERSEY, B CLARK, S MCFADDEN, SA TARATOOT, R AF LAMIELLE, M ROSENTHAL MILLER BELL BERKSON, J HERSEY, B CLARK, S MCFADDEN, SA TARATOOT, R TI PROCEEDINGS OF THE CONFERENCE ON LOW-LEVEL EXPOSURE TO CHEMICALS AND NEUROBIOLOGICAL SENSITIVITY 6-7 APRIL, 1994 BALTIMORE, MARYLAND - PATIENT COMMENTS PANEL SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Discussion C1 UNIV TEXAS,HLTH SCI CTR,DEPT FAMILY PRACTICE,SAN ANTONIO,TX 78284. NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT PSYCHIAT SECT,BETHESDA,MD 20892. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PSYCHIAT,TUCSON,AZ 85723. TUCSON VET AFFAIRS MED CTR,TUCSON,AZ 85723. RP LAMIELLE, M (reprint author), NATL CTR ENVIRONM HLTH STRATEGIES,VOORHEES,NJ, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 619 EP 621 PG 3 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300031 ER PT J AU ROSENTHAL, NE AF ROSENTHAL, NE TI MULTIPLE CHEMICAL-SENSITIVITY - LESSONS FROM SEASONAL AFFECTIVE-DISORDER SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT Conference on Low-Level Exposure to Chemicals and Neurobiologic Sensitivity CY APR 06-07, 1994 CL BALTIMORE, MD SP US DEP HLTH & HUMAN SERV, PUBLIC HLTH SERV, AGCY TOX SUBST & DIS REGISTRY ID ENVIRONMENTAL ILLNESS; LIGHT THERAPY RP ROSENTHAL, NE (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT PSYCHIAT SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 623 EP 632 PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300032 PM 7778119 ER PT J AU KIPEN, H BELL, I LETZ, R ROSENTHAL, NE MILLER, C LAMIELLE, M WEISS, B AF KIPEN, H BELL, I LETZ, R ROSENTHAL, NE MILLER, C LAMIELLE, M WEISS, B TI PROCEEDINGS OF THE CONFERENCE ON LOW-LEVEL EXPOSURE TO CHEMICALS AND NEUROBIOLOGICAL SENSITIVITY 6-7 APRIL, 1994 BALTIMORE, MARYLAND - NEUROSCIENCE RESEARCH AGENDA OPTIONS PANEL SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT Conference on Low-Level Exposure to Chemicals and Neurobiologic Sensitivity CY APR 06-07, 1994 CL BALTIMORE, MD SP US DEP HLTH & HUMAN SERV, PUBLIC HLTH SERV, AGCY TOX SUBST & DIS REGISTRY C1 NATL CTR ENVIRONM HLTH STRATEGIES,VOORHEES,NJ. NIMH,CLIN PSYCHOBIOL BRANCH,ENVIRONM PSYCHIAT SECT,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED & DENT,DEPT ENVIRONM MED,ROCHESTER,NY. UNIV ARIZONA,HLTH SCI CTR,DEPT PSYCHIAT,TUCSON,AZ. EMORY UNIV,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,ATLANTA,GA. UNIV TEXAS,HLTH SCI CTR,DEPT FAMILY PRACTICE,SAN ANTONIO,TX 78285. RP KIPEN, H (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,INST ENVIRONM & OCCUPAT HLTH SCI,PISCATAWAY,NJ 08854, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-OCT PY 1994 VL 10 IS 4-5 BP 645 EP 652 PG 8 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA QM283 UT WOS:A1994QM28300034 ER PT J AU BARTON, EN MORGAN, OS SMIKLE, MF BLATTNER, WA AF BARTON, EN MORGAN, OS SMIKLE, MF BLATTNER, WA TI SEROPREVALENCE OF HTLV-1 IN CHRONIC DISEASE PATIENTS IN JAMAICA SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; ANTIBODIES; INFECTION AB A high seropositivity rate of human T cell lymphotropic virus type 1 (HTLV-1) infection was found in Jamaican patients with chronic diseases. However, except for tropical spastic paraparesis, polymyositis, adult T cell leukaemia/lymphoma and polyneuropathies of undetermined cause, HTLV-1 seropositivity rates in chronic disease patients were not significantly different from that found in healthy Jamaicans. These results indicate that there is no increased risk of HTLV-1 infection or HTLV-1 associated disease in patients with chronic diseases compared to the general Jamaican population. The association of unclassified polyneuropathies with HTLV-1 reported herein is a novel one which requires further studies to elucidate its nature. C1 UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. UNIV W INDIES,DEPT MICROBIOL,KINGSTON 7,JAMAICA. NIH,BETHESDA,MD 20892. NR 14 TC 4 Z9 4 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD JUL-AUG PY 1994 VL 88 IS 4 BP 410 EP 411 DI 10.1016/0035-9203(94)90403-0 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA PE901 UT WOS:A1994PE90100013 PM 7570819 ER PT J AU VIANA, IRC SHER, A CARVALHO, OS MASSARA, CL ELOISANTOS, SM PEARCE, EJ COLLEY, DG GAZZINELLI, G CORREAOLIVEIRA, R AF VIANA, IRC SHER, A CARVALHO, OS MASSARA, CL ELOISANTOS, SM PEARCE, EJ COLLEY, DG GAZZINELLI, G CORREAOLIVEIRA, R TI INTERFERON-GAMMA PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM RESIDENTS OF AN AREA ENDEMIC FOR SCHISTOSOMA-MANSONI SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INVITRO CELLULAR RESPONSIVENESS; INVIVO MOLECULAR ANALYSIS; DIFFERENT CLINICAL FORMS; MURINE IMMUNE-RESPONSE; MESENTERIC LYMPH-NODES; SOLUBLE EGG ANTIGENS; ADULT WORM ANTIGENS; IL-4 MESSENGER-RNA; GRANULOMATOUS LIVERS; BLOCKING ANTIBODIES AB During human schistosomiasis host responses to antigens of various parasite life-cycle stages may contribute to whether the severe, hepatosplenic state develops or the patient remains relatively asymptomatic throughout infection, and may play a role in resistance. This study evaluated production of interferon gamma (IFN-gamma) in vitro by schistosome antigen-stimulated peripheral blood mononuclear cells (PBMCs) from asymptomatic patients, and by PBMCs from apparently uninfected, untreated persons living in areas endemic for Schistosoma mansoni ('endemic normals'). IFN-gamma production parallels PBMC proliferation in that schistosomal egg antigens stimulate patent patients' cells poorly, but strongly stimulate PBMCs from 'endemic normals'. This is proportionally true for antigens from adult worms and cercariae. Although asymptomatic patent patients' cells produced little or no IFN-gamma in response to the 3 schistosomal antigenic extracts, their PBMCs, and PBMCs from 'endemic normals', produced expected amounts of IFN-gamma when exposed to phytohaemagglutinin. This implies that persons with patent infections have schistosome antigen-specific defects in their ability to respond to IFN-gamma production that are not exhibited by putatively resistant 'endemic normals'. C1 US PHS,CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV PARASIT DIS,ATLANTA,GA 30341. UNIV FED MINAS GERAIS,DEPT BIOQUIM IMUNOL,BR-30190002 BELO HORIZONT,MG,BRAZIL. NIAID,BETHESDA,MD 20892. FIOCRUZ MS,CTR PESQUISAS RENE RACHOU,BR-30190 BELO HORIZONT,MG,BRAZIL. CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT MICROBIOL IMMUNOL & PARASITOL,ITHACA,NY 14853. FU NIAID NIH HHS [AI26505] NR 45 TC 60 Z9 60 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD JUL-AUG PY 1994 VL 88 IS 4 BP 466 EP 470 DI 10.1016/0035-9203(94)90436-7 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA PE901 UT WOS:A1994PE90100041 PM 7570847 ER PT J AU LENFANT, C AF LENFANT, C TI NHLBI AND THE SCIENTIFIC COMMUNITY - A PARTNERSHIP SO TRANSFUSION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 31,ROOM 5A52,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 1994 VL 34 IS 7 BP 627 EP 629 DI 10.1046/j.1537-2995.1994.34794330019.x PG 3 WC Hematology SC Hematology GA PC356 UT WOS:A1994PC35600014 PM 8053043 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - SLANTS AND SPOTS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Hardware Review AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some of the unexpected and sometimes unexplained blotches that may appear on your gels or film plates. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1994 VL 19 IS 7 BP 300 EP 301 DI 10.1016/0968-0004(94)90009-4 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY061 UT WOS:A1994NY06100009 PM 8048171 ER PT J AU STOJILKOVIC, SS KRSMANOVIC, LZ SPERGEL, DJ CATT, KJ AF STOJILKOVIC, SS KRSMANOVIC, LZ SPERGEL, DJ CATT, KJ TI GONADOTROPIN-RELEASING-HORMONE NEURONS - INTRINSIC PULSATILITY AND RECEPTOR-MEDIATED REGULATION SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID IMMORTALIZED HYPOTHALAMIC NEURONS; METHYL-D-ASPARTATE; LUTEINIZING-HORMONE; PREOPTIC AREA; PULSE-GENERATOR; MEDIOBASAL HYPOTHALAMUS; TYROSINE-HYDROXYLASE; LHRH NEURONS; IMMUNOREACTIVE NEURONS; DEPENDENT MECHANISM AB The pulsatile pattern of gonadotropin-releasing hormone (GnRH) release from the hypothalamus is driven by a functionally interconnected and synchronized net work of GnRH neurons termed the GnRH pulse generator. Several recent observations have revealed that immortalized GnRH neurons can generate an episodic pattern of GnRH release when cultured in the absence of other cell types, The in vitro operation of the pulse generator depends on the development of synaptic contacts among GnRH neurons, the electrical properties of individual GnRH neurons, and the GnRH-induced modulation of its secretory mechanism. The expression of several other receptors by GnRH neurons provides the means for integrated regulation of pulse generator activity from without the network by agonists including glutamate, GABA, endothelin, and catecholamines. RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. RI Spergel, David/A-4410-2011 NR 75 TC 44 Z9 44 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL PY 1994 VL 5 IS 5 BP 201 EP 209 DI 10.1016/1043-2760(94)90078-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC359 UT WOS:A1994PC35900004 PM 18407209 ER PT J AU CROWE, JE BUI, PT DAVIS, AR CHANOCK, RM MURPHY, BR AF CROWE, JE BUI, PT DAVIS, AR CHANOCK, RM MURPHY, BR TI A FURTHER ATTENUATED DERIVATIVE OF A COLD-PASSAGED TEMPERATURE-SENSITIVE MUTANT OF HUMAN RESPIRATORY SYNCYTIAL VIRUS RETAINS IMMUNOGENICITY AND PROTECTIVE EFFICACY AGAINST WILD-TYPE CHALLENGE IN SERONEGATIVE CHIMPANZEES SO VACCINE LA English DT Article DE RESPIRATORY SYNCYTIAL VIRUS; COLD PASSAGE; TEMPERATURE SENSITIVE ID COTTON RATS; SURFACE GLYCOPROTEINS; LIVE; RECOMBINANTS; VACCINES; CHILDREN; RSV; PURIFICATION; IMMUNIZATION; INFECTION AB A cold-passaged (cp), temperature-sensitive (ts) RSV mutant designated RSV cpts-248 (shut-off temperature 38 degrees C), which possesses host-range mutations acquired during 52 passages at low temperature in bovine tissue culture and a ts phenotype introduced by subsequent chemical mutagenesis, was found previously to be attenuated, immunogenic, and protective against wild-type challenge in seronegative chimpanzees. We sought to introduce additional attenuating mutations such as small-plaque (sp) and ts mutations into RSV cpts-248 by chemical mutagenesis with 5-fluorouracil with the intent of obtaining cpts-248 derivatives that are more attenuated in mice or chimpanzees and that are move genetically stable following replication in vivo. Ten mutants of RSV cpts-248 which had acquired a sp phenotype or a second ts mutation were generated by chemical mutagenesis. Five cpts-248 derivatives which had acquired mutations that specified a 36 degrees C shut-off temperature for plaque formation and one which had acquired only a sp phenotype were more restricted in replication in Balb/c mice than the cpts-248 parental strain. One mutant, designated RSV cpts-248/404 (shut-off temperature 36 degrees C), was 100 times more restricted in replication in the nasal turbinates of mice and 1000 times more restricted in the nasopharynx of seronegative chimpanzees than its cpts-248 parent. The cpts-248/404 mutant was completely restricted in replication in the lower respiratory tract of chimpanzees even following direct intratracheal administration. The ts phenotype of the cpts-248/404 mutant was stable during replication in vivo in mice and chimpanzees. Chimpanzees immunized with cpts-248/404 were fully protected against upper respiratory tract disease and lower respiratory tract virus replication upon subsequent challenge with wild-type virus. The cpts-248/404 virus and related mutants exhibit many desirable characteristics which make them promising vaccine candidates. C1 WYETH AYERST RES,DIV MOLEC BIOL,RADNOR,PA. RP CROWE, JE (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892, USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 29 TC 79 Z9 83 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUL PY 1994 VL 12 IS 9 BP 783 EP 790 DI 10.1016/0264-410X(94)90286-0 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NQ622 UT WOS:A1994NQ62200004 PM 7975856 ER PT J AU POLETTE, M GILBERT, N STAS, I NAWROCKI, B NOEL, A REMACLE, A STETLERSTEVENSON, WG BIREMBAUT, P FOIDART, M AF POLETTE, M GILBERT, N STAS, I NAWROCKI, B NOEL, A REMACLE, A STETLERSTEVENSON, WG BIREMBAUT, P FOIDART, M TI GELATINASE-A EXPRESSION AND LOCALIZATION IN HUMAN BREAST CANCERS - AN IN-SITU HYBRIDIZATION STUDY AND IMMUNOHISTOCHEMICAL DETECTION USING CONFOCAL MICROSCOPY SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE GELATINASE A; BREAST CARCINOMA; BASEMENT MEMBRANE; INVASION ID TIMP-2 MESSENGER-RNAS; IV COLLAGENASE; TISSUE INHIBITOR; TUMOR INVASION; STROMAL CELLS; MR 72,000; MATRIX; ADENOCARCINOMA; PROGELATINASE; FIBROBLASTS AB The gelatinase A (72 kDa type IV collagenase) is a matrix metallo-proteinase which degrades basement membrane collagens. Various studies emphasize its role in stromal invasion of cancers, but there is some controversy about its origin. Gelatinase A was localized by immunohistochemistry using confocal microscopy in 15 human mammary carcinomas. In addition, the cells responsible for the synthesis of this enzyme were detected by in situ hybridization. Most invasive and non-invasive tumour cells were labelled by immunohistochemistry. Of particular interest was the pattern observed in some pre-invasive areas. Gelatinase A was found in fibroblasts in close contact with pre-invasive tumour clusters. Confocal observation allowed a more precise localization of gelatinase A to the periphery of tumour clusters along the basement membranes and in peritumour fibroblasts. The malignant epithelial cells were negative by immunohistochemistry in these areas. By in situ hybridization, mRNAs encoding gelatinase A were detected only in fibroblasts in close contact with pre-invasive and well differentiated tumour clusters. These findings support the hypothesis that peritumour fibroblasts produce gelatinase A and that breast cancer cells may bind this enzyme to their cell surface and/or internalize it. C1 UNIV LIEGE,BIOL LAB,LIEGE,BELGIUM. NCI,PATHOL LAB,BETHESDA,MD 20892. RP POLETTE, M (reprint author), INSERM,U314,45 RUE COGNACQ JAY,F-51100 REIMS,FRANCE. RI Stetler-Stevenson, William/H-6956-2012; BIREMBAUT, Philippe/P-5210-2016; Raby, Beatrice/P-5666-2016; POLETTE, Myriam/P-5147-2016; OI Stetler-Stevenson, William/0000-0002-5500-5808; Noel, Agnes/0000-0002-7670-6179 NR 26 TC 81 Z9 83 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD JUL PY 1994 VL 424 IS 6 BP 641 EP 645 DI 10.1007/BF01069745 PG 5 WC Pathology SC Pathology GA PA585 UT WOS:A1994PA58500011 PM 8055158 ER PT J AU DUBE, DK DUBE, S ERENSOY, S JONES, B BRYZGORNIA, V SPICER, T LOVE, J SAKSENA, N LECHAT, MF SHRAGER, DI DOSIK, H GLASER, J LEVIS, W BLATTNER, W MONTAGNA, R BLUMBERG, BS POIESZ, BJ AF DUBE, DK DUBE, S ERENSOY, S JONES, B BRYZGORNIA, V SPICER, T LOVE, J SAKSENA, N LECHAT, MF SHRAGER, DI DOSIK, H GLASER, J LEVIS, W BLATTNER, W MONTAGNA, R BLUMBERG, BS POIESZ, BJ TI SEROLOGICAL AND NUCLEIC-ACID ANALYSES FOR HIV AND HTLV INFECTION ON ARCHIVAL HUMAN PLASMA SAMPLES FROM ZAIRE SO VIROLOGY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; COMPLETE NUCLEOTIDE-SEQUENCE; PAPUA-NEW-GUINEA; TROPICAL SPASTIC PARAPARESIS; LYMPHOMA VIRUS; PHYLOGENETIC ANALYSES; MYCOSIS-FUNGOIDES; SOLOMON-ISLANDS; VARIANT AB In order to better understand the genomic diversity and molecular phylogeny of the human retroviruses, the plasmas from 250 Zairean patients collected in 1969 were tested for antibodies to human T-cell lymphoma and human immunodeficiency viruses (HTLV or HIV) using ELISA and confirmatory Western blots and for viral nucleic acids by reverse transcriptase-directed PCR (RT-PCR). Interestingly, none of the patients was confirmed positive for HIV, even though this region is now endemic for HIV-1. However, 74 (30%) and 3 (1%) of the samples were positive for antibodies to HTLV-I and II, respectively. Forty-four of 74 (59%) Western blot-positive Zairean samples were RT-PCR positive for HTLV-I, while 1 of 3 (33%) of HTLV-II-seropositive samples was RT-PCR positive. On the contrary, none of the Western blot-negative or indeterminate samples were RT-PCR positive for either HTLV-I or HTLV-II, We have cloned and sequenced 140 bp of the pol gene flanked by SK110/SK111 from 8 HTLV-I- and 1 HTLV-II-positive archival samples from Zaire, The HTLV-I isolates from Zaire cluster together as a phylogenetic group, diverging from the prototype Japanese HTLV-I (ATK) by a range of 1.4 to 3.6%. Their close homology to some African STLV-I isolates suggests relatively recent interspecies transmission. The Zairean HTLV-II isolate is closely grouped with the HTLV-II substrain of isolates found in Paleo-Amerindians of the New World, making it unlikely that it represents an endemic African strain. (C) 1994 Academic Press, Inc C1 SUNY HLTH SCI CTR, DEPT MED, SYRACUSE, NY 13210 USA. SUNY HLTH SCI CTR, DEPT ANAT, SYRACUSE, NY 13210 USA. FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. UNIV LOUVAIN, LOUVAIN, BELGIUM. STATEN ISL UNIV HOSP, STATEN ISL, NY 10305 USA. INTERFAITH MED CTR, BROOKLYN, NY 11238 USA. NCI, ROCKVILLE, MD 20852 USA. CELLULAR PROD, BUFFALO, NY 14202 USA. FU NCI NIH HHS [5P01CA40737]; NIAID NIH HHS [5-U01-AI-27658]; PHS HHS [R01-43602-01] NR 69 TC 36 Z9 36 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1994 VL 202 IS 1 BP 379 EP 389 DI 10.1006/viro.1994.1354 PG 11 WC Virology SC Virology GA NQ858 UT WOS:A1994NQ85800039 PM 7912021 ER PT J AU SECCHIERO, P BERNEMAN, ZN GALLO, RC LUSSO, P AF SECCHIERO, P BERNEMAN, ZN GALLO, RC LUSSO, P TI BIOLOGICAL AND MOLECULAR CHARACTERISTICS OF HUMAN HERPESVIRUS .7. IN-VITRO GROWTH OPTIMIZATION AND DEVELOPMENT OF A SYNCYTIA INHIBITION TEST SO VIROLOGY LA English DT Note ID B-LYMPHOTROPIC VIRUS; T-CELLS; MARROW TRANSPLANTATION; FATIGUE SYNDROME; INFECTION; ANTIBODY; RETROVIRUS; HBLV; DIFFERENTIATION; IDENTIFICATION AB Two isolates of human herpesvirus 7 (HHV-7) were recovered from phytohemagglutinin-activated peripheral blood mononuclear cells of a patient with chronic fatigue syndrome and of a healthy blood donor. A genetic polymorphism between the two isolates was detected by Southern blot analysis using a novel HHV-7 genomic clone (pVL8) as a probe. We developed optimized conditions for the in vitro propagation of HHV-7 by using enriched populations of activated CD4(+) T lymphocytes derived from normal peripheral blood, resulting in the production of high-titered extracellular virus (> 10(6) cell culture infectious doses/ml). Bona fide syncytia formation was documented both in normal CD4(+) T lymphocytes and in the Sup-T1 CD4(+) T-cell line following infection with high-titered HHV-7. To identify neutralizing antibodies to HHV-7, a syncytia-inhibition test was developed. Variable titers of syncytia-neutralizing antibodies were detected in all the human sera tested, thus confirming the high prevalence of HHV-7 in the human population. (C) 1994 Academic Press, Inc. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 42 TC 40 Z9 41 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1994 VL 202 IS 1 BP 506 EP 512 DI 10.1006/viro.1994.1371 PG 7 WC Virology SC Virology GA NQ858 UT WOS:A1994NQ85800056 PM 8009865 ER PT J AU SADAIE, MR HAGER, GL AF SADAIE, MR HAGER, GL TI INDUCTION OF DEVELOPMENTALLY PROGRAMMED CELL-DEATH AND ACTIVATION OF HIV BY SODIUM-BUTYRATE SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLOBIN GENE-EXPRESSION; T-CELLS; INFECTION; APOPTOSIS; DIFFERENTIATION; RNA; REPLICATION; PROMOTER; GROWTH AB Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat(-) (HLM1) or tat(+) (U1,ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB. (C) 1994 Academic Press, Inc. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RP SADAIE, MR (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,HFM-310,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 37 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1994 VL 202 IS 1 BP 513 EP 518 DI 10.1006/viro.1994.1372 PG 6 WC Virology SC Virology GA NQ858 UT WOS:A1994NQ85800057 PM 8009866 ER PT J AU KAWANO, K INOUE, Y TAKEMURA, A MILES, FA AF KAWANO, K INOUE, Y TAKEMURA, A MILES, FA TI EFFECT OF DISPARITY IN THE PERIPHERAL FIELD ON SHORT-LATENCY OCULAR FOLLOWING RESPONSES SO VISUAL NEUROSCIENCE LA English DT Note DE DISPARITY; MONKEY; OCULAR FOLLOWING RESPONSE; VIEWING DISTANCE ID VIEWING DISTANCE; MONKEY; DEPENDENCE; MOTION; TRANSLATION; NEURONS AB Ocular following responses induced by brief movements of the visual scene were examined in monkeys for their dependence on disparity in the peripheral field. A random dot pattern was projected onto a tangent screen and partitioned into central and peripheral regions. Test stimuli were velocity steps applied in the central region, while stimuli in the periphery were stationary. The visual images in the central region were seen always in the plane of the screen, while stimuli in the periphery could be seen in front, behind, or in the plane of the screen (achieved by a system of polarizing filters). Initial ocular following responses were larger when the peripheral stimuli were presented with an uncrossed disparity than without disparity. On the other hand, responses were smaller when the peripheral stimuli were presented with crossed disparity (<5.0 deg) than without disparity. The result is consistent with the idea that ocular following responses are dependent on the perceived viewing distance. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. RP KAWANO, K (reprint author), ELECTROTECH LAB,NEUROSCI SECT,1-1-4 UMEZONO,IBARAKI,OSAKA 305,JAPAN. NR 15 TC 4 Z9 4 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JUL-AUG PY 1994 VL 11 IS 4 BP 833 EP 837 PG 5 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA NT650 UT WOS:A1994NT65000019 PM 7918233 ER PT J AU ALTER, HJ AF ALTER, HJ TI TRANSFUSION-TRANSMITTED HEPATITIS-C AND NON-A, NON-B, NON-C SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT Scientific Programme of the XXIIIrd Congress of the International-Society-of-Blood-Transfusion CY JUL 02-08, 1994 CL AMSTERDAM, NETHERLANDS SP INT SOC BLOOD TRANSFUS DE TRANSFUSION ASSOCIATED HEPATITIS; POSTTRANSFUSION HEPATITIS; NON-A; NON-B HEPATITIS; NON-C HEPATITIS; HEPATITIS F VIRUS ID POSTTRANSFUSION HEPATITIS; ALANINE AMINOTRANSFERASE; VIRUS-INFECTION; RECIPIENTS; DONORS; RISK RP ALTER, HJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892, USA. NR 19 TC 49 Z9 50 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 1994 VL 67 SU 3 BP 19 EP 24 PG 6 WC Hematology SC Hematology GA PB885 UT WOS:A1994PB88500005 PM 7975490 ER PT J AU OMATA, Y SAKAMOTO, H ROBINSON, RC PINCUS, MR FRIEDMAN, FK AF OMATA, Y SAKAMOTO, H ROBINSON, RC PINCUS, MR FRIEDMAN, FK TI INTERACTION BETWEEN CYTOCHROME-P450 2B1 AND CYTOCHROME B(5) - INHIBITION BY SYNTHETIC PEPTIDES INDICATES A ROLE FOR P450 RESIDUES LYS-122 AND ARG-125 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; HEPATIC-MICROSOMAL CYTOCHROME-P-450; RAT-LIVER; PURIFICATION; B5; REDUCTASE; COMPLEX; ASSOCIATION; METABOLISM; MEMBRANE AB Binding of cytochrome b(5) to rat cytochrome P450 2B1 was inhibited (by 75%) by a synthetic peptide corresponding to P450 residues 116-134. The roles of Lys-122 and Arg-125 were evaluated using peptides in which one or both of these basic residues were replaced with Glu. The Lys-122 substitution nearly abolished while the Arg-125 replacement decreased (by 20%) the inhibitory potential of the peptide. Substitution of both residues resulted in a peptide with no inhibitory activity. These results thus indicate a role for a specific P450 region as well as two basic residues within this region In the cytochrome P450-cytochrome b(5) interaction. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY 13210. RI Sakamoto, Hiroshi/A-3181-2011; Friedman, Fred/D-4208-2016 NR 30 TC 31 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 30 PY 1994 VL 201 IS 3 BP 1090 EP 1095 DI 10.1006/bbrc.1994.1817 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NU977 UT WOS:A1994NU97700006 PM 8024550 ER PT J AU BURKE, TR NOMIZU, M OTAKA, A SMYTH, MS ROLLER, PP CASE, RD WOLF, G SHOELSON, SE AF BURKE, TR NOMIZU, M OTAKA, A SMYTH, MS ROLLER, PP CASE, RD WOLF, G SHOELSON, SE TI CYCLIC PEPTIDE INHIBITORS OF PHOSPHATIDYLINOSITOL 3-KINASE P85 SH2 DOMAIN BINDING SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; SOLID-PHASE SYNTHESIS; RECEPTOR; TARGETS; ANALOGS; KINASE AB Cyclic hexameric peptides based on the amino acid sequence ''Gly-Xxx-Val-Pro-Met-Leu'', where Xxx Is either phosphotyrosyl (pTyr) residue or a hydrolytically stable pTyr mimetic, were examined for their ability to bind to the C-terminal SH2 domain of the p85 phosphoinositol 3-kinase (PI 3-kinase). The cyclic peptides retained significant binding affinity relative to their linear counterparts. Potency varied depending on Xxx in the order: phosphonomethyl phenylalanine (Pmp, ID50 = 5.2 mu M) < phosphonodifluoromethyl phenylalanine (F(2)Pmp, ID50 = 2.2 mu M) < pTyr (ID50 = 1.0 mu M), With Xxx = Tyr being inactive (ID50 > 500 M). Greatly reduced potency was observed when Xxx was of the unnatural D-configuration. The cyclic peptides represent conformationally constrained ligands which should be useful in the development of p85 SH2 domain-directed inhibitors. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 28 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 30 PY 1994 VL 201 IS 3 BP 1148 EP 1153 DI 10.1006/bbrc.1994.1825 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NU977 UT WOS:A1994NU97700014 PM 8024556 ER PT J AU BENO, DWA RAPP, UR DAVIS, BH AF BENO, DWA RAPP, UR DAVIS, BH TI PROSTAGLANDIN-E SUPPRESSION OF PLATELET-DERIVED-GROWTH-FACTOR-INDUCED ITO CELL MITOGENESIS OCCURS INDEPENDENT OF RAF PERINUCLEAR TRANSLOCATION AND NUCLEAR PROTOONCOGENE EXPRESSION SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PDGF; ITO CELL; PGE; RAF; MITOGENESIS; PROTOONCOGENE EXPRESSION ID FAT-STORING CELLS; FACTOR-BETA; SIGNAL TRANSDUCTION; FACTOR RECEPTOR; RETINOIC ACID; COLLAGEN FORMATION; GENE-EXPRESSION; KINASE; PROLIFERATION; ACTIVATION AB Ito cell mitogenesis occurs during liver injury and fibrogenesis in vivo coincident with the de novo expression of Ito cell PDGF beta receptor messenger RNA, PDGF-induced mitogenesis was studied in cultured rat hepatic Ito cells which resemble the myofibroblast associated with liver injury. Pretreatment with prostaglandin E markedly suppressed the PDGF response in a dose-dependent fashion. The PDGF-induced cascade was studied with or without PGE to determine the level of regulation which induced the observed suppression. PGE caused no apparent diminution in the abundance of the surface PDGF beta receptor nor its subsequent activation and tyrosine phosphorylation following PDGF stimulation. The cytoplasmic 'secondary messengers' mitogen-activated protein kinase pp42-44 and raf kinase, appeared to be comparably induced and therefore unaffected by PGE. Raf perinuclear translocation was also intact and comparable degrees of nuclear egr, fos, and jun expression occurred. Since other studies have suggested that many of these features of the PDGF cascade may be causally and sequentially linked, the data collectively suggests that the dominant PGE mitogenic suppressive effect resides at a raf-MAP parallel pathway or at a nuclear level distal to the induction of these early growth response genes. C1 UNIV CHICAGO,DEPT MED,GASTROENTEROL SECT,CHICAGO,IL 60637. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. FU NIDDK NIH HHS [DK 07074-18, DK 42086, DK40223] NR 32 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUN 30 PY 1994 VL 1222 IS 2 BP 292 EP 300 DI 10.1016/0167-4889(94)90181-3 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NV851 UT WOS:A1994NV85100021 PM 8031866 ER PT J AU LAPPE, M RAUSCHECKER, JP AF LAPPE, M RAUSCHECKER, JP TI HEADING DETECTION FROM OPTIC FLOW SO NATURE LA English DT Letter ID DIRECTION; MOTION; FIELD; PERCEPTION; MACAQUE; MONKEY; AREA C1 RUHR UNIV BOCHUM,DEPT NEUROBIOL,BOCHUM,GERMANY. NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. RP LAPPE, M (reprint author), RUHR UNIV BOCHUM,DEPT ZOOL,D-44780 BOCHUM,GERMANY. RI Rauschecker, Josef/A-4120-2013 NR 11 TC 38 Z9 38 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 30 PY 1994 VL 369 IS 6483 BP 712 EP 713 DI 10.1038/369712a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NU581 UT WOS:A1994NU58100039 PM 8008064 ER PT J AU ROOS, BO MERCHAN, M MCDIARMID, R XING, X AF ROOS, BO MERCHAN, M MCDIARMID, R XING, X TI THEORETICAL AND EXPERIMENTAL-DETERMINATION OF THE ELECTRONIC-SPECTRUM OF NORBORNADIENE SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-ORBITAL THEORY; 2ND-ORDER PERTURBATION-THEORY; NEGATIVE-ION STATES; EXCITED-STATES; ABSORPTION-SPECTRUM; IMPACT SPECTROSCOPY; BASIS-SETS; CYCLOPENTADIENE; TRANSITIONS; BENZENE AB The electronic spectrum of the nonplanar, indirectly conjugated molecule norbornadiene has been studied theoretically, using multiconfigurational second-order perturbation theory (CASPT2) with extended ANO-type basis sets, and experimentally, using optical absorption and polarization-selected two-photon resonant-enhanced multiphoton ionization (REMPI) spectroscopies. The calculations comprise five valence excited states and the 3s, 3p, and 3d members of the Rydberg series converging on the first two ionizations. The two lowest triplet states have also been studied. The experiments enabled definitive assignments to be made for four Rydberg transitions and three valence transitions. The computed excitation energies were found to be within 0.2 eV of the experimental energies for correctly correlated transitions; the computed oscillator strengths were in good relative: agreement with their experimental values. Comparisons are made between this and other theoretical calculations and also between the electronic spectra of norbornadiene, cis-butadiene, and cyclopentadiene. C1 UNIV VALENCIA,DEPT QUIM FIS,E-46100 VALENCIA,SPAIN. NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. RP ROOS, BO (reprint author), CHEM CTR LUND,DEPT THEORET CHEM,POB 124,S-22100 LUND,SWEDEN. NR 49 TC 35 Z9 35 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 29 PY 1994 VL 116 IS 13 BP 5927 EP 5936 DI 10.1021/ja00092a049 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA NV421 UT WOS:A1994NV42100049 ER PT J AU FAN, P AF FAN, P TI INHIBITION OF THE 5-HT3 RECEPTOR-MEDIATED CURRENT BY THE PROTEIN-KINASE INHIBITOR, H-7 SO BRAIN RESEARCH LA English DT Note DE NODOSE GANGLION; 5-HT3 RECEPTOR; PATCH CLAMP; H-7; H-8; PROTEIN KINASE ID CELLS AB The effect of the protein kinase inhibitor, H-7, on the inward current mediated by 5-HT3 receptors was investigated with the whole-cell patch-clamp technique. H-7 inhibited the peak 5-HT current with an IC50 of 1.79 mu M. The inhibition was quick, reversible and not blocked by the presence of 50 mu M intracellular H-7. It is concluded that the effect of H-7 was independent of protein kinase activity. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 27 PY 1994 VL 649 IS 1-2 BP 310 EP 312 DI 10.1016/0006-8993(94)91078-2 PG 3 WC Neurosciences SC Neurosciences & Neurology GA NU986 UT WOS:A1994NU98600038 PM 7525009 ER PT J AU CHEN, FS WAGNER, PD AF CHEN, FS WAGNER, PD TI 14-3-3-PROTEINS BIND TO HISTONE AND AFFECT BOTH HISTONE PHOSPHORYLATION AND DEPHOSPHORYLATION SO FEBS LETTERS LA English DT Article DE 14-3-3 PROTEIN; PROTEIN PHOSPHATASE; PROTEIN KINASE C; SECRETION ID ADRENAL CHROMAFFIN CELLS; ACTIVATES TRYPTOPHAN 5-MONOOXYGENASE; CALCIUM-DEPENDENT EXOCYTOSIS; LIGHT CHAIN KINASE; SMOOTH-MUSCLE; CA2+-DEPENDENT SECRETION; NOREPINEPHRINE SECRETION; TYROSINE 3-MONOOXYGENASE; CYTOSOLIC PROTEINS; SHEEP BRAIN AB 14-3-3 proteins appear to play a critical role in Ca2+-stimulated secretion in permeabilized chromaffin cells. 14-3-3 proteins have been reported to be both stimulators and inhibitors of protein kinase C (PKC). We have found that 14-3-3 proteins, isolated on the basis of their ability to enhance secretory activity, stimulated histone phosphorylation by PKC, but they had no effect on myosin light chain phosphorylation by PKC. 14-3-3 proteins were also found to inhibit the rate of [P-32]histone dephosphorylation but not the rate of [P-32]myosin light chain dephosphorylation. Cross-linking experiments and affinity chromatography demonstrated that 14-3-3 proteins bind to histones. These results suggest that at least some of the reported effects of 14-3-3 proteins on PKC activity may result from 14-3-3 proteins binding to histone. RP CHEN, FS (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 32 TC 28 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 27 PY 1994 VL 347 IS 2-3 BP 128 EP 132 DI 10.1016/0014-5793(94)00520-6 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NV022 UT WOS:A1994NV02200005 PM 8033989 ER PT J AU CHEN, Y FAN, Y LIU, J MESTEK, A TIAN, MT KOZAK, CA YU, L AF CHEN, Y FAN, Y LIU, J MESTEK, A TIAN, MT KOZAK, CA YU, L TI MOLECULAR-CLONING, TISSUE DISTRIBUTION AND CHROMOSOMAL LOCALIZATION OF A NOVEL MEMBER OF THE OPIOID RECEPTOR GENE FAMILY SO FEBS LETTERS LA English DT Article DE OPIOID RECEPTOR; MOLECULAR CLONING; TISSUE DISTRIBUTION; CHROMOSOME MAPPING ID FUNCTIONAL EXPRESSION; BRAIN; CDNA; CHANNEL AB A cDNA was isolated from rat brain by low stringency hybridization with the rat mu opioid receptor cDNA. Sequence analysis of this clone indicated that it contains an open reading frame capable of encoding a 367 amino acid protein. The deduced amino acid sequence of this protein shows high degrees of homology to all three opioid receptors, mu, kappa, and delta, suggesting that it is a member of the opioid receptor gene family. RNA blot analysis detected high level expression of the receptor mRNA in the brain. Southern blot analysis suggests that it is a single-copy gene, and mapping studies localized the gene on mouse chromosome 2. Despite the high sequence homologies between this protein and the other opioid receptors, expression studies of this clone in COS-7 cells did not show binding to [H-3]diprenorphine, a ligand that binds to the other three opioid receptors. Furthermore, co-expression of this receptor with a G protein-activated potassium channel in Xenopus oocytes did not show functional coupling upon stimulation with mu, kappa and delta agonists. Given the similar degrees of high homology to the mu, kappa and delta opioid receptors and the lack of apparent affinity for their ligands, this receptor does not appear to belong to any of the three known classes of opioid receptors. Rather, it represents a novel member of the opioid receptor gene family, not identified from previous pharmacological studies. C1 INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. FU NICHD NIH HHS [T32HD07373]; NINDS NIH HHS [NS01557, NS28190] NR 25 TC 300 Z9 304 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 27 PY 1994 VL 347 IS 2-3 BP 279 EP 283 DI 10.1016/0014-5793(94)00560-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NV022 UT WOS:A1994NV02200038 PM 8034018 ER PT J AU BRINGMANN, G GULDEN, KP HALLOCK, YF MANFREDI, KP CARDELLINA, JH BOYD, MR KRAMER, B FLEISCHHAUER, J AF BRINGMANN, G GULDEN, KP HALLOCK, YF MANFREDI, KP CARDELLINA, JH BOYD, MR KRAMER, B FLEISCHHAUER, J TI CIRCULAR-DICHROISM OF MICHELLAMINES - INDEPENDENT ASSIGNMENT OF AXIAL CHIRALITY BY CALCULATED AND EXPERIMENTAL CD-SPECTRA SO TETRAHEDRON LA English DT Article ID ANCISTROCLADUS-ABBREVIATUS; ALKALOIDS AB The circular dichroic behavior of the michellamines, dimeric naphthylisoquinoline alkaloids, was investigated. Due to the molecular size and conformational flexibility, which makes direct calculations of the CD spectra very difficult, and because of the lack of direct standards for an empirical comparison, there is no simple possibility for the interpretation of the CD spectra of such quateraryls. The chiroptical contributions of the particular stereogenic elements were shown to behave largely additively and thus allow comparison of spectra of the quateraryls with those of the corresponding 'monomeric' naphthylisoquinolines. This comparison was performed first of all with the experimental and theoretical CD spectra of ancistrobrevine B, then with the predicted spectra of the authentic molecular 'halves' of the michellamines. C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RHEIN WESTFAL TH AACHEN KLINIKUM,LEHR & FORSCH GEBIET THEORET CHEM,D-52074 AACHEN,GERMANY. RP BRINGMANN, G (reprint author), UNIV WURZBURG,INST ORGAN CHEM,HUBLAND,D-97074 WURZBURG,GERMANY. NR 11 TC 36 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUN 27 PY 1994 VL 50 IS 26 BP 7807 EP 7814 DI 10.1016/S0040-4020(01)85264-9 PG 8 WC Chemistry, Organic SC Chemistry GA NT825 UT WOS:A1994NT82500007 ER PT J AU BRIDBORD, K WILLOUGHBY, A AF BRIDBORD, K WILLOUGHBY, A TI VITAMIN-A AND MOTHER-TO-CHILD HIV-1 TRANSMISSION SO LANCET LA English DT Editorial Material C1 NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. RP BRIDBORD, K (reprint author), NICHHD,FOGARTY INT CTR,INT STUDIES BRANCH,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 25 PY 1994 VL 343 IS 8913 BP 1585 EP 1586 DI 10.1016/S0140-6736(94)93052-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NU354 UT WOS:A1994NU35400005 PM 7911915 ER PT J AU HARRIS, T ROUBENOFF, R KIEL, D LANGLOIS, J HAVLIK, R WILSON, P AF HARRIS, T ROUBENOFF, R KIEL, D LANGLOIS, J HAVLIK, R WILSON, P TI DIAGNOSIS OF GROWTH-HORMONE DEFICIENCY IN ADULTS SO LANCET LA English DT Letter C1 TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. HEBREW REHABIL CTR AGED,BOSTON,MA. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. RP HARRIS, T (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892, USA. OI Kiel, Douglas/0000-0001-8474-0310 NR 2 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 25 PY 1994 VL 343 IS 8913 BP 1646 EP 1646 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NU354 UT WOS:A1994NU35400062 PM 7911955 ER PT J AU LUSSO, P GALLO, RC AF LUSSO, P GALLO, RC TI HHV-6 AND CMV PNEUMONITIS IN IMMUNOCOMPROMISED PATIENTS SO LANCET LA English DT Letter ID HUMAN HERPESVIRUS-6 INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS RP LUSSO, P (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 7 TC 6 Z9 7 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 25 PY 1994 VL 343 IS 8913 BP 1647 EP 1648 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NU354 UT WOS:A1994NU35400064 PM 7911958 ER PT J AU CHAMBERLIN, ME LEI, KJ CHOU, JY AF CHAMBERLIN, ME LEI, KJ CHOU, JY TI SUBTLE DIFFERENCES IN HUMAN PREGNANCY-SPECIFIC GLYCOPROTEIN GENE PROMOTERS ALLOW FOR DIFFERENTIAL EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; MOLECULAR-CLONING; BETA-1-GLYCOPROTEIN GENES; MESSENGER-RNA; FAMILY; PROTEINS; CDNA; SEQUENCE; MEMBER; CELLS AB Eleven pregnancy-specific glycoprotein (PSG) genes reside on human chromosome 19. The sequence of these genes is extremely similar and that similarity extends to their putative control regions. However, the expression pattern of each PSG gene differs in the placenta, the primary site of PSG synthesis. To understand the molecular mechanisms underlying differential PSG expression, we characterized promoter elements of six PSG genes. We have shown previously that nucleotides -172 to -34 with respect to the translation start site constitute a minimal promoter in the PSG12 gene (class 1). We now show that PSG1-I and PSG3 are also members of class 1 genes. In contrast, only nucleotides -172 to -80 are necessary for promoter activity in PSG5, PSG6, and PSG11 genes (class 2). Class 2 genes contain a perfect Sp1 recognition sequence (CCCCGCCC) at nucleotides -148 to -141 which is necessary for promoter activity. Placental cell extracts formed three protein-DNA complexes with nucleotides -172 to -80 of all six PSG genes. One of the components of these complexes is an Sp1-like molecule. We have previously reported activator sequences within nucleotides -83 to -34 in PSG12. We now show that a 50-kDa protein binds to this region of PSG11, and the resultant complex can be supershifted by a monoclonal antibody to PEA3. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 44 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 1994 VL 269 IS 25 BP 17152 EP 17159 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT846 UT WOS:A1994NT84600029 PM 8006022 ER PT J AU JIN, DJ AF JIN, DJ TI SLIPPAGE SYNTHESIS AT THE GALP2 PROMOTER OF ESCHERICHIA-COLI AND ITS REGULATION BY UTP CONCENTRATION AND CAMP-CENTER-DOT-CAMP RECEPTOR PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE; TRANSCRIPTION INITIATION; GALACTOSE OPERON; ACID; SEQUENCES; INVITRO; POOLS; GENE AB An intriguing mechanism in regulating transcription initiation from the gal operon in Escherichia coli is described. Initiation from galP2, one of the two promoters of the E. coli galactose operon, is shown to be subject to promoter clearance control in responding to changes in UTP concentration. In vitro, RNA polymerase (RNAP) makes a large amount of nonproductive ''stuttering'' initiation products at the galP2 promoter at high concentrations of UTP and less of the stuttered products at low concentrations of UTP. Conversely, RNAP makes more productive initiation products at low UTP concentration than at high UTP concentration. The transcription factor cAMP CRP complex which normally inhibits transcription from galP2 also represses the stuttering synthesis from galP2. When galactose is used as a sole carbon source and the internal UTP pools are adjusted externally, a cya mutant (in which galP2 is mainly responsible for the expression of the gal operon and galP1 activity is minimal) has a slower growth rate and lower expression of the gal operon at high UTP pools than at low UTP pools. Such an apparent correlation between the in vitro and in vivo results allows one to speculate that changes in UTP concentration can modulate the expression of the gal operon. The implication of a gal promoter being controlled by UTP is discussed. RP JIN, DJ (reprint author), NCI,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BLDG 37,RM 2E14,BETHESDA,MD 20892, USA. NR 29 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 1994 VL 269 IS 25 BP 17221 EP 17227 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT846 UT WOS:A1994NT84600038 PM 7516334 ER PT J AU BRANDT, R NORMANNO, N GULLICK, WJ LIN, JH HARKINS, R SCHNEIDER, D JONES, BW CIARDIELLO, F PERSICO, MG ARMENANTE, F KIM, N SALOMON, DS AF BRANDT, R NORMANNO, N GULLICK, WJ LIN, JH HARKINS, R SCHNEIDER, D JONES, BW CIARDIELLO, F PERSICO, MG ARMENANTE, F KIM, N SALOMON, DS TI IDENTIFICATION AND BIOLOGICAL CHARACTERIZATION OF AN EPIDERMAL GROWTH FACTOR-RELATED PROTEIN - CRIPTO-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HAMSTER OVARY CELLS; MAMMARY EPITHELIAL-CELLS; FACTOR-ALPHA; TYROSINE PHOSPHORYLATION; INVITRO TRANSFORMATION; COLORECTAL TUMORS; FACTOR GENE; EXPRESSION; AMPHIREGULIN; EGF AB The human and mouse cripto-1 (CR-1) genes can code for proteins related in structure to epidermal growth factor (EGF). A specific 36-kDa immunoreactive protein was detected by Western blot analysis in human cell lines that express CR-1 mRNA but not in cell lines that fail to express this transcript. Immunoprecipitation of GEO colon carcinoma or mouse embryonal carcinoma cells detected 27-29-kDa and 24-kDa proteins, respectively. Cell lysates and conditioned medium that were prepared from several CHO clones and were expressing either a recombinant human or mouse CR-1 cDNA contained immunospecific 27-29-kDa and 24 kDa proteins, respectively. Monensin or tunicamycin treatment resulted in a shift of the 27-29-kDa human CR-1 protein to 24 kDa and 20 kDa, respectively. The 20-kDa protein was also observed after digestion of the 27-29-kDa human CR-1 protein with N-glycosidase F. Using two CR-1 synthetic refolded peptides that correspond to the EGF-like domain of the human CR-1 sequence or conditioned medium obtained from human CR-1 expressing CHO cells, growth stimulatory activity could be detected on nontransformed human mammary epithelial cells and on two human breast cancer cell lines. EGF receptor-blocking antibody did not inhibit the growth stimulatory action of the CR-1 protein. Likewise, the CR-1 refolded peptides or conditioned medium from the human CR-1-expressing CHO cells failed to inhibit the binding of I-125-EGF in an EGF-radioreceptor assay. These data demonstrate that the CR-1 is a glycoprotein that can function as a growth factor through an EGF receptor-independent pathway. C1 NCI, TUMOR IMMUNOL & BIOL LAB, TUMOR GROWTH FACTOR SECT, BETHESDA, MD 20892 USA. HAMMERSMITH HOSP, IMPERIAL CANC RES FUND, MOLEC ONCOL UNIT, LONDON W12 0NN, ENGLAND. BERLEX BIOSCI INC, RICHMOND, CA 94804 USA. UNIV NAPLES FEDERICO II, FAC MED & CHIRURG, CATTEDRA ONCOL MED, I-80131 NAPLES, ITALY. INT INST GENET & BIOPHYS, CNR, I-80125 NAPLES, ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 51 TC 88 Z9 91 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 1994 VL 269 IS 25 BP 17320 EP 17328 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT846 UT WOS:A1994NT84600052 PM 8006041 ER PT J AU ITO, Y MA, Y AF ITO, Y MA, Y TI PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY - A DISPLACEMENT MODE APPLIED TO SEPARATION OF DINITROPHENYL AMINO-ACIDS SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article AB A new mode of pH-zone-refining counter-current chromatography operates in a manner analogous to displacement chromatography. The method uses a retainer base (acid) in the stationary phase to retain analytes in the column and a displacer acid (base) to elute the analytes in the decreasing order of pK(a) and hydrophobicity. The elution produces a train of highly concentrated rectangular solute peaks with minimum overlap. Utility of the method is demonstrated in the separation of dinitrophenyl amino acids in a two-phase solvent system composed of methyl tert.-butyl ether and water. Compared with the original mode of pH-zone-refining counter-current chromatography, the present mode is more amenable to ligand-affinity separation which may cover a broader range of analytes including non-ionizable compounds. RP ITO, Y (reprint author), NHLBI,BIOPHYS CHEM LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 11 TC 28 Z9 30 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 24 PY 1994 VL 672 IS 1-2 BP 101 EP 108 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NV718 UT WOS:A1994NV71800009 PM 8069392 ER PT J AU NEUWALD, AF GREEN, P AF NEUWALD, AF GREEN, P TI DETECTING PATTERNS IN PROTEIN SEQUENCES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PATTERN RECOGNITION; STATISTICAL SIGNIFICANCE; ALIGNMENT ALGORITHMS; SEQUENCE COMPARISON; AMINO ACID SEQUENCE ID HELIX-TURN-HELIX; AMINO-ACID SEQUENCE; STRANDED-RNA VIRUS; ESCHERICHIA-COLI; DNA-BINDING; N-ACETYLTRANSFERASE; PROFILE ANALYSIS; ALPHA-SUBUNIT; MOTIFS; DEHYDROGENASE C1 WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. RP NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. FU NLM NIH HHS [5-T-LM07049] NR 58 TC 65 Z9 65 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 24 PY 1994 VL 239 IS 5 BP 698 EP 712 DI 10.1006/jmbi.1994.1407 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT740 UT WOS:A1994NT74000006 PM 8014990 ER PT J AU MILLER, LH GOOD, MF MILON, G AF MILLER, LH GOOD, MF MILON, G TI MALARIA PATHOGENESIS SO SCIENCE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FALCIPARUM-INFECTED ERYTHROCYTES; HUMAN CEREBRAL MALARIA; PLASMODIUM-FALCIPARUM; ANTIGENIC VARIATION; P-FALCIPARUM; T-CELLS; SURFACE; PARASITES; INVASION AB Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity. C1 QUEENSLAND INST MED RES,MALARIA & ARBOVIRUS UNIT,BRISBANE,QLD 4029,AUSTRALIA. INST PASTEUR,F-75724 PARIS 15,FRANCE. RP MILLER, LH (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 83 TC 377 Z9 379 U1 5 U2 46 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 24 PY 1994 VL 264 IS 5167 BP 1878 EP 1883 DI 10.1126/science.8009217 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT847 UT WOS:A1994NT84700032 PM 8009217 ER PT J AU LETTERIO, JJ GEISER, AG KULKARNI, AB ROCHE, NS SPORN, MB ROBERTS, AB AF LETTERIO, JJ GEISER, AG KULKARNI, AB ROCHE, NS SPORN, MB ROBERTS, AB TI MATERNAL RESCUE OF TRANSFORMING GROWTH-FACTOR-BETA-1 NULL MICE SO SCIENCE LA English DT Article ID FACTOR-BETA; EXPRESSION; MOUSE; RATS; LYMPHOCYTES; ANTIBODIES; DISEASE; ANTIGEN AB Maternal sources of transforming growth factor-beta 1 (TGF-beta 1) are shown here to contribute to the normal appearance and perinatal survival of TGF-beta 1 null newborn mice. Labeled TGF-beta 1 crossed the placenta and was recovered intact from various tissues after oral administration to mouse pups. TGF beta-1 protein was also detected in cells recovered from breast milk. In immunohistochemical analyses, TGF-beta 1 null embryos and null newborn pups born to TGF-beta 1 heterozygotes stained positive for TGF-beta 1, whereas those born to a null female were negative and had severe cardiac abnormalities. These results suggest an important role for maternal sources of TGF-beta 1 during development and, more generally, provide evidence for maternal rescue of targeted gene disruption in the fetus. C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. RP LETTERIO, JJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 29 TC 406 Z9 413 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 24 PY 1994 VL 264 IS 5167 BP 1936 EP 1938 DI 10.1126/science.8009224 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT847 UT WOS:A1994NT84700046 PM 8009224 ER PT J AU SIM, BKL CHITNIS, CE WASNIOWSKA, K HADLEY, TJ MILLER, LH AF SIM, BKL CHITNIS, CE WASNIOWSKA, K HADLEY, TJ MILLER, LH TI RECEPTOR AND LIGAND DOMAINS FOR INVASION OF ERYTHROCYTES BY PLASMODIUM-FALCIPARUM SO SCIENCE LA English DT Article ID BINDING ANTIGEN; GLYCOPHORIN-A; MALARIA PARASITES; AMINO-ACID; GLYCOPROTEIN; MEMBRANE; POLYMORPHISM; KNOWLESI; PROTEINS; SEQUENCE AB A 175-kilodalton erythrocyte binding protein, EBA-175, of the parasite Plasmodium falciparum mediates the invasion of erythrocytes. The erythrocyte receptor for EBA-175 is dependent on sialic acid. The domain of EBA-175 that binds erythrocytes was identified as region II with the use of truncated portions of EBA-175 expressed on COS cells. Region II, which contains a cysteine-rich motif, and native EBA-175 bind specifically to glycophorin A, but not to glycophorin B, on the erythrocyte membrane. Erythrocyte recognition of EBA-175 requires both sialic acid and the peptide backbone of glycophorin A. The identification of both the receptor and ligand domains may suggest rational designs for receptor blockade and vaccines. C1 NIH,MALARIA RES LAB,BETHESDA,MD 20892. UNIV LOUISVILLE,DEPT MED,LOUISVILLE,KY 40292. POLISH ACAD SCI,INST IMMUNOL & EXPTL THERAPY,DEPT IMMUNOCHEM,PL-53114 WROCLAW,POLAND. NR 24 TC 400 Z9 414 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 24 PY 1994 VL 264 IS 5167 BP 1941 EP 1944 DI 10.1126/science.8009226 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT847 UT WOS:A1994NT84700048 PM 8009226 ER PT J AU MATZINGER, P AF MATZINGER, P TI IMMUNOLOGY - MEMORIES ARE MADE OF THIS SO NATURE LA English DT Editorial Material ID T-CELL MEMORY; ANTIGEN; ABSENCE RP MATZINGER, P (reprint author), NIH,BLDG 4,ROOM 111,BETHESDA,MD 20892, USA. NR 9 TC 83 Z9 85 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 23 PY 1994 VL 369 IS 6482 BP 605 EP 606 DI 10.1038/369605a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT459 UT WOS:A1994NT45900025 PM 8208285 ER PT J AU BATENJANY, MM WANG, ZQ HUANG, CH LEVIN, IW AF BATENJANY, MM WANG, ZQ HUANG, CH LEVIN, IW TI BILAYER PACKING CHARACTERISTICS OF MIXED CHAIN PHOSPHOLIPID DERIVATIVES - RAMAN-SPECTROSCOPIC AND DIFFERENTIAL SCANNING CALORIMETRIC STUDIES OF 1-STEAROYL-2-CAPRYL-SN-GLYCERO-3-PHOSPHOCHOLINE (C(18)C(10)PC) AND 1-STEAROYL-2-CAPRYL-SN-GLYCERO-3-PHOSPHO-N-TRIMETHYLPROPANOLAMINE (C(18)C(10)TMPC) SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE RAMAN SPECTROSCOPY; DSC; MIXED INTERDIGITATED ACYL CHAIN BILAYER; 1-STEAROYL-2-CAPRYL-SN-GLYCERO-3-PHOSPHO-N-TRIMETHYLPROPANOLAMINE; 1-STEAROYL-2-CAPRYL-SN-GLYCERO-3-PHOSPHOCHOLINE; PHOSPHATIDYLCHOLINE TRANS HEADGROUP ID H STRETCHING REGION; POLYMETHYLENE CHAIN; MOLECULAR-STRUCTURE; PHOSPHATIDYLCHOLINE; CONFORMATION; MODEL; PHOSPHATIDYLETHANOLAMINE; DISPERSIONS; MEMBRANES; DIHYDRATE AB Raman spectroscopy and high-sensitivity differential scanning calorimetry (DSC) were used to compare the effects of headgroup conformation on the acyl chain packing arrangements in two highly asymmetric phosphatidylcholine (PC) analogues, 1-stearoyl-2-capryl-sn-glycero-3-phosphocholine (C(18):C(10)PC) and a polar headgroup derivative of C(18):C(10)PC, 1-stearoyl-2-capryl-sn-glycero-3-phospho-N-trimethylpropanolamine (C(18):C(10)TMPC), which contains an additional methylene group within the choline moiety; namely, -P-O-(CH2)(3)-N(CH3)(3). The C(18):C(10)TMPC headgroup exhibits an extended trans conformation which is independent of bilayer phase. A comparison of gel phase spectral order parameters of the two lipid species indicates a mixed interdigitated state characteristic of three chains per headgroup for C(18):C(10)TMPC. A more intermolecularly ordered liquid crystalline phase is observed, however, for the C(18):C(10)TMPC bilayers. The phase transition cooperative unit size estimated for the C(18):C(10)PC bilayers (similar to 140 molecules per unit) is about 7-fold greater than that for the C(18):C(10)TMPC dispersions (similar to 20 molecules per unit). We suggest that the extended headgroup for C(18):C(10)TMPC induces a slight tilt in the gel phase packing arrangements for the acyl chains, which may persist in the partially interdigitated liquid crystalline phase bilayer. Macroscopically, tighter packed multilamellar dispersions of C(18):C(1O)TMPC occur for systems prepared first in the presence of a higher ionic strength medium. The stacked bilayers may then be transferred to a lower ionic strength environment without loss of their more closely packed adjacent lamellae. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22908. NR 30 TC 13 Z9 13 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JUN 22 PY 1994 VL 1192 IS 2 BP 205 EP 214 DI 10.1016/0005-2736(94)90120-1 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NU752 UT WOS:A1994NU75200008 PM 8018701 ER PT J AU MURPHY, PM AF MURPHY, PM TI VIRAL IMITATIONS OF HOST-DEFENSE PROTEINS - FLATTERY THAT TURNS TO BATTERY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; VACCINIA VIRUS; FUNCTIONAL EXPRESSION; HUMAN CYTOMEGALOVIRUS; HERPESVIRUS SAIMIRI; CHEMOKINE RECEPTOR; PLASMODIUM-VIVAX; MYXOMA VIRUS; HOMOLOG; CELL RP MURPHY, PM (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N-113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 22 PY 1994 VL 271 IS 24 BP 1948 EP 1952 DI 10.1001/jama.271.24.1948 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NR598 UT WOS:A1994NR59800033 PM 8201740 ER PT J AU PERLMAN, ME DAVIS, DG KOSZALKA, GW TUTTLE, JV LONDON, RE AF PERLMAN, ME DAVIS, DG KOSZALKA, GW TUTTLE, JV LONDON, RE TI STUDIES OF INHIBITOR FINDING TO ESCHERICHIA-COLI PURINE NUCLEOSIDE PHOSPHORYLASE USING THE TRANSFERRED NUCLEAR OVERHAUSER EFFECT AND ROTATING-FRAME NUCLEAR OVERHAUSER ENHANCEMENT SO BIOCHEMISTRY LA English DT Article ID DIHYDROFOLATE-REDUCTASE; CHEMICAL-EXCHANGE; SALMONELLA-TYPHIMURIUM; STRUCTURAL-ANALYSIS; PHOSPHORYLASE; CONFORMATIONS; RELAXATION; BINDING; NOE; COMPLEXES AB NMR studies of the adenosine analog tubercidin have been carried out in the presence of Escherichia coli purine nucleoside phosphorylase (PNP) in order to characterize the conformation of the enzyme-complexed nucleoside. Although analysis of transferred NOE data at various enzyme/inhibitor ratios indicated a predominantly syn nucleoside conformation in the enzyme-complexed state, the results, particularly the 8{1'} and 8{3'} NOE interactions, were not quantitatively consistent with any single bound conformation. Dissociation rate constants for the tubercidin-PNP complex were determined based on analysis of chemical shift and line width data as a function of enzyme/inhibitor ratio, Carr-Purcell-Meiboom-Gill measurements of the transverse relaxation rate as a function of pulse rate, and T-1 rho, experiments as a function of the spin-lock field strength. Dissociation rate constants of 2100 s(-1) at 20 degrees C and 1400 s(-1) at 10 degrees C were determined using the latter two methods. These rates are sufficiently high to justify the validity of the transferred NOE method for an enzyme as large as PNP. The possible significance of spin diffusion was investigated by the use of the deuterated analog [2'-H-2]tubercidin, for which many of the intraligand spin diffusion pathways are eliminated, and by performing a series of transferred ROE experiments. A comparison of data obtained using transferred NOE and ROE measurements provides a basis for separating direct and indirect relaxation pathways. Both approaches indicated that the relatively significant 8{3'} NOE interaction was not dominated by spin diffusion. Furthermore, analysis of chemical shift and transverse relaxation data for the tubercidin H-2 resonance gave inconsistent results for the chemical shift of the bound species and was inconsistent with the assumption of a single, bound conformation. These results were interpreted in terms of a 2:1 ratio of a syn, 3'-exo:anti, 3'-endo geometry for bound tubercidin. Ligand competition experiments using 9-deazainosine show that all of the tubercidin TRNOE effects are reversed by addition of the second nucleoside, suggesting that the TRNOE data for tubercidin arise due to interactions at the active sites of PNP rather than as a consequence of nonspecific binding to the enzyme. C1 NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. WELLCOME RES LABS, DIV EXPTL THERAPY, RES TRIANGLE PK, NC 27709 USA. NR 60 TC 26 Z9 26 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 21 PY 1994 VL 33 IS 24 BP 7547 EP 7559 DI 10.1021/bi00190a007 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU490 UT WOS:A1994NU49000007 PM 8011620 ER PT J AU PARKER, KC BIDDISON, WE COLIGAN, JE AF PARKER, KC BIDDISON, WE COLIGAN, JE TI POCKET MUTATIONS OF HLA-B27 SHOW THAT ANCHOR RESIDUES ACT CUMULATIVELY TO STABILIZE PEPTIDE BINDING SO BIOCHEMISTRY LA English DT Article ID CLASS-I MOLECULES; VIRAL PEPTIDES; MHC COMPLEXES; SIDE-CHAINS; HLA-A2; MOTIFS; RECOGNITION; ANTIGEN; IDENTIFICATION; SPECIFICITY AB Major histocompatibility complex (MHC) class I molecules bind endogenously synthesized peptides for presentation to cytotoxic T-cells. The human class I molecule HLA-B27 consists of a trimolecular complex containing the HLA-B27 heavy chain, a peptide that is usually nine amino acid residues (aa) long, and beta(2)-microglobulin (beta(2)m). The key interactions for peptide selectivity are between Glu-45, which forms a salt bridge with the Arg at P2 of the peptide, and Asp-116 which favors the binding of peptides containing a Lys or Arg at P9. The t(1/2) of dissociation of [I-125]beta(2)m was measured for peptide-specific HLA-B27 wild-type (wt) and mutant complexes. HLA-B27 wt and HLA-B27 D116F formed relatively stable complexes, with a t(1/2) Of dissociation on the scale of hours, with appropriate peptides that contained Arg at P2, whereas HLA-B27 E45T required a Gln at P2. Similarly, kinetically stable D116F complexes were formed only with peptides that contained a Leu or Val at P9 instead of Arg or Lys. The [I-125]beta(2)m dissociation rate data were fit to a set of equations in order to calculate relative binding coefficients for each anchor residue at P2 and P9. The P2 coefficients were sensitive to the E45T mutation but not the D116F mutation, whereas the P9 coefficients were sensitive only to the D116F mutation. Thus, drastic structural changes in one subsite do not affect the other subsite, indicating that the dominant anchor residues at P2 and P9 independently contribute to stabilizing the class I/peptide complex. C1 NINCDS,NEUROIMMUNOL BRANCH,MOLEC IMMUNOL SECT,BETHESDA,MD 20892. RP PARKER, KC (reprint author), NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892, USA. OI Parker, Kenneth/0000-0002-6282-2478 NR 38 TC 35 Z9 35 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 21 PY 1994 VL 33 IS 24 BP 7736 EP 7743 DI 10.1021/bi00190a029 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU490 UT WOS:A1994NU49000029 PM 8011638 ER PT J AU OBRIEN, SJ AF OBRIEN, SJ TI A ROLE FOR MOLECULAR-GENETICS IN BIOLOGICAL CONSERVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review ID CHEETAH ACINONYX-JUBATUS; FREE-RANGING CHEETAHS; NORTH-AMERICAN ZOOS; MITOCHONDRIAL-DNA; HUMPBACK WHALES; AFRICAN CHEETAH; FLORIDA PANTHER; POPULATION; LIONS; DIVERSITY AB The recognition of recent accelerated depletion of species as a consequence of human industrial development has spawned a wide interest in identifying threats to endangered species. In addition to ecological and demographic perils, it has become clear that small populations that narrowly survive demographic contraction may undergo close inbreeding, genetic drift, and loss of overall genomic variation due to allelic loss or reduction to homozygosity. I review here the consequences of such genetic depletion revealed by applying molecular population genetic analysis to four endangered mammals: African cheetah, lion, Florida panther, and humpback whale, The accumulated genetic results, combined with physiological, ecological, and ethological data, provide a multifaceted perspective of the process of species diminution. An emerging role of population genetics, phylogenetics, and phylogeography as indicators of a population's natural history and its future prognosis provides valuable data of use in the development of conservation management plans for endangered species. RP OBRIEN, SJ (reprint author), NCI, FREDERICK CANC RES & DEV CTR, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NR 83 TC 157 Z9 165 U1 17 U2 78 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5748 EP 5755 DI 10.1073/pnas.91.13.5748 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100004 PM 7912434 ER PT J AU MAZUMDER, A COONEY, D AGBARIA, R GUPTA, M POMMIER, Y AF MAZUMDER, A COONEY, D AGBARIA, R GUPTA, M POMMIER, Y TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE BY 3'-AZIDO-3'-DEOXYTHYMIDYLATE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA-VIRUS; HIV DNA INTEGRATION; REVERSE-TRANSCRIPTASE; ZIDOVUDINE AZT; POL GENE; INVITRO; CELLS; PROTEIN; MONOPHOSPHATE; METABOLISM AB The effects of 3'-azido-3'-deoxythymidine (AZT) and three of its intracellular metabolites, azido- thymidine mono-, di-, and triphosphates, on the human immunodeficiency virus type 1 integrase have been determined. AZT mono-, di-, and triphosphate have an IC50 for integration between 110 and 150 mu M, whereas AZT does not inhibit the integrase. The inhibition by AZT monophosphate can be partially reversed by coincubation with either thymidine monophosphate or 2',3'-dideoxythymidine monophosphate, suggesting that either of these monophosphates can bind to the integrase but that the azido group at the 3' position could be responsible for the inhibition, Integrase inhibition is associated with reduced enzyme-DNA binding but does not appear to be competitive with respect to the DNA substrate. Inhibition of an integrase deletion mutant containing only amino acids 50-212 suggests that these nucleotides bind in the catalytic core, Concentrations up to 1 mM AZT monophosphate can accumulate in vivo, indicating that integrase inhibition may contribute to the antiviral effects of AZT. The increasing incidence of AZT-resistant virus strains may, therefore, be associated with mutations not only in the reverse transcriptase but also in the human immunodeficiency virus integrase. Finally, these observations suggest that additional strategies for antiviral drug development could be based upon nucleotide analogs as inhibitors of human immunodeficiency virus integrase. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 33 TC 76 Z9 76 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5771 EP 5775 DI 10.1073/pnas.91.13.5771 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100008 PM 8016063 ER PT J AU WEITZMAN, MD KYOSTIO, SRM KOTIN, RM OWENS, RA AF WEITZMAN, MD KYOSTIO, SRM KOTIN, RM OWENS, RA TI ADENOASSOCIATED VIRUS (AAV) REP PROTEINS MEDIATE COMPLEX-FORMATION BETWEEN AAV DNA AND ITS INTEGRATION SITE IN HUMAN DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADENOASSOCIATED VIRUS; CELLS; EXPRESSION; ORIGIN; IDENTIFICATION; REPLICATION; VECTOR; TYPE-2; RECOMBINATION; ORGANIZATION AB AAV is unique among eukaryotic viruses in the ability of its DNA to integrate preferentially into a specific region of the human genome. Understanding AAV integration may aid in developing gene therapy systems with predictable integration sites. Using a gel mobility-shift assay, we have identified a DNA sequence within the AAV integration locus on human chromosome 19 which is specifically bound by the AAV Rep78 and Rep68 proteins. This Rep recognition sequence is a GCTC repeating moth very similar to sequences within the inverted terminal repeats of the AAV genome which are also bound by Rep78 and Rep68. Cloned oligonucleotides containing the recognition sequence can direct specific binding by Rep proteins. Binding assays with mutant Rep proteins show that the amino-terminal portion of Rep78 and Rep68 can direct binding to either the AAV terminal repeat hairpin DNA or chromosome 19. This human genomic DNA can be complexed with AAV DNA by Rep proteins as demonstrated by a dual-label (P-32/biotin) assay. These results suggest a role for Rep in targeting viral integration. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD 20878. RI kotin, robert/B-8954-2008 NR 28 TC 270 Z9 273 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5808 EP 5812 DI 10.1073/pnas.91.13.5808 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100016 PM 8016070 ER PT J AU LANGER, JA RASHIDBAIGI, A GAROTTA, G KEMPNER, E AF LANGER, JA RASHIDBAIGI, A GAROTTA, G KEMPNER, E TI RADIATION INACTIVATION OF HUMAN GAMMA-INTERFERON - CELLULAR ACTIVATION REQUIRES 2 DIMERS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TARGET SIZE; RECEPTOR ID HUMAN IMMUNE INTERFERON; DNA-BINDING PROTEINS; HUMAN GROWTH-HORMONE; TYROSINE PHOSPHORYLATION; EXTRACELLULAR DOMAIN; PARTIAL-PURIFICATION; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; EUKARYOTIC CELLS AB gamma-Interferon (IFN-gamma) is a 17-kDa broad-spectrum cytokine which exerts its effects on a variety of target cells through its interaction with the IFN-gamma receptor. Although physicochemical studies of Escherichia coli-derived IFN-gamma, as well as its crystal structure, demonstrate that it is a homodimer in solution (M(r) 34,000), previous radiation inactivation studies yielded a functional size for IFN-gamma of 63-73 kDa in an antiviral assay. To understand the relationship between the solution form of IFN-gamma and the moiety that actually binds to the cellular receptor and activates cells, we examined irradiated nonradioactive and P-32-labeled IFN-gamma for its migration in SDS/polyacrylamide gels (to determine its physical integrity), its binding to cells, its reactivity in an ELISA, and its antiviral activity. The functional size of IFN-gamma differed in the assays, being 22 +/- 2 kDa for the physical destruction of IFN-gamma, 56 +/- 2 kDa for the cellular binding assay, 45-50 kDa for reactivity in the ELISA, and 72 +/- 6 kDa for antiviral activity. The results from the binding assays constitute direct evidence that IFN-gamma binds to its cellular receptor as a dimer. However, for antiviral activity, the functional mass is equivalent to a tetramer. This is consistent with models involving ligand-induced receptor dimerization, whereby two dimers acting in concert (equivalent to the target size of a tetramer) are required to activate cells in the antiviral assay. C1 HOFFMANN LA ROCHE AG,DEPT IMMUNOL,BASEL,SWITZERLAND. NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. RP LANGER, JA (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOLEC GENET & MICROBIOL,PISCATAWAY,NJ 08854, USA. NR 57 TC 18 Z9 19 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5818 EP 5822 DI 10.1073/pnas.91.13.5818 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100018 PM 8016072 ER PT J AU PRUSS, D BUSHMAN, FD WOLFFE, AP AF PRUSS, D BUSHMAN, FD WOLFFE, AP TI HUMAN-IMMUNODEFICIENCY-VIRUS INTEGRASE DIRECTS INTEGRATION TO SITES OF SEVERE DNA DISTORTION WITHIN THE NUCLEOSOME CORE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA STRUCTURE; CHROMATIN; KINKS ID I-HYPERSENSITIVE SITES; RETROVIRAL INTEGRATION; PREFERRED TARGETS; PROTEIN INVITRO; CHROMATIN; MAP; MINICHROMOSOMES; RESOLUTION; SUPERHELIX; HOTSPOTS AB We have examined the consequences of DNA distortion and specific histone-DNA contacts within the nucleosome for integration mediated by the human immunodeficiency virus (HIV)-encoded Integrase enzyme. We find that sites of high-frequency integration cluster in the most severely deformed, kinked DNA regions within the nucleosome core. This may reflect either a preference for a wide major groove for association of the integrase or a requirement for target DNA distortion in the DNA strand transfer mechanism. Both the distortion and folding of the target DNA through packaging into nucleosomes may influence the selection of HIV integration sites within the chromosome. C1 SALK INST BIOL STUDIES,INFECT DIS LAB,LA JOLLA,CA 93014. RP PRUSS, D (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01 AI 34786] NR 28 TC 190 Z9 192 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5913 EP 5917 DI 10.1073/pnas.91.13.5913 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100037 PM 8016088 ER PT J AU BERRETTINI, WH FERRARO, TN GOLDIN, LR WEEKS, DE DETERAWADLEIGH, S NURNBERGER, JI GERSHON, ES AF BERRETTINI, WH FERRARO, TN GOLDIN, LR WEEKS, DE DETERAWADLEIGH, S NURNBERGER, JI GERSHON, ES TI CHROMOSOME-18 DNA MARKERS AND MANIC-DEPRESSIVE ILLNESS - EVIDENCE FOR A SUSCEPTIBILITY GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BIPOLAR ILLNESS; LINKAGE; GENETIC VULNERABILITY ID PEDIGREE-MEMBER METHOD; LINKAGE ANALYSIS; AFFECTIVE-DISORDERS; MAP; INVOLVEMENT; PROTEINS; GENOME; SEARCH; LOCI; GOLF AB In the course of a systematic genomic survey, 22 manic-depressive (bipolar) families were examined for linkage to 11 chromosome 18 pericentromeric marker loci, under dominant and recessive models. Overall logarithm of odds score analysis for the pedigree series was not significant under either model, but several families yielded logarithm of odds scores consistent with linkage under dominant or recessive models. Affected sibling pair analysis of these data yielded evidence for linkage (P < 0.001) at D18S21. Affected pedigree member analysis also suggests linkage, with multilocus results for five loci giving P < 0.0001 and P = 0.0007 for weighting functions f(p) = 1 and 1/root p, respectively, where p is the allele frequency. These results imply a susceptibility gene in the pericentromeric region of chromosome 18, with a complex mode of inheritance. Two plausible candidate genes, a corticotropin receptor and the alpha subunit of a GTP binding protein, have been localized to this region. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT GENET,PITTSBURGH,PA 15261. INDIANA UNIV,INST PSYCHIAT RES,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202. RP BERRETTINI, WH (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT & HUMAN BEHAV,1025 WALNUT ST,312 COLL,PHILADELPHIA,PA 19107, USA. RI Weeks, Daniel/B-2995-2012; OI Nurnberger, John/0000-0002-7674-1767; Weeks, Daniel/0000-0001-9410-7228 FU NCRR NIH HHS [1 P41 RR03655] NR 47 TC 347 Z9 350 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5918 EP 5921 DI 10.1073/pnas.91.13.5918 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100038 PM 8016089 ER PT J AU FABIAN, JR VOJTEK, AB COOPER, JA MORRISON, DK AF FABIAN, JR VOJTEK, AB COOPER, JA MORRISON, DK TI A SINGLE AMINO-ACID CHANGE IN RAF-1 INHIBITS RAS BINDING AND ALTERS RAF-1 FUNCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; GTP-BINDING PROTEIN; PROTEIN-SERINE; THREONINE KINASES ID THREONINE PROTEIN-KINASE; SIGNAL TRANSDUCTION; XENOPUS-OOCYTES; ONCOGENIC P21(RAS); GROWTH-FACTORS; MAP KINASE; HA-RAS; PHOSPHORYLATION; MATURATION; DOWNSTREAM AB Ras and Raf-1 are key proteins involved in the transmission of developmental and proliferative signals generated by receptor and nonreceptor tyrosine kinases. Genetic and biochemical studies demonstrate that Raf-1 functions downstream of Ras in many signaling pathways. Although Raf-1 directly associates with GTP-bound Ras, an effect of this interaction on Raf-1 activity in vivo has not been established. To examine the biological consequence of the Ras/Raf-1 interaction in vivo, we set out to identify key residues of Raf-1 required for Ras binding. In this report, we show that a single amino acid mutation in Raf-1 (Arg(89) to Leu) disrupted the interaction with Ras in vitro and in the yeast two-hybrid system. This mutation prevented Ras-mediated but not tyrosine kinase-mediated enzymatic activation of Raf-1 in the baculovirus/Sf9 expression system. Furthermore, kinase defective Raf-1 proteins containing the Arg(89) --> Leu mutation were no longer dominant-inhibitory or capable of blocking Ras-mediated signal transduction in Xenopus laevis oocytes. These results demonstrate that the association of Raf-1 and Ras modulates both the kinase activity and the biological function of Raf-1 and identify Arg(89) as a critical residue involved in this interaction. In addition, the finding that tyrosine kinases can stimulate the enzymatic activity of Raf-1 proteins containing a mutation at the Ras-interaction site suggests that Raf-1 can be activated by Ras-independent pathways. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP FABIAN, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC MECHANISMS CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [CA54786, N01-CO-74101] NR 42 TC 153 Z9 153 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5982 EP 5986 DI 10.1073/pnas.91.13.5982 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100051 PM 8016101 ER PT J AU VENKATARAMAN, G SASISEKHARAN, V COONEY, CL LANGER, R SASISEKHARAN, R AF VENKATARAMAN, G SASISEKHARAN, V COONEY, CL LANGER, R SASISEKHARAN, R TI A STEREOCHEMICAL APPROACH TO PYRANOSE RING FLEXIBILITY - ITS IMPLICATIONS FOR THE CONFORMATION OF DERMATAN SULFATE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CONFORMATIONAL FLEXIBILITY; GLYCOSAMINOGLYCANS; STEREOCHEMISTRY ID L-IDURONATE RESIDUE; FORCE-FIELD; NMR; GLYCOSAMINOGLYCANS; HEPARIN; STATE AB Glycosaminoglycans, such as heparin, heparan sulfate, and dermatan sulfate, are characterized by a disaccharide repeating unit of a uronate and a hexosamine and are increasingly understood to be important physiologically as soluble components of the extracellular matrix. The secondary structure of this class of acidic polysaccharides is believed to play a key role in determining the wide range of biological specificities. Central to the structural diversity of the glycosaminoglycans is the experimentally documented conformational flexibility of the iduronate residue. Here, we outline an approach to explore the iduronate conformational flexibility by imposing stereochemical criteria of nonbonded contact distances. By performing a complete search of all possible torsions that define the iduronate ring geometry, we eliminate any prior bias with regard to minimum energy conformers. The approach led to alternative feasible conformers for the iduronate ring that are stereochemically satisfactory and are consistent with the available physico-chemical data. C1 MIT, HARVARD MIT DIV HLTH SCI & TECHNOL, CAMBRIDGE, MA 02139 USA. MIT, DEPT CHEM ENGN, CAMBRIDGE, MA 02139 USA. NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM 25810] NR 29 TC 32 Z9 32 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 6171 EP 6175 DI 10.1073/pnas.91.13.6171 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100090 PM 8016133 ER PT J AU SUPRYNOWICZ, FA PRUSMACK, C WHALLEY, T AF SUPRYNOWICZ, FA PRUSMACK, C WHALLEY, T TI CA2+ TRIGGERS PREMATURE INACTIVATION OF THE CDC2 PROTEIN-KINASE IN PERMEABILIZED SEA-URCHIN EMBRYOS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MITOSIS; ELECTROPORATION; CYCLIN ID MATURATION-PROMOTING FACTOR; NUCLEAR-ENVELOPE BREAKDOWN; INTRACELLULAR FREE CALCIUM; SAND DOLLAR EMBRYOS; CELL-FREE SYSTEM; MITOTIC APPARATUS; M-PHASE; SACCHAROMYCES-CEREVISIAE; CA-2+-TRANSPORT SYSTEM; CYCLIN DESTRUCTION AB Exit from mitosis requires inactivation of the cyclin B-p34(cdc2) protein kinase complex. Since increased cytosolic Ca2+ has been implicated as a potential trigger of mitotic progression, we directly tested the possibility that Ca2+ triggers the pathway responsible for inactivating the cdc2 kinase, using sea urchin embryos permeabilized at various stages of the cell cycle. In cells permeabilized during late interphase and prophase, micromolar Ca2+ induced premature inactivation of the cdc2 kinase without affecting the absolute amount of p34(cdc2) protein. Inactivation was selective for the cdc2 kinase, as elevated Ca2+ had no effect on cAMP-dependent protein kinase activity. Premature cdc2 kinase inactivation did not require cyclin B destruction, but did coincide with the dissociation of cyclin B-q34(cdc2) complexes. In cells permeabilized during prometaphase and metaphase, cdc2 kinase inactivation was Ca2+-independent, presumably because at these later times the inactivating pathway had been enabled prior to permeabilization. This work provides evidence that Ca2+ is the physiological trigger enabling cdc2 kinase inactivation during mitosis. RP SUPRYNOWICZ, FA (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. OI Whalley, Tim/0000-0003-3362-0006 NR 50 TC 19 Z9 20 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 6176 EP 6180 DI 10.1073/pnas.91.13.6176 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100091 PM 8016134 ER PT J AU HOFFMAN, RC SCHALKHIHI, C CASTNER, BJ GIBSON, MG RASMUSSEN, BD ZDANOV, A GUSTCHINA, A MARCH, CJ WLODAWER, A AF HOFFMAN, RC SCHALKHIHI, C CASTNER, BJ GIBSON, MG RASMUSSEN, BD ZDANOV, A GUSTCHINA, A MARCH, CJ WLODAWER, A TI STOICHIOMETRY OF THE COMPLEX OF HUMAN INTERLEUKIN-4 WITH ITS RECEPTOR SO FEBS LETTERS LA English DT Article DE INTERLEUKIN-4; INTERLEUKIN-4 RECEPTOR; CYTOKINE; STOICHIOMETRY ID HUMAN GROWTH-HORMONE; CRYSTAL-STRUCTURE; GAMMA-CHAIN; EXTRACELLULAR DOMAIN; FUNCTIONAL COMPONENT; CYTOKINES; SUPERFAMILY; CELLS; IL-2 AB A large number of cytokines have been shown to possess a four-helix bundle structure with a unique up-up-down-down connectivity. The receptors for this family of cytokines have been shown to be homologous as well, each possessing two tandem repeats of a fibronectin type III-like domain. The crystal structure of human growth hormone bound to the soluble portion of its receptor has served as the only experimentally-determined example of the interaction between the four-helix bundle cytokines and their receptors: two identical receptor subunits bind to different epitopes on the same growth hormone ligand. We have conducted a series of experiments to determine if this structural paradigm is true for interleukin-4 and interleukin-4 receptor. Native polyacrylamide gel electrophoresis and gel filtration chromatography reveal that interleukin-4 forms a tight 1:1 complex with the soluble portion of interleukin-4 receptor and is thus unlike the growth hormone system. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 26 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 20 PY 1994 VL 347 IS 1 BP 17 EP 21 DI 10.1016/0014-5793(94)00496-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NU389 UT WOS:A1994NU38900005 PM 8013654 ER PT J AU TALPIR, R BENAYAHU, Y KASHMAN, Y PANNELL, L SCHLEYER, M AF TALPIR, R BENAYAHU, Y KASHMAN, Y PANNELL, L SCHLEYER, M TI HEMIASTERLIN AND GEODIAMOLIDE-TA - 2 NEW CYTOTOXIC PEPTIDES FROM THE MARINE SPONGE HEMIASTERELLA-MINOR (KIRKPATRICK) SO TETRAHEDRON LETTERS LA English DT Article ID ANTIMICROBIAL PEPTIDE; DISCODERMIA-KIIENSIS; METABOLITES AB Three cytotoxic peptides, Jaspamide (1) and the two new peptides hemiasterlin (2) and geodiamolide TA (3), have been isolated from the sponge Hemiasterella minor. The structures of the three were determined by interpretating the NMR and mass spectra. Hemiasterlin (2) is a novel linear tripeptide embodying two unique, new natural aminoacids and geodiamolide TA (3) is a higher homologe of geodiamolides A-F. C1 TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,DEPT ZOOL,IL-69978 TEL AVIV,ISRAEL. NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. OCEANOG INST,DURBAN,SOUTH AFRICA. NR 9 TC 119 Z9 123 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 20 PY 1994 VL 35 IS 25 BP 4453 EP 4456 DI 10.1016/S0040-4039(00)73382-X PG 4 WC Chemistry, Organic SC Chemistry GA NT655 UT WOS:A1994NT65500053 ER PT J AU YAN, XJ WANG, SM HODOSCEK, M MILNE, GWA AF YAN, XJ WANG, SM HODOSCEK, M MILNE, GWA TI PREDICTION OF GEOMETRIES AND INTERACTION ENERGIES OF COMPLEXES FORMED BY SMALL MOLECULES USING SEMIEMPIRICAL AND AB-INITIO METHODS SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article ID GROUND-STATES; MINDO-3 CALCULATIONS; PARAMETERS; HYDROGEN; OPTIMIZATION; MODEL AB The accuracy of the semiempirical quantum mechanics methods (AMI and PM3), and the ab initio methods (6-31G** and MP2/6-31G**) in predicting intermolecular geometries and interaction energies have been evaluated by detailed studies of 17 bimolecular complexes formed by small molecules. Comparisons between calculated and experimental geometries for 12 complexes are presented. It was found that AM1 gave reasonably good predictions of the geometries of complexes such as CH4 ... CH4, which have very weak interactions, but it is not as good as other methods in predicting intermolecular geometry for complexes where hydrogen bonding interactions play an important role. This is consistent with its inability to reproduce the charge transfer in the formation of hydrogen bonds in these complexes. PM3 is able to predict intermolecular geometries for most complexes, including those with hydrogen bonding; its. major flaw is its tendency to overestimate the strength of the interactions between hydrogen atoms. Care should be taken therefore in using PM3 to study complicated molecular systems with multiple hydrogen atom interactions and the method's weakness in handling complexes in which electrostatic forces are important should also be noted. Among ab initio methods, both the 6-31G** and the MP2/6-31G** were found to outperform AM1 and PM3 in prediction of intermolecular geometry. Both of these ab initio methods showed excellent consistency in geometry prediction for most of the complexes studied, although MP2/6-31G** is better than 6-31G**. It is noted that the MP2/6-31G** did not produce the correct geometry for the CO2 ... HF complex. For 12 complexes for which experimental geometry data are available, AMI, PM3, 6-31G**, and MP2/6-31G** successfully predicted the geometry in 10, 12, 12, and 11 cases, respectively. The average errors given by AM1 in the predicted intermolecular distances were 0.264, 0.272, 0.091, and 0.061 angstrom, respectively. In comparison to the ab initio methods, AM1 and PM3 commonly underestimated the molecular interaction energy in such complexes by approximately 1-2 kcal mol-1. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JUN 20 PY 1994 VL 115 IS 3 BP 279 EP 294 PG 16 WC Chemistry, Physical SC Chemistry GA NX185 UT WOS:A1994NX18500007 ER PT J AU CLERICI, M BEVILACQUA, M VAGO, T VILLA, ML SHEARER, GM NORBIATO, G AF CLERICI, M BEVILACQUA, M VAGO, T VILLA, ML SHEARER, GM NORBIATO, G TI AN IMMUNOENDOCRINOLOGICAL HYPOTHESIS OF HIV-INFECTION SO LANCET LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HUMAN MEDULLARY THYMOCYTES; GLUCOCORTICOID RECEPTOR; T-CELLS; IMMUNE-RESPONSES; IMMUNOGLOBULIN-E; GENE-EXPRESSION; INTERLEUKIN-2; DEHYDROEPIANDROSTERONE; SYSTEM C1 OSPED L SACCO,SERV ENDOCRINOL,MILAN,ITALY. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CLERICI, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,VIA VENEZIA 1,I-20133 MILAN,ITALY. NR 27 TC 55 Z9 55 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 18 PY 1994 VL 343 IS 8912 BP 1552 EP 1553 DI 10.1016/S0140-6736(94)92944-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NR329 UT WOS:A1994NR32900014 PM 7911876 ER PT J AU BOUVET, P WOLFFE, AP AF BOUVET, P WOLFFE, AP TI A ROLE FOR TRANSCRIPTION AND FRGY2 IN MASKING MATERNAL MESSENGER-RNA WITHIN XENOPUS-OOCYTES SO CELL LA English DT Article ID RNA-BINDING-PROTEINS; MESSENGER-RIBONUCLEOPROTEIN PARTICLES; HISTONE GENE CLUSTERS; POLYMERASE-III; LAEVIS OOCYTES; TRANSLATION; NUCLEAR; EMBRYOS; DNA; IDENTIFICATION AB We find that mRNA synthesized within the Xenopus oocyte nucleus is translated with an efficiency 50 times less than that of mRNA injected into the oocyte cytoplasm. For histone H1 mRNA this effect is independent of mRNA splicing, nuclear export, and the promoter driving transcription. The mRNA synthesized in vivo is translationally competent but is masked from the translational machinery in the cytoplasm through association with proteins including frog Y-box protein 2 (FRGY2). We find that overexpression of FRGY2 facilitates the translational repression of mRNA synthesized within Xenopus oocytes. The requirement for transcription to occur in vivo before a translationally repressed state can be established suggests that these two events are functionally coupled in Xenopus oocytes. RP BOUVET, P (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 70 TC 164 Z9 170 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 17 PY 1994 VL 77 IS 6 BP 931 EP 941 DI 10.1016/0092-8674(94)90141-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT331 UT WOS:A1994NT33100017 PM 8004679 ER PT J AU JI, H LEUNG, M ZHANG, Y CATT, KJ SANDBERG, K AF JI, H LEUNG, M ZHANG, Y CATT, KJ SANDBERG, K TI DIFFERENTIAL STRUCTURAL REQUIREMENTS FOR SPECIFIC BINDING OF NONPEPTIDE AND PEPTIDE ANTAGONISTS TO THE AT(1) ANGIOTENSIN RECEPTOR - IDENTIFICATION OF AMINO-ACID-RESIDUES THAT DETERMINE BINDING OF THE ANTIHYPERTENSIVE DRUG LOSARTAN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PROTEIN-COUPLED RECEPTORS; BETA-ADRENERGIC-RECEPTOR; II TYPE-1 RECEPTOR; MOLECULAR-CLONING; SUBSTANCE-P; EXPRESSION; SUBTYPE; MUTAGENESIS; DISTINCT AB The biphenylimidazole derivative losartan exemplifies a novel class of nonpeptide antagonists that selectively inhibit angiotensin II binding to the mammalian AT(1) receptor and have potentially wide application as anti-hypertensive agents. In contrast to mammalian AT(1) receptors, which have high affinity for both peptide antagonists and losartan, amphibian and avian angiotensin II receptors are pharmacologically distinct and recognize peptide but not nonpeptide antagonists. Mutant rat AT(1) receptors in which non conserved amino acids were replaced by the corresponding amphibian residues were constructed to identify specific sites in the AT(1) receptor that determine losartan binding. Only minor changes in binding affinity for peptide antagonists were observed in COS-7 cells transiently expressing mutant receptors, indicating that the structural integrity of the receptor was maintained. However, analysis of receptors with single point and combined mutations revealed that specific residues in transmembrane domains III, IV, V, VI, and VII are involved in binding of the nonpeptide antagonist to the mammalian AT(1) receptor. The most marked attenuation of losartan binding (IC50 > 50 mu M) was observed in a mutant receptor containing amino acid substitutions at Val(108), Ala(163), Thr(198), Ser(252), Leu(300), and Phe(301). These results have demonstrated that the inding site of a potent nonpeptide antagonist of the AT(1) receptor is defined by epitopes located within the membrane-spanning regions of the receptor and is distinct from the site at which peptide antagonists bind to the AT(1) receptor. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 30 TC 129 Z9 133 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16533 EP 16536 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600004 PM 8206967 ER PT J AU MOROZOV, VE FALZON, M ANDERSON, CW KUFF, EL AF MOROZOV, VE FALZON, M ANDERSON, CW KUFF, EL TI DNA-DEPENDENT PROTEIN-KINASE IS ACTIVATED BY NICKS AND LARGER SINGLE-STRANDED GAPS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; TERMINAL TRANSACTIVATION DOMAIN; VIRUS-40 T-ANTIGEN; KU PROTEIN; CELL-CYCLE; HUMAN P53; PHOSPHORYLATION; BINDING; AUTOANTIGEN; EBP-80 AB DNA-PK is a DNA-activated serine/threonine protein kinase capable of phosphorylating a number of nuclear DNA-binding proteins. Purified human DNA-PK has two subunits, a 350-kDa polypeptide, Prkdc, which binds ATP and is presumed to contain the catalytic site, and the Ku autoantigen which mediates DNA binding and activation. Previous studies have shown that DNA-PK is activated in vitro by linear double-stranded DNA fragments; however, the Ku subunit binds a broader range of DNA structures. Here we show that EBP-80, a protein originally isolated as a transcription factor for a retroviral long terminal repeat element and subsequently found to be similar to if not identical with Ku, also mediates kinase activation. The EBP-80-Prkdc complex is activated by nanomolar concentrations of DNA constructs containing single-to-double strand transitions, including a closed stem-loop structure and single strand gaps of 0 (nick), 6, and 30 nucleotides. Kinase activation parallels the ability of EBP-80 to bind these and other constructs. Our results extend the range of DNA configurations known to activate DNA-PK and are consistent with the participation of this enzyme complex in several nuclear functions. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV TEXAS,DEPT PHARMACOL & TOXICOL,GALVESTON,TX 77555. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. NR 34 TC 131 Z9 132 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16684 EP 16688 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600028 PM 8206988 ER PT J AU MENENDEZARIAS, L WEBER, IT SOSS, J HARRISON, RW GOTTE, D OROSZLAN, S AF MENENDEZARIAS, L WEBER, IT SOSS, J HARRISON, RW GOTTE, D OROSZLAN, S TI KINETIC AND MODELING STUDIES OF SUBSITES S-4-S-3' OF MOLONEY MURINE LEUKEMIA-VIRUS PROTEASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA VIRUS; MYELOBLASTOSIS-ASSOCIATED VIRUS; INFECTIOUS-ANEMIA VIRUS; MAMMARY-TUMOR VIRUS; HIV-1 PROTEINASE; ASPARTIC PROTEASE; CRYSTAL-STRUCTURE; CRYSTALLOGRAPHIC STRUCTURE; SUBSTRATE-SPECIFICITY AB The substrate specificity of the Moloney murine leukemia virus protease (Mo-MuLV PR) was analyzed by using the oligopeptide substrate Val-Ser-Gln-Asn-Tyr down arrow Pro-Ile-Val-Gln-NH2 and a series of analogs containing single amino acid substitutions in the P-4-P-3' positions. Mo-MuLV PR appears to act similarly to the human immunodeficiency virus (HIV) PRs, except for peptides having substitutions at P-4 and P-2 positions. Mo-MuLV PR shows a strong preference for the analogs having hydrophobic residues, such as Val or Ile at P-4, and Ile and Leu at P-2, in contrast to HIV-1 and HIV-2 PRs, which prefer smaller or more polar residues at both positions. We built a molecular model of Mo-MuLV PR on the basis of the crystal structure of the related HIV PR. Although the overall structure of Mo-MuLV PR is predicted to be close to that of HIV-1 PR, almost all of the residues forming the subsites are different. The increased hydrophobicity due to the pro(12) insertion and the presence of more aromatic residues in the S-4 subsite of Mo-MuLV PR compared to HIV-1 and HIV-2 PRs can be correlated with the observed differences using P-4-substituted analogs of VSQNYPIVQ. The preference of Mo-MuLV PR for larger hydrophobic residues at the P-2 position can be correlated with the larger size of its S-2 subsite, due in part to the presence of Val(39) Ala(57), and His(84) in Mo-MuLV PR, instead of Ile(32), Ile(50), and Met(76), respectively, as occurs in HIV-2 PR. C1 THOMAS JEFFERSON UNIV, JEFFERSON CANC INST, DEPT PHARMACOL, PHILADELPHIA, PA 19107 USA. RP MENENDEZARIAS, L (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RI Menendez Arias, Luis /G-2436-2016; Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 FU NCI NIH HHS [N01-CO-74101] NR 54 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16795 EP 16801 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600046 PM 8207003 ER PT J AU HATZ, P WHALEN, G KEHRL, JH AF HATZ, P WHALEN, G KEHRL, JH TI DIFFERENTIAL EXPRESSION OF A NOVEL PROTEIN-KINASE IN HUMAN B-LYMPHOCYTES - PREFERENTIAL LOCALIZATION IN THE GERMINAL CENTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; PRIMARY IMMUNE-RESPONSE; SACCHAROMYCES-CEREVISIAE; CONSERVED FEATURES; ANTIGEN; ENCODES; (4-HYDROXY-3-NITROPHENYL)ACETYL; IDENTIFICATION; ACTIVATION; GENERATION AB B lymphocytes which reside in the germinal center region of lymphoid follicles are functionally and phenotypically distinct from the surrounding mantle zone B cells. We have isolated cDNA clones for several genes that are differentially expressed between these two populations of B lymphocytes. One such gene, BL44, is preferentially expressed in germinal center B cells. The nucleotide sequence of a 2,874-base pair EL44 cDNA was determined and a 2,451-bp open reading frame found that encodes for a 97-kDa serine/threonine protein kinase referred to as GC kinase. It has an NH2-terminal catalytic domain most similar to that of the Drosophila NinaC protein and the yeast STE20 protein. GC kinase mRNA transcripts are not unique to germinal center E cells and are found in several other tissues, including brain, lung, and placenta. The GC kinase protein was immunoprecipitated from transfected COS cells and from the Burkitt cell line RAMOS. GC kinase immunoprecipitated from transfected COS cells phosphorylated the substrates casein and myelin basic protein. In addition, a 97-kDa phosphoprotein likely to be GC kinase itself was detected. GC kinase may participate in an important signal transduction pathway in germinal center B cells. C1 NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, MED CTR, DEPT MED, DIV RHEUMATOL IMMUNOL & ALLERGY, WASHINGTON, DC 20007 USA. OI Kehrl, John/0000-0002-6526-159X NR 35 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16802 EP 16809 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600047 ER PT J AU GARCIAMORALES, P SACEDA, M KENNEY, N KIM, N SALOMON, DS GOTTARDIS, MM SOLOMON, HB SHOLLER, PF JORDAN, VC MARTIN, MB AF GARCIAMORALES, P SACEDA, M KENNEY, N KIM, N SALOMON, DS GOTTARDIS, MM SOLOMON, HB SHOLLER, PF JORDAN, VC MARTIN, MB TI EFFECT OF CADMIUM ON ESTROGEN-RECEPTOR LEVELS AND ESTROGEN-INDUCED RESPONSES IN HUMAN BREAST-CANCER CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; SINGLE CALCIUM CHANNELS; GROWTH FACTOR-ALPHA; MCF-7 CELLS; GENE-TRANSCRIPTION; HEAVY-METALS; RAT-BRAIN; EXPRESSION; DNA; PROTEIN AB The effects of cadmium on estrogen receptor and other estrogen-regulated genes in the human breast cancer cell line MCF-7 were studied. Treatment of MCF-7 cells with 1 mu M cadmium decreased the level of estrogen receptor 58%. Cadmium induced a parallel decrease in estrogen receptor mRNA (62%). Progesterone receptor levels increased 3.2-fold after cadmium treatment. This induction was blocked by the anti-estrogen ICI-164,384. Progesterone receptor mRNA was also increased by cadmium, as well as cathepsin D mRNA. An in vitro nuclear transcription run-on assay showed that cadmium increased the transcription of the progesterone receptor and pS2 genes and decreased transcription of the estrogen receptor gene. These are not general effects of heavy metals, as zinc, 25 and 100 mu M, did not affect progesterone receptor protein and mRNA levels. Cadmium stimulated pS2 and progesterone receptor mRNAs in a clone of MDA-MB-231 cells transfected with the human estrogen receptor, but had no effect in MDA-MB-231 cells transfected with antisense estrogen receptor. Cadmium also stimulated an estrogen response element in transient transfection experiments. These data suggest that the effects of cadmium are mediated by the estrogen receptor independent of estradiol. In addition to its effect on gene expression, cadmium induced the growth of MCF-7 cells 5.6-fold. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,DEPT MED ONCOL,WASHINGTON,DC 20007. NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,MADISON,WI 53792. RI Saceda, Miguel/A-1581-2008; Jordan, V. Craig/H-4491-2011 NR 44 TC 172 Z9 176 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16896 EP 16901 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600058 PM 8207012 ER PT J AU MINOGUCHI, K BENHAMOU, M SWAIM, WD KAWAKAMI, Y KAWAKAMI, T SIRAGANIAN, RP AF MINOGUCHI, K BENHAMOU, M SWAIM, WD KAWAKAMI, Y KAWAKAMI, T SIRAGANIAN, RP TI ACTIVATION OF PROTEIN-TYROSINE KINASE P72(SYK) BY FC-EPSILON-RI AGGREGATION IN RAT BASOPHILIC LEUKEMIA-CELLS P72(SYK) IS A MINOR COMPONENT BUT THE MAJOR PROTEIN-TYROSINE KINASE OF PP72 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY; ANTIGEN RECEPTOR; IMMUNOGLOBULIN-E; PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; MAST-CELLS; ZETA-CHAIN; MONOCLONAL-ANTIBODIES; CROSS-LINKING; RBL-2H3 CELLS AB Aggregation of the high affinity IgE receptors (Fc epsilon RI) on rat basophilic leukemia RBL-2H3 cells results in protein tyrosine phosphorylations. Previously we reported that there is prominent tyrosine phosphorylation of similar to 72-kDa proteins (pp72) and that the tyrosine kinase p72(syk) is one component of pp72. Here we studied further the relationship of p72(syk) to pp72. The aggregation of Fc epsilon RI induced the activation of p72(syk) which was parallel to its tyrosine phosphorylation. By in vitro kinase assay of immune complexes purified with anti-phosphotyrosine antibodies, p72(syk) was the major pp72 tyrosine kinase. However, by immunoblotting with anti-phosphotyrosine antibodies, p72(syk) was a minor component of pp72. The heterogeneous nature of pp72 was indicated by different studies. Under optimum conditions of one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, pp72 consisted of a heterogeneous group of 69-, 71-, and 72-kDa tyrosine-phosphorylated proteins. There were differences in the tyrosine phosphorylation of these proteins in cells activated in the absence of extracellular calcium or when stimulation was with the calcium ionophore A23187 or with phorbol myristate acetate. One of the proteins migrating at 69 kDa was p72(syk). By two-dimensional gel electrophoresis pp72 was found to consist of multiple tyrosine-phosphorylated proteins including 71-80-kDa proteins that associate with p53/56(lyn). A 75-kDa tyrosine-phosphorylated protein, different from pp72, was identified as p75(HS1) (SPY75). These results demonstrate the heterogeneous nature of the pp72 and that p72(syk) is activated after Fc epsilon RI aggregation. C1 LA JOLLA INST ALLERGY & IMMUNOL,DIV IMMUNOBIOL,LA JOLLA,CA 92037. RP MINOGUCHI, K (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. RI Kawakami, Toshiaki/O-1616-2015 NR 49 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16902 EP 16908 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600059 PM 7515887 ER PT J AU KOEPKE, MBK SCHMIEDEKAMP, AM MICHEJDA, CJ AF KOEPKE, MBK SCHMIEDEKAMP, AM MICHEJDA, CJ TI THEORETICAL INVESTIGATION OF REACTION PATHWAYS OF 3-METHYLOXADIAZOLINIUM ION AND 1,2,3-OXADIAZOLINE - CORRELATION WITH EXPERIMENTAL FINDINGS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID HYDROXYLATED NITROSAMINES; DECOMPOSITION; RATS AB Quantum mechanical calculations were used to investigate the stability of the 3-methyloxadiazolinium ion and 1,2,3-oxadiazoline and to determine the most probable thermal decomposition pathway of the oxadiazoline. Ab initio RHF calculations were carried out at the 3-21G and 6-31G* basis set level to obtain the optimized SCF energies and geometries of these molecules, as well as that of the protonated 4,5-dihydro-2,3-oxadiazolidine. Only the N2-protonated oxadiazoline was found to be stable; the N1- and O-protonated oxadiazolines underwent immediate decomposition. Calculations on the oxadiazolinium ion confirmed experimental results regarding the most likely site of nucleophilic attach on the molecule. Sequential bond-stretching of the N-O, N-C, and O-C bonds of the optimized oxadiazoline molecule revealed that breakage of the N-O bond leading to diazomethane and formaldehyde was energetically the most favorable pathway at all levels of theory (energy of activation (E(a)) of 18.8 kcal/mol at the MP2/6-31G* level). This result is consistent with the experimental finding of methylation of DNA guanine by N-(2-hydroxyethyl)-N-nitrosomethylamine [C-14]-labeled in the ethyl group, which has been postulated to involve the oxadiazoline as the methylating agent. Breakage of the N-C bond led to nitrogen gas and acetaldehyde as products with an E(a) of 25.2 kcal/mol, while the stretching of the O-C bond led to the production of nitrous oxide and ethene with an E(a) of 28.8 kcal/mol. Breakage of the N-O bond in the N2-protonated oxadiazoline occurred with an E(a) of 40.0 kcal/mol, the least energetically favorable process. Optimized geometries and energies for the reactant, transition state, and product molecules were obtained at post Hartree-Fock using MP2 and QCISD, as well as the density functional code, DGauss. Comparison of the optimized geometries of the transition states from the three different bond-breakage processes revealed minor differences in these structures at the various levels of theory. RP KOEPKE, MBK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702, USA. NR 31 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 17 PY 1994 VL 59 IS 12 BP 3301 EP 3306 PG 6 WC Chemistry, Organic SC Chemistry GA NU181 UT WOS:A1994NU18100016 ER PT J AU VARMUS, H AF VARMUS, H TI NIH R-AND-D PRIORITIES SO SCIENCE LA English DT Letter RP VARMUS, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 17 PY 1994 VL 264 IS 5166 BP 1649 EP 1649 DI 10.1126/science.8209238 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR600 UT WOS:A1994NR60000002 PM 8209238 ER PT J AU NAVERI, L STROMBERG, C SAAVEDRA, JM AF NAVERI, L STROMBERG, C SAAVEDRA, JM TI ANGIOTENSIN-II AT(2) RECEPTOR STIMULATION INCREASES CEREBROVASCULAR RESISTANCE DURING HEMORRHAGIC HYPOTENSION IN RATS SO REGULATORY PEPTIDES LA English DT Article DE PD 123319; LOSARTAN; LASER-DOPPLER FLOWMETRY; CEREBRAL BLOOD FLOW; SAR(1),ILE(8)-ANG II ID CEREBRAL BLOOD-FLOW; UPPER LIMIT; ARTERIES; BRAIN; MICROCIRCULATION; HYPOPERFUSION; CONTRACTIONS; HYPERTENSION; PRESSURE; PD123177 AB The effects of the angiotensin II (ANG II) AT(2) ligand PD 123319 and the AT, antagonist losartan on cerebral blood flow (CBF) were studied during hemorrhagic hypotension in anesthetized rats using laser-Doppler flowmetry. In the control group CBF remained stable when mean arterial blood pressure (MABP) was lowered from 84 mmHg (baseline) to 45 mmHg, whereafter there was a pressure dependent decrease in CBF indicating inadequacy of autoregulation. Cerebrovascular resistance (CVR) was reduced until MABP 40 mmHg, where a maximum dilation was reached. PD 123319 dose-dependently (3-30 mg/kg i.v.) increased CVR through all blood pressures. Losartan 3 mg/kg i.v. had an effect similar to PD 123319. Selective stimulation of AT(2) receptors with intravenous ANG II infusion, in the presence of AT(1) receptor blockade by losartan, also increased CVR. As a result, reduced CBF was seen in the treatment groups. The effects of ANG II and PD 123319 30 mg/kg were antagonized by the nonselective ANG II antagonist Sar(1),Ile(8)-ANG II (4 mu g/kg/min i.v.). None of the treatments affected baseline CBF. The results confirm that ANG II contributes to cerebrovascular resistance and participates in the regulation of CBF apparently through AT(2) receptors. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. NR 38 TC 31 Z9 31 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUN 16 PY 1994 VL 52 IS 1 BP 21 EP 29 DI 10.1016/0167-0115(94)90017-5 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA NV629 UT WOS:A1994NV62900003 PM 7972928 ER PT J AU GRANDINETTI, A MORENS, DM REED, D MACEACHERN, D AF GRANDINETTI, A MORENS, DM REED, D MACEACHERN, D TI PROSPECTIVE-STUDY OF CIGARETTE-SMOKING AND THE RISK OF DEVELOPING IDIOPATHIC PARKINSONS-DISEASE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE PARKINSON DISEASE; SMOKING ID OLFACTORY FUNCTION; YOUNG-ONSET; HYPOTHESIS; NEUROTOXICITY; EPIDEMIOLOGY; EXPOSURE; ETIOLOGY; HABITS; PAIRS; TWIN AB A 26-year follow-up study of 8,006 men enrolled in the Honolulu Heart Program examined the effect of cigarette smoking on the risk of developing idiopathic Parkinson's disease. Cases were identified through an ongoing search of hospital records and by the review of death certificates and medical records of local neurologists. Men who had smoked cigarettes at any time prior to study enrollment in 1965 had a reduced risk of developing idiopathic Parkinson's disease (relative risk = 0.39). Examination of smoking by pack-years revealed an apparent dose-response effect on the risk of idiopathic Parkinson's disease, but not on the age of onset. Coffee drinking was also associated with reduced risk, apparently because of its association with cigarette smoking. Although the detrimental health effects of cigarette smoking would far outweigh any possible protective effect for smoking and Parkinson's disease, the association of smoking with apparent protection may contribute to understanding the underlying pathogenetic mechanisms. C1 UNIV HAWAII,SCH PUBL HLTH,HONOLULU,HI 96822. EAST WEST CTR,HONOLULU,HI 96848. UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI 96822. NHLBI,BETHESDA,MD 20892. FU NINDS NIH HHS [R01 NS30371] NR 68 TC 143 Z9 147 U1 0 U2 5 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1994 VL 139 IS 12 BP 1129 EP 1138 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NT490 UT WOS:A1994NT49000001 PM 8209872 ER PT J AU KULLER, L BORHANI, N FURBERG, C GARDIN, J MANOLIO, T OLEARY, D PSATY, B ROBBINS, J AF KULLER, L BORHANI, N FURBERG, C GARDIN, J MANOLIO, T OLEARY, D PSATY, B ROBBINS, J TI PREVALENCE OF SUBCLINICAL ATHEROSCLEROSIS AND CARDIOVASCULAR-DISEASE AND ASSOCIATION WITH RISK-FACTORS IN THE CARDIOVASCULAR HEALTH STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGING; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASES; CAROTID ARTERY DISEASES; CORONARY DISEASE; RISK FACTORS ID CORONARY-ARTERY DISEASE; HEART-DISEASE; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; OLDER; NECROPSY; PLAQUE; LIPIDS; MODE AB The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged greater than or equal to 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36% in women and 38.7% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease. C1 CARDIOVASC HLTH STUDY COORDINATING CTR,SEATTLE,WA. BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC. UNIV CALIF IRVINE,IRVINE MED CTR,ORANGE,CA 92668. NHLBI,BETHESDA,MD 20892. GEISINGER MED CTR,DANVILLE,PA 17822. CALIF STATE UNIV SACRAMENTO,CTR CARDIOVASC HLTH STUDY FIELD,SACRAMENTO,CA 95819. RP KULLER, L (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,130 DESOTO ST,PITTSBURGH,PA 15261, USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 36 TC 178 Z9 183 U1 2 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1994 VL 139 IS 12 BP 1164 EP 1179 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NT490 UT WOS:A1994NT49000004 PM 8209875 ER PT J AU BLOCK, G COYLE, LM HARTMAN, AM SCOPPA, SM AF BLOCK, G COYLE, LM HARTMAN, AM SCOPPA, SM TI REVISION OF DIETARY ANALYSIS SOFTWARE FOR THE HEALTH HABITS AND HISTORY QUESTIONNAIRE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE DIET; EPIDEMIOLOGIC METHODS; NUTRITION ASSESSMENT; NUTRITION SURVEYS ID NHANES-II SURVEY; QUANTITATIVE DATA; NUTRIENT SOURCES; AMERICAN DIET; RECORDS; VALIDATION; WOMEN AB The software for analysis of the Health Habits and History Questionnaire (HHHQ) has been revised and is available to researchers. As in earlier versions of the software, questionnaires other than the standard National Cancer institute versions can be analyzed. Foods can be added or dropped, nutrients can be added or changed, and many other revisions and options are facilitated. Estimates of 33 nutrients and up to 20 user-defined food groups are produced. The validity is unchanged from the previous software. Other features include a data entry key-and-verify system, standardized editing, a computer-assisted interview, and the calculation of health indices including pack-years of smoking and social network index. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. NCI,APPL RES BRANCH,BETHESDA,MD 20892. RP BLOCK, G (reprint author), UNIV CALIF BERKELEY,SCH PUBL HLTH,419 EARL WARREN HALL,BERKELEY,CA 94720, USA. RI Block, Gladys/E-3304-2010 NR 17 TC 204 Z9 206 U1 2 U2 9 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1994 VL 139 IS 12 BP 1190 EP 1196 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NT490 UT WOS:A1994NT49000006 PM 8209877 ER PT J AU POLYMEROPOULOS, MH COON, H BYERLEY, W GERSHON, ES GOLDIN, L CROW, TJ RUBENSTEIN, J HOFF, M HOLIK, J SMITH, AM SHIELDS, G BASS, NJ POULTER, M LOFTHOUSE, R VITA, A MORGANTI, C MERRIL, CR DELISI, LE AF POLYMEROPOULOS, MH COON, H BYERLEY, W GERSHON, ES GOLDIN, L CROW, TJ RUBENSTEIN, J HOFF, M HOLIK, J SMITH, AM SHIELDS, G BASS, NJ POULTER, M LOFTHOUSE, R VITA, A MORGANTI, C MERRIL, CR DELISI, LE TI SEARCH FOR A SCHIZOPHRENIA SUSCEPTIBILITY LOCUS ON HUMAN-CHROMOSOME-22 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE LINKAGE; SIB-PAIR; AFFECTED PEDIGREE METHOD; SCHIZOPHRENIA ID DINUCLEOTIDE REPEAT POLYMORPHISM; LINKAGE ANALYSIS; SCHIZOAFFECTIVE DISORDER; GENE AB We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected pedigree member analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions. (C) 1994 Wiley-Liss, Inc. C1 NIMH,BIOCHEM GENET LAB,WASHINGTON,DC. UNIV UTAH,MED CTR,DEPT PSYCHIAT,SALT LAKE CITY,UT. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. CLIN RES CTR,DIV PSYCHIAT,HARROW HA1 3UJ,MIDDX,ENGLAND. UNIV MILAN,MILAN,ITALY. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RI crow, timothy/M-8327-2014; OI crow, timothy/0000-0002-5482-6655; Coon, Hilary/0000-0002-8877-5446 FU NCRR NIH HHS [1 P41 RR03655]; NIMH NIH HHS [MH10168-F32, MH4412] NR 19 TC 69 Z9 69 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 15 PY 1994 VL 54 IS 2 BP 93 EP 99 DI 10.1002/ajmg.1320540203 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NM999 UT WOS:A1994NM99900002 PM 8074169 ER PT J AU CHAN, CC PALESTINE, AG LI, Q NUSSENBLATT, RB AF CHAN, CC PALESTINE, AG LI, Q NUSSENBLATT, RB TI DIAGNOSIS OF OCULAR TOXOPLASMOSIS BY THE USE OF IMMUNOCYTOLOGY AND THE POLYMERASE CHAIN-REACTION SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Letter ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N103,BETHESDA,MD 20892, USA. NR 5 TC 15 Z9 16 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN 15 PY 1994 VL 117 IS 6 BP 803 EP 805 PG 3 WC Ophthalmology SC Ophthalmology GA NP644 UT WOS:A1994NP64400015 PM 7911007 ER PT J AU RADER, DJ HOEG, JM BREWER, HB AF RADER, DJ HOEG, JM BREWER, HB TI QUANTITATION OF PLASMA APOLIPOPROTEINS IN THE PRIMARY AND SECONDARY PREVENTION OF CORONARY-ARTERY DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Review DE CORONARY DISEASE; APOLIPOPROTEINS; ATHEROSCLEROSIS; CHOLESTEROL; TRIGLYCERIDES ID HIGH-DENSITY-LIPOPROTEINS; ISCHEMIC-HEART-DISEASE; FAMILIAL COMBINED HYPERLIPIDEMIA; ACUTE MYOCARDIAL-INFARCTION; MIDDLE-AGED MEN; CHEMISTRY STANDARDIZATION PROJECT; B-CONTAINING LIPOPROTEINS; A-I; RISK-FACTORS; SERUM LIPOPROTEIN(A) AB Purpose: To review current knowledge of apolipoprotein quantitation used in the clinical management of persons with or at risk for the development of premature coronary artery disease. Data Sources: The English-language literature was analyzed using MEDLINE (1975 to 1993) with key words ''apolipoproteins,'' ''quantitation,'' and ''coronary artery disease.'' Article bibliographies were also reviewed to obtain additional references. Study Selection: Published, peer-reviewed retrospective and prospective studies relevant to the association of plasma apolipoprotein levels with coronary artery disease in humans. Data Synthesis: Most studies concerned apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein(a) [Lp(a)]. In retrospective cross-sectional studies, apo A-I levels were not substantially more predictive of coronary artery disease than were high-density lipoprotein (HDL) cholesterol levels. In contrast, levels of apo B and Lp(a) were often more strongly associated with coronary artery disease than were traditional lipid measurements. In studies of the relation between apolipoprotein levels in children and premature coronary artery disease in their parents, Lp(a) levels, but not apo A-I and apo B levels, were consistently predictive of familial coronary artery disease. Prospective studies have yielded variable results for all three apolipoproteins. Low apo A-I levels were consistently associated with coronary artery disease in six prospective studies but were not more predictive than HDL levels. Apolipoprotein B levels were strongly associated with coronary artery disease in four of five prospective studies but were more predictive of coronary artery disease than were total cholesterol levels in only two of the four studies. Lipoprotein(a) levels were strongly associated with coronary artery disease in five of seven prospective studies but were not associated in two of the four largest studies. Conclusions: Too few large prospective studies of apolipoprotein quantitation using validated assay methods, both in general unselected populations and in subgroups of persons with premature coronary artery disease or family histories of premature coronary artery disease, are available to make definitive recommendations concerning clinical utility. The data do not support use of apolipoprotein quantitation as a screening tool to predict coronary artery disease risk in the general population. However, the data suggest that quantitation of apo B and Lp(a) may be indicated in subgroups of persons with premature coronary artery disease or with family histories of premature coronary artery disease. In these persons, an increased apo B or Lp(a) level or both could be a clinical indication for more aggressive treatment of low-density lipoprotein cholesterol. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. RP RADER, DJ (reprint author), UNIV PENN,MED CTR,INST HUMAN GENE THERAPY,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 188 TC 167 Z9 170 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1994 VL 120 IS 12 BP 1012 EP 1025 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA NQ964 UT WOS:A1994NQ96400008 PM 8185133 ER PT J AU BAMBERGER, CM CHROUSOS, G AF BAMBERGER, CM CHROUSOS, G TI GLUCOCORTICOID RESISTANCE - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID RECEPTOR RP BAMBERGER, CM (reprint author), US DEPT HLTH & HUMAN SERV,NIH,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1994 VL 120 IS 12 BP 1047 EP 1048 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NQ964 UT WOS:A1994NQ96400017 ER PT J AU KRAMER, BS AF KRAMER, BS TI PROSTATE-CANCER SCREENING - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP KRAMER, BS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1994 VL 120 IS 12 BP 1053 EP 1053 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NQ964 UT WOS:A1994NQ96400030 ER PT J AU LOSIEWICZ, MD CARLSON, BA KAUR, G SAUSVILLE, EA WORLAND, PJ AF LOSIEWICZ, MD CARLSON, BA KAUR, G SAUSVILLE, EA WORLAND, PJ TI POTENT INHIBITION OF CDC2 KINASE-ACTIVITY BY THE FLAVONOID L86-8275 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; TYROSINE KINASE; CARCINOMA-CELLS; PROTEIN; PHOSPHORYLATION; ACTIVATION; P34CDC2; VERTEBRATES; INVITRO AB L86-8275 [(-) cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1-methyl)-piperidinyl]-4H-benzopyran-4-one] directly inhibits immunoprecipitated Cdc2 kinase activity from G2/M synchronized MDA-MB-468 breast carcinoma cells and is at least 250-fold more potent than either quercetin or genistein. Purified sea-star Cdc2 kinase (IC50 = 0.5 mu M) was inhibited with a similar potency to immunoprecipitated Cdc2 kinase from MDA-MB-468 cells (IC50 = 0.4 mu M). This inhibition was competitive with respect to ATP (K-iATP= 0.041 mu M) and noncompetitive with respect to a synthetic peptide substrate, CDK1S1 (AAKAKKTPKKAKK-CONH2, K-iCDK1S1 = 0.14 mu M). These data suggest L86-8275 as a lead structure for the development of inhibitors of the cyclin-dependent kinases. (C) 1994 Academic Press, Inc. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NR 36 TC 276 Z9 279 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 589 EP 595 DI 10.1006/bbrc.1994.1742 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500015 PM 8002990 ER PT J AU XU, NZ VOYNOYASENETSKAYA, T GUTKIND, JS AF XU, NZ VOYNOYASENETSKAYA, T GUTKIND, JS TI POTENT TRANSFORMING ACTIVITY OF THE G(13) ALPHA-SUBUNIT DEFINES A NOVEL FAMILY OF ONCOGENES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NIH 3T3 CELLS; MALIGNANT TRANSFORMATION; NIH-3T3 CELLS; PROTEIN; RECEPTOR; EXPRESSION AB The finding of GTPase inhibiting mutations in genes for a subunits of G(s) and G(i2) in certain endocrine tumors suggests that heterotrimeric G proteins might contribute to neoplasia. Expression of these activated forms of alpha(s) or alpha(i2) in NIH 3T3 murine fibroblasts induces certain alterations in cell growth, but is weakly transforming. Mutationally activated forms of the alpha subunit of another G protein family, G(q) are fully oncogenic in NIH 3T3 cells, although with a very low potency. In contrast, we have recently shown that overexpression of the alpha subunit of a novel G protein, G(12), is itself transforming, and an activated mutant of alpha(12) behaves as one of the most potent oncogenes known. In this study, we have explored whether another member of the G alpha(12) family, G alpha(13), harbors transforming potential. Our data demonstrate that G alpha(13) can behave as a potent dominant acting oncogene. These findings strongly suggest that the G(12) family of G proteins represents a novel class of oncogenes. (C) 1994 Academic Press, Inc. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALLING UNIT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PHARMACOL,SAN FRANCISCO,CA 94143. RI Gutkind, J. Silvio/A-1053-2009 NR 23 TC 73 Z9 73 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 603 EP 609 DI 10.1006/bbrc.1994.1744 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500017 PM 8002992 ER PT J AU HOFFMAN, PW CHERNAK, JM AF HOFFMAN, PW CHERNAK, JM TI THE RAT AMYLOID PRECURSOR PROTEIN PROMOTER CONTAINS 2 DNA REGULATORY ELEMENTS WHICH INFLUENCE HIGH-LEVEL GENE-EXPRESSION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALZHEIMERS-DISEASE; REGION; MOUSE; APP AB We have investigated the transcriptional activity and regulatory elements of the rat amyloid precursor protein promoter. A DNA fragment containing 375 base pairs upstream of the start codon drives transcription in rat PC12 cells at a level greater than five-fold that of the SV40 promoter. This fragment contains a predominant transcription start point and several additional start points which are similar to those found in the human promoter. The strong promoter activity appears to be dependent upon two small DNA regulatory elements. Deletion of one element at positions -260 through -248 reduces activity by 85%. This is the first report of a positive regulatory element at this location. Deletion of a second element at positions -223 through -192 reduces activity by 30%. Gel mobility shift assays with nuclear extracts from whole rat brain suggest that nuclear proteins interact directly with the second element but not with the first one. (C) 1994 Academic Press, Inc. C1 NIA,MOLEC NEUROBIOL UNIT,BALTIMORE,MD 21224. NR 15 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 610 EP 617 DI 10.1006/bbrc.1994.1745 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500018 PM 8002993 ER PT J AU DHAWAN, S HEREDIA, A LA, RB WAHL, LM EPSTEIN, JS HEWLETT, IK AF DHAWAN, S HEREDIA, A LA, RB WAHL, LM EPSTEIN, JS HEWLETT, IK TI INTERFERON-GAMMA INDUCES RESISTANCE IN PRIMARY MONOCYTES AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NECROSIS-FACTOR-ALPHA; HIV REPLICATION; T-CELLS; RESTRICTION; MACROPHAGES AB Treatment of monocytes with interferon-gamma 1 day before, or at the time of infection with human immunodeficiency virus type-1 (HIV-1) induced complete resistance in monocytes against HIV-1 infection. There was no evidence of viral RNA, proviral DNA, p24 antigen, or reverse transcriptase activity through 2 weeks after inoculation. Ultrastructural examination of these cells showed no detectable virus particles. When interferon-gamma was added to monocytes 1 to 3 days post-infection, virus integration occurred, but the viral expression was either ablated (1 day postinfection) or significantly inhibited (3 days post-infection). Treatment of monocytes with interferon-gamma before or after infection with HIV-1 produced significantly higher levels of tumor necrosis factor-alpha and interleukin-8 than untreated or uninfected monocytes. These results suggest that altered regulation of cytokines may mediate antiviral activity of interferon-gamma in monocytes. (C) 1994 Academic Press, Inc. C1 CTR DIS CONTROL,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP DHAWAN, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC VIROL LAB,HFM-310,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 756 EP 761 DI 10.1006/bbrc.1994.1765 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500038 PM 8003012 ER PT J AU ZIMMER, A ZIMMER, A REYNOLDS, K AF ZIMMER, A ZIMMER, A REYNOLDS, K TI GENE TARGETING CONSTRUCTS - EFFECTS OF VECTOR TOPOLOGY ON COEXPRESSION EFFICIENCY OF POSITIVE AND NEGATIVE SELECTABLE MARKER GENES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID STEM-CELLS; MICE; DISRUPTION; GROWTH AB Targeting of DNA into specific chromosomal loci often involves the use of a negative selectable marker gene to enrich for cell clones that have undergone homologous recombination. In this study we asked if the arrangement of the positive and negative markers in 'knockout' constructs can influence the expression of a lacZ gene that was used as a negative marker. We show that constructs which differ only in their topology have vastly different co-expression efficiencies. The site of DNA linearization was critical. While linearizing at the 5'-end of the lacZ gene was compatible with efficient lacZ expression, linearizing at the 3'-end was always detrimental. We also demonstrate that the topology of the template was more important than the promoter used to drive lacZ expression. (C) 1994 Academic Press, Inc. RP ZIMMER, A (reprint author), NIMH, CELL BIOL LAB, DEV BIOL UNIT, BLDG 36, BETHESDA, MD 20892 USA. RI Zimmer, Andreas/B-8357-2009 NR 11 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 943 EP 949 DI 10.1006/bbrc.1994.1793 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500066 PM 8003035 ER PT J AU CHOCK, SP SCHMAUDERCHOCK, EA CORDELLAMIELE, E MIELE, L MUKHERJEE, AB AF CHOCK, SP SCHMAUDERCHOCK, EA CORDELLAMIELE, E MIELE, L MUKHERJEE, AB TI THE LOCALIZATION OF PHOSPHOLIPASE A(2) IN THE SECRETORY GRANULE SO BIOCHEMICAL JOURNAL LA English DT Article ID PLATELET-ACTIVATING-FACTOR; HUMAN SYNOVIAL-FLUID; MAST-CELL; EXTRACELLULAR PHOSPHOLIPASE-A2; RHEUMATOID-ARTHRITIS; PURIFICATION; INFLAMMATION; INHIBITORS; MEDIATORS; DISEASES AB A heat-resistant phospholipase A, has been detected in the secretory granules of the mast cell [Chock, Rhee, Tang and Schmauder-Chock (1991) fur. J. Biochem. 195, 707-713]. By using ultrastructural immunocytochemical techniques, we have now localized this enzyme to the matrix of the secretory granule. Like the cyclo-oxygenase [Schmauder-Chock and Chock (1989) J. Histochem. Cytochem. 37, 1319-1328], this enzyme also adheres tightly to the ribbon-like granule matrix components. The results from Western-blot analysis suggest that it has a molecular mass of about 14 kDa. The localization of the phospholipase A(2), the presence of a phospholipid store with millimolar concentrations of calcium and the localization of the enzymes of the arachidonic acid cascade make the secretory granule a natural site for lipid-mediator synthesis. The packaging of phospholipase A(2), together with its substrate and the components of the arachidonic acid cascade, in the secretory granule represents a physical arrangement by which the initiation of the cascade and the release of mediators can be directly linked to the stimulation of cell-surface receptors. C1 ARMED FORCES RADIOBIOL RES INST,DEPT EXPTL HEMATOL,BETHESDA,MD 20889. NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20893. HOWARD UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC. NR 40 TC 38 Z9 38 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1994 VL 300 BP 619 EP 622 PN 3 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU755 UT WOS:A1994NU75500002 PM 8010941 ER PT J AU MARGOLIS, RL CHUANG, DM POST, RM AF MARGOLIS, RL CHUANG, DM POST, RM TI PROGRAMMED CELL-DEATH - IMPLICATIONS FOR NEUROPSYCHIATRIC DISORDERS SO BIOLOGICAL PSYCHIATRY LA English DT Review DE APOPTOSIS; NEUROPSYCHIATRY; CELL DEATH; NEURODEVELOPMENT; NEURODEGENERATION; MOLECULAR BIOLOGY ID NERVE GROWTH-FACTOR; NEMATODE CAENORHABDITIS-ELEGANS; CEREBELLAR GRANULE CELLS; FINCH SONG SYSTEM; DNA FRAGMENTATION; C-ELEGANS; SYMPATHETIC NEURONS; GENE-EXPRESSION; SULFATED GLYCOPROTEIN-2; SEXUAL-DIFFERENTIATION AB Programmed cell death, sometimes referred to as apoptosis, occurs through an active process requiring new gene transcription, in contrast to the passive cell death produced by metabolic toxins. Programmed cell death is an essential part of normal development, particularly in the nervous system. Spatial, temporal, or quantitative errors in the stimuli that initiate programmed cell death, or errors within the programmed cell death pathway itself can result in an abnormal number of neurons and pathological neural development. Excesses and deficits in neuronal numbers have now been observed not only in typical neurodegenerative disorders such as Alzheimer's and Huntington's diseases, bur also in several neurodevelopmental disorders, including schizophrenia and autism. Recent investigations into the mechanisms of cell death during C. elegans neurodevelopment thymocyte negative selection, and withdrawal of sympathetic ganglion cells trophic support provides intriguing clues to the etiology and pathophysiology of these neuropsychiatric disorders. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 126 TC 102 Z9 104 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1994 VL 35 IS 12 BP 946 EP 956 DI 10.1016/0006-3223(94)91241-6 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NU004 UT WOS:A1994NU00400008 PM 8080894 ER PT J AU BOSCO, MC ESPINOZADELGADO, I SCHWABE, M RUSSELL, SM LEONARD, WJ LONGO, DL VARESIO, L AF BOSCO, MC ESPINOZADELGADO, I SCHWABE, M RUSSELL, SM LEONARD, WJ LONGO, DL VARESIO, L TI THE GAMMA-SUBUNIT OF THE INTERLEUKIN-2 RECEPTOR IS EXPRESSED IN HUMAN MONOCYTES AND MODULATED BY INTERLEUKIN-2, INTERFERON-GAMMA, AND TRANSFORMING GROWTH-FACTOR BETA(1) SO BLOOD LA English DT Note ID STIMULATED HUMAN-MONOCYTES; MESSENGER-RNA EXPRESSION; IL-2 RECEPTOR; IFN-GAMMA; FUNCTIONAL COMPONENT; BLOOD MONOCYTES; CHAIN; SECRETION; GENE; P64 C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. NCI,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. RP BOSCO, MC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,FREDERICK,MD 21702, USA. RI Russell, Sarah/B-9341-2009; Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Russell, Sarah/0000-0001-5826-9641; Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 39 TC 55 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1994 VL 83 IS 12 BP 3462 EP 3467 PG 6 WC Hematology SC Hematology GA NR905 UT WOS:A1994NR90500007 PM 8204874 ER PT J AU SAVILLE, MW TAGA, K FOLI, A BRODER, S TOSATO, G YARCHOAN, R AF SAVILLE, MW TAGA, K FOLI, A BRODER, S TOSATO, G YARCHOAN, R TI INTERLEUKIN-10 SUPPRESSES HUMAN IMMUNODEFICIENCY VIRUS-1 REPLICATION IN-VITRO IN CELLS OF THE MONOCYTE/MACROPHAGE LINEAGE SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; GROWTH-FACTOR-BETA; RETROVIRUS-INDUCED IMMUNODEFICIENCY; INHIBITS CYTOKINE PRODUCTION; T-CELL; B-CELLS; ACTIVATED MACROPHAGES; STIMULATORY FACTOR; HUMAN-MONOCYTES; DOWN-REGULATION C1 NCI,OFF DIRECTOR,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BETHESDA,MD. RP SAVILLE, MW (reprint author), NCI,MED BRANCH,RETROVIRAL DIS SECT,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 65 TC 72 Z9 72 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1994 VL 83 IS 12 BP 3591 EP 3599 PG 9 WC Hematology SC Hematology GA NR905 UT WOS:A1994NR90500022 PM 7911340 ER PT J AU NICHOLSON, HS FEARS, TR BYRNE, J AF NICHOLSON, HS FEARS, TR BYRNE, J TI DEATH DURING ADULTHOOD IN SURVIVORS OF CHILDHOOD AND ADOLESCENT CANCER SO CANCER LA English DT Article DE CHILDHOOD CANCER; LATE MORTALITY; CANCER SURVIVORS; LATE EFFECTS; 2ND CANCERS; RADIATION THERAPY; ALKYLATING AGENT CHEMOTHERAPY ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; HODGKINS-DISEASE; CHILDREN; RADIOTHERAPY; CHEMOTHERAPY; MORTALITY; TUMORS; LIFE AB Background. Therapeutic advances have extended survival for most children and adolescents with cancer beyond 5 years from diagnosis. However, excess mortality continues beyond 5 years, and a significant portion results from causes other than the primary cancer. Risk factors for these deaths are not currently known. Thus, the authors studied mortality in a cohort of adult survivors of childhood and adolescent cancer to determine whether survivor characteristics were associated with increased relative risk of death from other causes. Methods. Using 3255 siblings as control subjects, the authors studied survival in a retrospective cohort study of 2319 adults who were at least 5-year survivors of cancer diagnosed before reaching 20 years of age and between 1945 and 1974 (the NCI Five Center Study). Follow-up occurred between 1980 and 1983 at a mean survivor age of 32 years (range, 21-55 years). Results. Between cohort entry and follow-up, 292 (13%) survivors and 50 (2%) controls died. One-third of the deaths in survivors were from causes other than the primary malignancy. Compared with control subjects, between ages 21 and 40 years, survivors had a more than threefold risk of death from other causes. The relative risk (RR) for death from other causes was greatest for survivors treated with radiation and alkylating agents (RR = 6.1; 95% confidence interval [CI], 3.0-12.4) and for those treated with radiation alone (RR = 3.8; 95% CI, 2.3-6.2; Cox regression analysis containing terms for treatment and cancer diagnosis). Conclusions. Adult survivors of childhood and adolescent cancer had a higher death rate than their siblings, even after removing the effect of primary cancer as the direct cause. Moreover, death from other causes was most strongly associated with increasing intensity of therapy, and this excess risk did not diminish with increasing age and duration of cancer survival. Because contemporary anticancer therapy is, in general, even more intensive than that received by the survivors described in this study, medical surveillance of cancer survivors is increasingly important to diagnose and treat potentially life-threatening complications that may occur decades after therapy has ceased. C1 CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NCI,EPIDEMIOL METHODS SECT,BETHESDA,MD 20892. BOYNE RES FDN,WASHINGTON,DC. RP NICHOLSON, HS (reprint author), NCI,CLIN EPIDEMIOL BRANCH,BLDG EPN,ROOM 400,BETHESDA,MD 20892, USA. NR 29 TC 56 Z9 58 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1994 VL 73 IS 12 BP 3094 EP 3102 PG 9 WC Oncology SC Oncology GA NQ408 UT WOS:A1994NQ40800030 PM 8200008 ER PT J AU KELLEY, MJ SNIDER, RH BECKER, KL JOHNSON, BE AF KELLEY, MJ SNIDER, RH BECKER, KL JOHNSON, BE TI SMALL-CELL LUNG-CARCINOMA CELL-LINES EXPRESS MESSENGER-RNA FOR CALCITONIN AND ALPHA-CALCITONIN AND BETA-CALCITONIN GENE-RELATED PEPTIDES SO CANCER LETTERS LA English DT Article DE CALCITONIN; CALCITONIN GENE RELATED PEPTIDE; LUNG NEOPLASM; TUMOR CELL LINES; MESSENGER-RNA; RADIOIMMUNOASSAY; NEUROPEPTIDE ID DORSAL-ROOT GANGLION; CGRP MESSENGER-RNAS; BINDING; IDENTIFICATION; LOCALIZATION; SEQUENCES; PROTEINS; ENHANCER AB Calcitonin (CT) and calcitonin gene related peptide (CGRP) are derived from preprohormones encoded by three mRNAs (CT, alpha-CGRP and beta-CGRP) from two genes (CALC1 and CALC2) on chromosome 11. Among 16 small cell lung cancer cell lines examined by RNase protection assay, 9 (56%) had detectable CT mRNA, 8 (50%) had alpha-CGRP mRNA, and 13 (81%) had beta-CGRP mRNA. At least one CALC1 transcript (CT or alpha-CGRP) was found in 11 (69%) cell lines with three having only CT mRNA, two having only alpha-CGRP mRNA, and six having both. beta-CGRP mRNA was detected in all of these 11 cell lines expressing a CALC1 transcript. Immunoreactive CT was detected by radioimmunoassay in eight of nine SCLC cell lines expressing CT mRNA, and immunoreactive CGRP was detected in 12 of 13 cell lines expressing a CGRP mRNA. The variety of expression of these three peptides in different cell lines of the same cell type should provide a useful system for further study of the control of expression of these peptides. C1 VET AFFAIRS MED CTR,WASHINGTON,DC 20422. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20037. RP KELLEY, MJ (reprint author), NCI,USN,MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. OI Kelley, Michael/0000-0001-9523-6080 NR 23 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 15 PY 1994 VL 81 IS 1 BP 19 EP 25 DI 10.1016/0304-3835(94)90159-7 PG 7 WC Oncology SC Oncology GA NV118 UT WOS:A1994NV11800004 PM 8019984 ER PT J AU WALKER, C RUTTEN, F YUAN, XQ PASS, H MEW, DM EVERITT, J AF WALKER, C RUTTEN, F YUAN, XQ PASS, H MEW, DM EVERITT, J TI WILMS-TUMOR SUPPRESSOR GENE-EXPRESSION IN RAT AND HUMAN MESOTHELIOMA SO CANCER RESEARCH LA English DT Note ID ASBESTOS-INDUCED MESOTHELIOMAS; ZINC FINGER PROTEIN; FACTOR-A-CHAIN; GROWTH-FACTOR; MALIGNANT MESOTHELIOMA; CELL-LINES; RNA EXPRESSION; WT1 GENE; LOCUS; CARCINOGENICITY AB Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, Lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors. C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NCI,BETHESDA,MD 20892. RP WALKER, C (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SCI PK RES DIV,POB 389,SMITHVILLE,TX 78957, USA. FU NIEHS NIH HHS [NIEHS ES 06658-01] NR 46 TC 80 Z9 81 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1994 VL 54 IS 12 BP 3101 EP 3106 PG 6 WC Oncology SC Oncology GA NQ724 UT WOS:A1994NQ72400006 PM 8205524 ER PT J AU ROBBINS, PF ELGAMIL, M KAWAKAMI, Y ROSENBERG, SA AF ROBBINS, PF ELGAMIL, M KAWAKAMI, Y ROSENBERG, SA TI RECOGNITION OF TYROSINASE BY TUMOR-INFILTRATING LYMPHOCYTES FROM A PATIENT RESPONDING TO IMMUNOTHERAPY SO CANCER RESEARCH LA English DT Note ID CYTOLYTIC T-LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; MELANOMA; GENE; FREQUENCY; INVIVO; CDNA AB The observation that allogeneic melanoma cells matched for particular HLA class I alleles stimulate T-cells isolated from patients suggests that widely shared antigens exist on these tumors. A transient expression system was developed for screening a melanoma complementary DNA library using the highly transfectable human kidney cell line 293. Using this system, large numbers of complementary DNA clones can be rapidly screened for the expression of antigens which stimulate T-cells. Tumorinfiltrating lymphocytes from patient 888, which recognized melanoma in the context of HLA-A24, were used to screen a complementary DNA library made from the autologous melanoma. Our results demonstrate that these tumor-infiltrating lymphocytes recognize tyrosinase, a gene previously shown to be recognized by T-cells only in the context of HLA-A2. These data demonstrate that a single antigen can be recognized in the context of two different class I HLA alleles. In addition, this study suggests that recognition of tyrosinase by antigen-specific T-cells may be involved in tumor rejection. RP ROBBINS, PF (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 20 TC 222 Z9 223 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1994 VL 54 IS 12 BP 3124 EP 3126 PG 3 WC Oncology SC Oncology GA NQ724 UT WOS:A1994NQ72400011 PM 8205528 ER PT J AU BOONE, CW WATTENBERG, LW AF BOONE, CW WATTENBERG, LW TI CURRENT STRATEGIES OF CANCER CHEMOPREVENTION - 13TH SAPPORO CANCER SEMINAR SO CANCER RESEARCH LA English DT Editorial Material ID GREEN TEA; PREVENTION; RISK; SKIN; MICE C1 UNIV MINNESOTA,DEPT PATHOL,MINNEAPOLIS,MN 55455. RP BOONE, CW (reprint author), NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT INVEST STUDIES BRANCH,BETHESDA,MD 20852, USA. NR 18 TC 24 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1994 VL 54 IS 12 BP 3315 EP 3318 PG 4 WC Oncology SC Oncology GA NQ724 UT WOS:A1994NQ72400044 PM 7911397 ER PT J AU KRYLOV, D MIKHAILENKO, I VINSON, C AF KRYLOV, D MIKHAILENKO, I VINSON, C TI A THERMODYNAMIC SCALE FOR LEUCINE-ZIPPER STABILITY AND DIMERIZATION SPECIFICITY - E-INTERHELICAL AND G-INTERHELICAL INTERACTIONS SO EMBO JOURNAL LA English DT Article DE COILED COIL; DIMERIZATION SPECIFICITY; LEUCINE ZIPPER; THERMODYNAMIC CYCLE ID DNA-BINDING DOMAIN; IMMUNOGLOBULIN ENHANCER BINDING; HELIX-FORMING TENDENCIES; SURFACE SALT BRIDGES; X-RAY STRUCTURE; COILED-COILS; TRANSCRIPTION FACTOR; PROTEIN STABILITY; AMINO-ACID; FOS-JUN AB The leucine zipper is a dimeric coiled-coil protein structure composed of two amphipathic alpha-helices with the hydrophobic surfaces interacting to create the dimer interface. This structure has been found to mediate the dimerization of two abundant classes of DNA binding proteins: the bZIP and bHLH-Zip proteins. Several workers have reported that amino acids in the e and g positions of the coiled coil can modulate dimerization stability and specificity. Using the bZTP protein VBP as a host molecule, we report a thermodynamic scale (Delta Delta G) for 27 interhelical interactions in 35 proteins between amino acids in the g and the following e positions (g <----> e ') of a leucine zipper coiled coil. We have examined the four commonly occurring amino acids in the e and g positions of bZIP proteins, lysine (K), arginine (R), glutamine (Q), glutamic acid (E), as well as the only other remaining charged amino acid aspartic acid (D), and finally alanine (A) as a reference amino acid. These results indicate that E <---->-R is the most stable interhelical pair, being 0.35 kcal/mol more stable than E <----> K. A thermodynamic cycle analysis shows that the E <---->-R pair is 1.33 kcal/mol more stable than A <----> A with -1.14 kcal/mol of coupling energy (Delta Delta G(int)) coming from the interaction of E with R. The E-K coupling energy is only -0.14 kcal/mol. E interacts with more specificity than Q. The R-R pair is less stable than the K <----> K by 0.24 kcal/mol. R interacts with more specificity than K. Q forms more stable pairs with the basic amino acids K and R rather than with E. Changing amino acids in the e position to A creates bZIP proteins that form tetramers. RP KRYLOV, D (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4D06,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-04328] NR 69 TC 199 Z9 200 U1 0 U2 13 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1994 VL 13 IS 12 BP 2849 EP 2861 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT761 UT WOS:A1994NT76100013 PM 8026470 ER PT J AU HUANG, LM JOSHI, A WILLEY, R ORENSTEIN, J JEANG, KT AF HUANG, LM JOSHI, A WILLEY, R ORENSTEIN, J JEANG, KT TI HUMAN IMMUNODEFICIENCY VIRUSES REGULATED BY ALTERNATIVE TRANS-ACTIVATORS - GENETIC-EVIDENCE FOR A NOVEL NON-TRANSCRIPTIONAL FUNCTION OF TAT IN VIRION INFECTIVITY SO EMBO JOURNAL LA English DT Article DE CYTOPATHICITY; HIV; TAT; TRANSCRIPTION REGULATION; VIRUS INFECTIVITY ID LONG TERMINAL REPEAT; HIV-1 TAT; BIOLOGICAL PROPERTIES; MUTATIONAL ANALYSIS; RESPONSIVE REGION; LOOP SEQUENCE; NASCENT RNA; NEF GENE; HTLV-I; TYPE-1 AB Thirteen genetically altered HIV-l proviruses were created. These various genomes can be segregated into three groups: (i) a set of tat(-) viruses that have a functional HTLV-I Tax inserted in nef; (ii) a set of tat(-) viruses,vith Gal4 binding sites inserted in U3 and a Gal4-VP16 cDNA inserted in nef; and (iii) a set of tat(+) HIV genomes that are 5 ' and 3 ' TAR(-) and are Gal4-binding-site(+) in U3 and Ga14-VP16(+) in nef. We found that viruses in groups (i) and (ii), although tat(-), were fully complemented for viral gene expression based on quantitative measurements of viral protein synthesis and on the visualization by electron microscopy of the proper assembly of morphologically correct virions. Interestingly, group (i) and (ii) virions were defective in a spreading cytopathic infection when assayed in T-lymphocytes. Group (iii) viruses, although capable of producing intact Tat protein, also could not use Tat for transcription/gene expression because of the TAR(-) genotype. However, this class of viral genomes produced viruses that were highly infectious and cytopathic in primary and in continuously propagated T-lymphocytes. These three groups of viruses are all transcriptionally Tat-TAR independent. Their distinct differences in infectivity/cytopathicity provide genetic evidence that Tat provides a transcriptionally independent function in determining infectivity and cytopathicity in the setting of a spreading viral infection. Given that all HIV virions normally contain four intact copies of TAR RNA, our findings suggest a re-examination of whether Tat could be a virion-TAR-associated protein and the possible implications of this for virus infectivity/cytopathicity. C1 NIAID,MOLEC MICROBIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. RI Jeang, Kuan-Teh/A-2424-2008; OI Huang, Li-Min/0000-0002-9291-260X NR 77 TC 89 Z9 89 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1994 VL 13 IS 12 BP 2886 EP 2896 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT761 UT WOS:A1994NT76100017 PM 8026473 ER PT J AU JIN, MJ HUI, HX ROBERTSON, DL MULLER, MC BARRESINOUSSI, F HIRSCH, VM ALLAN, JS SHAW, GM SHARP, PM HAHN, BH AF JIN, MJ HUI, HX ROBERTSON, DL MULLER, MC BARRESINOUSSI, F HIRSCH, VM ALLAN, JS SHAW, GM SHARP, PM HAHN, BH TI MOSAIC GENOME STRUCTURE OF SIMIAN IMMUNODEFICIENCY VIRUS FROM WEST-AFRICAN GREEN MONKEYS SO EMBO JOURNAL LA English DT Article DE AIDS; CROSS-SPECIES TRANSMISSION; LENTIVIRAL RECOMBINATION; SABAEUS MONKEYS; TAR SEQUENCE ID POLYMERASE CHAIN-REACTION; MULTIPLE SEQUENCE ALIGNMENT; HIGHLY DIVERGENT; MOLECULAR CHARACTERIZATION; RETROVIRAL RECOMBINATION; SEROEPIDEMIOLOGIC SURVEY; PRIMATE LENTIVIRUSES; GENETIC-VARIABILITY; FUNCTIONAL-ANALYSIS; TANTALUS MONKEYS AB Elucidation of the phylogenetic origins of simian and human immunodeficiency viruses (SIV and HIV) is fundamental to the understanding of HIV pathogenesis and the spread of AIDS worldwide. In this study, we molecularly characterized multiple SIVAGM isolates from four different African green monkey species (vervet, grivet, sabaeus and tantalus monkeys). Phylogenetic analysis of partial (1 kb) env sequences indicated that all SIVAGM strains cluster together, and that they fall into four distinct sequence sub-groups according to their species of origin. However, alignment of long terminal repeat sequences revealed that STVs from West African sabaeus monkeys contain a structural feature (a duplication of the transactivation response element) thus far only found in otherwise highly divergent lentiviruses infecting sooty mangabeys (SIVSM) and humans (HIV-2). To determine whether there were additional similarities with the SIVSM/HIV-2 group, a full-length replication competent sabaeus provirus was cloned and sequenced. In phylogenetic trees derived from the central and 3 ' coding regions, the sabaeus virus clustered with SIVAGM isolates from other African green monkey species. However, in trees derived from the 3 ' half of gag and the adjacent 5 ' region of pol, the sabaeus virus grouped with the SIVSM/HIV-2 lineage. These results indicated that the sabaeus virus comprised a mosaic genome which must have resulted from recombination of divergent lentiviruses in the distant past. A second, independent sabaeus isolate exhibited similar phylogenetic relationships, suggesting that all West African green monkey viruses share this complex evolutionary history. Taken together, these results indicate that African green monkeys have been infected with SIVAGM for very long periods of time, and that recombination and cross-species transmission in the, wild have contributed to the genetic complexity of primate lentiviruses. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,ROCKVILLE,MD 20852. SW FDN BIOMED RES,DEPT VIROL,SAN ANTONIO,TX 78228. SW FDN BIOMED RES,DEPT IMMUNOL,SAN ANTONIO,TX 78228. UNIV NOTTINGHAM HOSP,QUEENS MED CTR,DEPT GENET,NOTTINGHAM NG7 2UH,ENGLAND. INST PASTEUR,UNITE BIOL RETROVIRUS,F-75724 PARIS,FRANCE. RI Sharp, Paul/F-5783-2010; Barre-Sinoussi, Francoise/G-8355-2011 OI Sharp, Paul/0000-0001-9771-543X; FU NIAID NIH HHS [P30 AI27767] NR 75 TC 159 Z9 160 U1 1 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1994 VL 13 IS 12 BP 2935 EP 2947 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT761 UT WOS:A1994NT76100022 PM 8026477 ER PT J AU HELLEWELL, SB BRUCE, A FEINSTEIN, G ORRINGER, J WILLIAMS, W BOWEN, WD AF HELLEWELL, SB BRUCE, A FEINSTEIN, G ORRINGER, J WILLIAMS, W BOWEN, WD TI RAT-LIVER AND KIDNEY CONTAIN HIGH-DENSITIES OF SIGMA(1) AND SIGMA(2) RECEPTORS - CHARACTERIZATION BY LIGAND-BINDING AND PHOTOAFFINITY-LABELING SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE SIGMA RECEPTOR; LIVER; KIDNEY; HALOPERIDOL; PENTAZOCINE; PHOTOAFFINITY LABELING ID GUINEA-PIG BRAIN; HIGH-AFFINITY; H-3 (+)-PENTAZOCINE; SITES; DEXTROMETHORPHAN; MEMBRANES; SUGGEST; CYTOCHROME-P-450; MODULATION; POTENT AB Rat liver and kidney were investigated for the presence of sigma (sigma) receptor subtypes by radioligand binding with three highly selective sigma probes and by photoaffinity labeling using [H-3]azido-di-o-tolylguanidine ([H-3]azido-DTG). [H-3](+)-Pentazocine, a highly selective sigma(1) probe, bound to sites in liver membranes with K-d = 7.5 nM and B-max = 2929 fmol/mg protein. [H-3](+)-Pentazocine binding sites in kidney had K-d = 23.3 nM and B-max = 229 fmol/mg protein. [H-3]1,3-Di-o-tolylguanidine ([H-3]DTG) and [H-3](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([H-3](+)-3-PPP) label both sigma(1) and sigma(2) receptors. Parameters for [H-3]DTG in the liver were K-d = 17.9 nM and B-max = 11895 fmol/mg protein. Similar parameters were observed for [H-3](+)-3-PPP, K-d = 51.9 nM and B-max = 11070 fmol/mg protein. [H-3]DTG bound to rat kidney with K-d = 45.8 nM and B-max = 1190 fmol/mg protein. The observation that either [H-3]DTG or [H-3](+)-3-PPP and [H-3](+)-3-PPP labeled a higher number of sites relative to [H-3](+)-pentazocine suggested that liver and kidney contain both subtypes of sigma receptor. This was confirmed by competition studies vs. [H-3](+)-pentazocine and [H-3]DTG (in the presence of dextrallorphan to mask sigma(1) sites). In both tissues, [H-3](+)-pentazocine labeled sites with high affinity for haloperidol and enantioselectivity for (+)-benzomorphans over (-)-benzomorphans. [H-3]DTG + dextrallorphan labeled sites in both tissues which also had high affinity for haloperidol, but which had the characteristic sigma(2) properly of low affinity for (+)-benzomorphans and enantioselectivity for (-)-benzomorphans over the corresponding(+)-isomer. Similar results were obtained with [H-3](+)-3-PPP + dextrallorphan. Several novel aryl diamines, such as 1S,2R-cis-N-[2-(3,4-dichlorophenylethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737) and N-[2-(3,4-dichlbrophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD1008), bound to both sites with high affinity. Photoaffinity labeling with 10 nM [H-3]azido-DTG resulted in specific labeling of polypeptides of 25 kDa and 21.5 kDa. Dextrallorphan (100 nM or 500 nM) completely blocked labeling of the 25 kDa polypeptide, but had no effect on labeling of the lower molecular weight protein. (+)-10,11-Dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine((+)-MK-801) had no effect on labeling of either polypeptide. These data are consistent with the notion that the 25 kDa and 21.5 kDa proteins represent sigma(1) and sigma(2) receptors, respectively. Thus, rat liver and kidney contain high densities of sigma(1) and sigma(2) receptors, with sigma(2) sites comprising 75-80% of the total sigma population. The high density of sigma receptor subtypes may indicate important functions in hepatic and renal tissues. C1 NIDDKD,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BETHESDA,MD 20892. BROWN UNIV,DIV BIOL & MED,BIOCHEM SECT,PROVIDENCE,RI 02912. FU NIDA NIH HHS [DA03776]; NINDS NIH HHS [NS26746] NR 46 TC 280 Z9 285 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD JUN 15 PY 1994 VL 268 IS 1 BP 9 EP 18 DI 10.1016/0922-4106(94)90115-5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NU806 UT WOS:A1994NU80600002 PM 7925616 ER PT J AU IJZERMAN, AP VANDERWENDEN, EM VANGALEN, PJM JACOBSON, KA AF IJZERMAN, AP VANDERWENDEN, EM VANGALEN, PJM JACOBSON, KA TI MOLECULAR MODELING OF ADENOSINE RECEPTORS - THE LIGAND-BINDING SITE ON THE RAT ADENOSINE A(2A) RECEPTOR SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE MOLECULAR MODELING; ADENOSINE RECEPTOR; RECEPTOR BINDING AND ACTIVATION; BACTERIORHODOPSIN; HISTIDINE RESIDUE ID PROTEIN-COUPLED RECEPTORS; SELECTIVE CORONARY VASODILATORS; HISTIDINE-RESIDUES; CLONING; AGONISTS; POTENT; ANTAGONISTS; RHODOPSIN; BACTERIORHODOPSIN; CONFORMATION AB The amino acid sequence of the rat adenosine A(2A) receptor and the atomic coordinates of bacteriorhodopsin were combined to generate a three-dimensional model for the adenosine A(2A) receptor. This model consists of seven amphipathic alpha-helices, forming a pore that is rather hydrophilic compared to the hydrophobic outside of the protein. Subsequently, a highly potent and selective ligand for this receptor, 2-(cyclohexylmethylidinehydrazino)adenosine (SHA 174), was docked into this cavity. A binding site is proposed that takes into account the conformational characteristics of the ligand. Moreover, it involves two histidine residues that were shown to be important for ligand coordination from chemical modification studies. Subsequently, the deduced binding site was used to model other potent ligands, including 8-(3-chlorostyryl)caffeine, a new A(2)-selective antagonist, that could all be accommodated consistent with earlier biochemical and pharmacological findings. Finally, some thoughts on how adenosine receptor activation might proceed are put forward, based on structural analogies with the enzyme family of serine proteases. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP IJZERMAN, AP (reprint author), LEIDEN AMSTERDAM CTR DRUG RES,DIV MED CHEM,POB 9502,2300 RA LEIDEN,NETHERLANDS. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 41 TC 43 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD JUN 15 PY 1994 VL 268 IS 1 BP 95 EP 104 DI 10.1016/0922-4106(94)90124-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NU806 UT WOS:A1994NU80600011 PM 7925617 ER PT J AU SIMPSON, WJ CIEPLAK, W SCHRUMPF, ME BARBOUR, AG SCHWAN, TG AF SIMPSON, WJ CIEPLAK, W SCHRUMPF, ME BARBOUR, AG SCHWAN, TG TI NUCLEOTIDE-SEQUENCE AND ANALYSIS OF THE GENE IN BORRELIA-BURGDORFERI ENCODING THE IMMUNOGENIC P39 ANTIGEN SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE BORRELIA BURGDORFERI; P39 GENE; LYME DISEASE ID LYME-DISEASE AGENT; 34-KILODALTON MEMBRANE IMMUNOGEN; TREPONEMA-PALLIDUM; MOLECULAR ANALYSIS; SURFACE-PROTEINS; OSPC GENE; LIPOPROTEIN; PLASMID; SPIROCHETE; ANTIBODY AB The P39 antigen is a specific, highly conserved, and immunogenic protein of Lyme disease spirochetes, Borrelia burgdorferi sensu lato. The nucleotide sequence of the gene encoding this protein was determined and found to be the first of two tandemly arranged open reading frames located on the spirochete's chromosome. These two open reading frames were designated bmpA for the gene encoding P39 and bmpB for the gene encoding the putative protein ORF2 encoded by the second open reading frame. The nucleic acid sequence identity for the two open reading frames was 62% while their deduced amino acid sequences were 52% identical. Comparison to sequence data bases demonstrated that the deduced amino acid sequences of both P39 and ORF2 were homologous to TmpC, a putative outer or cytoplasmic membrane lipoprotein of the syphilis spirochete, Treponema pallidum. C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 FU NIAID NIH HHS [AI29731] NR 26 TC 48 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUN 15 PY 1994 VL 119 IS 3 BP 381 EP 387 DI 10.1016/0378-1097(94)90444-8 PG 7 WC Microbiology SC Microbiology GA NT213 UT WOS:A1994NT21300020 PM 8050720 ER PT J AU COOPER, JP ROTH, SY SIMPSON, RT AF COOPER, JP ROTH, SY SIMPSON, RT TI THE GLOBAL TRANSCRIPTIONAL REGULATORS, SSN6 AND TUP1, PLAY DISTINCT ROLES IN THE ESTABLISHMENT OF A REPRESSIVE CHROMATIN STRUCTURE SO GENES & DEVELOPMENT LA English DT Article DE MCM1; ALPHA-2; CHROMATIN; TRANSCRIPTIONAL REPRESSION; SACCHAROMYCES CEREVISIAE ID NUCLEASE-SENSITIVE REGIONS; YEAST ALPHA-2 REPRESSOR; MATING-TYPE LOCUS; SACCHAROMYCES-CEREVISIAE; POSITIONED NUCLEOSOMES; BETA-SUBUNIT; CELL-TYPE; INVERTASE SYNTHESIS; GLUCOSE REPRESSION; PLASMID CHROMATIN AB Repression of a-cell specific gene expression in yeast alpha cells requires MAT alpha 2 and MCM1, as well as two global repressors, SSN6 and TUP1. Previous studies demonstrated that nucleosomes positioned adjacent to the alpha 2/MCM1 operator in alpha cells directly contribute to repression. To investigate the possibility that SSN6 and TUP1 provide a link between MAT alpha 2/MCM1 and neighboring histones, nucleosome locations were examined in ssn6 and tup1 alpha cells. In both cases, nucleosome positions downstream of the operator were disrupted, and the severity of the disruption correlated with the degree of derepression. Nevertheless, the observed changes in chromatin structure were not dependent on transcription. Our data strongly indicate that SSN6 and TUP1 directly organize repressive regions of chromatin. C1 NIDDKD, CELLULAR & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 70 TC 158 Z9 158 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD JUN 15 PY 1994 VL 8 IS 12 BP 1400 EP 1410 DI 10.1101/gad.8.12.1400 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NU353 UT WOS:A1994NU35300004 PM 7926740 ER PT J AU JAEGER, RG FEX, J KACHAR, B AF JAEGER, RG FEX, J KACHAR, B TI STRUCTURAL BASIS FOR MECHANICAL TRANSDUCTION IN THE FROG VESTIBULAR SENSORY APPARATUS .2. THE ROLE OF MICROTUBULES IN THE ORGANIZATION OF THE CUTICULAR PLATE SO HEARING RESEARCH LA English DT Article DE MICROTUBULES; MICROTUBULE-ASSOCIATED PROTEINS; CUTICULAR PLATE; MECHANICAL TRANSDUCTION; VESTIBULAR SENSORY MACULA; FROG VESTIBULAR SENSORY ORGAN ID COCHLEAR HAIR-CELLS; ACTIN-FILAMENTS; INNER-EAR; MECHANOELECTRICAL TRANSDUCTION; IMMUNOELECTRON MICROSCOPY; MOLECULAR-STRUCTURE; BIRD COCHLEA; STEREOCILIA; CYTOSKELETAL; MOTILITY AB The actin matrix of the cuticular plate, which supports the sensory stereocilia bundle, is coupled to the axial cytoskeleton of the hair cell through a well defined microtubule columnar framework. A collection of axial microtubules in a columnar organization penetrate deep into the dense actin matrix of the cuticular plate. Each microtubule displays at the end a 300-500 nm long fuzzy cap that enmeshes with the actin matrix of the cuticular plate. The microtubule associated proteins MAP-1A and MAP-1B were localized by confocal immunofluorescence to the point of microtubule insertion in the cuticular plate. These proteins are likely components of the microtubule capping structure and may mediate the interaction of the microtubules with the actin matrix. The structural interaction of the microtubules with the cuticular plate provides important mechanical coupling of the transduction apparatus to the axial cytoskeleton of the hair cell. C1 NIDCD,CELLULAR BIOL LAB,STRUCT CELL BIOL SECT,ROCKVILLE,MD 20850. NIDCD,MOLEC BIOL LAB,ROCKVILLE,MD 20850. RI Jaeger, Ruy/G-8230-2011 NR 34 TC 23 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN 15 PY 1994 VL 77 IS 1-2 BP 207 EP 215 DI 10.1016/0378-5955(94)90268-2 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA NV015 UT WOS:A1994NV01500021 PM 7928733 ER PT J AU LIU, SF DAWSEY, SM WANG, GQ NIEBERG, RK WANG, ZY WEINER, M ZHOU, B CAO, J YU, Y GUO, WD LI, JY BLOT, WJ LI, B TAYLOR, PR SHEN, Q AF LIU, SF DAWSEY, SM WANG, GQ NIEBERG, RK WANG, ZY WEINER, M ZHOU, B CAO, J YU, Y GUO, WD LI, JY BLOT, WJ LI, B TAYLOR, PR SHEN, Q TI ESOPHAGEAL BALLOON CYTOLOGY AND SUBSEQUENT RISK OF ESOPHAGEAL AND GASTRIC-CARDIA CANCER IN A HIGH-RISK CHINESE POPULATION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LINXIAN AB Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world. In 1983, esophageal balloon cytology screening was performed in 3 communes in northern Linxian. Of the participants, 10,066 with no evidence of cancer were followed prospectively for 7 1/2 years to evaluate the ability of the initial cytologic diagnoses to identify individuals at increased risk for developing cancer of the esophagus or gastric cardia. A total of 747 incident cases of esophageal or cardia cancer and 322 deaths due to these tumors were identified during the follow-up period and used in this analysis. The risks for esophageal or cardia cancer incidence and mortality increased in parallel with the presumed severity of the 1983 Chinese cytologic diagnoses. After adjusting for potential confounding factors, relative risks for esophageal or cardia cancer incidence, by initial cytologic diagnosis, were normal = 1.00 (reference), hyperplasia = 1.25, dysplasia I = 2.20, dysplasia 2 = 4.22 and near-cancer 5.96. Our results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1983, successfully identified individuals at increased risk for developing cancer of the esophagus or gastric cardia. (C) 1994 Wiley-Liss, Inc. C1 NCI,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. HENAN MED UNIV,ZHENGZHOU,PEOPLES R CHINA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. NR 15 TC 30 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 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 1994 VL 57 IS 6 BP 775 EP 780 DI 10.1002/ijc.2910570603 PG 6 WC Oncology SC Oncology GA NR234 UT WOS:A1994NR23400002 PM 8206671 ER PT J AU KREITMAN, RJ CHANG, CN HUDSON, DV QUEEN, C BAILON, P PASTAN, I AF KREITMAN, RJ CHANG, CN HUDSON, DV QUEEN, C BAILON, P PASTAN, I TI ANTI-TAC(FAB)-PE40, A RECOMBINANT DOUBLE-CHAIN IMMUNOTOXIN WHICH KILLS INTERLEUKIN-2-RECEPTOR-BEARING CELLS AND INDUCES COMPLETE REMISSION IN AN IN-VIVO TUMOR-MODEL SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RICIN-A-CHAIN; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; INTERLEUKIN-2 RECEPTOR; NUCLEOTIDE-SEQUENCE; ANTIBODY; TOXIN; MICE; GENE; REGRESSION AB We have produced a single plasmid encoding both the heavy chain Fd domain (V-H + CHI) of the anti-interleukin-2 receptor (IL2R) monoclonal antibody anti-Tac, and the anti-Tac light chain fused to PE40, a truncated derivative of Pseudomonas exotoxin. The active immunotoxin anti-Tac(Fab)-PE40 could be recovered from E. coli from either periplasm or renatured inclusion bodies. The double-chain immunotoxin was very cytotoxic toward IL2R-bearing cell lines, human activated T cells and fresh adult-T-cell-leukemia cells. The cytotoxicity was similar to that of anti-Tac(Fv)-PE40, the single-chain recombinant toxin containing only the variable domains of anti-Tac. IL2R-binding affinity was also equivalent to that of anti-Tac(Fv)PE40, which is one-third that of anti-Tac. The serum half-life in mice was significantly prolonged as compared with anti-Tac(Fv)PE40, with a beta phase of 430 vs. 57 minutes, but the LD(50)s were equivalent when the immunotoxins were administered in 3 daily doses. Anti-Tac(Fab)-PE40 was very cytotoxic in vitro toward transfected ATAC-4 carcinoma cells which express IL2Rs. In mice bearing ATAC-4 tumors, anti-Tac(Fab)-PE40 showed significant anti-tumor activity, inducing complete remissions in 80 and 100% of treated animals at approximately 7 and 14% respectively of the LD(50). Anti-Tac(Fab)-PE40 was much more effective in vitro and in vivo than chemical conjugates between anti-Tac and truncated PE molecules. The recombinant Fab toxin should be studied further as potential treatment for IL2R-related malignancies, particularly if smaller recombinant immunotoxins have insufficient half-life in humans. (C) 1994 Wiley-Liss, Inc. C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. PROT DESIGN LABS INC, MT VIEW, CA 94043 USA. HOFFMANN LA ROCHE INC, DEPT PROT BIOCHEM, NUTLEY, NJ 07110 USA. NR 24 TC 19 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 1994 VL 57 IS 6 BP 856 EP 864 DI 10.1002/ijc.2910570615 PG 9 WC Oncology SC Oncology GA NR234 UT WOS:A1994NR23400014 PM 8206679 ER PT J AU LIEBMANN, J COOK, JA FISHER, J TEAGUE, D MITCHELL, JB AF LIEBMANN, J COOK, JA FISHER, J TEAGUE, D MITCHELL, JB TI CHANGES IN RADIATION SURVIVAL-CURVE PARAMETERS IN HUMAN TUMOR AND RODENT CELLS EXPOSED TO PACLITAXEL (TAXOL(R)) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD AB Purpose: Late G(2) and M are the most radiosensitive phases of the cell cycle. Cells exposed to paclitaxel develop a cell cycle arrest in G(2)/M. These studies were performed to assess the in vitro radiosensitization properties of paclitaxel in human tumor and rodent cell lines. Methods and Materials: The effect of paclitaxel on the radiation sensitivity of human breast (MCF-7) lung (A549), ovary (OVG-1) adenocarcinoma and Chinese hamster lung fibroblast V79 cells was determined with clonogenic assays. DNA flow cytometry studies were performed to define the cell cycle characteristics of the cells during irradiation. Survival curve parameters for all cell lines were determined with the use of a computer program which represents cell survival after radiation by a linear-quadratic model. Results: All cell lines developed a G(2)/M block after exposure to paclitaxel for 24 h. However, the degree of radiosensitization produced by paclitaxel varied among the cell lines. The maximal sensitizer enhancement ratio (SER) of paclitaxel was 1.8 in MCF-7 cells, 1.6 in OVG-1 cells, and 1.7 in V79 cells. However, no concentration of paclitaxel was able to enhance the radiation sensitivity of A549 cells. Paclitaxel increased the linear (alpha) component of the radiation survival curves in all cell lines. The quadratic (beta) component was unaffected by paclitaxel in the rodent cells. High concentrations of paclitaxel (greater than or equal to 1000 nM) increased beta slightly in the human cell lines but there was considerable variation in the effect of paclitaxel on beta. The cells which were sensitized to radiation by paclitaxel had a relatively small baseline alpha component, while A549 cells had a large alpha component. Conclusion: We conclude that paclitaxel is a modest radiosensitizer in some, but not all, human tumor cells. Paclitaxel appears to cause radiosensitization mainly by increasing the cu component of radiation survival curves. Cells that normally have a relatively small alpha component should exhibit the most radiosensitization in response to paclitaxel while cells with a large cu component should show little or no radiosensitzation after paclitaxel treatment. Because the greatest effect of paclitaxel is on the linear component of radiation survival curves, these results indicate that paclitaxel may be an RP LIEBMANN, J (reprint author), NCI,RADIAT BIOL BRANCH,BLDG 10,ROOM B3B69,BETHESDA,MD 20892, USA. NR 16 TC 81 Z9 86 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1994 VL 29 IS 3 BP 559 EP 564 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NQ843 UT WOS:A1994NQ84300027 PM 7911794 ER PT J AU KURMAN, RJ HENSON, DE HERBST, AL NOLLER, KL SCHIFFMAN, MH BONFIGLIO, T BUCK, H CRUM, C CURTIN, JP GREENBERG, M HATCH, K JENSON, AB JOHNSON, P JONES, H KAMINETSKY, H KLEIN, L KOSS, L KRUMHOLZ, B LEE, N LUFF, R MANDELBLATT, J REID, R RICHART, R SEDLACEK, T SNEIDERMAN, C SOLOMON, D STOLER, M TAUB, F TRIMBLE, E TUCKER, E TWIGGS, LB WILKINSON, E ATKINSON, B AVERETTE, HE CREASMAN, W FRYHOFER, S NOY, J NIELSEN, M NOLLER, K PARK, R WESTHOFF, D AF KURMAN, RJ HENSON, DE HERBST, AL NOLLER, KL SCHIFFMAN, MH BONFIGLIO, T BUCK, H CRUM, C CURTIN, JP GREENBERG, M HATCH, K JENSON, AB JOHNSON, P JONES, H KAMINETSKY, H KLEIN, L KOSS, L KRUMHOLZ, B LEE, N LUFF, R MANDELBLATT, J REID, R RICHART, R SEDLACEK, T SNEIDERMAN, C SOLOMON, D STOLER, M TAUB, F TRIMBLE, E TUCKER, E TWIGGS, LB WILKINSON, E ATKINSON, B AVERETTE, HE CREASMAN, W FRYHOFER, S NOY, J NIELSEN, M NOLLER, K PARK, R WESTHOFF, D TI INTERIM GUIDELINES FOR MANAGEMENT OF ABNORMAL CERVICAL CYTOLOGY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; PAPANICOLAOU SMEAR; ENDOCERVICAL CELLS; BETHESDA SYSTEM; YOUNG-WOMEN; CANCER; ADENOCARCINOMA; DIAGNOSIS; EPIDEMIOLOGY; NEOPLASIA C1 JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD. NCI,EARLY DETECT BRANCH,BETHESDA,MD. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,DEPT OBSTET & GYNECOL,WORCESTER,MA. UNIV CHICAGO,SCH MED,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. UNIV ROCHESTER,SCH MED,ROCHESTER,NY. UNIV KANSAS,LAWRENCE,KS. BRIGHAM & WOMENS HOSP,BOSTON,MA. MEM HOSP CANC & ALLIED DIS,NEW YORK,NY. GRAD HOSP PHILADELPHIA,PHILADELPHIA,PA. UNIV ARIZONA,TUCSON,AZ. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. CTR DIS CONTROL & PREVENT,ATLANTA,GA. VANDERBILT UNIV SCH MED,NASHVILLE,TN. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. EMORY UNIV,SCH MED,ATLANTA,GA. MONTEFIORE MED CTR,BRONX,NY. LONG ISL JEWISH MED CTR,NEW HYDE PK,NY. SACRED HEART HOSP,ALLENTOWN,PA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY. CARSON CTR,SOUTHFIELD,MI. SLOANE HOSP WOMEN,NEW YORK,NY. NATL LIB MED,BETHESDA,MD. CLEVELAND CLIN FDN,CLEVELAND,OH. SYNCHROCELL,SILVER SPRING,MD. AMER SOC CLIN PATHOLOGISTS,CHICAGO,IL. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN. UNIV FLORIDA,COLL MED,GAINESVILLE,FL. AMER SOC CLIN PATHOLOGISTS,PHILADELPHIA,PA. AMER CANC SOC,MIAMI,FL. SOC GYNECOL ONCOLOGISTS,CHARLESTON,SC. AMER COLL PHYSICIANS,ATLANTA,GA. AMER ACAD FAMILY PRACTICE,HOUSTON,TX. COLL AMER PATHOLOGISTS,WICHITA,KS. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WORCESTER,MA. GYNECOL ONCOL GRP,PHILADELPHIA,PA. AMER SOC INTERNAL MED,JEFFERSON CITY,MO. RP KURMAN, RJ (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT OBSTET GYNECOL,600 N WOLFE ST,711 PATHOL,BALTIMORE,MD 21287, USA. NR 30 TC 460 Z9 474 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 15 PY 1994 VL 271 IS 23 BP 1866 EP 1869 DI 10.1001/jama.271.23.1866 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900032 PM 8196145 ER PT J AU TACHIBANA, M WENTHOLD, RJ MORIOKA, H PETRALIA, RS AF TACHIBANA, M WENTHOLD, RJ MORIOKA, H PETRALIA, RS TI LIGHT AND ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMICAL LOCALIZATION OF AMPA-SELECTIVE GLUTAMATE RECEPTORS IN THE RAT SPINAL-CORD SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE DORSAL HORN; VENTRAL HORN; MOTONEURON; DORSAL ROOT GANGLION; MOUSE ID GENE-RELATED PEPTIDE; AMINO-ACID RECEPTORS; DORSAL-ROOT GANGLIA; METHYL-D-ASPARTATE; SYMPATHETIC INTERMEDIOLATERAL NUCLEUS; SUBSTANTIA-GELATINOSA NEURONS; IA RECIPROCAL INHIBITION; DIMORPHIC MOTOR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; ZONE LAMINA-I AB alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors are probably the most widespread excitatory neurotransmitter receptors of the central nervous system, and they play a role in most normal and pathological neural activities. However, previous detailed studies of AMPA subunit distribution have been limited mainly to the brain. Thus, a comprehensive study of AMPA receptor subunit distribution was carried out on sections of rat spinal cord and dorsal root ganglia, which were immunolabeled with antibodies made against peptides corresponding to C-terminal portions of the AMPA receptor subunits: GluR1, GluR2/3, and GluR4. In the spinal cord, labeling was most prominent in the superficial dorsal horn, motoneurons, and nuclei containing preganglionic autonomic neurons. Immunostaining also was observed in neurons in other regions including those known to contain Renshaw cells and Ia inhibitory cells. Although overall immunostaining was lighter with antibody to GluR1 than with GluR2/3 and 4, there were neurons that preferentially stained with antibody to GluR1. These ''GluR1 intense'' neurons were usually fusiform and most concentrated in lamina X. In dorsal root ganglia, immunostaining of ganglion cell bodies was moderate to dense with antibody to GluR2/3 and light to moderate with antibody to GluR4. Possible neuroglia in the spinal cord (mainly GluR2/3 and 4) and satellite cells in dorsal root ganglia (GluR4) were immunostained. Electron microscopic studies of the superficial dorsal horn and lateral motor column showed staining that was restricted mainly to postsynaptic densities and associated dendritic and cell body cytoplasm. In dorsal horn, colocalization of dense-cored vesicles with clear, round synaptic vesicles was observed in unstained presynaptic terminals apposed to stained postsynaptic densities. Subsynaptic dense bodies (Taxi-bodies) were associated with some stained postsynaptic densities in both the superficial dorsal horn and lateral motor column. Based on several morphological features including vesicle structure and presence of Taxi-bodies, it is likely that at least some of the postsynaptic staining seen in this study is apposed to glutamatergic input from primary sensory afferent terminals. (C) 1994 Wiley-Liss, Inc. C1 NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. KYOTO PREFECTURAL UNIV MED,ELECTRON MICROSCOPY LAB,KYOTO 602,JAPAN. RP TACHIBANA, M (reprint author), NIDCD,MOLEC BIOL LAB,BLDG 36,RM 5D08,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 118 TC 112 Z9 114 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 15 PY 1994 VL 344 IS 3 BP 431 EP 454 DI 10.1002/cne.903440307 PG 24 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA NN514 UT WOS:A1994NN51400006 PM 8063961 ER PT J AU LEE, MG SHARROW, SO FARR, AG SINGER, A UDEY, MC AF LEE, MG SHARROW, SO FARR, AG SINGER, A UDEY, MC TI EXPRESSION OF THE HOMOTYPIC ADHESION MOLECULE E-CADHERIN BY IMMATURE MURINE THYMOCYTES AND THYMIC EPITHELIAL-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; STROMAL CELLS; RECEPTOR; DETERMINANTS; ACTIVATION; INTEGRIN; ANTIGEN; CD2 AB Cadherins mediate homotypic adhesion between lineage-related cells in epithelia and other tissues. One cadherin, E-cadherin, is also responsible for adhesion of murine epidermal Langerhans cells to keratinocytes in vitro, and may play a role in the localization of Langerhans cells in epidermis. The thymus is another tissue in which important adhesive interactions between bone marrow-derived cells and keratinizing epithelia occur. To determine whether cadherins might be involved in interactions between thymocytes and thymic epithelial cells, we examined thymocytes from C57BL/6 mice of various gestational ages for cadherin expression. Most day 14 (D14) and essentially all D16 isolated fetal thymocytes expressed cell surface E-cadherin. After D16, the proportion of fetal thymocytes expressing E-cadherin and the level of E-cadherin expressed by individual thymocytes decreased with increasing gestational age. A minority of neonatal thymocytes and very few adult thymocytes expressed E-cadherin. E-cadherin was maximally expressed by the least mature (CD4(-)CD8(-), HSA (J11d)(high), CD5 (Ly-1)(low), CD25 (IL-2R alpha)(+)) thymocytes. P-cadherin, another epithelial cadherin, was not detected on thymocytes at any stage of development. Immunohistologic studies revealed that thymic epithelial cells also expressed E-cadherin. Similar levels of E-cadherin were expressed by neonatal and adult thymic epithelial cells in situ, and E-cadherin was easily demonstrable on the thymic epithelial cell line, TE-71. In contrast, P-cadherin was transiently expressed by thymic epithelial cells in situ, and only small amounts of P-cadherin were detected on TE-71 cells. These studies demonstrate that thymocytes and thymic epithelial cells each have the capacity to express the homotypic adhesion molecule E-cadherin. E-cadherin may play a role in developmentally regulated interactions between early thymocytes and thymic stromal cells. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV WASHINGTON,SCH MED,DEPT BIOL STRUCT,SEATTLE,WA 98195. FU NIA NIH HHS [AG 04360] NR 31 TC 58 Z9 58 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1994 VL 152 IS 12 BP 5653 EP 5659 PG 7 WC Immunology SC Immunology GA NQ732 UT WOS:A1994NQ73200006 PM 8207198 ER PT J AU KOMSCHLIES, KL GREGORIO, TA GRUYS, ME BACK, TC FALTYNEK, CR WILTROUT, RH AF KOMSCHLIES, KL GREGORIO, TA GRUYS, ME BACK, TC FALTYNEK, CR WILTROUT, RH TI ADMINISTRATION OF RECOMBINANT HUMAN IL-7 TO MICE ALTERS THE COMPOSITION OF B-LINEAGE CELLS AND T-CELL SUBSETS, ENHANCES T-CELL FUNCTION, AND INDUCES REGRESSION OF ESTABLISHED METASTASES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; HUMAN PERIPHERAL-BLOOD; ACTIVATED KILLER-CELLS; GROWTH-FACTOR; MURINE INTERLEUKIN-7; PROLIFERATION; EXPRESSION; RECEPTOR; MOUSE; IMMUNOTHERAPY AB These studies investigate the effects of exogenously administered recombinant human IL-7 (rhIL-7) on mouse leukocyte subsets in vivo in normal and tumor-bearing mice. The administration of rhIL-7 to normal mice caused a pronounced leukocytosis (three- to fivefold increase over background) in the spleen and lymph nodes, with B-lineage and T cells, NK cells, and macrophages all being increased. CD8(+) T cells increased disproportionately, such that the CD4 to CD8 ratio decreased dramatically. The rhIL-7-induced effects were dose-dependent, increased with duration of treatment, and were reversible after cessation of rhIL-7 administration. T cell number increases after rhIL-7 treatment were primarily a result of an expansion of the peripheral T cell population. Importantly, splenocytes from rhIL-7-treated mice have enhanced proliferative responses to various T cell stimuli in vitro and were able to potentiate an allogeneic CTL response in vivo. The rhIL-7-induced changes in T cell number and the CD4 to CD8 ratio also were observed in mice bearing early Renca renal adenocarcinoma pulmonary metastases, and these changes coincided with up to a 75% reduction in pulmonary metastases. Overall, these results demonstrate that the administration of rhIL-7 to mice profoundly increases the number of B and T cells, and reduces the number of pulmonary metastases. The results also suggest that IL-7 may be useful for restoring lymphoid subsets in immunosuppressed hosts and in enhancing T cell-mediated immune responses. Such effects may be useful in the treatment of microbial diseases and cancer. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. STERLING WINTHROP INC,COLLEGEVILLE,PA 19426. RP KOMSCHLIES, KL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 41 TC 71 Z9 72 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1994 VL 152 IS 12 BP 5776 EP 5784 PG 9 WC Immunology SC Immunology GA NQ732 UT WOS:A1994NQ73200019 PM 8207207 ER PT J AU AICHER, WK HEER, AH TRABANDT, A BRIDGES, SL SCHROEDER, HW GAY, RE EIBEL, H PETER, HH SIEBENLIST, U KOOPMAN, WJ GAY, S AF AICHER, WK HEER, AH TRABANDT, A BRIDGES, SL SCHROEDER, HW GAY, RE EIBEL, H PETER, HH SIEBENLIST, U KOOPMAN, WJ GAY, S TI OVEREXPRESSION OF ZINC-FINGER TRANSCRIPTION FACTOR Z-225/EGR-1 IN SYNOVIOCYTES FROM RHEUMATOID-ARTHRITIS PATIENTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EGR-1 MESSENGER-RNA; JOINT DESTRUCTION; RESPONSE GENE; SYNOVIAL-CELLS; CATHEPSIN-L; C-FOS; EXPRESSION; PROTEIN; MICE; RECEPTOR AB In rheumatoid arthritis (RA) the proliferation of synovial lining cells appears to be one of the initial pathologic changes that contributes to the destruction of articular joints. To understand the pathomechanisms involved in these functional changes, we analyzed the transcriptional regulation of the zinc-finger gene 225 (Z-225/Egr-1), a transcription factor expressed in the immediate early events of cellular activation. We found that Z-225 transcripts were significantly up-regulated in RA synoviocytes. In primary and long term culture Z-225 was spontaneously transcribed at elevated levels. In situ hybridization of zinc-finger probe showed characteristic Z-225 transcripts in RA synovial tissues. Identity of these signals to the Z-225 gene product were confirmed in freshly isolated synovial tissue by enzymatic amplification of cDNA by the PCR technique. Z-225 transcripts were also detected and characterized in a cDNA library established from a RA synovial explant. We therefore conclude that RA synoviocytes spontaneously produce Z-225 gene products at elevated levels. Because early growth response gene Z-225 is involved in the regulation of expression of other genes such as proto-oncogenes c-ras and c-sis, which are also up-regulated in the RA synovium, activation of Z-225 transcription in RA may represent a key event in articular joint destruction. C1 UNIV ALABAMA,DIV CLIN IMMUNOL & RHEUMATOL,BIRMINGHAM,AL 35294. UNIV FREIBURG,SCH MED,CLIN RES GRP RHEUMATOL,FREIBURG,GERMANY. VET ADM MED CTR,BIRMINGHAM,AL. NIH,BETHESDA,MD 20892. NR 43 TC 72 Z9 74 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1994 VL 152 IS 12 BP 5940 EP 5948 PG 9 WC Immunology SC Immunology GA NQ732 UT WOS:A1994NQ73200038 PM 8207219 ER PT J AU EISENSTEIN, EM CHUA, K STROBER, W AF EISENSTEIN, EM CHUA, K STROBER, W TI B-CELL DIFFERENTIATION DEFECTS IN COMMON VARIABLE IMMUNODEFICIENCY ARE AMELIORATED AFTER STIMULATION WITH ANTI-CD40 ANTIBODY AND IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED IMMUNODEFICIENCY; HUMAN LYMPHOCYTES-B; HYPER-IGM SYNDROME; T-CELL; CD40 LIGAND; IMMUNOGLOBULIN DEFICIENCY; BLOOD-LYMPHOCYTES; PERIPHERAL-BLOOD; ACCESSORY CELL; EXPRESSION AB In these studies we show that although purified B cells of patients with common variable immunodeficiency (CVI) have a normal capacity to proliferate, they manifest differentiation defects at multiple levels. Compared with controls, circulating CVI B cell populations contain reduced numbers of slgG(+) and slgA(+) cells with a commensurate increase in slgM(+) B cells, suggesting an in vivo defect in isotype switch. In addition, CVI B cells manifest Ig secretion defects on stimulation with either anti-CD40 and IL-10 or SAC and IL-2 and IL-10, which are of increasing severity for IgM, Igc, and IgA, respectively. These Ig secretion defects are not overcome by addition of a variety of cytokines, including TGF-beta, to anti-CD40-driven cultures. In further studies we show that despite the above abnormalities, CVI B cells are induced to express normal or near-normal levels of C mu, C gamma, and C alpha mRNA after 7 days of stimulation with anti-CD40 and IL-10. That this C-H mRNA expression represents a recovery of CVI B cell differentiation is supported by studies of Ig secretion in which CVI B cells that are first stimulated for 7 days with anti-CD40 and IL-10 and then restimulated in coculture with activated normal allogeneic T cells and IL-10, secrete substantial levels of IgM and IgG and increased amounts of IgA. Overall, therefore, CVI B cell function can be significantly improved by maintenance in culture. These data suggest the abnormalities of B cell differentiation in CVI are reversible and that the defect is a form of B cell anergy. RP EISENSTEIN, EM (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N-238,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 56 Z9 57 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1994 VL 152 IS 12 BP 5957 EP 5968 PG 12 WC Immunology SC Immunology GA NQ732 UT WOS:A1994NQ73200040 PM 7515919 ER PT J AU ZAHM, SH BLAIR, A FRAUMENI, JF AF ZAHM, SH BLAIR, A FRAUMENI, JF TI HAIR COLORING PRODUCTS - SAFE OR STILL SUSPECT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID DYE USE; BREAST-CANCER; MULTIPLE-MYELOMA; LEUKEMIA RP ZAHM, SH (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EPN,RM 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 16 TC 5 Z9 5 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 15 PY 1994 VL 86 IS 12 BP 941 EP 943 DI 10.1093/jnci/86.12.941-a PG 3 WC Oncology SC Oncology GA NT529 UT WOS:A1994NT52900014 PM 8196085 ER PT J AU QIN, J CLORE, GM GRONENBORN, AM AF QIN, J CLORE, GM GRONENBORN, AM TI THE HIGH-RESOLUTION 3-DIMENSIONAL SOLUTION STRUCTURES OF THE OXIDIZED AND REDUCED STATES OF HUMAN THIOREDOXIN SO STRUCTURE LA English DT Article DE HETERONUCLEAR MULTIDIMENSIONAL NMR; HUMAN THIOREDOXIN; OXIDIZED STATE; REDUCED STATE; SOLUTION STRUCTURE ID NUCLEAR-MAGNETIC-RESONANCE; ESCHERICHIA-COLI THIOREDOXIN; INTERPROTON DISTANCE RESTRAINTS; ISOTOPICALLY ENRICHED PROTEINS; POTATO CARBOXYPEPTIDASE INHIBITOR; 3-DIMENSIONAL SOLUTION STRUCTURE; PULSED-FIELD GRADIENTS; SIDE-CHAIN RESONANCES; MOLECULAR-DYNAMICS; LARGER PROTEINS AB Background: Thioredoxin is a ubiquitous protein and is involved in a variety of fundamental biological functions. Its active site is conserved and has two redox active cysteines in the sequence Trp-Cys-Gly-Pro-Cys. No structures of the oxidized and reduced states from the same species have been determined at high resolution under the same conditions and using the same methods. Hence, any detailed comparison of the two oxidation states has been previously precluded. Results: The reduced and oxidized states of the (C62A, C63A, C73A) mutant of human thioredoxin have been investigated by multidimensional heteronuclear NMR. Structures for both states were determined on the basis of approximately 28 experimental restraints per residue, and the resulting precision of the two structures is very high. Consequently, subtle differences between the oxidized and reduced states can be reliably assessed and evaluated. Small differences, particularly within and around the active site can be discerned. Conclusions: Overall, the structures of the reduced and oxidized states of the (C62A, C63A, C73A) mutant of human thioredoxin are very similar (with a backbone atomic root mean square difference of about 0.9 Angstrom) and the packing of side chains within the protein core is nearly identical. The conformational change between oxidized and reduced human thioredoxin is very small and localized to areas in spatial proximity to the redox active cysteines. These subtle structural differences, in addition to the restriction of conformational freedom within the active site upon oxidation, may be important for the different activities of thioredoxin involving a variety of target proteins. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 88 TC 137 Z9 139 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD JUN 15 PY 1994 VL 2 IS 6 BP 503 EP 522 DI 10.1016/S0969-2126(00)00051-4 PG 20 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NV651 UT WOS:A1994NV65100006 PM 7922028 ER PT J AU PAN, CJ CHAMBERLIN, ME WU, SM CHAN, WY CHOU, JY AF PAN, CJ CHAMBERLIN, ME WU, SM CHAN, WY CHOU, JY TI PREGNANCY-SPECIFIC GLYCOPROTEIN GENE-EXPRESSION AND THE INDUCTION BY 5-BROMO-2'-DEOXYURIDINE SO BIOCHEMISTRY LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; MOLECULAR-CLONING; BETA-1-GLYCOPROTEIN; FAMILY; CDNA; PROTEINS; SP1; MEMBERS; MALIGNANCIES; SEQUENCE AB The pregnancy-specific glycoproteins (PSGs) of the placenta, members of the immunoglobulin superfamily, are encoded by multiple linked genes located on chromosome 19. To study the control of PSG expression, we have immortalized differentiated human placental cells (HP-A1) temperature-sensitive for transformation by a recombinant adenovirus-(ori(-))-Sv40 tsA mutant virus. We now show that expression of the PSG gene in HP-A1 cells is temperature-sensitive. At the permissive temperature (33 degrees C), these cells expressed low levels of PSG mRNA and synthesized a 64-kDa PSG. Shifting HP-A1 cells to a nonpermissive temperature (39.5 degrees C) increased PSG mRNA expression and biosynthesis with preferential increase in the synthesis of a 54-kDa and a low level of a 72-kDa PSG. Moreover, PSG expression was greatly induced by 5-bromo-2'-deoxyuridine (BudR), which selectively increased synthesis of PSGs of 72 and 54 kDa. In the presence of BudR, HP-A1 synthesized PSGs of 72, 64, and 54 kDa, similar to the pattern seen with placental PSGs. Ribonuclease protection assays demonstrated that HP-A1 cells express the majority of PSG mRNAs and BudR stimulated expression of PSG1 and PSG1-like transcripts. Reverse transcription and polymerase chain reaction analysis using PSG gene-specific primers demonstrated that untreated HP-A1 cells expressed primarily PSG1, PSG2, PSG4, and PSG5 mRNAs. BudR stimulated the expression of all PSG transcripts except PSG4. Moreover, in transient expression assays, BudR increased chloramphenicol acetyltransferase (CAT) expression directed by PSG1-I, PSG4, PSG5, PSG6, and PSG11 promoter-CAT fusion genes. Our data indicate that the increase in PSG expression by BudR is regulated at both transcriptional and post-transcriptional levels. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. NR 42 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 14 PY 1994 VL 33 IS 23 BP 7260 EP 7266 DI 10.1021/bi00189a030 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT328 UT WOS:A1994NT32800030 PM 8003489 ER PT J AU OMATA, Y ROBINSON, RC GELBOIN, HV PINCUS, MR FRIEDMAN, FK AF OMATA, Y ROBINSON, RC GELBOIN, HV PINCUS, MR FRIEDMAN, FK TI SPECIFICITY OF THE CYTOCHROME-P-450 INTERACTION WITH CYTOCHROME B(5) SO FEBS LETTERS LA English DT Article DE CYTOCHROME P-450; CYTOCHROME B(5); MOLECULAR MODELING; PROTEIN-PROTEIN INTERACTION ID PROTEIN-PROTEIN INTERACTIONS; INDUCED RAT-LIVER; HEPATIC-MICROSOMAL CYTOCHROME-P-450; MONOCLONAL-ANTIBODIES; CATALYTIC ACTIVITY; PURIFICATION; B5; METABOLISM; ENZYMES; COMPLEX AB The specificity of the interaction of cytochrome b(5) with different forms of cytochrome P-450 was examined. Immunopurification of cytochromes P-450 1A1, 2B1 and 2E1 from rat liver microsomes resulted in co-purification of cytochrome b(5) with cytochrome P-450 forms 2B1 and 2E1 but not 1A1. This specificity was evaluated in conjunction with multiple sequence alignment of the three cytochrome P-450s and a molecular model of the cytochrome P-450-cytochrome b(5) complex [(1989) Biochemistry 28, 8201-8205]. These analyses suggest two basic residues in the arginine cluster region of P-450, which are present in P-450s 2B1 and 2E1 but are absent in P-450 1A1, as potential binding sites for cytochrome b(5). C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY 13210. RI Friedman, Fred/D-4208-2016 NR 46 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 13 PY 1994 VL 346 IS 2-3 BP 241 EP 245 DI 10.1016/0014-5793(94)00482-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NR569 UT WOS:A1994NR56900023 PM 8013641 ER PT J AU BURNS, DN GELLERT, GA CRONE, RK AF BURNS, DN GELLERT, GA CRONE, RK TI TUBERCULOSIS IN EASTERN-EUROPE AND THE FORMER SOVIET-UNION - HOW CONCERNED SHOULD WE BE SO LANCET LA English DT Editorial Material C1 PROJECT HOPE,CTR HLTH SCI EDUC,MILLWOOD,VA. RP BURNS, DN (reprint author), NIH,BETHESDA,MD 20892, USA. NR 8 TC 17 Z9 17 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 11 PY 1994 VL 343 IS 8911 BP 1445 EP 1446 DI 10.1016/S0140-6736(94)92576-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NQ415 UT WOS:A1994NQ41500003 PM 7911172 ER PT J AU STRAUS, SE COREY, L BURKE, RL SAVARESE, B BARNUM, G KRAUSE, PR KOST, RG MEIER, JL SEKULOVICH, R ADAIR, SF DEKKER, CL AF STRAUS, SE COREY, L BURKE, RL SAVARESE, B BARNUM, G KRAUSE, PR KOST, RG MEIER, JL SEKULOVICH, R ADAIR, SF DEKKER, CL TI PLACEBO-CONTROLLED TRIAL OF VACCINATION WITH RECOMBINANT GLYCOPROTEIN-D OF HERPES-SIMPLEX VIRUS TYPE-2 FOR IMMUNOTHERAPY OF GENITAL HERPES SO LANCET LA English DT Article ID T-CELL CLONES; MONOCLONAL-ANTIBODIES; ORAL ACYCLOVIR; DOUBLE-BLIND; INFECTION; PROTECTION; EFFICACY; ANTIGEN; RISK; MICE AB Immunotherapy of chronic viral diseases with vaccines is an important but unproven concept. We investigated the effect of a vaccine containing recombinant glycoprotein D (gD2) of herpes simplex virus type 2 (HSV-2) on the frequency of symptomatic outbreaks in patients with genital herpes. 98 patients with documented genital herpes who reported 4-14 recurrences per year were enrolled in a double-blind, placebo-controlled trial. Subjects received injections of either 100 mu g gD2 in alum or alum alone (placebo) at 0 and 2 months, and recurrences were documented for 1 year. The vaccine was well tolerated, gD2 recipients reported fewer recurrences per month than placebo recipients (mean 0.42 [SE 0.05] vs 0.55 [0.05]; p = 0.055), had fewer virologically confirmed recurrences per month (0.18 [0.03] vs 0.28 [0.03]; p = 0.019), and had a lower median number of recurrences for the study year (4 [range 0-17] vs 6 [0-15]; p = 0.039). Neither genital recurrence nor the placebo vaccine had any discernible effect on HSV-2-specific antibody responses, but gD2 vaccine boosted neutralising antibodies to HSV-2 fourfold and gD2-specific titres sevenfold over baseline levels. These results inspire optimism about the potential use of vaccine for the treatment of chronic,recurring viral diseases. C1 UNIV WASHINGTON,DEPT LAB MED,DIV VIROL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. BIOCINE CO,EMERYVILLE,CA. RP STRAUS, SE (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,ROOM 11N-228,BETHESDA,MD 20892, USA. NR 28 TC 162 Z9 166 U1 0 U2 6 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 11 PY 1994 VL 343 IS 8911 BP 1460 EP 1463 DI 10.1016/S0140-6736(94)92581-X PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NQ415 UT WOS:A1994NQ41500008 PM 7911177 ER PT J AU BERGAN, R CONNELL, Y FAHMY, B KYLE, E NECKERS, L AF BERGAN, R CONNELL, Y FAHMY, B KYLE, E NECKERS, L TI APTAMERIC INHIBITION OF P210(BCR-ABL) TYROSINE KINASE AUTOPHOSPHORYLATION BY OLIGODEOXYNUCLEOTIDES OF DEFINED SEQUENCE AND BACKBONE STRUCTURE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; PROTEIN-KINASE; BCR-ABL; CELLULAR PROTEINS; EGF RECEPTOR; GROWTH; CELLS; TRANSFORMATION; FAMILY; DOMAIN AB Protein tyrosine kinases play key roles in cellular physiology. Specific inhibitors of these enzymes are important laboratory tools and may prove to be novel therapeutic agents. In this report we describe a new class of tyrosine kinase inhibitor, synthetic oligodeoxynucleotides (ODNs). An ODN is described which specifically inhibits p210(bcr-abl) tyrosine kinase autophosphorylation in vitro with a K-i of 0.5 mu M. Inhibition is non-competitive with respect to ATP. The effects upon inhibitory activity of ODN structure modifications are described. The inhibition described is not mediated by classical antisense mechanisms and represents an example of the recently recognized aptameric properties of ODNs. RP NCI, CLIN PHARMACOL BRANCH, BETHESDA, MD 20892 USA. NR 37 TC 60 Z9 60 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1994 VL 22 IS 11 BP 2150 EP 2154 DI 10.1093/nar/22.11.2150 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT818 UT WOS:A1994NT81800031 PM 8029025 ER PT J AU KOONIN, EV BORK, P SANDER, C AF KOONIN, EV BORK, P SANDER, C TI A NOVEL RNA-BINDING MOTIF IN OMNIPOTENT SUPPRESSORS OF TRANSLATION TERMINATION, RIBOSOMAL-PROTEINS AND A RIBOSOME MODIFICATION ENZYME SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; RAM PROTEIN; YEAST; SEQUENCE; GENE; FIDELITY; PRODUCT; SUP45 AB Using computer methods for database search, multiple alignment, protein sequence motif analysis and secondary structure prediction, a putative new RNA-binding motif was identified. The novel motif is conserved in yeast omnipotent translation termination suppressor SUP1, the related DOM34 protein and its pseudogene homologue; three groups of eukaryotic and archaeal ribosomal proteins, namely L30e, L7Ae/S6e and S12e; an uncharacterized Bacillus subtilis protein related to the L7A/S6e group; and Escherichia coli ribosomal protein modification enzyme RimK. We hypothesize that a new type of RNA-binding domain may be utilized to deliver additional activities to the ribosome. C1 MOLEC BIOL LAB, D-69012 HEIDELBERG, GERMANY. MAX DELBRUCK CTR MOLEC MED, D-13189 BERLIN, GERMANY. RP KOONIN, EV (reprint author), NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RI sander, chris/H-1452-2011; Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 20 TC 87 Z9 87 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1994 VL 22 IS 11 BP 2166 EP 2167 DI 10.1093/nar/22.11.2166 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT818 UT WOS:A1994NT81800034 PM 7518079 ER PT J AU CHO, HS WOLFFE, AP AF CHO, HS WOLFFE, AP TI XENOPUS-LAEVIS B4, AN INTRON-CONTAINING OOCYTE-SPECIFIC LINKER HISTONE-ENCODING GENE SO GENE LA English DT Note DE RECOMBINANT DNA; NUCLEOTIDE SEQUENCE; EXPRESSION; TRANSCRIPTIONAL REGULATION; UPSTREAM CONTROL ELEMENT; CHROMATIN ID TRANSCRIPTION FACTOR-IIIA; RNA POLYMERASE-II; DEVELOPMENTAL REGULATION; MESSENGER-RNA; SOMATIC-CELLS; EXPRESSION; BINDING; IDENTIFICATION; EMBRYOGENESIS; ORGANIZATION AB We have isolated genomic clones of the Xenopus laevis B4 gene, which encodes a linker histone, and characterized the B4 promoter. B4 mRNA is synthesized in X. laevis oocytes and disappears from the embryo by gastrulation. We find that B4 is present in only one or two copies per haploid genome and that it contains introns. Tissue-specific expression, a low copy number and presence of introns are all unusual features for vertebrate genes encoding linker histones. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 26 TC 28 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 10 PY 1994 VL 143 IS 2 BP 233 EP 238 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA NR565 UT WOS:A1994NR56500012 PM 8206379 ER PT J AU LI, H HODGE, DR PEI, GK SETH, A AF LI, H HODGE, DR PEI, GK SETH, A TI ISOLATION AND SEQUENCE-ANALYSIS OF THE HUMAN SYNTAXIN-ENCODING GENE SO GENE LA English DT Note DE CLONING; NUCLEOTIDE SEQUENCE; HOMOLOGY TO RAT; TRANSPORT RECEPTORS; PROTEIN PHOSPHORYLATION AB STX-related genes (encoding syntaxin) have been identified in rat and yeast; however, no human STX gene has been isolated thus far. Here, we describe the nucleotide sequence of the first human STX gene isolated from a placental library. It encodes a 297-amino-acid (aa) protein and is 89% identical to the aa sequence of rat STX4a. C1 NCI,FREDERICK CANC RES & DEV CTR,ONCOL MOLEC LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NR 3 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 10 PY 1994 VL 143 IS 2 BP 303 EP 304 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA NR565 UT WOS:A1994NR56500027 PM 8206394 ER PT J AU AKIYAMA, SK YAMADA, SS YAMADA, KM LAFLAMME, SE AF AKIYAMA, SK YAMADA, SS YAMADA, KM LAFLAMME, SE TI TRANSMEMBRANE SIGNAL-TRANSDUCTION BY INTEGRIN CYTOPLASMIC DOMAINS EXPRESSED IN SINGLE-SUBUNIT CHIMERAS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PROTEIN-TYROSINE KINASE; HUMAN INTERLEUKIN-2 RECEPTOR; CELL-SURFACE RECEPTORS; EXTRACELLULAR-MATRIX; FIBRONECTIN RECEPTOR; BETA-SUBUNIT; MONOCLONAL-ANTIBODIES; BOMBESIN STIMULATION; MOLECULAR-CLONING; FOCAL ADHESIONS AB Integrins are heterodimeric, transmembrane cell adhesion receptors that have recently been shown to function in transmembrane signal transduction. To examine the specific role of integrin intracellular domains in signal transduction, chimeric receptors containing various integrin intracellular domains coupled to a reporter consisting of the transmembrane and extracellular domains of the small, non-signaling subunit of the interleukin-2 receptor were expressed in cultured human fibroblasts and assayed for their ability to trigger tyrosine phosphorylation of the 125-kDa cytoplasmic tyrosine kinase, pp125(FAK). Tyrosine phosphorylation of pp125(FAK) was induced in cultured fibroblasts that transiently expressed chimeric receptors containing either the beta(1), beta(3), beta(5) integrin intracellular domain and were selected by magnetic bead sorting. However, expression of chimeric receptors containing either the alpha(5) or an alternatively spliced form of the beta(3) intracellular domain (beta(3B)), as well as those lacking an intracellular domain, failed to induce tyrosine phosphorylation of pp125(FAK). These results indicate that information contained in the beta(1), beta(3), or beta(5) integrin intracellular domain is sufficient to stimulate integrin-mediated tyrosine phosphorylation of specific intracellular proteins and that integrin extracellular and transmembrane domains are not required for inducing tyrosine phosphorylation. Our results also indicate that alternative splicing can regulate the ability of beta integrin intracellular domains to participate in signal transduction, and they further suggest that the carboxyl-terminal region of specific beta integrins may play a role in the signal transduction pathway involving extracellular matrix molecules. RP AKIYAMA, SK (reprint author), NIDR,DEV BIOL LAB,BLDG 30,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 57 TC 150 Z9 151 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 1994 VL 269 IS 23 BP 15961 EP 15964 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ729 UT WOS:A1994NQ72900002 PM 7515874 ER PT J AU BALLA, T NAKANISHI, S CATT, KJ AF BALLA, T NAKANISHI, S CATT, KJ TI CATION SENSITIVITY OF INOSITOL 1,4,5-TRISPHOSPHATE PRODUCTION AND METABOLISM IN AGONIST-STIMULATED ADRENAL GLOMERULOSA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOLIPASE-C; ANGIOTENSIN-II; POLYPHOSPHATE METABOLISM; SARCOPLASMIC-RETICULUM; ENDOTHELIAL-CELLS; TUMOR PROMOTER; CALCIUM ENTRY; ACINAR-CELLS; FREE CA-2+; THAPSIGARGIN AB Angiotensin II (AII) evokes a biphasic increase in inositol 1, 4, 5-trisphosphate (Ins(1,4,5)P-3) levels in adrenal glomerulosa cells, with an extracellular Ca2+-independent early peak followed by a secondary sustained elevation that is highly dependent on the presence of extracellular Ca2+. The Ca2+ dependent sustained phase of agonist-induced Ins(1,4,5)P-3 production was closely correlated with Ca2+ influx and was inhibited by inorganic Ca2+ channel blockers with the potency ratio: La3+ >> Cd2+ > Mn2+ > Co2+ > Ni2+. Of the two Ca2+ surrogates, Sr2+ and Ba2+, Sr2+ was partially active compared with Ca2+, and Ba2+ was inactive in restoring Ins(1,4,5)P-3 formation in cells stimulated with AII in Ca2+-free medium. However, unlike Ca2+, Sr2+ only weakly supported and Ba2+ failed to affect the calmodulin activation of Ins(1,4,5)P-3 3-kinase. Also, there was an accumulation of Ins(1,4,5)P-3 and diminished formation of Ins(1,3,4,5)P-4 and Ins(1,3,4)P-3 when intact glomerulosa cells were stimulated by AII in the presence of Sr2+. This difference between the Sr2+ sensitivity of phospholipase C and Ins(1,4,5)P-3 3-kinase provides a means for the potentiation of agonist-induced elevations of Ins(1,4,5)P-3 in the intact cell and for direct analysis of the role of the inositol tris-/tetrakisphosphate pathway in cellular signaling. RP BALLA, T (reprint author), NIH,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,RM 6A36,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 38 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 1994 VL 269 IS 23 BP 16101 EP 16107 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ729 UT WOS:A1994NQ72900025 PM 7515876 ER PT J AU DEMENDEZ, I GARRETT, MC ADAMS, AG LETO, TL AF DEMENDEZ, I GARRETT, MC ADAMS, AG LETO, TL TI ROLE OF P67-PHOX SH3 DOMAINS IN ASSEMBLY OF THE NADPH OXIDASE SYSTEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; GTP-BINDING PROTEIN; RESPIRATORY BURST OXIDASE; PHOSPHATIDYLINOSITOL 3-KINASE; CRYSTAL-STRUCTURE; TYROSINE KINASES; NEUTROPHIL; COMPONENTS; REGION; GRB2 AB Src homology 3 (SH3) domains direct cellular localization and signal transduction through specific protein-protein interactions with proline-rich target sequences. The two SH3 domain in p67-phox, a cytosolic component of the phagocyte NADPH oxidase system, may mediate interactions within the oxidase complex and direct its translocation to membranes. The requirement for SH3 domains in p67-phox was studied both in cell-free and whole cell oxidase assay systems. The amino-terminal domain of p67-phox (amino acids 1-246) that lacks both SH3 domains was active in vitro. Various forms of p67-phox lacking one or both SH3 domains were produced in whole cells using episomal expression vectors to stably transfect p67-phox-deficient Epstein-Barr virus-B cells derived from chronic granulomatous disease patients. Complete restoration of NADPH oxidase activity was achieved with full-length p67-phox cDNA expression. Deletion of either SH3 domain resulted in dramatic reductions of NADPH oxidase activity relative to corrected transfected cells, which correlated with decreases in membrane binding. Deletion of both SH3 domains completely abolished p67-phox membrane binding and oxidase activity. Thus, in contrast to oxidase reconstitution in a cell-free system, we observed a requirement for both SH3 motifs for restoration of oxidase activity and binding of p67-phox to membranes. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 36 TC 94 Z9 95 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 1994 VL 269 IS 23 BP 16326 EP 16332 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ729 UT WOS:A1994NQ72900058 PM 8206939 ER PT J AU CREEDON, KA RATHOD, PK WELLEMS, TE AF CREEDON, KA RATHOD, PK WELLEMS, TE TI PLASMODIUM-FALCIPARUM S-ADENOSYLHOMOCYSTEINE HYDROLASE - CDNA IDENTIFICATION, PREDICTED PROTEIN-SEQUENCE, AND EXPRESSION IN ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID L-HOMOCYSTEINE HYDROLASE; ADENOSYL-L-HOMOCYSTEINE; AMINO-ACID SEQUENCE; RAT-LIVER; NEPLANOCIN-A; ANTIMALARIAL ACTIVITY; CHEMICAL MODIFICATION; GENOMIC ORGANIZATION; NUCLEOTIDE-SEQUENCE; MALARIA PARASITES AB Compounds that specifically inhibit S-adenosylhomocysteine hydrolase (SAHH; EC 3.3.1.1) interfere with the proliferation of Plasmodium malarial parasites, but efforts to identify the enzyme directly in parasite extracts have been unsuccessful. Here we report genetic and biochemical evidence for the presence of a gene encoding P. falciparum SAHH. The gene is transcribed as a 2.8-kilobase mRNA in erythrocytic stage parasites. Analysis of the open reading frame predicts a 53.9-kDa protein having conserved regions thought to be involved in NAD binding. The cDNA sequence has been incorporated into an Escherichia coli expression construct to confirm the function of the sahh product. Transformed E. coli cells produce a protein with a relative molecular weight of 56,000 which possesses SAHH activity as evidenced by the conversion of 3-deazaadenosine to S-3-deazaadenosylhomocysteine. Several amino acid residues that have been suggested to be at the SAHH active site in other organisms show nonconserved replacements in P. falciparum, suggesting that some current proposals for the enzyme mechanism may need to be revised. The structural differences between the P. falciparum and mammalian SAHH enzymes may foster innovative strategies for drug development against malaria. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. CATHOLIC UNIV AMER,INST BIOMOLEC STUDIES,DEPT BIOL,WASHINGTON,DC 20064. FU NIAID NIH HHS [NIAID AI26912, AI01112] NR 66 TC 47 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 1994 VL 269 IS 23 BP 16364 EP 16370 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ729 UT WOS:A1994NQ72900063 PM 8206944 ER PT J AU AHMED, SA MILES, EW AF AHMED, SA MILES, EW TI ALIPHATIC-ALCOHOLS STABILIZE AN ALTERNATIVE CONFORMATION OF THE TRYPTOPHAN SYNTHASE ALPHA(2)BETA(2) COMPLEX FROM SALMONELLA-TYPHIMURIUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET FACTOR-IV; ESCHERICHIA-COLI; BETA-SUBUNIT; ORGANIC-SOLVENTS; ALPHA; IDENTIFICATION; ASSOCIATION; PROTEINS; CLEAVAGE; SITE AB The conformational changes that accompany association of the tryptophan synthase alpha and beta(2) s are probed by investigating the effects of solvents on the catalytic and spectroscopic properties of tryptophan synthase. Low concentrations of ethanol, propanol, and butanol inhibit conversion of L-serine and indole to L-tryptophan by the alpha(2) beta(2) complex. Inhibition depends on the concentration, chain length, and hydrophobicity of the alcohol. In contrast, these alcohols increase the rates of conversion of beta-chloro-L-alanine and indole to L-tryptophan and of L-serine to pyruvate. Thus, alcohols alter the substrate specificity and reaction specificity of the alpha(2) beta(2) complex. These altered specificities are similar to those of the free beta(2) subunit in aqueous solution. The spectroscopic properties of enzyme-substrate intermediates formed by the alpha(2) beta(2) complex in 3 M ethanol and 0.5 M 1-butanol also resemble the intermediates formed by the free beta(2) subunit in aqueous solution. Experiments using gel-filtration, membrane ultrafiltration, and limited proteolysis show that the alpha(2) beta(2) complex does not dissociate at low concentrations of alcohols. Our results provide evidence that alcohols can stabilize an alternative conformation of the alpha(2) beta(2) complex which is similar to the open conformation of the free beta(2) aqueous solution. RP AHMED, SA (reprint author), NIDDK, BIOCHEM PHARMACOL LAB, BLDG 8, RM 2A-05, BETHESDA, MD 20892 USA. NR 32 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 1994 VL 269 IS 23 BP 16486 EP 16492 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ729 UT WOS:A1994NQ72900079 PM 8206958 ER PT J AU JOHN, CS VILNER, BJ BOWEN, WD AF JOHN, CS VILNER, BJ BOWEN, WD TI SYNTHESIS AND CHARACTERIZATION OF [I-125] N-(N-BENZYLPIPERIDIN-4-YL)-4-IODOBENZAMIDE, A NEW SIGMA-RECEPTOR RADIOPHARMACEUTICAL - HIGH-AFFINITY BINDING TO MCF-7 BREAST-TUMOR CELLS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID MALIGNANT-MELANOMA; ANTIPSYCHOTIC-DRUGS; H-3 (+)-PENTAZOCINE; ENDOCRINE; LIGAND; POTENT; SITE C1 NIDDK,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BETHESDA,MD 20892. RP JOHN, CS (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,RADIOPHARMACEUT CHEM SECT,661 ROSS HALL,2300 I ST NW,WASHINGTON,DC 20037, USA. FU NCI NIH HHS [R29 CA58496] NR 28 TC 64 Z9 66 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 10 PY 1994 VL 37 IS 12 BP 1737 EP 1739 DI 10.1021/jm00038a002 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NR647 UT WOS:A1994NR64700002 PM 8021913 ER PT J AU BOYD, MR HALLOCK, YF MANFREDI, KP BLUNT, JW MCMAHON, JB BUCKHEIT, RW BRINGMANN, G SCHAFFER, M CRAGG, GM THOMAS, DW JATO, JG CARDELLINA, JH AF BOYD, MR HALLOCK, YF MANFREDI, KP BLUNT, JW MCMAHON, JB BUCKHEIT, RW BRINGMANN, G SCHAFFER, M CRAGG, GM THOMAS, DW JATO, JG CARDELLINA, JH TI ANTI-HIV MICHELLAMINES FROM ANCISTROCLADUS-KORUPENSIS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID ABSOLUTE-CONFIGURATION; ALKALOIDS AB Here we report details of the isolation and determination of the absolute configurations and comparative anti-HIV activities of novel, atropisomeric naphthylisoquinoline alkaloid dimers, michellamines A, B, and C, from a newly described species of Ancistrocladus from the Korup rainforest of Cameroon. We further provide a more extensive analysis of the range of anti-HIV activity of michellamine B, the most potent and abundant member of the series. Michellamine B inhibited HIV-induced cell killing and viral replication in a variety of human cell lines, as well as in cultures of human peripheral blood leukocytes and monocytes. Michellamine B was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6 and the pyridinone-resistant strain A17; the compound also inhibited several strains of HIV-2. C1 FREDERICK CANC RES & DEV CTR,SO RES INST,DIV VIROL RES,FREDERICK,MD 21701. UNIV WURZBURG,INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,NAT PROD BRANCH,FREDERICK,MD 21702. OREGON STATE UNIV,DEPT INT RES & DEV,CORVALLIS,OR 97331. UNIV YAOUNDE,FAC MED & BIOMED SCI,YAOUNDE,CAMEROON. RP BOYD, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21702, USA. OI Blunt, John/0000-0003-4053-4376 NR 18 TC 177 Z9 183 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 10 PY 1994 VL 37 IS 12 BP 1740 EP 1745 DI 10.1021/jm00038a003 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NR647 UT WOS:A1994NR64700003 PM 8021914 ER PT J AU LEE, JW SHARMA, R TENG, K LEWIN, NE BLUMBERG, PM MARQUEZ, VE AF LEE, JW SHARMA, R TENG, K LEWIN, NE BLUMBERG, PM MARQUEZ, VE TI CONFORMATIONALLY CONSTRAINED ANALOGS OF DAG .8. CHANGES IN PK-C BINDING-AFFINITY PRODUCED BY ISOSTERIC GROUPS OF THE 3-O-ACYL FUNCTION IN 2-DEOXY-L-RIBONOLACTONES SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PROTEIN-KINASE-C; GAMMA-LACTONES; DIACYLGLYCEROL; DERIVATIVES; FAMILY AB Syntheses of a series of 2-deoxy-L-ribonolactones modified at C-3 with groups isosteric to the 3-O-acyl moiety of the parent 3-O-tetradecanoyl-2-deoxy-L-ribonolactone (1) are reported. Lipophilicity of the molecules was kept constant by maintaining invariant the length of the aliphatic chain. Compound 5 was identified as having an affinity equal to that of 1 in a competitive binding assay that measured the ability of the ligands to displace [H-3]-phorbol-12,13-dibutyrate from PK-C. The reverse ester function in 5 makes this compound more stable than 1 by preventing beta-elimination. Other changes in 1 led to a reduction in affinity. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 13 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 9 PY 1994 VL 4 IS 11 BP 1369 EP 1374 DI 10.1016/S0960-894X(01)80364-4 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA NR426 UT WOS:A1994NR42600020 ER PT J AU HARLAN, WR AF HARLAN, WR TI CREATING AN NIH CLINICAL-TRIALS REGISTRY - A USER-FRIENDLY APPROACH TO HEALTH-CARE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HARLAN, WR (reprint author), NIH,BETHESDA,MD 20892, USA. NR 2 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 8 PY 1994 VL 271 IS 22 BP 1729 EP 1729 DI 10.1001/jama.271.22.1729 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NN725 UT WOS:A1994NN72500003 PM 8196103 ER PT J AU SMITH, DE LEWIS, CE CAVENY, JL PERKINS, LL BURKE, GL BILD, DE AF SMITH, DE LEWIS, CE CAVENY, JL PERKINS, LL BURKE, GL BILD, DE TI LONGITUDINAL CHANGES IN ADIPOSITY ASSOCIATED WITH PREGNANCY - THE CARDIA STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-FAT DISTRIBUTION; WEIGHT-GAIN; POSTPARTUM WEIGHT; METABOLIC-RATE; RISK-FACTORS; MASS INDEX; WOMEN; OBESITY; ADULTS; BLACK AB Objective.-To examine the longitudinal associations between a pregnancy and persistent changes in adiposity in young black and white women. Design.-Prospective cohort study with 5 years of follow-up. Setting.-Participants recruited by community-based sampling (Birmingham, Ala; Chicago, Ill; and Minneapolis, Minn) and through the membership of a large prepaid health care plan (Oakland, Calif). Participants.-A total of 2788 women (53% black) aged 18 through 30 years were assessed at baseline (1985 through 1986) and reassessed at examination 2 (91% retention; 1987 through 1988) and examination 3 (86% retention; 1990 through 1991). Women who remained nulliparous (n=925) during the 5-year follow-up were compared with women who had a single pregnancy of 28 weeks' duration during that period and who were at least 12 months postpartum at follow-up (primiparas, n=89; multiparas, n=114). Main Outcome Measures.-Change in body weight and in waist-to-hip ratio during the 5-year period. Analyses were adjusted for demographic factors (age and education), behavioral variables (smoking and physical activity), and baseline level of adiposity. Results.-Primiparas within both race groups gained 2 to 3 kg more weight during the 5-year period than did nulliparas in both adjusted and unadjusted analyses. Primiparas also had greater increases in waist-to-hip ratio that were independent of weight gain. Multiparas did not differ from nulliparas in adiposity change in either race group. At each level of parity, black women demonstrated greater adverse changes in adiposity than did white women. Conclusions.-These data suggest that women experience modest but adverse increases in body weight and fat distribution after a first pregnancy and that these changes are persistent. C1 DOW CORNING CORP,MIDLAND,MI. BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD. RP SMITH, DE (reprint author), UNIV ALABAMA,SCH MED,DIV PREVENT MED,BEHAV MED UNIT,1717 11TH AVE S,SUITE 101,BIRMINGHAM,AL 35205, USA. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48047, N01-HC-48049] NR 38 TC 199 Z9 201 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 8 PY 1994 VL 271 IS 22 BP 1747 EP 1751 DI 10.1001/jama.271.22.1747 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NN725 UT WOS:A1994NN72500023 PM 8196117 ER PT J AU STEINER, H GERFEN, CR AF STEINER, H GERFEN, CR TI TACTILE SENSORY INPUT REGULATES BASAL AND APOMORPHINE-INDUCED IMMEDIATE-EARLY GENE-EXPRESSION IN RAT BARREL CORTEX SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE SENSORY DEPRIVATION; ZIF268; C-FOS; VIBRISSAE; DOPAMINE ID C-FOS; SOMATOSENSORY NEOCORTEX; CORTICAL BARRELS; SNOUT CONTACT; AWAKE RATS; STRIATUM; NEURONS; MOUSE; STIMULATION; ASYMMETRIES AB Clipping of mystacial vibrissae on one side of the rat's snout results in sensorimotor asymmetries in normal behavior and in behavior induced by the dopamine receptor agonist, apomorphine. Immediate-early gene expression, a marker for short-term changes in neuron function, was used to examine whether this sensory deprivation leads to functional changes in the somatosensory barrel cortex under experimental conditions which reveal behavioral asymmetries. The expression of c-fos and zif 268 immediate-early genes was assessed with in situ hybridization histochemistry. Four hours after unilateral clipping of the mystacial vibrissae, the level of zif 268 mRNA was reduced in the corresponding part of the contralateral barrel field. Injection of apomorphine (5 mg/kg) resulted in increased expression of both c-fos and zif 268 immediate-early genes in cortex and striatum. This apomorphine-induced increase was blocked in the sensory-deprived somatosensory cortex. Laminar analysis of gene regulation showed that vibrissae removal affected immediate-early gene expression in all layers of the barrel cortex. These results demonstrate that: (1) basal zif 268 gene expression in neurons of the somatosensory cortex is dependent on sensory input, (2) cortical immediate-early gene expression is increased after dopamine receptor activation, and (3) in the barrel cortex, this increase is also dependent on sensory input. We suggest that the observed reduction in gene expression after vibrissae removal reflects decreased activation of neurons in the barrel column by removal of sensory input. (C) 1994 Wiley-Liss, Inc. RP STEINER, H (reprint author), NIMH,CELL BIOL LAB,NEUROANAT SECT,BLDG 36,ROOM 2D-10,BETHESDA,MD 20892, USA. NR 48 TC 45 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 8 PY 1994 VL 344 IS 2 BP 297 EP 304 DI 10.1002/cne.903440210 PG 8 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA NL356 UT WOS:A1994NL35600009 PM 8077463 ER PT J AU STEMMER, PM KLEE, CB AF STEMMER, PM KLEE, CB TI DUAL CALCIUM-ION REGULATION OF CALCINEURIN BY CALMODULIN AND CALCINEURIN-B SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN PHOSPHATASE; BOVINE BRAIN CALMODULIN; LIGHT CHAIN KINASE; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; MOLECULAR-CLONING; BINDING-PROTEINS; PEPTIDE COMPLEX; CDNA CLONE; ACTIVATION AB The dependence of calcineurin on Ca2+ for activity is the result of the concerted action of calmodulin, which increases the turnover rate of the enzyme and modulates its response to Ca2+ transients, and of calcineurin B, which decreases the K-m of the enzyme for its substrate. The calmodulin-stimulated protein phosphatase calcineurin is under the control of two functionally distinct, but structurally similar, Ca2+-regulated proteins, calmodulin and calcineurin B. The Ca2+-dependent activation of calcineurin by calmodulin is highly cooperative (Hill coefficient of 2.8-3), and the concentration of Ca2+ needed for half-maximum activation decreases from 1.3 to 0.6 mu M when the concentration of calmodulin is increased from 0.03 to 20 mu M. Conversely, the affinity of calmodulin for Ca2+ is increased by more than 2 orders of magnitude in the presence of a peptide corresponding to the calmodulin-binding domain of calcineurin A. Calmodulin increases the V-max without changing the K-m value of the enzyme. Unlike calmodulin, calcineurin B interacts with calcineurin A in the presence of EGTA, and Ca2+ binding to calcineurin B stimulates native calcineurin up to only 10% of the maximum activity achieved with calmodulin. The Ca2+-dependent activation of a proteolyzed derivative of calcineurin, calcineurin-45, which lacks the regulatory domain, was used to study the role of calcineurin B. Removal of the regulatory domain increases the V-max of calcineurin, as does binding of calmodulin, but it also increases the affinity of calcineurin for Ca2+. Ca2+ binding to calcineurin B decreases the K-m value of calcineurin without changing its V-max. Like native calcineurin, calcineurin-45 contains two high-affinity Ca2+ sites (K-d < 0.07 mu M) and one or two low-affinity sites (K-d > 0.07 mu M). C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 57 TC 206 Z9 208 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 7 PY 1994 VL 33 IS 22 BP 6859 EP 6866 DI 10.1021/bi00188a015 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ730 UT WOS:A1994NQ73000015 PM 8204620 ER PT J AU SHIRVAN, A SRIVASTAVA, M WANG, MG CULTRARO, C MAGENDZO, K MCBRIDE, OW POLLARD, HB BURNS, AL AF SHIRVAN, A SRIVASTAVA, M WANG, MG CULTRARO, C MAGENDZO, K MCBRIDE, OW POLLARD, HB BURNS, AL TI DIVERGENT STRUCTURE OF THE HUMAN SYNEXIN (ANNEXIN-VII) GENE AND ASSIGNMENT TO CHROMOSOME-10 SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; CALCIUM-CHANNEL ACTIVITY; MURINE LEUKEMIA-VIRUS; PRE-MESSENGER RNA; III ANX3 GENE; MEMBRANE-FUSION; LIPOCORTIN-I; REGULATORY SEQUENCES; BINDING PROTEIN; INSITU HYBRIDIZATION AB The human synexin (annexin VII) gene occurs as a single copy at chromosome 10q21.1-21.2 and substantially deviates in size and in the location of splice junctions from the other two well-characterized members of the annexin gene family, lipocortin I (annexin I) and calpactin I (annexin II). The synexin gene contains 14 exons, including an alternatively spliced cassette exon, and spans approximately 34 kb of DNA. Only five of the fourteen splice junctions are conserved compared to other annexins, and the differences are particularly pronounced in the exons that encode the C-terminal third and fourth conserved repeats in the gene product. Although parallels between exons and protein domains were not apparent, we did observe clustering of splice junctions corresponding to either the unique N-terminal domain or the conserved C-terminal tetrad repeat domain, which is common to all annexins. Furthermore, a complete analysis of the 5' flanking region of the annexin VII gene revealed an entirely different set of cis-acting and enhancer elements compared to other annexin genes. We conclude that the annexin VII gene may have arisen by a divergence from the evolutionary pathway taken by both annexins I and II. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 66 TC 26 Z9 27 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 7 PY 1994 VL 33 IS 22 BP 6888 EP 6901 DI 10.1021/bi00188a019 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ730 UT WOS:A1994NQ73000019 PM 7515686 ER PT J AU BANG, YJ PIRNIA, F FANG, WG KANG, WK SARTOR, O WHITESELL, L HA, MJ TSOKOS, M SHEAHAN, MD NGUYEN, P NIKLINSKI, WT MYERS, CE TREPEL, JB AF BANG, YJ PIRNIA, F FANG, WG KANG, WK SARTOR, O WHITESELL, L HA, MJ TSOKOS, M SHEAHAN, MD NGUYEN, P NIKLINSKI, WT MYERS, CE TREPEL, JB TI TERMINAL NEUROENDOCRINE DIFFERENTIATION OF HUMAN PROSTATE CARCINOMA-CELLS IN RESPONSE TO INCREASED INTRACELLULAR CYCLIC-AMP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HORMONE REFRACTORY; PP60(C-SRC); MULTIPOTENTIAL ID NEURO-ENDOCRINE DIFFERENTIATION; EXPRESS HIGH-LEVELS; CHROMOGRANIN-A; EPITHELIAL GLYCOPROTEIN; SPECIFICITY AB Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC 3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60(c-src), and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M tells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60(c-src), and in both cell lines expression of KS1/4 and stage specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G(1) synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer. C1 NCI,CLIN PHARMACOL BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 22 TC 190 Z9 200 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5330 EP 5334 DI 10.1073/pnas.91.12.5330 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500024 PM 8202489 ER PT J AU VALDES, JM TAGLE, DA COLLINS, FS AF VALDES, JM TAGLE, DA COLLINS, FS TI ISLAND RESCUE PCR - A RAPID AND EFFICIENT METHOD FOR ISOLATING TRANSCRIBED SEQUENCES FROM YEAST ARTIFICIAL CHROMOSOMES AND COSMIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYPE-1 NEUROFIBROMATOSIS GENE; CPG ISLANDS; HUNTINGTONS-DISEASE; CANDIDATE REGION; DNA; IDENTIFICATION; AMPLIFICATION; LOCALIZATION; MARKERS; CLONING AB The identification of transcripts from large genomic regions cloned in yeast artificial chromosomes (YACs) or cosmids continues to be a critical and often rate-limiting step in positional cloning of human disease genes. We have developed a PCR-based method for rapid and efficient generation of probes from YACs or cosmids that can be used for cDNA library screening. The method, which we call island rescue PCR (IRP), is based upon the observation that the 5' ends of many genes are associated with (G+C)-rich regions called CpG islands. In IRP, the YAC of interest is digested with a restriction enzyme that recognizes sequences of high CpG content, and vectorette linkers are ligated to the cleaved ends. The PCR is used to amplify the region extending from the cleaved restriction enzyme site to the nearest SINE (Alu) repeat. In many cases this product contains sequences from the 5' end of the associated gene. cDNA clones isolated with these products are then verified by mapping them back to the original YAC. The method allows rapid screening of >500 kb of human genomic insert in one experiment, is tolerant of contaminating yeast sequences, and cab also be applied to cosmid pools. In a control experiment, the method was able to identify cDNA clones for the neurofibromatosis type 1 (NF1) gene using a probe generated from a YAC in the region. application of IRP has yielded nine other genes from YACs isolated from chromosome locations 4p16.3 and 17q21. C1 UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,PROGRAM MOLEC & CELLULAR BIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NHGRI NIH HHS [HG00209] NR 25 TC 33 Z9 33 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5377 EP 5381 DI 10.1073/pnas.91.12.5377 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500034 PM 8202494 ER PT J AU THIRMAN, MJ ALBRECHT, JH KRUEGER, MA ERICKSON, RR CHERWITZ, DL PARK, SS GELBOIN, HV HOLTZMAN, JL AF THIRMAN, MJ ALBRECHT, JH KRUEGER, MA ERICKSON, RR CHERWITZ, DL PARK, SS GELBOIN, HV HOLTZMAN, JL TI INDUCTION OF CYTOCHROME CYPIA1 AND FORMATION OF TOXIC METABOLITES OF BENZO[A]PYRENE BY RAT AORTA - A POSSIBLE ROLE IN ATHEROGENESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; MONOCLONAL-ANTIBODIES; ADVANCED ATHEROSCLEROSIS; AROMATIC-HYDROCARBONS; HEPATIC MICROSOMES; RAPID PRODUCTION; DIOL EPOXIDE; DNA INVITRO; LIVER; CHOLESTEROL AB Cigarette smoking is a leading risk factor for atherosclerosis. Endothelial injury may be the initial event in this process. The carcinogenic metabolites of the polycyclic aromatic hydrocarbons found in cigarette smoke tars could cause this injury. We tested this model by examining the effect of 3-methylcholanthrene administration on aortic polycyclic aromatic hydrocarbon metabolism. Immunoblotting with a monoclonal antibody (mAb 1-7-1) specific for cytochromes CYPIA1 and CYPIA2 showed that aortic microsomes from treated, but not from control, animals contained CYPIA1; the CYPIA1 was primarily in the endothelium. Aortic microsomes from induced animals metabolized benzo[a]pyrene (BaP) to the 7R,8S,9,10-tetrahydrotetrol-, 7,8-dihydrodiol-, 1,6 quinone-, 3,6 quinone-, 6,12 quinone-, 3-hydroxy-, and 9-hydroxy-BaP. mAb 1-7-1 inhibited the formation of the tetrahydrotetrol, the dihydrodiol-BaP, and the 3-hydroxy-BaP but did not inhibit the quinones or the 9-hydroxy-BaP. Arachidonic acid did not affect metabolism. These data suggest that the aortas of induced animals metabolize the BaP in cigarette smoke to carcinogenic and toxic products and that this metabolism may initiate vessel injury and lead to the accelerated atherosclerosis seen in cigarette smokers. C1 VET AFFAIRS MED CTR,MED SERV,MINNEAPOLIS,MN 55417. VET AFFAIRS MED CTR,RES SERV,MINNEAPOLIS,MN 55417. VET AFFAIRS MED CTR,LAB SERV,MINNEAPOLIS,MN 55417. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 48 TC 61 Z9 64 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5397 EP 5401 DI 10.1073/pnas.91.12.5397 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500038 PM 8202497 ER PT J AU RUTLEDGE, JC SHOURBAJI, AG HUGHES, LA POLIFKA, JE CRUZ, YP BISHOP, JB GENEROSO, WM AF RUTLEDGE, JC SHOURBAJI, AG HUGHES, LA POLIFKA, JE CRUZ, YP BISHOP, JB GENEROSO, WM TI LIMB AND LOWER-BODY DUPLICATIONS INDUCED BY RETINOIC ACID IN MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PATTERN FORMATION; PREGASTRULATION DEVELOPMENT; DEVELOPMENTAL ABNORMALITIES ID ANOMALIES; DISORGANIZATION; EXPOSURE AB The zygote and subsequent preimplantation stages of early mammalian development are susceptible to certain chemical perturbations that cause abnormal development of the conceptus. In certain cases, disruption in patterns of gene expression could be a primary event leading to abnormal development. To investigate this hypothesis, we treated pregnant mice with hans-retinoic acid, a known modulator of gene expression. Treatments were administered at various times during pregastrulation stages and the presumed onset of gastrulation. trans-Retinoic acid induced a distinctive set of malformations, as manifest by supernumerary and ectopic limbs and duplication of portions of the lower body, but only when administered during the period of 4.5-5.5 days after mating. (Other malformations were induced at different stages.) The limb and lower-body duplications suggest that exogenous trans-retinoic acid may influence not only the pattern for the hindlimbs but also that for the entire lower body. Since it appears likely that the embryos were affected in the late blastocyst and proamniotic-embryo stages, the provocative possibility arises that aspects of pattern formation of limbs and lower body actually occur prior to gastrulation. C1 OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. CHILDRENS HOSP & MED CTR,DEPT LAB MED,SEATTLE,WA 98105. UNIV WASHINGTON,SCH MED,TERATOGEN INFORMAT SYST PROJECT,SEATTLE,WA 98105. OBERLIN COLL,DEPT BIOL,OBERLIN,OH 44074. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [Y01-ES-20085] NR 14 TC 85 Z9 88 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5436 EP 5440 DI 10.1073/pnas.91.12.5436 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500046 PM 8202504 ER PT J AU QUON, MJ GUERREMILLO, M ZARNOWSKI, MJ BUTTE, AJ EM, M CUSHMAN, SW TAYLOR, SI AF QUON, MJ GUERREMILLO, M ZARNOWSKI, MJ BUTTE, AJ EM, M CUSHMAN, SW TAYLOR, SI TI TYROSINE KINASE-DEFICIENT MUTANT HUMAN INSULIN-RECEPTORS (MET(1153)-]ILE) OVEREXPRESSED IN TRANSFECTED RAT ADIPOSE-CELLS FAIL TO MEDIATE TRANSLOCATION OF EPITOPE-TAGGED GLUT4 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INSULIN ACTION; HA1 EPITOPE; GLUCOSE TRANSPORTERS ID STIMULATED TRANSLOCATION; GLUCOSE TRANSPORTERS; BETA-SUBUNIT; DOMAIN; GENE; EXPRESSION; MUTATIONS; SURFACE; GROWTH AB Insulin regulates essential pathways for growth, differentiation, and metabolism in vivo. We report a physiologically relevant system for dissecting the molecular mechanisms of insulin signal transduction related to glucose transport. This is an extension of our recently reported method for transfection of DNA into rat adipose cells in primary culture. In the present work, cDNA coding for GLUT4 with an epitope tag (HA1) in the first exofacial loop is used as a reporter gene so that GLUT4 translocation can be studied exclusively in transfected cells. Insulin stimulates a 4.3-fold recruitment of transfected epitope-tagged GLUT4 to the cell surface. Cells cotransfected with the reporter gene and the human insulin receptor gene show an increase in cell surface GLUT4 in the basal state (no insulin) to levels comparable to those seen with maximal insulin stimulation of cells transfected with the reporter gene alone. In contrast, cells overexpressing a naturally occurring tyrosine kinase-deficient mutant insulin receptor (Met(1153) --> Ile) show no increase in the basal cell surface GLUT4 and no shift in the insulin dose-response curve relative to cells transfected with the reporter gene alone. These results demonstrate that insulin receptor tyrosine kinase activity is essential in insulin-stimulated glucose transport in adipose cells. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 28 TC 82 Z9 82 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5587 EP 5591 DI 10.1073/pnas.91.12.5587 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500077 PM 8202531 ER PT J AU KAPLAN, AH MICHAEL, SF WEHBIE, RS KNIGGE, MF PAUL, DA EVERITT, L KEMPF, DJ NORBECK, DW ERICKSON, JW SWANSTROM, R AF KAPLAN, AH MICHAEL, SF WEHBIE, RS KNIGGE, MF PAUL, DA EVERITT, L KEMPF, DJ NORBECK, DW ERICKSON, JW SWANSTROM, R TI SELECTION OF MULTIPLE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS THAT ENCODE VIRAL PROTEASES WITH DECREASED SENSITIVITY TO AN INHIBITOR OF THE VIRAL PROTEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIV-1 PROTEASE; SYMMETRICAL INHIBITORS; INFECTIVITY; ENZYME; GENE; GAG; DNA AB Inhibitors of the human immunodeficiency virus type 1 (HIV-1) protease represent a promising addition to the available agents used to inhibit virus replication in a therapeutic setting. HIV-1 is capable of generating phenotypic variants in the face of a variety of selective pressures. The potential to generate variants with reduced sensitivity to a protease inhibitor was examined by selecting for virus growth in cell culture in the presence of the protease inhibitor A-77003. Virus variants grew out in the presence of the inhibitor, and these variants encoded proteases with reduced sensitivity to the inhibitor. Variants were identified that encoded changes in each of the three subsites of the protease that interact with the inhibitor. HIV-1 displays significant potential for altering its interaction with this protease inhibitor, suggesting the need for multiple protease inhibitors with varying specificities. C1 UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA. ABBOTT LABS, DEPT EXPTL BIOL RES, ABBOTT PK, IL 60064 USA. ABBOTT LABS, DEPT DIAGNOST BIOL RES, ABBOTT PK, IL 60064 USA. ABBOTT LABS, DEPT ANTIINFECT RES, ABBOTT PK, IL 60064 USA. NCI, FREDERICK CANC RES & DEV CTR, STRUCT BIOCHEM PROGRAM, FREDERICK, MD 21702 USA. FU NIAID NIH HHS [R01-AI32892] NR 27 TC 158 Z9 159 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5597 EP 5601 DI 10.1073/pnas.91.12.5597 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500079 PM 8202533 ER PT J AU NI, BH ROSTECK, PR NADI, NS PAUL, SM AF NI, BH ROSTECK, PR NADI, NS PAUL, SM TI CLONING AND EXPRESSION OF A CDNA-ENCODING A BRAIN-SPECIFIC NA+-DEPENDENT INORGANIC-PHOSPHATE COTRANSPORTER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEURONAL PHOSPHATE TRANSPORT; ATP BIOSYNTHESIS; INTRACELLULAR PHOSPHATE ID CEREBELLAR GRANULE CELLS; ESCHERICHIA-COLI; TRANSPORT; SEQUENCE; PROTEIN AB We have isolated a brain-specific cDNA that encodes a Na+-dependent inorganic phosphate (P-i) cotransporter (BNPI). The nucleotide sequence of BNPI predicts a protein of 560 amino acids with 6-8 putative transmembrane-spanning segments that is approximate to 32% identical to the rabbit kidney Na+-dependent P-i cotransporter. Expression of BNPI mRNA in Xenopus oocytes results in Na+-dependent P-i transport similar to that reported for the recombinantly expressed or native kidney Na+-dependent cotransporter. RNA blot analysis reveals that BNPI mRNA is expressed predominantly (if not exclusively) in brain, and in situ hybridization histochemistry reveals BNPI transcripts in neurons of the cerebral cortex, hippocampus, and cerebellum. Furthermore, we have confirmed the presence of saturable Na+-dependent P-i cotransport in cultured cerebellar granule cells. Together, these data demonstrate the presence of a specific neuronal Na+-dependent transport system for P-i in brain. C1 ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 28 TC 241 Z9 253 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5607 EP 5611 DI 10.1073/pnas.91.12.5607 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500081 PM 8202535 ER PT J AU BOOY, FP TRUS, BL NEWCOMB, WW BROWN, JC CONWAY, JF STEVEN, AC AF BOOY, FP TRUS, BL NEWCOMB, WW BROWN, JC CONWAY, JF STEVEN, AC TI FINDING A NEEDLE IN A HAYSTACK - DETECTION OF A SMALL PROTEIN (THE 12-KDA VP26) IN A LARGE COMPLEX (THE 200-MDA CAPSID OF HERPES-SIMPLEX VIRUS) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 3-DIMENSIONAL RECONSTRUCTION; CRYOELECTRON MICROSCOPY; EQUINE HERPESVIRUS-1; SURFACE LATTICE; SIMIAN VIRUS-40; TYPE-1; LOCALIZATION; MICROGRAPHS; PARTICLES; PENTONS AB Macromolecular complexes that consist of homopolymeric protein frameworks with additional proteins attached at strategic sites for a variety of structural and functional purposes are widespread in subcellular biology. One such complex is the capsid of herpes simplex virus type 1 whose basic framework consists of 960 copies of the viral protein, VP5 (149 kDa), arranged in an icosahedrally symmetric shed. This shell also contains major amounts of three other proteins, including VP26 (12 kDa), a small protein that is approximately equimolar with VP5 and accounts for approximate to 6% of the capsid mass. With a view to inferring the role of VP26 in capsid assembly, we have localized it by quantitative difference imaging based on three-dimensional reconstructions calculated from cryoelectron micrographs. Purified capsids from which VP26 had been removed in vitro by treatment with guanidine hydrocholoride were compared with preparations of the same depleted capsids to which purified VP26 had been rebound and with native (undepleted) capsids. The resulting three-dimensional density maps indicate that six VP26 subunits are distributed symmetrically around the outer tip of each hexon protrusion on VP26-containing capsids. Because VP26 may be readily dissociated from and reattached to the capsid, it does not appear to contribute significantly to structural stabilization. Rather, its exposed location suggests that VP26 may be involved in linking the capsid to the surrounding tegument and envelope at a later stage of viral assembly. C1 NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 37 TC 95 Z9 99 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5652 EP 5656 DI 10.1073/pnas.91.12.5652 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500090 PM 8202543 ER PT J AU MCCARRON, RM DORON, DA SIREN, AL FEUERSTEIN, G HELDMAN, E POLLARD, HB SPATZ, M HALLENBECK, JM AF MCCARRON, RM DORON, DA SIREN, AL FEUERSTEIN, G HELDMAN, E POLLARD, HB SPATZ, M HALLENBECK, JM TI AGONIST-STIMULATED RELEASE OF VON-WILLEBRAND-FACTOR AND PROCOAGULANT FACTOR-VIII IN RATS WITH AND WITHOUT RISK-FACTORS FOR STROKE SO BRAIN RESEARCH LA English DT Article DE VON WILLEBRAND FACTOR; HYPERTENSION; LIPOPOLYSACCHARIDE; ENDOTHELIAL CELL; STROKE; MONOCYTE ID HUMAN-ENDOTHELIAL CELLS; TUMOR NECROSIS FACTOR; GRANULE MEMBRANE-PROTEIN; CEREBRAL MICRO-VESSELS; WEIBEL-PALADE BODIES; VONWILLEBRAND-FACTOR; FACTOR-XA; SECRETION; ANTIGEN; BRAIN AB Lipopolysaccharide (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats released significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII:c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as well as human umbilical vein EC (HUVEC) cultures constitutively released VWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-alpha (TNF alpha) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultures. Preincubation of cerebrovascular EC cultures with interleukin-1 (IL-1) +/- TNF alpha or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demonstrate that conditions of hypertension may affect endothelial cells and make them more responsive to agonist stimulation and thereby increase secretion of vWF, an important factor in hemostasis as well as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. It is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as VWF and factor VIII:c. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20892. SMITHKLINE BEECHAM,DEPT PHARMACOL,KING OF PRUSSIA,PA 19406. RP MCCARRON, RM (reprint author), NINCDS,STROKE BRANCH,BLDG 36,ROOM 4D-04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Siren, Anna-Leena/0000-0002-2217-0081 FU NINDS NIH HHS [NS-28225] NR 38 TC 10 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 1994 VL 647 IS 2 BP 265 EP 272 DI 10.1016/0006-8993(94)91326-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NT439 UT WOS:A1994NT43900011 PM 7922503 ER PT J AU ROSEN, JB PISHEVAR, SK WEISS, SRB SMITH, MA KLING, MA GOLD, PW SCHULKIN, J AF ROSEN, JB PISHEVAR, SK WEISS, SRB SMITH, MA KLING, MA GOLD, PW SCHULKIN, J TI GLUCOCORTICOID TREATMENT INCREASES THE ABILITY OF CRH TO INDUCE SEIZURES SO NEUROSCIENCE LETTERS LA English DT Article DE GLUCOCORTICOID; CORTICOTROPIN-RELEASING HORMONE; SEIZURE; AMYGDALA ID CORTICOTROPIN-RELEASING-FACTOR; RATS; FACILITATION; HORMONE AB We examined whether glucocorticoids could enhance the ability of corticotropin-releasing hormone (CRH) to induce seizures. Rats were treated with systemic glucocorticoids (dexamethasone, 100 mu g) or vehicle for either 3 days (chronic) or 2 h (acute) before intracerebroventricular CRH (3 or 10 mu g) or saline injections and then monitored for 8 h following each injection. Our results suggest that chronic, but not acute, glucocorticoid pretreatment increases the likelihood of CRH-induced seizures. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP ROSEN, JB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,BETHESDA,MD 20892, USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 15 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 6 PY 1994 VL 174 IS 1 BP 113 EP 116 DI 10.1016/0304-3940(94)90132-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NQ444 UT WOS:A1994NQ44400029 PM 7970144 ER PT J AU DATTA, AK NORTH, SL KASPRZAK, KS AF DATTA, AK NORTH, SL KASPRZAK, KS TI EFFECT OF NICKEL(II) AND TETRAGLYCINE ON HYDROXYLATION OF THE GUANINE MOIETY IN 2'-DEOXYGUANOSINE, DNA, AND NUCLEOHISTONE BY HYDROGEN-PEROXIDE SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article; Proceedings Paper CT 5th International Conference on Nickel Biochemistry, Toxicology, and Ecologic Issues CY SEP 07-11, 1992 CL SUDBURY, CANADA SP INT UNION PURE & APPL CHEM, INST ENVIRONM & HLTH, LAURENTIAN UNIV SUDBURY DE NICKEL; NI(II); 2'-DEOXYGUANOSINE; 8-HYDROXY-2'-DEOXYGUANOSINE; DNA; NUCLEOHISTONE; TETRAGLYCINE ID SITE-SPECIFIC MUTAGENESIS; LIPID-PEROXIDATION; IONIZING-RADIATION; DIFFERENT STRAINS; OXIDATIVE DAMAGE; CELL-NUCLEI; L-HISTIDINE; SUPEROXIDE; RADICALS; CARCINOGENESIS AB The purpose of this study was to determine whether the Ni(II)-tetraglycine complex system (NiG4) that is known to disproportionate H2O2 at pH greater-than-or-equal-to 8 can catalyze oxidation of the guanine residues in 2'-deoxyguanosine (dG), calf thymus DNA, and calf thymus nucleohistone (NH) by H2O2 at physiological pH. Incubation of dG with H2O2 in the presence of NiG4 at 37-degrees-C, produced two effects: (a) formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and (b) decomposition of dG to 2,6-diamino-4-hydroxy-5-formamidopyrimidine and several low molecular weight unidentified products. The magnitude of both effects depended on incubation time (1-48 h), H2O2 concentration (7.5-40 mM), NiG4 concentration (0.1 or 1 mM), and pH (6.0-8.0). The effects were not detected below pH 6 and above pH 8.0. For 0.1 mM NiG4 and 7.5 mM H2O2, production of 8-OH-dG from dG (0.75 mM) during 24 h at 37-degrees-C was significantly lower than from NH (1 mg/ml) or DNA (0.5 mg/ml), indicating possible specific effects that might be related to the strength of interaction of NiG4 with dG, NH, or DNA. The results indicate production of hydroxyl radical or other oxidizing species in the reaction of H2O2 with NiG4 at pH 7-8. Reactions like this may be relevant to the mechanisms of Ni(II)-mediated oxidative damage, observed in vitro and in vivo, which may contribute to the toxic and carcinogenic effects of this metal. C1 NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702. NR 32 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JUN 6 PY 1994 VL 148 IS 2-3 BP 207 EP 216 DI 10.1016/0048-9697(94)90398-0 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA NP252 UT WOS:A1994NP25200012 PM 8029697 ER PT J AU RALSTON, E BEUSHAUSEN, S PLOUG, T AF RALSTON, E BEUSHAUSEN, S PLOUG, T TI EXPRESSION OF THE SYNAPTIC VESICLE PROTEINS VAMPS/SYNAPTOBREVIN-1 AND VAMPS/SYNAPTOBREVIN-2 IN NONNEURAL TISSUES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID INTEGRAL MEMBRANE-PROTEIN; RAT SKELETAL-MUSCLE; GLUCOSE TRANSPORTER; SYSTEMIC DELIVERY; FUSION PROTEIN; INSULIN; GENES; IDENTIFICATION; SYNAPTOBREVIN; LOCALIZATION AB The VAMPs/synaptobrevins (Vp/Sybs) are small integral membrane proteins. Two isoforms, Vp/Syb 1 and Vp/Syb 2, are considered to be specific to neural tissue. They are associated with synaptic vesicles and are believed to play an important role in neurotransmitter release. A third isoform, cellubrevin, has recently been found in non-neural tissues. We now report that the distribution of Vp/Syb 1 and Vp/Syb 2 is wider than previously thought. RNA transcripts for both Vp/Syb 1 and Vp/Syb 2 were found in rat skeletal muscle and in several other rat non-neural tissues, and antibodies specific for Vp/Syb 2 detected a protein in the endoplasmic reticulum-Golgi area of skeletal muscle. Thus Vp/Sybs 1 and 2 are not restricted to the nervous system but appear to be co-expressed with cellubrevin in many different tissues. This redundancy of Vp/Sybs in a single cell may be required to control the specificity of vesicle-target interaction in the several pathways of intracellular vesicle traffic that are operative within each cell. C1 NIDDK,EXPTL DIABET METAB & NUTR SECT,DIABET BRANCH,BETHESDA,MD 20892. RP RALSTON, E (reprint author), NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 55 Z9 56 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15403 EP 15406 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300002 PM 8195178 ER PT J AU DEMORAIS, SMF WILKINSON, GR BLAISDELL, J NAKAMURA, K MEYER, UA GOLDSTEIN, JA AF DEMORAIS, SMF WILKINSON, GR BLAISDELL, J NAKAMURA, K MEYER, UA GOLDSTEIN, JA TI THE MAJOR GENETIC-DEFECT RESPONSIBLE FOR THE POLYMORPHISM OF S-MEPHENYTOIN METABOLISM IN HUMANS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID HYDROXYLATION POLYMORPHISM; OXIDATION POLYMORPHISM; LIVER-MICROSOMES; DEBRISOQUIN; DEFICIENCY; PHENOTYPE; JAPANESE AB The metabolism of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans, with the poor metabolizer trait being inherited in an autosomal recessive fashion. There are large interracial differences in the frequency of the poor metabolizer phenotype, with Oriental populations having a 5-fold greater frequency compared to Caucasians. Impaired metabolism of mephenytoin and a number of other currently used drugs results from a defect in a cytochrome P450 enzyme recently identified as CYP2C19. Attempts over the past decade to define the molecular genetic basis of the polymorphism have, however, been unsuccessful. We now report that the principal defect in poor metabolizers is a single base pair (G --> A) mutation in exon 5 of CYP2C19, which creates an aberrant splice site. This change alters the reading frame of the mRNA starting with amino acid 215 and produces a premature stop codon 20 amino acids downstream, which results in a truncated, non-functional protein. We further demonstrate that 7/10 Caucasian and 10/17 Japanese poor metabolizers are homozygous for this defect, indicating that this is the major defect responsible for the poor metabolizer phenotype. Finally, the familial inheritance of the deficient allele was found to be concordant with that of the phenotypic trait. C1 NIEHS,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,SCH MED,DEPT PHARMACOL,NASHVILLE,TN 37232. MED COLL OITA,DEPT CLIN PHARMACOL & THERAPEUT,OITA 87955,JAPAN. UNIV BASEL,BIOZENTRUM,DEPT PHARMACOL,CH-4056 BASEL,SWITZERLAND. RI Goldstein, Joyce/A-6681-2012 FU NIGMS NIH HHS [GM-31304] NR 30 TC 717 Z9 752 U1 4 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15419 EP 15422 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300006 PM 8195181 ER PT J AU OSAWA, Y FELLOWS, CS MEYER, CA WOODS, A CASTORO, JA COTTER, RJ WILKINS, CL HIGHET, RJ AF OSAWA, Y FELLOWS, CS MEYER, CA WOODS, A CASTORO, JA COTTER, RJ WILKINS, CL HIGHET, RJ TI STRUCTURE OF THE NOVEL HEME ADDUCT FORMED DURING THE REACTION OF HUMAN HEMOGLOBIN WITH BRCCL3 IN RED-CELL LYSATES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; PROSTHETIC HEME; MYOGLOBIN; METABOLISM; BENZOPYRENE; MECHANISM; BINDING; OXIDASE; MOUSE; RATS AB It was previously shown that the reductive debromination of BrCCl3 to trichloromethyl radical by human hemoglobin leads to formation of dissociable altered heme products, two of which are identical to those formed from myoglobin and one which is novel. In this study, we have elucidated the structure of this novel adduct with the use of mass spectrometry, as well as H-1 and C-13 NMR as a substitution product of a -C(Cl)=CCl2 moiety for a beta-hydrogen atom on the prosthetic heme's ring I vinyl group. From studies with the use of C-13-enriched BrCCl3, it was determined that the added carbon atoms were derived from 2 eq of BrCCl3. A mechanism that involves multiple reductive events and a radical cation heme intermediate is proposed. Consistent with this mechanism, cellular reductants were found to selectively enhance the amount of this novel dissociable heme adduct. These studies reveal fine differences between myoglobin and hemoglobin in the accessibility of reactive intermediates to the ring I vinyl group, as well as the potential importance of cellular reductants on the course of heme alteration. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. UNIV CALIF RIVERSIDE,DEPT CHEM,RIVERSIDE,CA 92521. JOHNS HOPKINS UNIV,SCH MED,MIDDLE ATLANTIC MASS SPECT LAB,BALTIMORE,MD 21205. RP OSAWA, Y (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Fellows, Christine/C-1433-2008; Wilkins, Charles/H-8274-2014 OI Wilkins, Charles/0000-0001-6471-6313 FU NIGMS NIH HHS [GM-44606] NR 34 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15481 EP 15487 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300016 PM 8195191 ER PT J AU WELSH, CF MOSS, J VAUGHAN, M AF WELSH, CF MOSS, J VAUGHAN, M TI ISOLATION OF RECOMBINANT ADP-RIBOSYLATION FACTOR-6, A SIMILAR-TO-20-KDA GUANINE-NUCLEOTIDE-BINDING PROTEIN, IN AN ACTIVATED GTP-BOUND STATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHOLERA-TOXIN; ESCHERICHIA-COLI; GOLGI MEMBRANES; BREFELDIN-A; BOVINE BRAIN; HUMAN GENE; FACTOR-III; FACTOR-I; ARF; EXCHANGE AB ADP-ribosylation factors (ARFs) are similar to 20-kDa guanine nucleotide-binding proteins, which, like other members of the ras superfamily, are activated by exchanging bound GDP for GTP and inactivated through hydrolysis of the gamma-phosphate of bound GTP to form GDP in a highly regulated cycle. ARF 6, a class III ARF, was expressed in Escherichia coli with its amino terminus fused to maltose-binding protein. Following release from maltose-binding protein, recombinant ARF 6 (rARF 6) exhibited maximal activity with or without GTP. Such constitutive activation was due to the predominance of ARF-GTP over ARF-GDP, as demonstrated by nucleotide analysis. rARF 6 expressed in E. coli without amino-terminal extension was bound primarily to GDP and exhibited typical GTP-dependent activity. After release from maltose-binding protein, rARF 6-GTP was stable; only a fraction of the nucleotide was removed using EDTA, whereas urea denaturation restored complete GTP dependence. [alpha-P-32]GTP bound to rARF 6 was in part protected from hydrolysis by alkaline phosphatase and resulted in the formation of [alpha-P-32]GTP, -GDP, and -GMP, whereas unbound nucleotide was completely hydrolyzed to guanosine. Thus, amino-terminal extension of rARF 6, by maltose-binding protein, promoted the formation of a constitutively activated GTP-bound species. By analysis of this species, we confirmed that rARF 6 lacks the intrinsic ability to hydrolyze bound GTP and speculate that maltose-binding protein may inhibit hydrolysis by extrinsic factors. C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NR 30 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15583 EP 15587 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300032 PM 8195204 ER PT J AU KUHNE, MR ZHAO, ZH ROWLES, J LAVAN, BE SHEN, SH FISCHER, EH LIENHARD, GE AF KUHNE, MR ZHAO, ZH ROWLES, J LAVAN, BE SHEN, SH FISCHER, EH LIENHARD, GE TI DEPHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 BY THE TYROSINE PHOSPHATASE PTP2C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; GROWTH-FACTOR RECEPTOR; INTACT-CELLS; PROTEIN; PHOSPHORYLATION; BINDING; KINASE; PURIFICATION; ACTIVATION; EXPRESSION AB The phosphotyrosine (Tyr(P)) form of insulin receptor substrate 1 (IRS-1) is a key component in insulin signaling. Our previous study revealed that Tyr(P) IRS-1 binds to the widely distributed tyrosine phosphatase PTP2C through the src homology 2 (SH2) domains of the latter. In the present study, we examined the activity of this enzyme and of a truncated form lacking the SH2 domains (Delta PTP2C) toward IRS-1 and also toward the cytoplasmic domain of the insulin receptor. Tyr(P) IRS-1 was prepared by phosphorylation of recombinant IRS-1 with recombinant cytoplasmic insulin receptor kinase (CIRK). PTP2C rapidly dephosphorylated Tyr(P) IRS-1; dephosphorylation by Delta PTP2C was approximately one-third as fast, Other substrates, including Tyr(P) CIRK, were not dephosphorylated as rapidly by PTP2C; moreover, Delta PTP2C was at least 10 times more active than PTP2C toward CIRK and other substrates. These results indicate that the binding of Tyr(P) residues on IRS-1 to the SH2 domain(s) of PTP2C enhances its activity toward IRS-1 and suggest that PTP2C is the phosphatase responsible for the dephosphorylation of IRS-1 in vivo. In addition, with the expectation that a PTP2C-resistant form of IRS-1 will be useful in investigations of IRS-1 function, we determined that IRS-1 can be thiophosphorylated with adenosine 5'-O-(3-thiotriphosphate) and CIRK and that this form of IRS-1 is resistant to PTP2C. C1 DARTMOUTH COLL,SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. UNIV WASHINGTON,DEPT BIOCHEM,SEATTLE,WA 98195. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NATL RES COUNCIL CANADA,BIOTECHNOL RES INST,MONTREAL H4P 2R2,PQ,CANADA. FU NIDDK NIH HHS [DK 07902, DK 42816, DK 07508] NR 23 TC 68 Z9 68 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15833 EP 15837 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300068 PM 7515062 ER PT J AU LEE, YC PARK, CS STROTT, CA AF LEE, YC PARK, CS STROTT, CA TI MOLECULAR-CLONING OF A CHIRAL-SPECIFIC 3-ALPHA-HYDROXYSTEROID SULFOTRANSFERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; PREGNENOLONE-BINDING PROTEIN; SULFATES BILE-ACIDS; PIG ADRENAL-CORTEX; ESTROGEN SULFOTRANSFERASE; RAT-LIVER; SEQUENCE-ANALYSIS; EXPRESSION; CDNA; PURIFICATION AB A novel stereoselective hydroxysteroid sulfotransferase (HST) that acts on neutral steroids having the 3-hydroxyl group in the a orientation but not on steroids where the 3-hydroxyl group is oriented in the beta position has been cloned and expressed. Primary screening of a guinea pig adrenal cDNA library was performed by colony hybridization using an oligonucleotide probe based on a highly homologous region among known steroid sulfotransferases. Selected clones consisted of overlapping sequences but were incomplete. The rapid amplification of cDNA ends procedure was used to construct a full-length guinea pig HST cDNA. The guinea pig HST cDNA transiently transfected into Chinese hamster ovary K1 cells expressed a protein identical in size to that of purified guinea pig HST specific for 3 alpha-hydroxylated neutral steroids that was recently reported (Driscoll, W. J., Martin, B. M., Chen, H.-C., and Strott, C. A. (1993) J. Biol. Chem. 268, 23496-23503). The expressed HST likewise exhibited sulfotransferase activity that was directed specifically toward steroid substrates containing a 3-hydroxyl group in the alpha orientation; on the other hand, steroids with a 3 beta-hydroxyl group were not sulfonated by the expressed HST. Thus, the cloned HST cDNA clearly coded for a steroid sulfotransferase with chiral specificity for 3 alpha-hydroxylated neutral steroids and was, therefore, given the designation of guinea pig 3 alpha-hydroxysteroid sulfotransferase (gp3 alpha-HST). The full-length gp3 alpha-HST cDNA consisted of 1182 base pairs and coded for a protein containing 287 amino acids. The deduced amino acid sequence of the protein shares 65/79, 65/80, and 62/76% identity/similarity with rat, mouse, and human HST, respectively. Northern blot analysis of guinea pig tissues revealed no apparent gender differences in either mRNA species or distribution; a single 1.4-kilobase HST mRNA species was present in adrenal and liver tissue. Interestingly, the adrenal mRNA content was considerably more abundant than that found in the liver. Evidence for 3 alpha-HST mRNA was not detected in kidney, heart, lung, muscle, spleen, or uterus. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,STEROIE REGULAT SECT,BETHESDA,MD 20892. NR 37 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15838 EP 15845 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300069 PM 8195238 ER PT J AU TSAIMORRIS, CH GENG, Y XIE, XZ BUCZKO, E DUFAU, ML AF TSAIMORRIS, CH GENG, Y XIE, XZ BUCZKO, E DUFAU, ML TI TRANSCRIPTIONAL PROTEIN-BINDING DOMAINS GOVERNING BASAL EXPRESSION OF THE RAT LUTEINIZING-HORMONE RECEPTOR GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; NUCLEAR FACTOR-I; PROMOTER SEQUENCES; SITE; INDUCTION; ELEMENTS; RECOGNITION; INITIATION; ENHANCER; ACTIVATE AB The functional importance of specific protein binding domains on transcription within the CC-rich 173-base pair promoter of the luteinizing hormone receptor gene was studied by mutagenesis and gel retardation analysis. Transcription was dependent on the presence of two Sp1 elements in the promoter domain of transfected expressing mouse Leydig tumor cells (mLTC) and nonexpressing Chinese hamster ovary cells. Mutation of two protein binding domains located downstream of the Sp1 elements (M1 and C-box) revealed tissue-specific regulation of promoter activity by each domain. Also, gel retardation studies indicated the presence of multiple trans factors that bind to the C-box and M1 domains. Removal of the AP-2 element from the C-box resulted in mLTC-specific transcriptional activation that may involve an M1/C-box interaction. In addition, competition by overlapping NF-1 and AP-2 elements was demonstrable in both the C-box and upstream R domain for separate trans factors that exhibit neutral or inhibitory functions, respectively. Competition between the inhibitory and neutral DNA binding factors within both upstream and promoter domains may be responsible for a mechanism that controls the on/off state of luteinizing hormone receptor gene expression in gonadal cells. These studies reveal a complex pattern of transcriptional regulation that may reflect targeted mechanisms for the control of luteinizing hormone receptor gene expression. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892. NR 25 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 1994 VL 269 IS 22 BP 15868 EP 15875 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300073 PM 8195242 ER PT J AU ZHURKIN, VB RAGHUNATHAN, G ULYANOV, NB CAMERINIOTERO, RD JERNIGAN, RL AF ZHURKIN, VB RAGHUNATHAN, G ULYANOV, NB CAMERINIOTERO, RD JERNIGAN, RL TI A PARALLEL DNA TRIPLER AS A MODEL FOR THE INTERMEDIATE IN HOMOLOGOUS RECOMBINATION SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RECOMBINATION; DNA TRIPLEX; DNA RECOGNITION; STRAND EXCHANGE ID ATOM POTENTIAL FUNCTIONS; COLI RECA PROTEIN; 3-STRANDED DNA; GENETIC-RECOMBINATION; NUCLEIC-ACIDS; STRAND EXCHANGE; C-H...O; HELIX; RECOGNITION; COMPLEXES C1 UNIV CALIF SAN FRANCISCO, DEPT PHARMACEUT CHEM, SAN FRANCISCO, CA 94143 USA. NIDDK, GENET & BIOCHEM BRANCH, BETHESDA, MD 20892 USA. RP ZHURKIN, VB (reprint author), NCI, MATH BIOL LAB, BETHESDA, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Ulyanov, Nikolai/G-6998-2014 NR 64 TC 121 Z9 124 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 3 PY 1994 VL 239 IS 2 BP 181 EP 200 DI 10.1006/jmbi.1994.1362 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP736 UT WOS:A1994NP73600003 PM 8196053 ER PT J AU MULARD, LA KOVAC, P GLAUDEMANS, CPJ AF MULARD, LA KOVAC, P GLAUDEMANS, CPJ TI SYNTHESIS OF LIGANDS RELATED TO THE O-SPECIFIC ANTIGEN OF SHIGELLA-DYSENTERIAE TYPE-1 .8. SYNTHESIS OF SPECIFICALLY MONOFLUORINATED LIGANDS RELATED TO THE O-POLYSACCHARIDE OF SHIGELLA-DYSENTERIAE TYPE-1 SO CARBOHYDRATE RESEARCH LA English DT Article ID BETA-D-GALACTOPYRANOSIDES; DEOXYFLUORO SUGARS; DERIVATIVES; ANTIBODIES; BINDING; ANALOGS; NMR; C-4 AB The synthesis is reported of galactopyranose nucleophiles monofluorinated at positions 3, 4, or 6 and protected by 4,6-O-benzylidene, 3,6-di-O-benzyl, or 3,4-O-isopropylidene groups, respectively. The condensation of these nucleophiles with 2,3,4-tri-O-benzoyl-alpha-L-rhamnosyl bromide gave, after deprotection, the disaccharide analogues of methyl O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-D-galactopyranoside, monofluorinated at position 3, 4, or 6 of the galactoside residue. C1 NIDDKD,BETHESDA,MD 20892. NR 33 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUN 2 PY 1994 VL 259 IS 1 BP 21 EP 34 DI 10.1016/0008-6215(94)84194-2 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NP396 UT WOS:A1994NP39600003 PM 7518745 ER PT J AU MULARD, LA KOVAC, P GLAUDEMANS, CPJ AF MULARD, LA KOVAC, P GLAUDEMANS, CPJ TI SYNTHESIS OF LIGANDS RELATED TO THE O-SPECIFIC ANTIGEN OF SHIGELLA-DYSENTERIAE TYPE-1 .7. FLUORINATION AT POSITION-6 OF DERIVATIVES OF METHYL ALPHA-D-GALACTOPYRANOSIDE SO CARBOHYDRATE RESEARCH LA English DT Note ID TRIS(DIMETHYLAMINO)SULFONIUM DIFLUOROTRIMETHYLSILICATE TASF; BETA-D-GALACTOPYRANOSIDES; DEOXYFLUORO SUGARS; RAPID SYNTHESIS; NMR; BINDING; ANALOGS C1 NIDDK,BETHESDA,MD 20892. NR 37 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUN 2 PY 1994 VL 259 IS 1 BP 117 EP 129 DI 10.1016/0008-6215(94)84202-7 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NP396 UT WOS:A1994NP39600011 PM 7518742 ER PT J AU CRESPO, P XU, NZ SIMONDS, WF GUTKIND, JS AF CRESPO, P XU, NZ SIMONDS, WF GUTKIND, JS TI RAS-DEPENDENT ACTIVATION OF MAP KINASE PATHWAY MEDIATED BY G-PROTEIN BETA-GAMMA-SUBUNITS SO NATURE LA English DT Article ID NIH 3T3 CELLS; ALPHA-SUBUNITS; RECEPTOR; EXPRESSION; TRANSFORMATION; PROLIFERATION; STIMULATION; FIBROBLASTS; INHIBITION; SIGNALS AB MITOGEN-ACTIVATED protein kinases, MAP kinases or ERKs (extracellular signal-regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors (1,2). In turn, ERKs phosphorylate and regulate key intracellular enzymes and transcription factors involved in the control of cellular proliferation(3,4). The tyrosine-kinase class of growth-factor receptors transmits signals to ERKs in a multistep process that involves Ras and a limited number of defined molecules(5). In contrast, ERK activation by G-protein-coupled receptors is poorly understood(3,6), as is the role of ras in this signalling pathway(7,8). We have explored in COS-7 cells the mechanism of ERKs activation by m1 and m2 muscarinic receptors, typical examples of receptors coupled through Gq proteins to induce phosphatidylinositol hydrolysis and to G(i) proteins to inhibit adenylyl cyclase, respectively(9). Here we present evidence that ERK activation is mediated by beta gamma subunits of heterotrimeric G proteins acting on a ras-dependent pathway. C1 NIDR, CELLULAR DEV & ONCOL LAB, MOLEC SIGNALLING UNIT, BETHESDA, MD 20892 USA. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 30 TC 743 Z9 749 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 2 PY 1994 VL 369 IS 6479 BP 418 EP 420 DI 10.1038/369418a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NP174 UT WOS:A1994NP17400062 PM 8196770 ER PT J AU KUSAMA, T WANG, JB SPIVAK, CE UHL, GR AF KUSAMA, T WANG, JB SPIVAK, CE UHL, GR TI MUTAGENESIS OF THE GABA RHO-1 RECEPTOR ALTERS AGONIST AFFINITY AND CHANNEL GATING SO NEUROREPORT LA English DT Article DE XENOPUS OOCYTE; AGONIST RECOGNITION; ALLOSTERIC COUPLING ID XENOPUS OOCYTES; BINDING-SITE; DOPAMINE TRANSPORTER; A-RECEPTOR; MEMORY AB SEVENTEEN site-directed mutations were constructed in the GABA rho 1 receptor with the aim of finding agonist binding domains common to rho 1 and rho 2 receptors but distinct from those identified in members of the family of homologous, ligand gated ion channels. Mutated cDNAs were expressed in Xenopus oocytes and tested by voltage clamp experiments. Five of the mutations abolished responsiveness to GABA. Mutation Q189H, in the conserved cystein loop, diminished apparent GABA affinity to about 1/10 of wild type values in a manner consistent with decreased allosteric cooperativity among agonist recognition sites. Mutation R316A, located in the extracellular loop between transmembrane domains II and III, increased the Hill coefficient to 3.9 in a fashion consistent with enhanced open probability of a receptor multimer. C1 NIDA, ADDICT RES CTR, MOLEC NEUROBIOL BRANCH, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21224 USA. NR 23 TC 33 Z9 33 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD JUN 2 PY 1994 VL 5 IS 10 BP 1209 EP 1212 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NU290 UT WOS:A1994NU29000009 PM 7919166 ER PT J AU CHAMBLEE, DA AF CHAMBLEE, DA TI SPONSORED RESEARCH AGREEMENTS - BALANCING RISKS AND BENEFITS SO ACADEMIC MEDICINE LA English DT Article RP CHAMBLEE, DA (reprint author), NIH,OFF SCI POLICY & TECHNOL TRANSFER,BETHESDA,MD 20892, 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 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1994 VL 69 IS 6 BP 466 EP 467 DI 10.1097/00001888-199406000-00007 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA NT082 UT WOS:A1994NT08200008 PM 8003160 ER PT J AU MIHALY, A RAPP, UR AF MIHALY, A RAPP, UR TI EXPRESSION OF THE RAF PROTOONCOGENE IN GLIAL-CELLS OF THE ADULT-RAT CEREBRAL-CORTEX, BRAIN-STEM AND SPINAL-CORD SO ACTA HISTOCHEMICA LA English DT Article DE GLIA; ASTROCYTE; PROTOONCOGENE; PROTEIN KINASE; RAT ID FACTOR RECEPTOR IMMUNOREACTIVITY; NERVE GROWTH-FACTOR; PROTEIN-KINASE; SIGNAL-TRANSDUCTION; HIPPOCAMPAL SLICES; GUINEA-PIGS; YOUNG-RATS; LOCALIZATION; ASTROCYTES; INJURY AB The raf protooncogenes encode cytoplasmic serine/threonine-specific protein kinases which can be activated from different growth factor receptors by phosphorylation. Our previous immunohistochemical studies proved that raf kinases are present in neurons of the mammalian central nervous system. The present study describes the immunohistochemical localization of raf kinases in glia-like cells of the rat cerebral cortex, spinal cord and brain stem. Small glia-like cells measuring 8 - 12 mu m were observed in the neocortex, the entorhinal and prepiriform allocortical areas and the subcortical white matter. In the hippocampus, the immunoreactive cells were most numerous in the fimbria, the alveus and the molecular layer of the dentate fascia. Ultrastructural studies following preembedding immunohistochemistry revealed that in the cerebral cortex only astrocytes contained raf-protein-like immunoreactivity. Our immunofluorescence studies showed, that the white matter of the spinal cord, the pyramids of the medulla and the basis of the pens contained small glia-like cells, too. No electron microscopic investigations were performed, but the location (white matter tracts) and size (6-12 mu m) of these cells suggested their glial nature. On the basis of data from other cell systems we expect that raf kinases participate in growth factor- and cytokine-regulated glial functions of the mammalian central nervous system. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RP MIHALY, A (reprint author), ALBERT SZENT GYORGYI MED UNIV,DEPT ANAT,POB 512,H-6701 SZEGED,HUNGARY. RI Mihaly, Andras/K-5096-2012 NR 28 TC 2 Z9 3 U1 0 U2 3 PU GUSTAV FISCHER VERLAG JENA PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0065-1281 J9 ACTA HISTOCHEM JI Acta Histochem. PD JUN PY 1994 VL 96 IS 2 BP 155 EP 164 PG 10 WC Cell Biology SC Cell Biology GA NV338 UT WOS:A1994NV33800003 PM 7976125 ER PT J AU CHIRMULE, N OYAIZU, N SAXINGER, C PAHWA, S AF CHIRMULE, N OYAIZU, N SAXINGER, C PAHWA, S TI NEF PROTEIN OF HIV-1 HAS B-CELL STIMULATORY ACTIVITY SO AIDS LA English DT Article DE NEF; INTERLEUKIN-6; B-CELL DIFFERENTIATION; T-B-CELL CONTACT ID IMMUNODEFICIENCY-VIRUS TYPE-1; INTERLEUKIN-2 MESSENGER-RNA; T-CELLS; ENVELOPE GLYCOPROTEIN; LYMPHOTROPIC VIRUS; HUMAN-LYMPHOCYTES; HTLV-III; ACTIVATION; INFECTION; INDUCTION AB Objective: To examine the B-cell stimulatory properties of the regulatory Nef protein of HIV-1. Methods: The effect of the HIV-1 regulatory proteins Nef, Tat and Vif, were analyzed for their ability to induce differentiation of normal B lymphocytes into immunoglobulin secreting cells (ISC). Results: A recombinant Nei protein, but neither Tat or Vif, was able to induce ISC in peripheral blood lymphocyte (PBL) cultures of HIV-1-seronegative donors. Another recombinant Nef protein, d-Nef, with a truncated amino terminal (deletion of 34 amino acids) failed to induce B-cell differentiation. Pretreatment of the Nef protein with a polyclonal anti-Nef-antibody abrogated its B-cell stimulatory activity. The Nef-induced B-cell differentiation was dependent on cell-to-cell contact. Cell surface molecules leukocyte function-associated molecule (LFA)-1, intracellular adhesion molecule (ICAM)-1, human lymphocyte antigen-DR and B7 were involved in the T-B-cell interaction because monoclonal antibodies to these molecules abrogated the Nef-induced B-cell differentiation response. The Nef protein was able to induce interleukin (IL)-6 messenger (m)RNA and IL-6 protein secretion in PBL, with monocytes as the primary source. Conclusions: These findings indicate that regulatory (Nef) proteins of HIV-1 contribute to the intense B-cell activation that occurs in association with HIV-1 infection. T-B-cell contact-dependent interaction and induction of IL-6 by these proteins appear to play major roles in this process. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD. RP CHIRMULE, N (reprint author), N SHORE UNIV HOSP,CORNELL UNIV MED COLL,DEPT PEDIAT,350 COMMUNITY DR,MANHASSET,NY 11030, USA. FU NCRR NIH HHS [RR05924-06]; NIAID NIH HHS [AI28281] NR 38 TC 34 Z9 34 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUN PY 1994 VL 8 IS 6 BP 733 EP 739 DI 10.1097/00002030-199406000-00002 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NP436 UT WOS:A1994NP43600002 PM 8086129 ER PT J AU STRETCHER, BN PESCE, AJ FRAME, PT GREENBERG, KA STEIN, DS AF STRETCHER, BN PESCE, AJ FRAME, PT GREENBERG, KA STEIN, DS TI CORRELATES OF ZIDOVUDINE PHOSPHORYLATION WITH MARKERS OF HIV DISEASE PROGRESSION AND DRUG TOXICITY SO AIDS LA English DT Article DE HIV INFECTION; ZIDOVUDINE PHOSPHORYLATION; PHARMACOKINETICS; PHARMACODYNAMICS; SURROGATE MARKERS ID HUMAN-IMMUNODEFICIENCY-VIRUS; 5'-TRIPHOSPHATE AB Objective: To determine the relationships between in vivo zidovudine (ZDV) phosphorylation in cells from HIV-infected patients and markers associated with disease progression and drug toxicity. Design: A pharmacokinetic study of ZDV metabolism sponsored by the AIDS Clinical Trials Group (protocol 161). Plasma and intracellular pharmacokinetics following a 100 mg oral dose of ZDV were determined at weeks 4 and 24 of initial therapy in adult patients. Plasma concentrations and phosphorylated ZDV were determined by radioimmunoassay, and area under the concentration-time curves (AUC) were compared with clinical data collected during the pharmacokinetic study. Setting: An outpatient setting at the University of Cincinnati AIDS Treatment Center, Cincinnati, Ohio, USA. Patients: HIV-infected adults with CD4+ lymphocyte counts 200-500 x 10(6) cells/l with no prior history of anti-HIV therapy and no active infections requiring systemic therapy. Of 30 patients enrolled, 21 were evaluable. Interventions: None. Main outcome measures: AUC of plasma ZDV and intracellular total phosphorylated ZDV were compared with change from baseline of the following surrogate markers: CD4+ lymphocyte count, %CD4+ lymphocytes, CD4+/CD8+ cell ratio, serum beta(2)-microglobulin, serum neopterin, neutrophils, red cell count, and hemoglobin. Results: No correlations between plasma AUC and markers of therapeutic response were observed. However, significant positive correlations were observed between the AUC of total phosphorylated ZDV and changes in the %CD4+ lymphocytes and CD4+/CD8+ lymphocyte ratio; a negative correlation was observed with change in hemoglobin. Patients who responded to ZDV therapy, as measured by these variables, demonstrated significantly higher intracellular AUC (> 3 pmol x h/10(6) cells) than those who did not (approximately 2 pmol x h/10(6) cells). Conclusions: The ability of HIV-infected patients to phosphorylate ZDV correlates with changes in markers associated with drug effect and toxicity. Potential individualization of therapy through monitoring of total phosphorylated ZDV in patients therefore warrants further exploration. C1 UNIV CINCINNATI,COLL MED,CINCINNATI,OH. NIAID,DIV AIDS,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-25897] NR 11 TC 55 Z9 55 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUN PY 1994 VL 8 IS 6 BP 763 EP 769 DI 10.1097/00002030-199406000-00007 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NP436 UT WOS:A1994NP43600007 PM 8086134 ER PT J AU ROSENBERG, PS GOEDERT, JJ BIGGAR, RJ AF ROSENBERG, PS GOEDERT, JJ BIGGAR, RJ TI EFFECT OF AGE AT SEROCONVERSION ON THE NATURAL AIDS INCUBATION DISTRIBUTION SO AIDS LA English DT Article DE AIDS; HIV; AGE; INCUBATION DISTRIBUTION; HOMOSEXUAL MEN; HEMOPHILIACS ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS TYPE-1; HOMOSEXUAL MEN; INFECTION; HIV; MEMORY; INDIVIDUALS; HEMOPHILIA; SUBSETS; TRIALS AB Objective: To estimate the age-specific relative risk of progression from HIV seroconversion to onset of AIDS in hemophiliacs and homosexual men. Design: Prospective follow-up data from HIV seroconversion to AIDS was analyzed for hemophiliacs in the Multicenter Hemophilia Cohort Study and for homosexual men in the International Registry of Seroconverters. Follow-up was censored at 1 July 1987 to obtain natural history estimates unaffected by therapies that were widely used after this date. The age-specific relative hazard of progression was estimated using nonparametric proportional hazards models and the baseline hazard function was described using spline models. Results: Among the 373 children and adults with hemophilia and the 1020 adult homosexual men, each 10-year increment in age at seroconversion was associated with a 1.6- and 1.4-fold increase in the hazard of progression, respectively. The effect of age was highly significant among hemophiliacs. The magnitude of the effect was consistent in different cohorts of homosexual men, although it was not nominally significant. Furthermore, there was a significant increase (1.9-fold higher) in progression rates among homosexual men above rather than below 35 years of age at seroconversion. After adjusting for age, progression Fates among hemophiliacs were significantly slower, possibly because Kaposi's sarcoma was rare. In both groups, the annual hazard rate increased during the first 5 years after seroconversion, but broad confidence limits prevented us from establishing hazard trends beyond this time. Conclusions: Estimates of the aggregate incubation time distribution were substantially shorter in older compared with younger individuals. The increasing risk with age was similar in hemophiliacs and homosexual men, suggesting that age is an endogenous host factor. These findings can be incorporated into newly developed backcalculation models to estimate HIV infection incidence by age group from age-specific AIDS surveillance data. C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. RP ROSENBERG, PS (reprint author), NCI,BIOSTAT BRANCH,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 29 TC 143 Z9 144 U1 2 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUN PY 1994 VL 8 IS 6 BP 803 EP 810 DI 10.1097/00002030-199406000-00013 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NP436 UT WOS:A1994NP43600013 PM 8086140 ER PT J AU EYSTER, ME SILVA, E AF EYSTER, ME SILVA, E TI IMPACT OF HIV AND ITS TREATMENT ON CHRONIC HEPATITIS-C IN HEMOPHILIACS SO AIDS PATIENT CARE LA English DT Article ID CHRONIC LIVER-DISEASE; VIRUS HCV; PREVALENCE; INFECTION; ANTIBODY C1 NIH,HEPATITIS SECT,BETHESDA,MD 20892. RP EYSTER, ME (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,HERSHEY,PA 17033, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0893-5068 J9 AIDS PATIENT CARE JI Aids Patient Care PD JUN PY 1994 VL 8 SU 1 BP S6 EP S9 PG 4 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA NY218 UT WOS:A1994NY21800002 ER PT J AU GOLDING, H DSOUZA, MP BRADAC, J MATHIESON, B FAST, P AF GOLDING, H DSOUZA, MP BRADAC, J MATHIESON, B FAST, P TI MEETING REPORT - NEUTRALIZATION OF HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; GP120 MOLECULES; ASSAY; INFECTION; CELL; SITE; SUSCEPTIBILITY; QUANTITATION; PEPTIDES AB A Workshop on Neutralization of HIV-1: Technology and reagents for analysis of prophylactic vaccines clinical trials, sponsored by the Food and Drug Administration (FDA) and the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), was held on April 19-20, 1993, in Bethesda, Maryland. This workshop brought together researchers who are involved in the development, testing, and evaluation of HIV-1 prophylactic vaccines. The major objectives were (1) to discuss critically the different neutralization and binding assays that are currently used in the evaluation of immune sera; (2) to identify assays that will measure the ''most relevant'' antibodies, which are likely to predict neutralization of primary isolates; and (3) to identify well-characterized reference reagents, which could be used to standardize neutralization assays used in laboratories around the world. C1 NIAID,DIV AIDS,PATHOGENESIS BRANCH,BRDP,ROCKVILLE,MD 20852. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BRDP,ROCKVILLE,MD 20852. RP GOLDING, H (reprint author), US FDA,CBER,DIV VIRAL PROD,RETROVIRUS RES LAB,8800 ROCKVILLE PIKE,HFM-457,BLDG 29A,BETHESDA,MD 20892, USA. NR 41 TC 52 Z9 52 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1994 VL 10 IS 6 BP 633 EP 643 DI 10.1089/aid.1994.10.633 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NU496 UT WOS:A1994NU49600002 PM 8074927 ER PT J AU DEGRASSI, A DEMARIA, A LISIGNOLI, G ZINI, N SABATELLI, P CIRILLO, L MONACO, MCG HILBERT, DM AMBESIIMPIOMBATO, FS MARALDI, NM FACCHINI, A AF DEGRASSI, A DEMARIA, A LISIGNOLI, G ZINI, N SABATELLI, P CIRILLO, L MONACO, MCG HILBERT, DM AMBESIIMPIOMBATO, FS MARALDI, NM FACCHINI, A TI TRANSFER OF HIV-1 TO HUMAN TONSILLAR STROMAL CELLS FOLLOWING COCULTIVATION WITH INFECTED LYMPHOCYTES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERSISTENT GENERALIZED LYMPHADENOPATHY; FOLLICULAR DENDRITIC CELLS; T-CELL; LYMPH-NODES; CD4-INDEPENDENT INFECTION; HOMOSEXUAL MEN; GLIAL-CELLS; HTLV-III; AIDS AB The susceptibility of normal human tonsillar stromal cells (HTSCs) to infection by HIV-1 was assessed using transmission electron microscopy (TEM), immunocytochemistry, and HIV-1-specific PCR analyses. Our results demonstrate that HTSCs are efficiently infected following cocultivation with the HIV-1-infected lymphoblastoid cell line GY1. Infected stromal cells contain intracellular viral particles present as free virus or associated with phagocytic vesicles. These particles express the HIV-1-specific p24 antigen as assessed by immunocytochemical analyses using an HIV-specific anti-p24 monoclonal antibody. Moreover, PCR analysis of genomic DNA isolated from particle-bearing tonsillar stromal cells identified HIV-1-specific sequences not present in either uninfected stromal cells or parental GY1 uninfected cells. The mechanism by which HIV-1 infects HTSCs does not appear to be CD4 mediated, as none of the human tonsillar stromal cell lines express CD4 as assessed by flow cytometry, immunohistochemistry, and PCR analysis. Taken together, these results demonstrate that human tonsillar stromal cells can be infected by HIV-1, and that subsequent to infection the viral genome is reverse transcribed, and integrated into the stromal cell DNA. The infection of HTSCs may contribute to HIV-1-mediated pathogenesis indirectly as a viral reservoir or directly by structural and functional modification of the lymphoid microenvironment. C1 CONSORZIO RIC BIOMED,UDINE,ITALY. UNIV GENOA,IST MALATTIE INFETT,GENOA,ITALY. IOR,IMMUNOL & GENET LAB,BOLOGNA,ITALY. IOR,CNR,IST CITOMORFOL NORMALE & PATOL,BOLOGNA,ITALY. NCI,GENET LAB,BETHESDA,MD 20892. UNIV BOLOGNA,IST CLIN MED & GASTROENTEROL,I-40126 BOLOGNA,ITALY. RP DEGRASSI, A (reprint author), UNIV UDINE,DIPARTIMENTO PATOL & MED SPERIMENTALE & CLIN,PIAZZALE S MARIA MISERICORDIA,I-33100 UDINE,ITALY. RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 53 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1994 VL 10 IS 6 BP 675 EP 682 DI 10.1089/aid.1994.10.675 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NU496 UT WOS:A1994NU49600007 PM 8074931 ER PT J AU KALEBIC, T SCHEIN, PS AF KALEBIC, T SCHEIN, PS TI ORGANIC THIOPHOSPHATE WR-151327 SUPPRESSES EXPRESSION OF HIV IN CHRONICALLY INFECTED-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; KAPPA-B TRANSLOCATION; HUMAN T-CELL; N-ACETYLCYSTEINE; HIV-1-INFECTED PATIENTS; GLUTATHIONE DEFICIENCY; MONOCYTIC CELLS; D-PENICILLAMINE; TRANSCRIPTION AB Reducing agents such as glutathione (GSH), glutathione ester (GSE), and N-acetylcysteine (NAC) have been shown to suppress the induction of HIV expression in chronically infected cells stimulated by cytokines. We present data which show the effects of the organic thiophosphate WR-151327 on the expression of latent HIV in U1 cells. The chronically infected promonocytic cell line U1 constitutively expresses low levels of HIV that can be increased by 13-phorbol 12-myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), and granulocyte/monocyte colony-stimulating factor (GM-CSF). WR-151327 suppressed, in dose-dependent fashion, the reverse transcriptase (RT) activity induced by TNF-alpha, GM-CSF, and PMA. The maximal decrease in RT activity was 70, 80, and 50%, respectively. Pretreatment with WR-151327 also suppressed the induction of total HIV protein synthesis, as shown by Western blot analysis. In addition, WR-151327 suppressed HIV-LTR-CAT activity in transfected human rhabdomyosarcoma cells (RD). Suppression of HIV expression by WR-151327 was observed in the absence of a cytotoxic or cytostatic effect. Incubation of WR-151327 with human recombinant TNF-alpha for 6 hr at 37 degrees C did not alter the capacity of TNF-alpha to induce the expression of HIV. Our observations further support the hypothesis that reducing agents are important in the control of HIV replication and that the clinical evaluation of WR-151327 may be indicated. C1 US BIOSCI,W CONSHOHOCKEN,PA 19428. RP KALEBIC, T (reprint author), NCI,PEDIAT BRANCH,GENET MOLEC LAB,BLDG 10,13C215,BETHESDA,MD 20892, USA. NR 44 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1994 VL 10 IS 6 BP 727 EP 733 DI 10.1089/aid.1994.10.727 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NU496 UT WOS:A1994NU49600014 PM 7521193 ER PT J AU KAGEYAMA, S HOEKZEMA, DT MURAKAWA, Y KOJIMA, E SHIRASAKA, T KEMPF, DJ NORBECK, DW ERICKSON, J MITSUYA, H AF KAGEYAMA, S HOEKZEMA, DT MURAKAWA, Y KOJIMA, E SHIRASAKA, T KEMPF, DJ NORBECK, DW ERICKSON, J MITSUYA, H TI A C-2 SYMMETRY-BASED HIV PROTEASE INHIBITOR, A77003, IRREVERSIBLY INHIBITS INFECTIVITY OF HIV-1 IN-VITRO SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEINASE-INHIBITOR; TYPE-1 PROTEASE; HTLV-III; CLEAVAGE; CELLS; DESIGN; FURIN; AIDS AB A C-2 symmetry-based HIV protease inhibitor, A77003, exerts potent antiviral activity against a wide spectrum of HIV isolates in vitro. In this study, we asked whether A77003 could cause irreversible conformational changes to HIV-1, whether the amounts of viral RNA and p24 capsid protein per virion were altered, and how the infectivity of the virus produced in the presence of the drug was affected. We found that the number of viral particles and per-virion viral RNA content of the virus produced in the presence of A77003 did not significantly differ from those of the virus produced in the absence of the drug, whereas significant morphological changes were observed as assessed by transmission electron microscopy. However, the virus produced in the presence of A77003 contained substantially less p24(gag) protein per virion particle as compared to those produced in the absence of the drug or in the presence of AZT. Virions produced in the presence of A77003 showed up to 50-fold less infectious capability in subsequent tissue culture than control virions produced in the absence of drug or in the presence of AZT. This reduction in infectivity was maintained for at least 10 days in culture. The present data suggest that A77003 impairs HIV-1 protease-mediated Gag processing, interferes with the assembly and maturation of the virus, and leads to an irreversible loss of the infectivity of the virus, although a low but positive level of reversion to infectivity during the 10-day assay occurs. These features of A77003 (and perhaps similar HIV protease inhibitors as well) anti-HIV activity should represent desirable properties for antiviral therapy of AIDS and related diseases. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. ADV BIOTECHNOL INC,COLUMBIA,MD. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. ABBOTT LABS,DIV PHARMACEUT PROD,ABBOTT PK,IL 60064. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 30 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1994 VL 10 IS 6 BP 735 EP 743 DI 10.1089/aid.1994.10.735 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NU496 UT WOS:A1994NU49600015 PM 8074936 ER PT J AU GEORGE, DT LINDQUIST, T ALIM, T FLOOD, M ECKARDT, MJ LINNOILA, M AF GEORGE, DT LINDQUIST, T ALIM, T FLOOD, M ECKARDT, MJ LINNOILA, M TI ABSTINENT ALCOHOLICS EXHIBIT AN EXAGGERATED STRESS-RESPONSE TO 2-DEOXY-D-GLUCOSE CHALLENGE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOLISM; 2-DEOXY-D-GLUCOSE; METABOLIC STRESS; HPA AXIS ID PROGESTERONE; HYPOGLYCEMIA; METABOLISM; VOLUNTEERS; ETHANOL; RATS AB Chronic excessive alcohol consumption can significantly disturb the hypothalamic control of glucose metabolism; however, the mechanism and clinical significance of this disturbance are poorly understood. We used 2-deoxy-D-glucose (2-DG), which produces intracellular glucoprivation, to compare neurochemical, physiological, and behavioral responses to glucoprivic stress between alcoholics abstinent for 3 weeks and healthy volunteers. Twenty-six male alcoholics and 15 male healthy volunteers received intravenous infusions of placebo, 12.5 mg/kg, and 25.0 mg/kg of body weight of 2-DG over 30 min on three separate days, following a random-ordered, double-blind procedure. Minimal effects were observed following administration of the 12.5 mg/kg of body weight dose of 2-DG. Following 25.0 mg/kg, alcoholics showed both exaggerated ACTH and cortisol responses and greater increases in caloric intake when compared with controls. Although anxiety, desire to consume alcohol, plasma progesterone, and sympathetic and adrenal medullary activity all increased following 2-DG, these responses did not differ between alcoholics and controls. The present findings suggest certain specificity for the exaggerated hypothalamic and adrenocortical responses to mild glucoprivic stress in 3-week-abstinent alcoholics. C1 NIH,CTR CLIN,DEPT NUTR,BETHESDA,MD 20892. DEPT VET AFFAIRS MED CTR,NATL INST DRUG ABUST,RES UNIT,WASHINGTON,DC. RP GEORGE, DT (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,ROOM 3B19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1994 VL 18 IS 3 BP 685 EP 691 DI 10.1111/j.1530-0277.1994.tb00931.x PG 7 WC Substance Abuse SC Substance Abuse GA NR675 UT WOS:A1994NR67500027 PM 7943676 ER PT J AU REED, T SLEMENDA, CW VIKEN, RJ CHRISTIAN, JC CARMELLI, D FABSITZ, RR AF REED, T SLEMENDA, CW VIKEN, RJ CHRISTIAN, JC CARMELLI, D FABSITZ, RR TI CORRELATIONS OF ALCOHOL-CONSUMPTION WITH RELATED COVARIATES AND HERITABILITY ESTIMATES IN OLDER ADULT MALES OVER A 14-YEAR TO 18-YEAR PERIOD - THE NHLBI TWIN STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL; TWINS; HERITABILITY; HOSTILITY; HDL-CHOLESTEROL ID DENSITY-LIPOPROTEIN CHOLESTEROL; HEALTH EXAMINATION DATA; DRINKING HABITS; GENETIC INFLUENCES; BLOOD-PRESSURE; RISK-FACTORS; FOLLOW-UP; PATTERNS; INHERITANCE; SAMPLE AB Consistent maximum likelihood heritability estimates of consumption of alcoholic beverages were observed at three separate times during a 14- to 18-year period in adult twin males initially aged 42-56 years in 1969-1973. Log transformation of the average number of drinks/week of the returnees to all three examinations was examined relative to potential covariates representing both antecedents of drinking alcohol and consequences of alcohol consumption. Significant relationships were noted for 38 of the covariates at one or more of the separate examinations, including positive correlations with smoking, coffee consumption, high-density lipoprotein cholesterol, mean corpuscular volume, systolic blood pressure, uric acid and behavioral measures, and negative correlations with blood urea nitrogen, red blood cell count, tea consumption, and tricep skinfolds. Analysis of the average alcohol consumption adjusted for nine independent covariates selected from multiple stepwise regression resulted in a modest decline in maximum-likelihood heritability estimates compared with unadjusted data, but little difference from heritability estimates obtained when abstainers from alcohol (no alcoholic beverages consumed at all three examinations) were excluded. The most striking effect of omitting abstainers from alcohol was the decline in the intraclass correlations in dizygotic twins. Bivariate analyses of alcohol and individual covariates revealed the phenotypic correlation between alcohol consumption and a measure of hostility was primarily environmental, that for high density lipoprotein, smoking and coffee drinking with alcohol was primarily genetic, and the phenotypic correlation between alcohol consumption and mean corpuscular volume had both significant genetic and environmental correlations. Comparison with other twin studies in males suggested relatively consistent estimates of genetic variance, despite wide variation in subject characteristics, study design and methods, and measure of alcohol consumption. C1 INDIANA UNIV,SCH MED,DEPT MED,DIV BIOSTAT,INDIANAPOLIS,IN. INDIANA UNIV,DEPT PSYCHOL,BLOOMINGTON,IN. SRI INT,HLTH SCI PROGRAM,MENLO PK,CA 94025. NHLBI,CLIN & GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP REED, T (reprint author), INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,975 W WALNUT ST,IB 130,INDIANAPOLIS,IN 46202, USA. FU NIAAA NIH HHS [P50-AA07611] NR 54 TC 17 Z9 17 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1994 VL 18 IS 3 BP 702 EP 710 DI 10.1111/j.1530-0277.1994.tb00934.x PG 9 WC Substance Abuse SC Substance Abuse GA NR675 UT WOS:A1994NR67500030 PM 7943679 ER PT J AU LANCASTER, FE AF LANCASTER, FE TI GENDER DIFFERENCES IN THE BRAIN - IMPLICATIONS FOR THE STUDY OF HUMAN ALCOHOLISM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL; GENDER; SEX DIFFERENCES; NEUROSTEROIDS; WOMEN ID GABA-A-RECEPTOR; DIAZEPAM-BINDING INHIBITOR; D-ASPARTATE RECEPTOR; SHORT-SLEEP MICE; PREGNENOLONE SULFATE; SEX-DIFFERENCES; DEHYDROEPIANDROSTERONE SULFATE; PORTACAVAL ANASTOMOSIS; DEHYDROGENASE ACTIVITY; 1ST-PASS METABOLISM AB Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol. C1 NIAAA,DIV BASIC RES,NEUROSCI & BEHAV RES BRANCH,ROCKVILLE,MD 20852. RP LANCASTER, FE (reprint author), TEXAS WOMANS UNIV,DEPT BIOL,POB 23971,DENTON,TX 76204, USA. NR 95 TC 39 Z9 39 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1994 VL 18 IS 3 BP 740 EP 746 DI 10.1111/j.1530-0277.1994.tb00940.x PG 7 WC Substance Abuse SC Substance Abuse GA NR675 UT WOS:A1994NR67500036 PM 7943685 ER PT J AU ROBERTS, WC KRAGEL, AH GERTZ, SD ROBERTS, CS AF ROBERTS, WC KRAGEL, AH GERTZ, SD ROBERTS, CS TI CORONARY-ARTERIES IN UNSTABLE ANGINA-PECTORIS, ACUTE MYOCARDIAL-INFARCTION, AND SUDDEN CORONARY DEATH SO AMERICAN HEART JOURNAL LA English DT Article ID ATHEROSCLEROTIC PLAQUES; NECROPSY PATIENTS; ANGIOGRAPHIC MORPHOLOGY; MORPHOMETRIC ANALYSIS; THROMBUS; FREQUENCY; DISEASE C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP ROBERTS, WC (reprint author), BAYLOR UNIV,MED CTR,BAYLOR CARDIOVASC INST,3500 GASTON AVE,DALLAS,TX 75246, USA. NR 19 TC 27 Z9 28 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1994 VL 127 IS 6 BP 1588 EP 1593 DI 10.1016/0002-8703(94)90390-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NQ301 UT WOS:A1994NQ30100023 PM 8197987 ER PT J AU KREGER, BE ODELL, PM DAGOSTINO, RB WILSON, PFW AF KREGER, BE ODELL, PM DAGOSTINO, RB WILSON, PFW TI LONG-TERM INTRAINDIVIDUAL CHOLESTEROL VARIABILITY - NATURAL COURSE AND ADVERSE IMPACT ON MORBIDITY AND MORTALITY - THE FRAMINGHAM-STUDY SO AMERICAN HEART JOURNAL LA English DT Article ID SERUM-CHOLESTEROL; LIPOPROTEIN CHOLESTEROL; MENSTRUAL-CYCLE; REGRESSION; POPULATION; WEIGHT C1 BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,GEN INTERNAL MED SECT,BOSTON,MA. BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA. NHLBI,FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. BRYANT COLL,DEPT MATH,SMITHFIELD,RI 02917. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. FU NHLBI NIH HHS [N01-HC-38038] NR 27 TC 12 Z9 12 U1 1 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1994 VL 127 IS 6 BP 1607 EP 1614 DI 10.1016/0002-8703(94)90393-X PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NQ301 UT WOS:A1994NQ30100026 PM 8197990 ER PT J AU MARON, BJ KLUES, HG AF MARON, BJ KLUES, HG TI SURVIVING COMPETITIVE ATHLETICS WITH HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; M-MODE ECHOCARDIOGRAPHY; SUDDEN CARDIAC DEATH; CLINICAL MANIFESTATIONS; PATHO-PHYSIOLOGY; YOUNG; INTERRELATIONS; PATTERNS; THERAPY; EXTENT AB Hypertrophic cardiomyopathy (HC) is probably the most common cause of sudden cardiac death in youthful athletes, and this diagnosis has represented a contraindication to continued participation in competitive sports. Less well appreciated is the fact that within the clinical spectrum of Pc are patients who, despite having this disease, have been able to undertake particularly intensive and often extraordinary levels of training for sports competition over many years without dying suddenly. Fourteen such patients (13 men and 1 woman, aged 30 to 66 years [mean 43]) form the present study group. Pc was initially identified at 24 to 57 years of age (mean 34), usually under fortuitous circumstances. Patients most often competed in distance running (including the marathon, 7), but also in swimming, triathalon, basketball, and football. The duration of training ranged from 6 to 22 years (mean 15) and 5 continue to train and compete actively. The magnitude of training, competition, and achievement was considerable in most patients; 12 of the 14 performed either at the national, collegiate or professional level in their sport, completed numerous marathon and triathalon events, or sustained particularly rigorous training regimens of greater than or equal to 50 miles/week. Echocardiographic studies demonstrated a left ventricular wall thickness of 18 to 28 mm (mean 20) in most patients (12 of 14) having a relatively localized pattern of ventricular septal hypertrophy. It is possible for some patients with Pc to tolerate particularly intense athletic training and competition for many years, and even maintain high levels of achievement without incurring symptoms and disease progression or dying suddenly. The explanation for such a favorable clinical course in these particular athletes with HC is uncertain, and provides an incentive for further efforts at risk stratification in such persons. C1 NHLBI,BETHESDA,MD 20892. UNIV HOSP RWTH,MED CLIN 1,DEPT CARDIOL,AACHEN,GERMANY. RP MARON, BJ (reprint author), MINNEAPOLIS HEART FDN,920 E 28TH ST,SUITE 40,MINNEAPOLIS,MN 55455, USA. NR 31 TC 29 Z9 30 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1994 VL 73 IS 15 BP 1098 EP 1104 DI 10.1016/0002-9149(94)90290-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NM836 UT WOS:A1994NM83600012 PM 8198037 ER PT J AU LEWIS, JF MARON, BJ AF LEWIS, JF MARON, BJ TI CLINICAL AND MORPHOLOGIC EXPRESSION OF HYPERTROPHIC CARDIOMYOPATHY IN PATIENTS GREATER-THAN-OR-EQUAL-TO-65 YEARS OF AGE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SYSTOLIC ANTERIOR MOTION; LEFT-VENTRICULAR HYPERTROPHY; M-MODE ECHOCARDIOGRAPHY; SUBAORTIC STENOSIS; MITRAL-VALVE; PRESSURE-GRADIENT; OBSTRUCTIVE CARDIOMYOPATHY; PATHO-PHYSIOLOGY; FEATURES; PATTERNS AB Hypertrophic cardiomyopathy (HC) is most often identified in patients in the second through fifth decades of life, but has been increasingly recognized in older patients. The present report characterizes morphologic and clinical features of no in 134 consecutively studied patients aged greater than or equal to 65 years referred to a tertiary center. Echocardiographic or clinical evaluation, or both, was performed in 134 patients aged 65 to 85 years (mean 72) at most recent evaluation. selected findings were compared with those in 64 youthful patients with HC aged 15 to 35 years (mean 25). Most elderly patients (120 of 134, 90%) developed marked symptoms that usually became evident after age 55 years; 94 of 120 experienced sustained improvement with medical treatment or operation. Elderly patients had relatively mild left ventricular (LV) wall thickening (20+/-3 mm), generally confined to the septum. in most (I.e., 68%), septal hypertrophy was uniformly distributed with parallel right and left borders and associated with elliptical LV cavity shape; however, in 32%, an inhomogeneously hypertrophied septum bulged into the left ventricle, disrupting normal cavity shape. Dynamic subaortic obstruction was present under basal or provocable conditions in a particularly small LV outflow tract in 103 of 134 patients (77%), and was usually produced by relatively restricted excursion of the anteriorly displaced mitral leaflets and posterior septal motion. he is characterized by age-related differences in both clinical and morphologic expression. Elderly patients with no characteristically demonstrate onset of cardiac symptoms late in life, as well as distinctive LV morphology and dynamics of outflow obstruction. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. MINNEAPOLIS HEART INST FDN,DIV CARDIOVASC RES,MINNEAPOLIS,MN. HOWARD UNIV,COLL MED,DEPT MED,DIV CARDIOVASC DIS,WASHINGTON,DC. FU NHLBI NIH HHS [HL01984] NR 31 TC 31 Z9 33 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 1994 VL 73 IS 15 BP 1105 EP 1111 DI 10.1016/0002-9149(94)90291-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NM836 UT WOS:A1994NM83600013 PM 8198038 ER PT J AU MELTZER, AA EVERHART, JE AF MELTZER, AA EVERHART, JE TI RISK-FACTORS FOR INTENTIONAL AND UNINTENTIONAL WEIGHT-LOSS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 SOCIAL & SCI SYST INC,BETHESDA,MD 20814. NIDDKD,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1994 VL 139 IS 11 SU S BP S55 EP S55 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NP863 UT WOS:A1994NP86300181 ER PT J AU NARAYAN, KMV HANSON, RL SMITH, CJ PETITTI, DJ NELSON, RG DECOURTEN, M KNOWLER, WC AF NARAYAN, KMV HANSON, RL SMITH, CJ PETITTI, DJ NELSON, RG DECOURTEN, M KNOWLER, WC TI POSITIVE ASSOCIATION BETWEEN DIETARY CALCIUM AND BLOOD-PRESSURE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ 85014. RI Narayan, K.M. Venkat /J-9819-2012; de Courten, Maximilian/B-3300-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405; de Courten, Maximilian/0000-0001-9997-9359 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1994 VL 139 IS 11 SU S BP S56 EP S56 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NP863 UT WOS:A1994NP86300184 ER PT J AU WILCOX, A SKJAERVEN, R IRGENS, L AF WILCOX, A SKJAERVEN, R IRGENS, L TI EFFECTS OF THE GERMAN OCCUPATION OF NORWAY ON PERINATAL-MORTALITY - AN AGE-PERIOD-COHORT ANALYSIS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV BERGEN,BERGEN,NORWAY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1994 VL 139 IS 11 SU S BP S73 EP S73 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NP863 UT WOS:A1994NP86300250 ER PT J AU PETTY, EM GREEN, JS MARX, SJ TAGGART, RT FARID, N BALE, AE AF PETTY, EM GREEN, JS MARX, SJ TAGGART, RT FARID, N BALE, AE TI MAPPING THE GENE FOR HEREDITARY HYPERPARATHYROIDISM AND PROLACTINOMA (MEN1(BURIN)) TO CHROMOSOME 11Q - EVIDENCE FOR A FOUNDER EFFECT IN PATIENTS FROM NEWFOUNDLAND SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; MEN1 LOCUS; RET PROTOONCOGENE; PHYSICAL MAP; SMALL REGION; LONG ARM; TYPE-1; LINKAGE; MARKERS; LOCALIZATION AB An autosomal dominant syndrome of prolactinomas, carcinoids, and hyperparathyroidism was described in four Newfoundland kindreds in 1980 and in one kindred from the Pacific Northwest in 1983. Because this syndrome shares many features with multiple endocrine neoplasia type 1, the gene for which maps to proximal chromosome 11q, we performed linkage studies with chromosome 11 markers in prolactinoma families to determine whether the two genes map to the same location. All proximal chromosome 11q markers gave positive LOD scores, and no recombinants were seen with PYGM (LOD score 15.25, recombination fraction.0). All affected individuals from Newfoundland shared the same PYGM allele, providing evidence for a founder effect. The disease in the Pacific Northwest kindred cosegregated with a different PYGM allele. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. MEM UNIV NEWFOUNDLAND,ST JOHNS,NF,CANADA. NIDDKD,BETHESDA,MD. WAYNE STATE UNIV,DEPT MOLEC BIOL & GENET,DETROIT,MI 48201. KING FAISAL SPECIALIST HOSP & RES CTR,DEPT MED,RIYADH 11211,SAUDI ARABIA. FU NCI NIH HHS [CA50497] NR 32 TC 53 Z9 53 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1994 VL 54 IS 6 BP 1060 EP 1066 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NP053 UT WOS:A1994NP05300015 PM 7911003 ER PT J AU MORI, S NOSE, M MIYAZAWA, M KYOGOKU, M WOLFINBARGER, JB BLOOM, ME AF MORI, S NOSE, M MIYAZAWA, M KYOGOKU, M WOLFINBARGER, JB BLOOM, ME TI INTERSTITIAL NEPHRITIS IN ALEUTIAN MINK DISEASE POSSIBLE ROLE OF CELL-MEDIATED-IMMUNITY AGAINST VIRUS-INFECTED TUBULAR EPITHELIAL-CELLS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; PARVOVIRUS INFECTION; VIRAL REPLICATION; ADULT MINK; IDENTIFICATION; HYBRIDIZATION; MAINTENANCE; PROTEINS; ANTIGEN; PROBES AB Aleutian mink disease (AD) has been characterized by immune complex glomerulonephritis associated with persistent infection of Aleutian mink disease parvovirus (ADV). Histopathological examination of kidneys from ADV-infected mink in this study revealed that interstitial nephritis characterized by prominent damage of renal tubuli and lymphocyte infiltration was also common in AD along with glomerulonelphritis. By using strand-specific in situ molecular hybridization technique, replication of ADV was observed in tubular eipithelial cells, in addition to epithelial cells of Bowman's capsules and some glomerular cells of the infected mink. Analysis of tubular lesions by a combination of immunohistochemistry and in situ hybridization revealed that the renal tubili positive for virion DNA or replicative form DNA/mRNA of ADV were also positive for an activation marker ofimmunocompetent cells, which is shared by B lymphocytes and thymic epithelial cells. Infiltration of a subpopulation of T lymphocytes around infected renal tubuli were observed but deposition of immune complexes in these tubular lesions was not demonstrable ADV replication in epithelial cells of renal tubuli and cell mediated immune responses to the infected epithelial cells may play a role in the pathogenesis of interstitial nephritis in Aleutian mink disease. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. TOHOKU UNIV,SCH MED,DEPT PATHOL,SENDAI 982,JAPAN. TOHOKU UNIV,SCH DENT,DEPT ORAL & MAXILLOFACIAL SURG 2,SENDAI 982,JAPAN. NR 21 TC 15 Z9 15 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1994 VL 144 IS 6 BP 1326 EP 1333 PG 8 WC Pathology SC Pathology GA NQ324 UT WOS:A1994NQ32400023 PM 8203470 ER PT J AU ANDRADE, ZA ANDRADE, SG CORREA, R SADIGURSKY, M FERRANS, VJ AF ANDRADE, ZA ANDRADE, SG CORREA, R SADIGURSKY, M FERRANS, VJ TI MYOCARDIAL CHANGES IN ACUTE TRYPANOSOMA-CRUZI INFECTION - ULTRASTRUCTURAL EVIDENCE OF IMMUNE DAMAGE AND THE ROLE OF MICROANGIOPATHY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHAGAS-DISEASE; CELLS; HEART; CARDIOMYOPATHY; PERFORIN; SYSTEM; MODEL; MICE AB Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. FIOCRUZ MS,GONCALO MONIZ RES CTR,SALVADOR,BA,BRAZIL. NR 40 TC 46 Z9 48 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1994 VL 144 IS 6 BP 1403 EP 1411 PG 9 WC Pathology SC Pathology GA NQ324 UT WOS:A1994NQ32400030 PM 8203476 ER PT J AU ROY, TA RUFF, CB PLATO, CC AF ROY, TA RUFF, CB PLATO, CC TI HAND DOMINANCE AND BILATERAL ASYMMETRY IN THE STRUCTURE OF THE 2ND METACARPAL SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE SKELETAL ASYMMETRY; CROSS-SECTIONAL GEOMETRY; HANDEDNESS ID CROSS-SECTIONAL GEOMETRY; MACAQUE FORELIMB BONES; PECOS PUEBLO FEMORA; DIRECTIONAL ASYMMETRY; 2ND METACARPAL; AGE; SEX; TIBIAE AB Bilateral asymmetry in the structure of the second metacarpal was examined in relation to functional hand dominance in a large, clinically nonselected, healthy population sample from the Baltimore Longitudinal Study of Aging. Bilateral bone measurements were made from anteroposterior hand radiographs of a total of 992 individuals, 609 males and 383 females, with an age range of 19-94 years. Hand dominance was determined on the basis of personal impression. Total width and medullary width at the midshaft of the second metacarpal were measured to 0.05 mm using a Helios caliper. These two measurements were used to derive cortical thickness, cortical bone area, periosteal (total) area, medullary area, percent cortical area, and the second moment of area in the mediolateral plane. In both right and left-handed individuals, statistically significant side differences were found in the calculated bone areas and the second moment of area, with the dominant hand being larger. Cortical thickness did not show significant side-related differences for either handedness. These results show that functional handedness leads to periosteal and endosteal expansion of the second metacarpal cortex on the dominant side, increasing bone strength without increasing cortical thickness. This is the first time this pattern of asymmetry has been reported in left-handers as well as right-handers. Our results argue for the primacy of environmental (mechanical) effects in determining bilateral asymmetry of limb bone structural properties. (C) 1994 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. RP ROY, TA (reprint author), NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 24 TC 68 Z9 69 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD JUN PY 1994 VL 94 IS 2 BP 203 EP 211 DI 10.1002/ajpa.1330940205 PG 9 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA NN791 UT WOS:A1994NN79100004 PM 8085612 ER PT J AU PAULAIS, M CRAGOE, EJ TURNER, RJ AF PAULAIS, M CRAGOE, EJ TURNER, RJ TI ION-TRANSPORT MECHANISMS IN RAT PAROTID INTRALOBULAR STRIATED DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SODIUM-HYDROGEN EXCHANGE; POTASSIUM-HYDROGEN EXCHANGE; SALIVARY DUCTS; EXOCRINE GLAND; POTASSIUM CHANNEL; HYDROGEN CHANNEL ID SUBMANDIBULAR GRANULAR DUCTS; ACINAR-CELLS; EXCHANGE; STIMULATION; EPITHELIUM; SECRETION; NEURONS; FLUXES; CA2+; PH AB The intracellular pH (pH(i)) indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein and microfluorimetry were used to characterize several ion transport mechanisms in rat parotid striated ducts. The recovery of ductal pH(i) from an acute acid load was Na+ dependent and inhibited by the amiloride analogue ethylisopropylamiloride with 50% inhibitory concentration 4.7 +/- 0.8 mu M, indicating the presence of a Na+-H+ exchanger of the amiloride-insensitive type. The rate of this recovery was stimulated similar to 20% in ducts pretreated with the muscarinic agonist carbachol (10(-5) M) and inhibited similar to 20% in ducts pretreated with the beta-adrenergic agonist isoproterenol (10(-6) M). Upon removal of extracellular K+, ductal pH(i) rapidly decreased (0.19 +/- 0.02 pH units/min), consistent with a coupling between K+ and H+ (or OH-) fluxes in this tissue. In HCO3--containing medium, the acidification due to K+ removal was blunted, arguing against ductal K+-HCO3- cotransport. However, the effect of K+ removal was inhibited by the K+ channel blocker Ba2+ (1 mM) and by the H+ channel blocker Zn2+ (25 mu M), consistent with the involvement of electrically coupled K+ and H+ channels. The effect of K+ removal was unaffected by pretreatment of ducts with isoproterenol (10(-6) M) but markedly inhibited (similar to 50%) by pretreatment with carbachol (10(-5) M). No evidence for a significant component of Cl--HCO3- exchange was found in striated ducts. The proper ties of the Na+-H+ exchanger and K+-H+ exchange mechanism identified here are consistent with their involvement in ductal salt reabsorption and secretion. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RI Paulais, Marc/E-5623-2017 NR 29 TC 30 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1994 VL 266 IS 6 BP C1594 EP C1602 PN 1 PG 9 WC Physiology SC Physiology GA NV809 UT WOS:A1994NV80900012 ER PT J AU PRITCHARD, JB SYKES, DB WALDEN, R MILLER, DS AF PRITCHARD, JB SYKES, DB WALDEN, R MILLER, DS TI ATP-DEPENDENT TRANSPORT OF TETRAETHYLAMMONIUM BY ENDOSOMES ISOLATED FROM RAT RENAL-CORTEX SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ORGANIC CATION SECRETION; PROTON-ADENOSINE-TRIPHOSPHATASE; MEMBRANE VESICLES; KIDNEY; ACIDIFYING INTRACELLULAR ORGANELLES; PROXIMAL TUBULE; ORGANIC CATION/PROTON EXCHANGE ID BORDER MEMBRANE-VESICLES; CARRIER-MEDIATED TRANSPORT; BRUSH-BORDER; BASOLATERAL MEMBRANE; KIDNEY CORTEX; ORGANIC-ANIONS; MULTIDRUG RESISTANCE; SECRETION; TUBULES; CATIONS AB During renal organic cation secretion by some species, intracellular concentrations greatly exceed the 10- to 15-fold ratio predicted by the potential-driven mechanism thought to mediate their basolateral uptake. Free cytoplasmic organic cation concentrations within the tubular cells might be decreased through sequestration within intracellular organelles. The data reported here show that endosomal vesicles isolated from rat renal cortex take up tetraethylammonium (TEA) by an ATP-dependent mechanism. Addition of 0.2-5 mM ATP to the medium stimulated uptake 5- to 10-fold at 5 min and 20-fold at 60 min. More than 80% of the ATP-dependent uptake was associated with an osmotically active space. The nonhydrolyzable ATP analogue, adenosine 5'-O-(3-thiotriphosphate), did not stimulate TEA uptake. Mg2+ and Cl- were required for stimulation. Uptake was inhibited by several organic cations, including TEA itself. Uptake was also inhibited by inhibitors of intravesicular acidification, e.g., monensin and N-ethylmaleimide. Furthermore, the ATP requirement could be bypassed by establishing a pH gradient (inside acidic). These data show that endosomal TEA accumulation is mediated by proton/TEA. exchange and is driven by the pH gradient maintained by Hf-adenosinetriphosphatase. This potent sequestration mechanism may play an important role in organic cation secretion. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INTRACELLULAR REGULAT SECT,RES TRIANGLE PK,NC 27709. RP PRITCHARD, JB (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,MAIL DROP 19-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 35 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1994 VL 266 IS 6 BP F966 EP F976 PN 2 PG 11 WC Physiology SC Physiology GA NV810 UT WOS:A1994NV81000108 PM 8023976 ER PT J AU MASTRANGELI, A OCONNELL, B ALADIB, W FOX, PC BAUM, BJ CRYSTAL, RG AF MASTRANGELI, A OCONNELL, B ALADIB, W FOX, PC BAUM, BJ CRYSTAL, RG TI DIRECT IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER TO SALIVARY-GLANDS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EXOCRINE GLANDS; BETA-GALACTOSIDASE; ALPHA-1-ANTITRYPSIN ID RAT SUBMANDIBULAR-GLAND; HUMAN ALPHA-1-ANTITRYPSIN; ACINAR-CELLS; EXPRESSION; INVIVO; RETROVIRUS; VECTORS; LONG; TRANSPLANTATION; EPITHELIUM AB Gene transfer to the salivary glands holds the potential for the therapy of salivary gland disorders and for delivery of therapeutic proteins to the mouth and upper gastrointestinal tract. Administration of the recombinant adenovirus vectors Ad.RSV beta gal [coding for the intracellular protein beta-galactosidase (beta-Gal)] and Ad alpha 1AT [coding for human alpha(1)-antitrypsin (alpha(1)-AT), a secreted protein] to salivary gland cell lines in vitro demonstrated exogenous gene expression. Retrograde ductal injection of the Ad.RSV beta gal vector to rat salivary glands in vivo resulted in beta-Gal expression in acinar and ductal cells. Exposure of submandibular glands in vivo to Ad alpha 1AT resulted in expression of alpha(1)-AT mRNA transcripts, de novo synthesis of alpha(1)-AT, and secretion in the saliva. To evaluate the feasibility of adenovirus-mediated gene transfer to human glands, human minor salivary glands were infected ex vivo with Ad.RSV beta gal, and implanted into severe combined immunodeficient mice. Evaluation of the human tissue demonstrated beta-Gal activity. These observations demonstrate that adenovirus vectors are capable of direct delivery of genes to the salivary glands, suggesting a variety of possible gene therapy applications. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NR 41 TC 110 Z9 112 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1994 VL 266 IS 6 BP G1146 EP G1155 PN 1 PG 10 WC Physiology SC Physiology GA NV809 UT WOS:A1994NV80900079 PM 8023944 ER PT J AU HANO, O THOMPSONGORMAN, SL ZWEIER, JL LAKATTA, EG AF HANO, O THOMPSONGORMAN, SL ZWEIER, JL LAKATTA, EG TI COENZYME Q(10) ENHANCES CARDIAC FUNCTIONAL AND METABOLIC RECOVERY AND REDUCES CA2+ OVERLOAD DURING POSTISCHEMIC REPERFUSION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ISCHEMIA; CALCIUM OSCILLATIONS; HIGH-ENERGY PHOSPHATES; FREE RADICALS ID CALCIUM OVERLOAD; RESTING FORCE; ISCHEMIA; INJURY; HEART; OSCILLATIONS; MUSCLE; TRANSIENTS; PROTECTION; GENERATION AB The effects of coenzyme Q(10) (CoQ) were studied in isolated, isovolumic rat hearts during a 30-min period of global ischemia followed by 40 min of reperfusion. After reperfusion 1) the relative recovery of developed pressure (DP) was increased by CoQ (75 vs. 40% of the preischemic value for 20 mu M CoQ and control hearts, respectively, P < 0.001); 2) diastolic pressure elevation was decreased by CoQ (20 vs. 50 mmHg in CoQ vs. control hearts, respectively, P < 0.001); and 3) recovery of high-energy phosphates and reduction of inorganic phosphate were approximately twofold greater in CoQ vs. control hearts (P < 0.001 for each parameter). The beneficial effects of CoQ were not observed when CoQ was added at the onset of reperfusion. The total free generation during reperfusion was not affected by CoQ. In unpaced hearts, in the presence of verapamil to prevent spontaneous beating, spontaneous Ca2+ oscillations were measured as scattered laser light intensity fluctuations (SLIF). The transient rise in SLIF in the postischemic reperfused myocardium, which previously has been shown to predict the extent of Ca2+ overload, was suppressed by CoQ (P < 0.001). These results suggest that while early CoQ treatment does not scavenge the primary burst of superoxide or hydroxy radical generation, which occurs on reperfusion, it markedly improves the functional recovery during reperfusion by enhancing the recovery of high-energy phosphates and preventing Ca2+ overload. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21224. NR 32 TC 27 Z9 27 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1994 VL 266 IS 6 BP H2174 EP H2181 PN 2 PG 8 WC Physiology SC Physiology GA NV810 UT WOS:A1994NV81000004 ER PT J AU SCHOLZ, TD BALABAN, RS AF SCHOLZ, TD BALABAN, RS TI MITOCHONDRIAL F1-ATPASE ACTIVITY OF CANINE MYOCARDIUM - EFFECTS OF HYPOXIA AND STIMULATION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MYOCARDIUM; ADENOSINE 5'-TRIPHOSPHATE SYNTHESIS; REGULATION ID ATPASE INHIBITOR PROTEIN; ISCHEMIC CARDIAC-MUSCLE; HEART-RATE HEARTS; OXIDATIVE-PHOSPHORYLATION; ADENOSINE 5'-TRIPHOSPHATASE; CITRATE SYNTHASE; CREATINE-KINASE; COMPLEX-V; BINDING; RELEASE AB Recent studies have suggested that modifications in mitochondrial F-1-adenosinetriphosphatase (ATPase) activity may play an important role in the regulation of myocardial oxidative phosphorylation. The goal of the present study was to develop and characterize an assay of F-1-ATPase activity that could be performed repeatedly on an intact heart under various physiological states. With the use of submitochondrial particles prepared from biopsy samples of canine myocardium, we found reproducible F-1-ATPase activity when normalized to the activity of the intramitochondrial enzyme citrate synthase. The oligomycin-sensitive component of the ATPase activity was found to be mainly F-1-ATPase. F-1-ATPase activity of normal myocardium increased by incubation in high salt-pH buffer, suggesting baseline inhibition. Five minutes after global ischemia, F-1-ATPase activity decreased to 60% of baseline. Hypoxia for 10 min resulted in no significant change in F-1-ATPase activity. With phenylephrine infusion, myocardial oxygen consumption more than doubled, whereas F-1-ATPase activity increased by similar to 30%. Both returned to baseline levels after discontinuation of the drug. With the use of an assay developed to measure F-1-ATPase activity of intact myocardium, changes of the enzyme activity were found during both ischemia and at increased work loads. These data suggest that alterations of F-1-ATPase activity may contribute to the regulation of myocardial oxidative phosphorylation. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 35 TC 51 Z9 51 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1994 VL 266 IS 6 BP H2396 EP H2403 PN 2 PG 8 WC Physiology SC Physiology GA NV810 UT WOS:A1994NV81000031 ER PT J AU ROSSE, RB KENDRICK, K WYATT, RJ ISAAC, A DEUTSCH, SI AF ROSSE, RB KENDRICK, K WYATT, RJ ISAAC, A DEUTSCH, SI TI GAZE DISCRIMINATION IN PATIENTS WITH SCHIZOPHRENIA - PRELIMINARY-REPORT SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID SUPERIOR AB The authors administered a gaze discrimination task to 24 patients with chronic schizophrenia and 25 subjects with no psychiatric history. Each subject was shown slides and asked, ''Is the person in the slide looking directly at you?'' Patients with schizophrenia were more likely than comparison subjects to perceive the person in the slide as looking at them when the person was looking away. Because there is evidence that gaze discrimination performance involves the superior temporal sulcus region of the brain and this region has been implicated in theories about the pathogenesis of schizophrenia, further study of the gaze discrimination task seems indicated. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 5 TC 27 Z9 29 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1994 VL 151 IS 6 BP 919 EP 921 PG 3 WC Psychiatry SC Psychiatry GA NN755 UT WOS:A1994NN75500021 PM 8185005 ER PT J AU WAGENER, DK SCHATZKIN, A AF WAGENER, DK SCHATZKIN, A TI TEMPORAL TRENDS IN THE SOCIOECONOMIC GRADIENT FOR BREAST-CANCER MORTALITY AMONG US WOMEN SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID UNITED-STATES; HEALTH; RECORDS; WHITES; BLACKS AB Temporal trends in breast cancer mortality among US women were examined for 1969 through 1989 by age, race, and county-level socioeconomic status (SES). The mortality ratio for high- relative to low-SES counties declined significantly among women 25 to 44, 45 to 64, and more than 65 years of age, respectively, from 1.13 to 0.96, 1.32 to 1.19, and 1.48 to 1.26. The narrowing of mortality occurred among Whites and, to a lesser extent, Blacks. A relative increase in either breast cancer incidence among women in lower SES counties or improved survival among women in higher SES counties (reflecting greater use of screening and treatment) could account for this relative worsening of breast cancer mortality among lower SES women in lower SES counties. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP WAGENER, DK (reprint author), NATL CTR HLTH STAT,OFF ANAL EPIDEMIOL & HLTH PROMOT,RM 750,6525 BELCREST RD,HYATTSVILLE,MD 20782, USA. NR 24 TC 47 Z9 47 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1994 VL 84 IS 6 BP 1003 EP 1006 DI 10.2105/AJPH.84.6.1003 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PB869 UT WOS:A1994PB86900025 PM 8203664 ER PT J AU SARID, R CHAJUT, A MALKINSON, M TRONICK, SR GAZIT, A YANIV, A AF SARID, R CHAJUT, A MALKINSON, M TRONICK, SR GAZIT, A YANIV, A TI DIAGNOSTIC-TEST FOR LYMPHOPROLIFERATIVE DISEASE VIRUS-INFECTION OF TURKEYS, USING THE POLYMERASE CHAIN-REACTION SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID C RETROVIRUS; ETIOLOGY AB Lymphoproliferative disease virus, a type-C retrovirus, is the etiologic agent of a naturally acquired lymphoproliferative disorder in turkeys. The disease is characterized by rapid induction of lymphoproliferative lesions with morphologic and histopathologic features resembling those of reticuloendotheliosis. Owing to lack of overt clinical manifestations, early detection of lymphoproliferative disease virus is essential for preventing the rapid horizontal spread of the disease that can decimate flocks. We describe development of a simple, rapid, sensitive, and highly specific assay, using the polymerase chain reaction, capable of providing differential diagnosis of the disease soon after infection. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. KIMRON VET INST,BET DAGAN,ISRAEL. NR 15 TC 3 Z9 3 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD JUN PY 1994 VL 55 IS 6 BP 769 EP 772 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA NN775 UT WOS:A1994NN77500005 PM 7944012 ER PT J AU LEWIS, EN TREADO, PJ LEVIN, IW AF LEWIS, EN TREADO, PJ LEVIN, IW TI NEAR-INFRARED AND RAMAN-SPECTROSCOPIC IMAGING SO AMERICAN LABORATORY LA English DT Article C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. RP LEWIS, EN (reprint author), NIDDKD,MOLEC BIOPHYS SECT,BLDG 5,RM B1-38,BETHESDA,MD 20892, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU INT SCIENTIFIC COMMUN INC PI SHELTON PA PO BOX 870, 30 CONTROLS DRIVE, SHELTON, CT 06484-0870 SN 0044-7749 J9 AM LAB JI Am. Lab. PD JUN PY 1994 VL 26 IS 9 BP 16 EP & PG 0 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA NR477 UT WOS:A1994NR47700002 ER PT J AU HEEGAARD, NHH ROBEY, FA AF HEEGAARD, NHH ROBEY, FA TI THE EMERGING ROLE OF CAPILLARY ELECTROPHORESIS AS A TOOL FOR THE STUDY OF BIOMOLECULAR NONCOVALENT INTERACTIONS SO AMERICAN LABORATORY LA English DT Article ID AMYLOID-P COMPONENT; C-REACTIVE PROTEIN; ZONE ELECTROPHORESIS; PEPTIDES; BINDING; SEPARATION; VANCOMYCIN C1 NIH,CELLULAR DEV & ONCOL LAB,IMMUNOL UNIT,BETHESDA,MD 20892. RP HEEGAARD, NHH (reprint author), STATENS SERUM INST,DEPT AUTOIMMUNOL,BLDG 81,RM 528,ARTILLERIVEJ 5,DK-2300 COPENHAGEN,DENMARK. NR 29 TC 15 Z9 16 U1 0 U2 1 PU INT SCIENTIFIC COMMUN INC PI SHELTON PA PO BOX 870, 30 CONTROLS DRIVE, SHELTON, CT 06484-0870 SN 0044-7749 J9 AM LAB JI Am. Lab. PD JUN PY 1994 VL 26 IS 9 BP T28 EP X28 PG 0 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA NR477 UT WOS:A1994NR47700006 ER PT J AU LALLEY, TL AF LALLEY, TL TI SHAH,SALEEM,A. (1931-1992) - OBITUARY SO AMERICAN PSYCHOLOGIST LA English DT Item About an Individual RP LALLEY, TL (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD JUN PY 1994 VL 49 IS 6 BP 520 EP 520 PG 1 WC Psychology, Multidisciplinary SC Psychology GA NP303 UT WOS:A1994NP30300006 ER PT J AU CHOI, WJ CABIB, E AF CHOI, WJ CABIB, E TI THE USE OF DIVALENT-CATIONS AND PH FOR THE DETERMINATION OF SPECIFIC YEAST CHITIN SYNTHETASES SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SYNTHASE-3; ENZYME AB Saccharomyces cerevisiae contains three chitin synthetases, Chs1, Chs2, and Chs3, performing different physiological. functions but catalyzing the same reaction. It has been found that Ni2+ is a powerful inhibitor of Chs1 and Chs2 activity but has very little effect on the activity of Chs3, especially in the presence of Co2+ These results, together with the previous knowledge that Co2+ stimulates Chs2 and Chs3 but inhibits Chs1 and that the three synthetases differ in their pH optimum, have enabled us to formulate conditions for the specific determination of each synthetase in the presence of the others. (C) 1994 Academic Press, Inc. RP CHOI, WJ (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. NR 12 TC 68 Z9 69 U1 1 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN PY 1994 VL 219 IS 2 BP 368 EP 372 DI 10.1006/abio.1994.1278 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NN590 UT WOS:A1994NN59000025 PM 8080094 ER PT J AU FLORIS, A DINO, M JACOBOWITZ, DM MUGNAINI, E AF FLORIS, A DINO, M JACOBOWITZ, DM MUGNAINI, E TI THE UNIPOLAR BRUSH CELLS OF THE RAT CEREBELLAR CORTEX AND COCHLEAR NUCLEUS ARE CALRETININ-POSITIVE - A STUDY BY LIGHT AND ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY SO ANATOMY AND EMBRYOLOGY LA English DT Article DE CALCIUM BINDING PROTEINS; RAT-302 CELL; PALE CELL; GOLGI CELL; VESTIBULO-CEREBELLUM ID CALCIUM-BINDING PROTEINS; IMMUNOHISTOCHEMICAL LOCALIZATION; CHOLINE-ACETYLTRANSFERASE; CHROMOGRANIN-A; GOLGI CELLS; GUINEA-PIG; NEURONS; CAT; BRAIN; IMMUNOREACTIVITY AB Cell class-specific markers are powerful tools for the study of individual neuronal populations. The peculiar unipolar brush cells of the mammalian cerebellar cortex have only recently been definitively identified by means of the Golgi method, and we have explored markers of cerebellar neurons with the purpose of facilitating the analysis of this new cell population and, especially, its distribution and ultrastructural features. By light microscopic immunocytochemistry, we demonstrate that, in the rat, the unipolar brush cells are the cortical neurons that are most densely immunostained with antiserum to calretinin, a recently discovered calcium-binding protein. The unipolar brush cells are highly concentrated in the flocculo-nodular lobe, the ventral uvula and the ventral paraflocculus, occur at relatively high density in the lingula, at moderate-to-low density in other folia of the vermis and in the narrow intermediate cortex, and at low to very low density, with the exception of a few hot spots, in the lateral regions of the cerebellar hemispheres and in the dorsal paraflocculus. Unipolar brush cells are also found in the cochlear nucleus. In addition to the unipolar brush cells, calretinin antibody distinctly stains certain messy fibers, and weakly to moderately stains other cerebellar elements, such as granule neurons and climbing fibers. In the lobules containing high densities of unipolar brush cells, the granule cell bodies and the parallel fibers are much less immunoreactive, and there are many more densely immunostained messy fibers than in the lobules, where these cells are rare, which suggests some relationships between these elements. In the cerebellar nuclei, small neurons are densely immunostained, while large neurons are immunonegative. The unipolar brush cells reside nearly exclusively in the granular layer. They are small neurons, intermediate in size between granule cells and Golgi cells, and their features are remarkably similar across all lobules. They usually have a single, relatively thick dendrite of varying length that terminates in a brush-like tip consisting of several short branchlets. Utilizing a pre-embedding protocol, we have identified unipolar brush cells with the electron microscope. The cytoplasm of these cells is partially obscured by the electron dense product of calretinin immunoreaction in all regions of the soma and processes. The cells are often covered with non-synaptic appendages and contain a peculiar cytoplasmic inclusion consisting of ringlet subunits. Other characteristic components are numerous neurofilaments, mitochondria and large, dense-core vesicles. Individual brushes enter one or two glomeruli, where the dendritic branchlets establish an unusually extensive synapse with messy fiber rosettes. In addition to their contact with the messy rosettes, the branchlets are postsynaptic to boutons presumably belonging to the axonal plexus of Golgi cells and are also presynaptic to small dendrites, displaying small, clear synaptic vesicles at the site of contact. The distinct calretinin-like immunoreactivity of the unipolar brush cells may be related to strong calcium influx at their extensive synapses with the messy fiber rosettes. C1 UNIV CONNECTICUT,BIOBEHAV SCI GRAD DEGREE PROGRAM,NEUROMORPHOL LAB,STORRS,CT 06269. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU NIDCD NIH HHS [DC 01805]; NINDS NIH HHS [NS 09904] NR 60 TC 107 Z9 107 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD JUN PY 1994 VL 189 IS 6 BP 495 EP 520 PG 26 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA NU522 UT WOS:A1994NU52200004 PM 7978355 ER PT J AU KERR, GS HALLAHAN, CW GIORDANO, J LEAVITT, RY FAUCI, AS ROTTEM, M HOFFMAN, GS AF KERR, GS HALLAHAN, CW GIORDANO, J LEAVITT, RY FAUCI, AS ROTTEM, M HOFFMAN, GS TI TAKAYASU ARTERITIS SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NORTH-AMERICAN PATIENTS; SURGICAL-TREATMENT; ANGIOGRAPHIC FINDINGS; DISEASE; AORTOARTERITIS; GRANULOMATOSIS; INVOLVEMENT; AORTITIS; METHOTREXATE; SARCOIDOSIS AB Objective: To evaluate prospectively the clinical features, angiographic findings, and response to treatment of patients with Takayasu arteritis. Design: 60 patients with Takayasu arteritis were studied at the National Institute of Allergy and Infectious Diseases between 1970 and 1990 and were followed for 6 months to 20 years (median follow-up, 5.3 years). Measurements: Data on clinical features, angiographic and laboratory findings, disease course, and response to therapy were all recorded and stored in a computer-based retrieval system. Setting: The Warren Magnuson Clinical Center of the National Institutes of Health. Results: In our series of patients, Takayasu arteritis was more common in Asian persons compared with persons from other racial groups. Females (97%) were most frequently affected. The median age at disease onset was 25 years. Juveniles had a delay in diagnosis that was about four times that of adults. The clinical presentation ranged from asymptomatic to catastrophic with stroke. The most common clinical finding was a bruit. Hypertension was most often associated with renal artery stenosis. Only 33% of all patients had systemic symptoms on presentation. Sixty-eight percent of patients had extensive vascular disease; stenotic lesions were 3.6-fold more common than were aneurysms (98% compared with 27%). The erythrocyte sedimentation rate was not a consistently reliable surrogate marker of disease activity. Surgical bypass biopsy specimens from clinically inactive patients showed histologically active disease in 44% of patients. Although clinically significant palliation usually occurred after angioplasty or bypass of severely stenotic vessels, restenosis was common. Medical therapy was required for 80% of patients, whereas 20% had monophasic self-limiting disease. Immunosuppressive treatment with glucocorticoids alone or in combination with a cytotoxic agent failed to induce remission in one fourth of patients; about half of those who achieved remission later relapsed. Conclusions: In North America, Takayasu arteritis is a rare disease. It is heterogeneous in presentation, progression, and response to therapy. Current laboratory markers of disease activity are insufficiently reliable to guide management. Most patients require repeated and, at times, prolonged courses of therapy. Although mortality was low, substantial morbidity occurred in most patients. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV HOSP,WASHINGTON,DC 20037. NR 63 TC 810 Z9 876 U1 3 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1994 VL 120 IS 11 BP 919 EP 929 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA NN110 UT WOS:A1994NN11000004 PM 7909656 ER PT J AU LANE, HC LAUGHON, BE FALLOON, J KOVACS, JA DAVEY, RT POLIS, MA MASUR, H AF LANE, HC LAUGHON, BE FALLOON, J KOVACS, JA DAVEY, RT POLIS, MA MASUR, H TI RECENT ADVANCES IN THE MANAGEMENT OF AIDS-RELATED OPPORTUNISTIC INFECTIONS SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTIDRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-AVIUM COMPLEX; PLACEBO-CONTROLLED TRIAL; TOXOPLASMA-GONDII; CYTOMEGALOVIRUS RETINITIS; HIV-INFECTION; TRIMETHOPRIM-SULFAMETHOXAZOLE; RANDOMIZED TRIAL AB Secondary infections remain the leading cause of death in patients with the acquired immunodeficiency syndrome (AIDS). Dealing with the rapidly evolving spectrum of infectious problems seen in patients with AIDS requires knowledge of current therapeutic and prophylactic strategies. Through an extensive preclinical trials network supported by both industry and government, an increasing number of new agents are being identified and rapidly moved into clinical trials. Several agents are now available to treat diseases caused by Pneumocystis carinii, and corticosteroids have become a useful adjunct to antimicrobial agents in the treatment of P. carinii pneumonia. Although the treatment of toxoplasmosis remains a challenge, alternatives to sulfadiazine and pyrimethamine are now available. Mycobacterial infections, particularly with Mycobacterium tuberculosis, have become an increasing problem for patients with AIDS, and both old and new combination drug regimens are being used. Cytomegalovirus disease, until recently an untreatable problem, can now at least be partially managed with antiviral agents. The use of more complete prophylactic regimens may decrease the morbidity and mortality from opportunistic infections. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP LANE, HC (reprint author), NIAID,BLDG 10,ROOM 11B09,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 76 TC 57 Z9 58 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1994 VL 120 IS 11 BP 945 EP 955 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA NN110 UT WOS:A1994NN11000007 PM 7909657 ER PT J AU MILETICH, RS BANKIEWICZ, KS QUARANTELLI, M PLUNKETT, RJ FRANK, J KOPIN, IJ DICHIRO, G AF MILETICH, RS BANKIEWICZ, KS QUARANTELLI, M PLUNKETT, RJ FRANK, J KOPIN, IJ DICHIRO, G TI MRI DETECTS ACUTE DEGENERATION OF THE NIGROSTRIATAL DOPAMINE SYSTEM AFTER MPTP EXPOSURE IN HEMIPARKINSONIAN MONKEYS SO ANNALS OF NEUROLOGY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; PARKINSONISM-INDUCING NEUROTOXIN; BRAIN EDEMA; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; RHESUS-MONKEY; PRIMATE BRAIN; ASTROCYTE RESPONSE; GLOBUS-PALLIDUS; MOUSE-BRAIN; RAT-BRAIN AB Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cause an acute chemical toxicity resulting in a parkinsonian state in humans and nonhuman primates. We wished to assess whether the toxicity from MPTP is associated with changes on magnetic resonance images of brain structures containing dopamine neuronal processes or with disrupture of the blood-brain barrier. Normal rhesus monkeys and monkeys at various times after being subjected to unilateral intracarotid injection of MPTP (0.4 mg/kg) were studied with magnetic resonance imaging using T1- and T2-weighted spin-echo and gradient-echo sequences. Disrupture of the blood-brain barrier was assessed also with magnetic resonance imaging after administration of gadolinium-diethylenetriamine pentaacetic acid. Parkinsonian symptoms contralateral to the infused carotid usually appeared within 1 day after MPTP exposure, reaching their peak severity by 7 days, when all monkeys showed clear clinical abnormalities. Magnetic resonance imaging changes developed in concomitance with the clinical signs and were characterized by increased signal intensity on T2-weighted images as well as decreased intensity on T1-weighted images of the ipsilateral caudate and putamen. T2 hyperintensity was also present just dorsal to the pars compacta of the substantia nigra, in the region of the proximal nigrostriatal tract. All magnetic resonance imaging changes dissipated in the next 2 weeks. There were no abnormalities at any time in the globus pallidus, nucleus actumbens, and other structures innervated by the mesocorticolimbic dopamine system. After MPTP exposure, there was no evidence of blood-brain barrier disrupture, suggesting that vasogenic edema was an unlikely factor in the production of the observed abnormalities. The signal intensity changes on magnetic resonance images are most probably asociated with cytotoxic edema caused by the acute MPTP-induced degeneration of nigrostriatal dopamine nerve terminals and axons. Follow-up by magnetic resonance imaging, to 3 years after MPTP infusion, failed to reveal any residual abnormalities. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD. RP MILETICH, RS (reprint author), NIH,DIAGNOST RADIOL RES LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 1C451,BETHESDA,MD 20892, USA. RI Quarantelli, Mario/A-6154-2009; OI Quarantelli, Mario/0000-0001-7836-454X NR 57 TC 23 Z9 24 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1994 VL 35 IS 6 BP 689 EP 697 DI 10.1002/ana.410350609 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NQ973 UT WOS:A1994NQ97300008 PM 8210225 ER PT J AU PASS, HI AF PASS, HI TI MALIGNANT PLEURAL MESOTHELIOMA - THE THORACIC SURGEON AND GENE-THERAPY SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID GROWTH FACTOR-I; CELLS; BETA RP PASS, HI (reprint author), NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,RM 2B07,BETHESDA,MD 20892, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1994 VL 57 IS 6 BP 1383 EP 1384 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NT346 UT WOS:A1994NT34600001 PM 8010776 ER PT J AU POGREBNIAK, HW WITT, CJ TERRILL, R KRANDA, K TRAVIS, WD ROSENBERG, SA PASS, HI AF POGREBNIAK, HW WITT, CJ TERRILL, R KRANDA, K TRAVIS, WD ROSENBERG, SA PASS, HI TI ISOLATED LUNG PERFUSION WITH TUMOR-NECROSIS-FACTOR - A SWINE MODEL IN PREPARATION OF HUMAN TRIALS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 04-06, 1993 CL PANAMA CITY BEACH, FL SP SO THORAC SURG ASSOC ID FACTOR-ALPHA; PULMONARY-EDEMA; INTERLEUKIN-2; HYPERTHERMIA; COMBINATION; MECHANISMS; EFFICACY; SARCOMA; CANCER AB Isolated lung perfusion with tumor necrosis factor (TNF) potentially could deliver high doses of drug and avoid systemic toxicity in patients with unresectable lung cancer or metastases. We investigated the feasibility of isolated lung perfusion with TNF in a pig model. Eleven animals had left-sided isolated lung perfusion with no TNF (n = 3), 40 mu g/kg TNF (n = 2), 80 mu g/kg TNF (n = 3), and 40 mu g/kg TNF at moderate (39.5 degrees C) hyperthermia (n = 3). Hemodynamic monitoring and measurement of systemic and pulmonary circuit TNF levels were performed. Surviving animals were electively sacrificed a minimum of 6 months after isolated lung perfusion. All sham-perfused pigs survived. Isolated lung perfusion elevated pulmonary artery pressure, decreased cardiac output, and had minimal effects on mean pressure (15 +/- 0 versus 32 +/- 8 mm Hg, 4.5 +/- 1.1 versus 3.03 +/- 0.03 L/min, 67 +/- 11 versus 61 +/- 2 mm Hg; before versus after 90 minutes of isolated lung perfusion). Both 40 mu g/kg animals and 2 of the 3 hyperthermic perfusion pigs survived, with 1 requiring pneumonectomy. Of the three 80 mu g/kg animals, 1 survived, 1 died, and 1 required pneumonectomy. Survivors, compared with dying animals, had lower systemic/pulmonary TNF ratios and lower peak systemic TNF levels. All surviving pigs were electively sacrificed. These data justify phase I human protocols of isolated lung perfusion with TNF and hyperthermia; however, intraoperative leak rates must be monitored to ensure pulmonary isolation because systemic TNF levels may dictate treatment morbidity/mortality. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,ANIM SCI LAB,BETHESDA,MD 20892. NR 23 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1994 VL 57 IS 6 BP 1477 EP 1483 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NT346 UT WOS:A1994NT34600017 PM 8010790 ER PT J AU LIEBMANN, J COOK, JA TEAGUE, D FISHER, J MITCHELL, JB AF LIEBMANN, J COOK, JA TEAGUE, D FISHER, J MITCHELL, JB TI CYCLOHEXIMIDE INHIBITS THE CYTOTOXICITY OF PACLITAXEL (TAXOL(R)) SO ANTI-CANCER DRUGS LA English DT Article DE ANTAGONISM; CELL CYCLE; CYCLOHEXIMIDE; PACLITAXEL ID PHASE-II; TOXICITY; AGENT; ABROGATION; ETOPOSIDE; MITOSIS; CANCER; CELLS AB Treatment of human breast (MCF-7) and lung (A549) adenocarcinoma cell lines with 10 mug/ml cycloheximide provided substantial protection from paclitaxel-induced cytotoxicity. Addition of cycloheximide to cells at 0, 6, 12 or 18 h into a 24 h exposure to paclitaxel resulted in cytotoxicity similar to that found in cells treated with paclitaxel alone for only 0, 6, 12 or 18 h, respectively. DNA flow cytometry showed that paclitaxel blocked cells in G2/M. Mitotic index studies demonstrated that paclitaxel arrested cells in mitosis and that prolonged exposure to paclitaxel resulted in the development of multiple micronuclei. Concurrent incubation of cells in cycloheximide prevented the development of a G2/M block, mitotic arrest and micronuclei formation. The addition of cycloheximide to cells at 6 or 12 h into a 24 h exposure to paclitaxel reduced the degree of G2/M block to that produced by incubation of cells in paclitaxel alone for only 6 or 12 h. Mitotic index studies confirmed that cells treated with cycloheximide during paclitaxel exposure had a marked reduction in the percentage of cells in mitosis. However, the percentage of paclitaxel-treated cells which had multiple micronuclei was increased in cells treated with cycloheximide. These results indicate that entry into mitosis is a prerequisite for paclitaxel-induced cytotoxicity and that cycloheximide reduces cytotoxicity due to paclitaxel by preventing cells from entering mitosis. However, once cells have entered mitosis in the presence of paclitaxel, protein synthesis is not required for the development of multiple micronuclei and cytotoxicity. RP LIEBMANN, J (reprint author), NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 12 Z9 13 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUN PY 1994 VL 5 IS 3 BP 287 EP 292 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NQ332 UT WOS:A1994NQ33200004 PM 7919452 ER PT J AU FIGG, WD WALLS, RG COOPER, MR THIBAULT, A SARTOR, O MCCALL, NA MYERS, CE SAMID, D AF FIGG, WD WALLS, RG COOPER, MR THIBAULT, A SARTOR, O MCCALL, NA MYERS, CE SAMID, D TI IN-VITRO ANTITUMOR EFFECT OF HYDROXYUREA ON HORMONE-REFRACTORY PROSTATE-CANCER CELLS AND ITS POTENTIATION BY PHENYLBUTYRATE SO ANTI-CANCER DRUGS LA English DT Article DE HYDROXYUREA; PHENYLBUTYRATE; PROSTATE CANCER ID DIFFERENTIATION; PHENYLACETATE AB Previous clinical trials have suggested that hydroxyurea may possess some activity against prostate cancer. The in vitro antiproliferative activity of hydroxyurea was evaluated in three hormone-refractory prostate cancer cell lines, PC-3, DU-145 and PC-3M. Fifty-percent inhibition of growth in all three cell lines required prolonged (120 h) exposure to hydroxyurea at a concentration of approximately 100 muM. Using pharmacokinetic data obtained during the course of a clinical trial of hydroxyurea, we simulated a dosing regimen that would sustain plasma drug concentrations above 100 muM for 120 h (1 g loading dose, followed by 500 mg every 6 h for 5 days in a 70 kg man). Since this dosing regimen is likely to generate an unacceptable degree of myelosuppression, in vitro combination studies were conducted with hydroxyurea and phenylbutyrate, a new differentiating agent with no myelosuppressive effects. These studies resulted in a reduction of the hydroxyurea concentration necessary for 50% growth inhibition (50 muM of hydroxyurea plus 0.5 mM of phenylbutyrate). A regimen designed to achieve that hydroxyurea concentration (400 mg loading dose, followed by 200 mg every 6 h for 5 days) should be clinically achievable. Based on these results, this combination deserves further evaluation in patients with stage D prostate cancer. RP FIGG, WD (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 5A01,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 25 TC 13 Z9 13 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUN PY 1994 VL 5 IS 3 BP 336 EP 342 DI 10.1097/00001813-199406000-00012 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NQ332 UT WOS:A1994NQ33200012 PM 7919459 ER PT J AU TIFFANY, LJ DOBBS, D GARMESTANI, K RAUBITSCHEK, A TINUBU, A BRECHBIEL, MW GOFFMAN, T GANSOW, OA WALDMANN, TA KOZAK, RW AF TIFFANY, LJ DOBBS, D GARMESTANI, K RAUBITSCHEK, A TINUBU, A BRECHBIEL, MW GOFFMAN, T GANSOW, OA WALDMANN, TA KOZAK, RW TI RADIOLABELED CHX(B)-2E4 IS STABLE IN-VIVO AND IS A SUITABLE IMMUNOCONJUGATE FOR TESTING ALPHA-PARTICLE-EMITTING BISMUTH RADIONUCLIDES IN INTERLEUKIN-2 RECEPTOR TARGETED IMMUNOTHERAPY SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article ID TAC MONOCLONAL-ANTIBODY; T-CELLS; RADIOIMMUNOTHERAPY; TRANSPLANTATION; STREPTAVIDIN; EXPRESSION; SURVIVAL; SUBUNIT; TUMOR; MICE AB A murine model system has been established to assess immunotherapeutic approaches to treating interleukin-2 receptor (IL-2R) expressing malignancies. A rat IgG(2c) anti-murine p55 lL-2R monoclonal antibody (2E4) was successfully chelate coupled and radiolabelled with either Indium-lll or Bismuth-206 while retaining full immunoreactivity. The chelating agent used in these studies was p(SCNBZ) CHX(B) DTPA. Indium-111 labeled 2E4 was used to test the in vivo behavior of the immunoconjugate and pre-select murine tumor lines based on in vivo radiolabel uptake. The CHX(B)-2E4 MAb was labelled with either Bismuth-206 or iodine-131 and the two independently radiolabelled antibodies given simultaneously to tumor-bearing nude mice. Both isotopes were found to have equivalent blood clearance and tissue distributions. In addition, 100 percent of the bismuth activity in 1 and 4 hour postinjection serum samples was able to bind to IL-2R expressing cells, while 3 percent bound to an equivalent number of IL-2R negative cells. The time course of in vivo tumor targeting indicated that 25-35 percent of the i.v. injected dose per gram tissue (ID/g) was taken up by a subcutaneous IL-2R positive murine solid tumor (EL4J3.4) by 24 h post-injection. In contrast, 8 percent (ID/g) was taken up by the IL-2R receptor negative parental tumor (EL4J). Hence, radiolabeled CHX(B)-2E4 is stable in vivo and is a suitable immunoconjugate for testing alpha-emitting bismuth radionuclides in anti-IL-2R immunotherapy. C1 US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NR 23 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD SUM PY 1994 VL 7 IS 2 BP 99 EP 115 PG 17 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA NW260 UT WOS:A1994NW26000001 ER PT J AU BERENGUER, J ALI, NM ALLENDE, MC LEE, J GARRETT, K BATTAGLIA, S PISCITELLI, SC RINALDI, MG PIZZO, PA WALSH, TJ AF BERENGUER, J ALI, NM ALLENDE, MC LEE, J GARRETT, K BATTAGLIA, S PISCITELLI, SC RINALDI, MG PIZZO, PA WALSH, TJ TI ITRACONAZOLE FOR EXPERIMENTAL PULMONARY ASPERGILLOSIS - COMPARISON WITH AMPHOTERICIN-B, INTERACTION WITH CYCLOSPORINE-A, AND CORRELATION BETWEEN THERAPEUTIC RESPONSE AND ITRACONAZOLE CONCENTRATIONS IN PLASMA SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE ASPERGILLOSIS; SYSTEMIC MYCOSES; ANTIFUNGAL; INVITRO; CRYPTOCOCCOSIS; AZOLES; PHARMACOKINETICS; INVIVO AB Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls, At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (log(10) CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 mu g/ml; range, <0.5 to 16.8 mu g/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden of A. fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden of A, fumigatus. This model demonstrated that levels in plasma of greater than 6 mu g/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 mu g/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,PHARMACOKINET RES LAB,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78229. AUDIE L MURPHY MEM VET ADM MED CTR,LAB SERV,SAN ANTONIO,TX 78221. OI Berenguer, Juan/0000-0001-8541-8200 NR 32 TC 60 Z9 61 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1994 VL 38 IS 6 BP 1303 EP 1308 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NN770 UT WOS:A1994NN77000015 PM 8092829 ER PT J AU GLASGOW, WC ELING, TE AF GLASGOW, WC ELING, TE TI STRUCTURE-ACTIVITY RELATIONSHIP FOR POTENTIATION OF EGF-DEPENDENT MITOGENESIS BY OXYGENATED METABOLITES OF LINOLEIC-ACID SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; ARACHIDONIC-ACID; FATTY-ACIDS; 13-HYDROXYOCTADECADIENOIC ACID; LIPOXYGENASE METABOLITES; GLUTATHIONE-PEROXIDASE; MAMMARY-TUMOR; RAT-LIVER; CELLS AB Epidermal growth factor induces the oxygenation of linoleic acid in Syrian hamster embryo fibroblasts, and the lipoxygenase-derived products potentiate the mitogenic signal. We have further characterized the linoleate metabolites of growth factor-activated cells by chiral phase HPLC analysis. The primary product was identified as the pure (S) enantiomer of 13-hydroxyoctadecadienoic acid (HODE). In comparison to 13(R)-HODE isomer, only the biologically derived 13(S)-HODE was active in augmenting DNA synthesis as assessed by [H-3]thymidine incorporation. To extend these investigations, we defined the structural requirements of analogous lipid compounds necessary for stimulation of mitogenesis in these cells. Carbon-chain length, degree of unsaturation, type of oxidized functionality, position of oxygenated moiety, double-bond geometry, and chirality were all identified as factors that modulate the mitogenic activity of related compounds. The results demonstrate a high degree of specificity for (S)-isomer hydro(pero)xylinoleic acid metabolites in stimulating DNA synthesis and further define the relationship between linoleic acid metabolism and growth-factor-dependent cell growth. (C) 1994 Academic Press, Inc. RP GLASGOW, WC (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,MD E4-09,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1994 VL 311 IS 2 BP 286 EP 292 DI 10.1006/abbi.1994.1239 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NP638 UT WOS:A1994NP63800013 PM 8203891 ER PT J AU RETTIE, AE LAWTON, MP SADEQUE, AJM MEIER, GP PHILPOT, RM AF RETTIE, AE LAWTON, MP SADEQUE, AJM MEIER, GP PHILPOT, RM TI PROCHIRAL SULFOXIDATION AS A PROBE FOR MULTIPLE FORMS OF THE MICROSOMAL FLAVIN-CONTAINING MONOOXYGENASE - STUDIES WITH RABBIT FMO1, FMO2, FMO3, AND FMO5 EXPRESSED IN ESCHERICHIA-COLI SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ADULT HUMAN LIVER; STEREOSELECTIVE SULFOXIDATION; SUBSTRATE SPECIFICITIES; MONO-OXYGENASE; S-OXYGENATION; MOUSE-LIVER; LUNG; ENZYMES; CLONING; RAT AB Multiple forms of the microsomal flavin-containing monooxygenase (FMO) exist in rabbit tissues. In order to better understand the catalytic properties of these isoforms, we have expressed rabbit FMO1, FMO2, FMO3, and FMO5 in Escherichia coli and examined their kinetic parameters and prochiral selectivities for the sulfoxidation of methyl-, ethyl-, n-propyl-, and n-butyl-substituted p-tolyl sulfides. FMO1 and FMO2 exhibited high affinities for these substrates (K-m<10 mu M), in contrast to the low-affinity FMO3 form for which K-m values ranged between 100 and 280 mu M. FMO5 did not form quantifiable levels of sulfoxide metabolites at the concentrations used. The individual stereochemical metabolite profiles generated by FMO1, FMO2, and FMO3 were unique and served to distinguish among these three cDNA-expressed isoforms. To investigate the relationship between the kinetic parameters for the cDNA-expressed enzymes and the native microsomal enzymes, we examined the kinetics and stereoselectivity of metabolism of methyl p-tolyl sulfide by detergent-solubilized rabbit liver microsomes. We analyzed these data with respect to FMO1 and FMO3, the two predominant hepatic isoforms. Sulfoxidation of methyl p-tolyl sulfide by FMO1 and FMO3 solubilized from E. coli microsomes proceeded with apparent K(m)s of 18 and 270 mu M, respectively. FMO1 was essentially stereospecific for formation of (R)-methyl p-tolyl sulfoxide, whereas FMO3 generated this metabolite with little prochiral selectivity. Sulfoxidation of methyl p-tolyl sulfide by detergent-solubilized rabbit liver microsomes was best described by a two-enzyme model, with apparent K-m values of 11 and 340 mu M. The enantiomeric purity of the (R)-methyl p-tolyl sulfoxide metabolite, generated by detergent-solubilized rabbit liver microsomes, decreased progressively with increasing substrate concentration, from a high of 96% enantiomeric excess at a substrate concentration of 5 mu M to a low of 63% enantiomeric excess at a substrate concentration of 2 mM. The kinetic and stereochemical properties of the high-affinity and low-affinity components of detergent-solubilized rabbit liver microsomes were similar to those exhibited by cDNA-expressed FMO1 and FMO3, respectively. Therefore, methyl p-tolyl sulfide, used at the appropriate substrate concentrations, is useful for discriminating between FMO1- and FMO3-mediated catalysis in rabbit liver microsomal preparations. (C) 1994 Academic Press, Inc. C1 MED UNIV S CAROLINA,DEPT PHARMACEUT SCI,CHARLESTON,SC 29425. NIEHS,MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP RETTIE, AE (reprint author), UNIV WASHINGTON,DEPT MED CHEM,BG-20,SEATTLE,WA 98195, USA. FU NIGMS NIH HHS [GM43511] NR 37 TC 37 Z9 37 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1994 VL 311 IS 2 BP 369 EP 377 DI 10.1006/abbi.1994.1250 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NP638 UT WOS:A1994NP63800024 PM 8203899 ER PT J AU CHANG, TKH GONZALEZ, FJ WAXMAN, DJ AF CHANG, TKH GONZALEZ, FJ WAXMAN, DJ TI EVALUATION OF TRIACETYLOLEANDOMYCIN, ALPHA-NAPHTHOFLAVONE AND DIETHYLDITHIOCARBAMATE AS SELECTIVE CHEMICAL PROBES FOR INHIBITION OF HUMAN CYTOCHROMES P450 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN-LIVER-MICROSOMES; CDNA-DIRECTED EXPRESSION; SACCHAROMYCES-CEREVISIAE; THEOPHYLLINE METABOLISM; COUMARIN 7-HYDROXYLASE; RECOVERING ALCOHOLICS; ENZYMES; OXIDATION; RAT; IDENTIFICATION AB A variety of chemicals, including triacetyloleandomycin (TAO), alpha-naphthoflavone (ANF), and diethyldithiocarbamate (DDC), are widely used as inhibitory probes for select individual human cytochrome P450 (CYP) enzymes, despite the fact that the selectivity of these inhibitors has not been rigorously evaluated. In the present study we take advantage of recent advances in cDNA-directed human P450 expression to evaluate directly the P450 form selectivity of TAO, ANF, and DDC, using a panel of 10 individual cDNA-expressed human P450s. Under experimental conditions known to yield maximal TAO complexation with P450 hemoproteins, TAO (20 mu M) inhibited the catalytic activity of expressed CYPs 3A3, 3A4, and 3A5, whereas it did not affect CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, or 2E1 activity. ANF inhibited not only CYPs 1A1 and 1A2 (IC50 = 0.4-0.5 mu M), but it was also similarly effective against CYPs 2C8 and 2C9. Increasing the concentration of ANF to 10 mu M led to inhibition of CYP2A6 and CYP2B6. Although a previous study suggested that DDC is a selective inhibitor of CYP2E1, the present investigation shows that at concentrations required to inhibit CYP2E1 (IC50 approximate to 125 mu M when preincubated with NADPH), DDC also inhibited CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 3A3, and 3A4. Decreasing the concentration of DDC to 10 mu M, however, led to inhibition of CYP2A6 (65% inhibition) and CYP2B6 (50% inhibition), but none of the other p450s examined, including CYP2E1. Overall, these results establish that (a) TAO is a selective inhibitor of the human CYP3A subfamily; (b) ANF potently inhibits CYP2C8 and CYP2C9, in addition to CYPs 1A1 and 1A2; and (c) DDC cannot be employed as a diagnostic inhibitory probe for CYP2E1. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-49248] NR 46 TC 252 Z9 252 U1 4 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1994 VL 311 IS 2 BP 437 EP 442 DI 10.1006/abbi.1994.1259 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NP638 UT WOS:A1994NP63800033 PM 8203907 ER PT J AU BASILION, JP KENNEDY, MC BEINERT, H MASSINOPLE, CM KLAUSNER, RD ROUAULT, TA AF BASILION, JP KENNEDY, MC BEINERT, H MASSINOPLE, CM KLAUSNER, RD ROUAULT, TA TI OVEREXPRESSION OF IRON-RESPONSIVE ELEMENT-BINDING PROTEIN AND ITS ANALYTICAL CHARACTERIZATION AS THE RNA-BINDING FORM, DEVOID OF AN IRON-SULFUR CLUSTER SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID SYNTHASE MESSENGER-RNA; ERYTHROID 5-AMINOLEVULINATE SYNTHASE; REGULATORY FACTOR; CYTOSOLIC ACONITASE; TRANSLATIONAL CONTROL; IRE-BP; PURIFICATION; EXPRESSION; CLONING; CDNA AB The iron-responsive element-binding protein (IRE-BP) has been defined and identified as an RNA-binding protein found in iron-deprived eukaryotic cells. IRE-BP binds to stem-loop structures, iron-responsive elements (IREs), which are located in the untranslated regions of the mRNAs for several genes including ferritin, and the transferrin receptor. When bound, IRE-BP prevents ferritin translation and stabilizes the transferrin receptor transcript. When cells are iron replete, an iron-sulfur cluster is ligated to the IRE-BP, the protein loses RNA binding properties, and it acquires aconitase activity. Cytosolic aconitase from liver can be converted into the IRE-BP by oxidative removal of its Fe-S cluster. We describe here overexpression of IRE-BP in baculovirus-infected insect cells which yields IRE-BP devoid of an iron-sulfur cluster. We describe a one-step purification of the IRE-BP and a quantitative analysis of Fe, S2-, S-0, protein, and enzyme activity on IRE-BP, as obtained in cell lysates, after purification, and after reconstitution to active aconitase. On the average not more than 3% of the over-expressed purified protein contained an intact Fe-S cluster, and it was demonstrated that that cluster was not lost during purification. Scatchard analysis of RNA-binding data was compatible with a single high-affinity RNA-binding form of the IRE-BP. Active aconitase could be reconstituted from the purified IRE-BP obtained from the expression system by addition of iron, thiol, and sulfide, and the characteristic epr spectrum of the 3Fe form of cytosolic aconitase was obtained after ferricyanide oxidation of the reconstituted material. (C) 1994 Academic Press, Inc. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. MED COLL WISCONSIN,DEPT ANESTHESIOL,MILWAUKEE,WI 53226. MED COLL WISCONSIN,BIOPHYS RES INST,MILWAUKEE,WI 53226. FU NIGMS NIH HHS [GM 34812] NR 39 TC 35 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1994 VL 311 IS 2 BP 517 EP 522 DI 10.1006/abbi.1994.1270 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NP638 UT WOS:A1994NP63800044 PM 8203918 ER PT J AU KETY, SS WENDER, PH JACOBSEN, B INGRAHAM, LJ JANSSON, L FABER, B KINNEY, DK AF KETY, SS WENDER, PH JACOBSEN, B INGRAHAM, LJ JANSSON, L FABER, B KINNEY, DK TI MENTAL-ILLNESS IN THE BIOLOGICAL AND ADOPTIVE RELATIVES OF SCHIZOPHRENIC ADOPTEES - REPLICATION OF THE COPENHAGEN STUDY IN THE REST OF DENMARK SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SOCIAL-CLASS; DSM-III; DISORDERS; FAMILY AB Background: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called ''latent schizophrenia'' (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. Methods: We now report the results of a replication of that study in the rest of Denmark (the ''Provincial Sample''). Results: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined ''National Sample'' of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. Conclusions: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors. C1 UNIV UTAH,DEPT PSYCHIAT,SALT LAKE CITY,UT. KOMMUNEHOSP COPENHAGEN,INST PREVENT MED,COPENHAGEN,DENMARK. HVIDOVRE UNIV HOSP,DK-2650 HVIDOVRE,DENMARK. HOSP FJORDEN,ROSKILDE,DENMARK. HARVARD UNIV,MCLEAN HOSP,MAILMAN RES CTR,BELMONT,MA 02178. RP KETY, SS (reprint author), NIMH,INTRAMURAL RES PROGRAM,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 31 TC 209 Z9 213 U1 1 U2 30 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1994 VL 51 IS 6 BP 442 EP 455 PG 14 WC Psychiatry SC Psychiatry GA PF975 UT WOS:A1994PF97500001 PM 8192547 ER PT J AU NAVARRO, S CAVAZZANA, AO LLOMBARTBOSCH, A TRICHE, TJ AF NAVARRO, S CAVAZZANA, AO LLOMBARTBOSCH, A TRICHE, TJ TI COMPARISON OF EWINGS-SARCOMA OF BONE AND PERIPHERAL NEUROEPITHELIOMA - AN IMMUNOCYTOCHEMICAL AND ULTRASTRUCTURAL ANALYSIS OF 2 PRIMITIVE NEUROECTODERMAL NEOPLASMS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NEURON-SPECIFIC ENOLASE; ROUND-CELL TUMORS; SOFT-TISSUE; EXPRESSION; RHABDOMYOSARCOMA; CYTOKERATIN; BLASTOMA; DIFFERENTIATION; PROTEIN; FEATURES AB Ewing's sarcoma of bone (ESB) and peripheral neuroepithelioma (PN) are frequently considered to be different tumors. Some researchers have suggested that PN is morphologically a neuroectodermal Ewing's sarcoma. We sought to determine the extent of neuroectodermal features in conventional ESB on direct patient material (25 cases) and to compare these tumors with a similar group of readily diagnosed PNs (10 cases). Light microscopic, ultrastructural, and immunophenotypic parameters were assessed and compared for both groups. The avidin-biotin complex method was used. All tumors were antigenically intact since all stained for vimentin or at least one marker. Neuroectodermal antigens (neuron-specific enolase, Leu-7 [HNK-1], neurofilament 200 kd, and S100) were found in nine of 10 cases of PN and in 17 of 25 cases of ESB. In ESB, an atypical light microscopic appearance correlated with the presence of neuroectodermal features in most cases, but neuroectodermal phenotype was more frequent (68%) than morphological evidence of neuroectodermal differentiation (36%). These data support the concept that ESB and PN are both peripheral primitive neuroectodermal neoplasms, differing only in extent of neuroectodermal phenotype and morphological differentiation. C1 UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027. UNIV PADUA,DEPT PATHOL,I-35100 PADUA,ITALY. UNIV VALENCIA,DEPT PATHOL,E-46100 VALENCIA,SPAIN. NCI,PATHOL LAB,ULTRASTRUCT PATHOL SECT,BETHESDA,MD 20892. NR 44 TC 48 Z9 49 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUN PY 1994 VL 118 IS 6 BP 608 EP 615 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA NQ005 UT WOS:A1994NQ00500015 PM 8204006 ER PT J AU PATSCH, W SHARRETT, AR CHEN, IY LINLEE, YC BROWN, SA GOTTO, AM BOERWINKLE, E AF PATSCH, W SHARRETT, AR CHEN, IY LINLEE, YC BROWN, SA GOTTO, AM BOERWINKLE, E TI ASSOCIATIONS OF ALLELIC DIFFERENCES AT THE A-I/C-III/A-IV GENE-CLUSTER WITH CAROTID-ARTERY INTIMA-MEDIA THICKNESS AND PLASMA-LIPID TRANSPORT IN HYPERCHOLESTEROLEMIC-HYPERTRIGLYCERIDEMIC HUMANS SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE CAROTID ATHEROSCLEROSIS; HYPERLIPIDEMIA; APOLIPOPROTEINS; GENE EXPRESSION ID APOLIPOPROTEIN-C-III; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; FAMILIAL COMBINED HYPERLIPIDEMIA; TRIGLYCERIDE-RICH LIPOPROTEINS; FRAGMENT-LENGTH-POLYMORPHISMS; IMPROVED LIPOLYTIC EFFICIENCY; DNA POLYMORPHISMS; RAT-LIVER; ENZYMATIC DETERMINATION AB Individuals with elevated levels of plasma cholesterol and triglyceride may be at higher risk for coronary artery disease than those with isolated elevations of either cholesterol or triglyceride. Sequence variation in the A-I/C-III/A-IV gene cluster has been implicated in the etiology of some disorders associated with premature atherosclerosis and/or hypertriglyceridemias with or without elevations of cholesterol. This led to the hypothesis that allelic variation at this gene locus alters plasma lipid transport and affects susceptibility for atherosclerosis. The study population, from the Atherosclerosis Risk in Communities (ARIC) Study, consisted of 50 normolipidemic individuals, 48 subjects with elevated plasma cholesterol, 47 subjects with elevated plasma triglyceride, and 123 subjects with both elevated plasma cholesterol and triglyceride who were used to evaluate associations between an Xmn I polymorphic site 2.5 kilobase pairs (kbp) upstream of the structural gene for apolipoprotein (ape) A-I, intimal-medial thickening of the extracranial carotid arteries, and several plasma lipid factors. The relative allele frequencies of the 8.3-kbp allele and the 6.6-kbp allele were .86 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P=.034) and higher plasma levels of apoA-I, high-density lipoprotein (HDL) cholesterol, and HDL, cholesterol (P<.02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV, and E to A-IV in plasma (P<.05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P=.026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertriglyceridemic persons who are at higher risk for atherosclerosis than others with the same lipoprotein phenotype. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,CTR GENET,HOUSTON,TX. FU NHLBI NIH HHS [N01-HC55015, N01-HC55016, N01-HC55018] NR 76 TC 27 Z9 27 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUN PY 1994 VL 14 IS 6 BP 874 EP 883 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ536 UT WOS:A1994NQ53600004 PM 8199177 ER PT J AU HOCHBERG, MC FRIED, L SKINNER, A GURALNIK, J AF HOCHBERG, MC FRIED, L SKINNER, A GURALNIK, J TI VALIDITY OF MEASURES OF SEVERITY OF RHEUMATOID AND OSTEOARTHRITIS IN COMMUNITY-BASED STUDIES - THE WOMENS HEALTH AND AGING STUDY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R30 EP R30 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000126 ER PT J AU KATZ, P WHALEN, G KEHRL, JH AF KATZ, P WHALEN, G KEHRL, JH TI CHARACTERIZATION OF A PROTEIN-KINASE PREFERENTIALLY EXPRESSED IN GERMINAL CENTER B-LYMPHOCYTES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20007. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R21 EP R21 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000071 ER PT J AU LETHBRIDGECEJKU, M HOCHBERG, MC SCOTT, WW REICHLE, R ZONDERMAN, A COSTA, P PLATO, C TOBIN, JD AF LETHBRIDGECEJKU, M HOCHBERG, MC SCOTT, WW REICHLE, R ZONDERMAN, A COSTA, P PLATO, C TOBIN, JD TI ASSOCIATION OF KNEE PAIN WITH RADIOGRAPHIC FEATURES OF OSTEOARTHRITIS - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R29 EP R29 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000124 ER PT J AU RIDER, LG SANTINI, F HIRASAWA, N BEAVEN, MA AF RIDER, LG SANTINI, F HIRASAWA, N BEAVEN, MA TI DEXAMETHASONE INHIBITS TYROSINE PHOSPHORYLATION OF P42-MITOGEN-ACTIVATED PROTEIN (MAP) KINASE IN RESPONSE TO ACTIVATION BY THE HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTOR (FC-EPSILON-RI) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R10 EP R10 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000024 ER PT J AU BARRETT, AJ AF BARRETT, AJ TI BONE-MARROW TRANSPLANTATION FOR ACUTE LYMPHOBLASTIC-LEUKEMIA SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article ID TOTAL-BODY IRRADIATION; 1ST COMPLETE REMISSION; MINIMAL RESIDUAL DISEASE; VERSUS-HOST DISEASE; ACUTE LYMPHOCYTIC-LEUKEMIA; HLA-IDENTICAL SIBLINGS; PEDIATRIC-ONCOLOGY-GROUP; T-CELL DEPLETION; 2ND REMISSION; HEMATOLOGIC MALIGNANCIES RP BARRETT, AJ (reprint author), NHLBI, HEMATOL BRANCH, BONE MARROW TRANSPLANT UNIT, BETHESDA, MD 20892 USA. NR 97 TC 16 Z9 16 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD JUN PY 1994 VL 7 IS 2 BP 377 EP 401 DI 10.1016/S0950-3536(05)80209-4 PG 25 WC Hematology SC Hematology GA NW127 UT WOS:A1994NW12700011 PM 7803908 ER PT J AU HALLETT, M FIELDMAN, J COHEN, LG SADATO, N PASCUALLEONE, A AF HALLETT, M FIELDMAN, J COHEN, LG SADATO, N PASCUALLEONE, A TI INVOLVEMENT OF PRIMARY MOTOR CORTEX IN MOTOR IMAGERY AND MENTAL PRACTICE SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion RP HALLETT, M (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892, USA. NR 1 TC 39 Z9 39 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1994 VL 17 IS 2 BP 210 EP 210 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA NR754 UT WOS:A1994NR75400012 ER PT J AU THIER, P ERICKSON, RG DICHGANS, J AF THIER, P ERICKSON, RG DICHGANS, J TI A CORTICAL SUBSTRATE FOR MOTION PERCEPTION DURING SELF-MOTION SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID INDUCED VISUAL-MOTION; NEURONS; MONKEY C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. RP THIER, P (reprint author), UNIV TUBINGEN,DEPT NEUROL,W-7400 TUBINGEN 1,GERMANY. NR 6 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1994 VL 17 IS 2 BP 335 EP 335 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA NR754 UT WOS:A1994NR75400089 ER PT J AU WESTERGAARD, GC AF WESTERGAARD, GC TI LANGUAGE, TOOLS, AND NEUROBEHAVIORAL LATERALITY SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID MONKEYS CEBUS-APELLA; CAPUCHIN MONKEYS; MANUFACTURE; OBJECT; HAND; AREA RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,BLDG 112,NIHAC,ELMER SCH RD,POOLESVILLE,MD 20837, USA. NR 26 TC 5 Z9 5 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 1994 VL 17 IS 2 BP 360 EP 361 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA NR754 UT WOS:A1994NR75400097 ER PT J AU MURRAY, EA GAFFAN, D AF MURRAY, EA GAFFAN, D TI REMOVAL OF THE AMYGDALA PLUS SUBJACENT CORTEX DISRUPTS THE RETENTION OF BOTH INTRAMODAL AND CROSSMODAL ASSOCIATIVE MEMORIES IN MONKEYS SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID IMPAIRMENT FOLLOWING LESIONS; HIPPOCAMPAL-FORMATION; DISCONNECTION; MACACA AB Naive rhesus monkeys (Macaca mulatta) were trained preoperatively in an automated test apparatus on an auditory-visual (crossmodal) conditional task or on a visual-visual (intramodal) conditional task that involved learning a fixed set of stimulus-stimulus associations or paired associates. After having learned their respective tasks, each monkey received bilateral removal of the amygdala plus subjacent cortex. The 2 experimental groups showed equally poor retention of the stimulus-stimulus associations and subsequently relearned their respective crossmodal and intramodal associations at the same rate. These data argue against the idea that the amygdala is specialized for crossmodal associations. Instead, the data indicate that the amygdala or its underlying cortex, or both, play a more generalized role in stimulus-stimulus associative memory. C1 UNIV OXFORD,DEPT EXPTL PSYCHOL,OXFORD OX1 3UD,ENGLAND. RP MURRAY, EA (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 25 TC 26 Z9 26 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 1994 VL 108 IS 3 BP 494 EP 500 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA NT438 UT WOS:A1994NT43800006 PM 7917043 ER PT J AU KIRKPATRICK, B CARTER, CS NEWMAN, SW INSEL, TR AF KIRKPATRICK, B CARTER, CS NEWMAN, SW INSEL, TR TI AXON-SPARING LESIONS OF THE MEDIAL NUCLEUS OF THE AMYGDALA DECREASE AFFILIATIVE BEHAVIORS IN THE PRAIRIE VOLE (MICROTUS-OCHROGASTER) - BEHAVIORAL AND ANATOMICAL SPECIFICITY SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID HAMSTER SEXUAL-BEHAVIOR; MATERNAL-BEHAVIOR; PEROMYSCUS-CALIFORNICUS; VOMERONASAL ORGAN; OLFACTORY TRACT; FEMALE RAT; SYSTEM; PENNSYLVANICUS; RESPONSIVENESS; VASOPRESSIN AB The neural basis of affiliative behavior was examined in the prairie vole, a rodent that exhibits high levels of social contact and paternal behavior. In the first study, the axon-sparing excitotoxin N-methyl-D,L-aspartic acid (NMA) produced lesions in the basolateral nucleus of the amygdala or the corticomedial amygdala. Males with corticomedial lesions showed significantly less contact with a familiar adult female and a pup when compared with males with lesions of the basolateral nucleus or controls. This behavioral change was not associated with changes in exploratory behavior, motor function, performance in an olfactory task, fearfulness, physical well-being, or body temperature. In a second study, NMA lesions restricted to the medial nucleus also decreased paternal behavior. Neurons in the medial nucleus of the amygdala appear to be essential for the normal expression of paternal care in this species. C1 UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. UNIV MICHIGAN,SCH MED,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. NIH,NEUROPHYSIOL LAB,POOLESVILLE,MD. RP KIRKPATRICK, B (reprint author), UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,POB 21247,BALTIMORE,MD 21228, USA. FU NIMH NIH HHS [MH00925] NR 60 TC 63 Z9 65 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 1994 VL 108 IS 3 BP 501 EP 513 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA NT438 UT WOS:A1994NT43800007 PM 7917044 ER PT J AU TIRELLI, E WITKIN, JM AF TIRELLI, E WITKIN, JM TI TRANSIENT HYPERSENSITIVITY TO APOMORPHINE-INDUCED GNAWING AFTER TERMINATION OF ACUTE EFFECTS OF A SINGLE HIGH-DOSE OF COCAINE SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE APOMORPHINE; CLIMBING; COCAINE; DEPENDENCE; GNAWING; HYPERSENSITIVITY; LOCOMOTION; MICE; SENSITIZATION; WITHDRAWAL ID DOPAMINE DEPLETION HYPOTHESIS; BASAL EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; LOCOMOTOR STIMULATION; STEREOTYPED BEHAVIORS; RECEPTOR ACTIVATION; MOUSE STRIATUM; RAT STRIATUM; MICE; WITHDRAWAL AB Physical dependence on cocaine has not been fully characterized or definitively identified. Since behavioral changes are typically not observed after cocaine withdrawal in animal studies, we sought to amplify or reveal any such changes in behavior by administration of the dopamine agonist apomorphine. C57BL/6J mice were tested for behavioral effects (climbing, gnawing, and locomotor activity) of apomorphine at various times after acute administration of cocaine. When tested at a time when most of the administered cocaine had disappeared from brain and when behavioral effects of cocaine had dissipated, at 2 and 4 h post cocaine administration, effects of apomorphine on gnawing were increased 4-fold. This dopaminergic hypersensitivity was induced by acute treatment with doses of 15 mg/kg cocaine and higher. Effects of apomorphine were not enhanced at later time periods (6 to 24 h after cocaine), indicating a rapid waning of the dopaminergic hypersensitivity. Hypersensitivity to apomorphine was not further augmented by 8 days of daily cocaine injections. Cocaine did not influence climbing acid hypomotility induced by apomorphine 4 h after its injection, demonstrating selectivity in the behavioral expression of the dopaminergic hypersensitivity. Further, cocaine did not induce sensitization to its own effects indicating that the hypersensitivity to apomorphine was not due to a typical sensitization phenomenon. The results of these experiments demonstrate a short-lived dopaminergic supersensitivity after termination of the acute effects of a single high dose of cocaine, the implications of which remain to be discovered. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD 21224. NR 70 TC 5 Z9 5 U1 2 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUN PY 1994 VL 5 IS 3 BP 289 EP 298 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA NR709 UT WOS:A1994NR70900007 ER PT J AU KERR, BM THUMMEL, KE WURDEN, CJ KLEIN, SM KROETZ, DL GONZALEZ, FJ LEVY, RH AF KERR, BM THUMMEL, KE WURDEN, CJ KLEIN, SM KROETZ, DL GONZALEZ, FJ LEVY, RH TI HUMAN LIVER CARBAMAZEPINE METABOLISM - ROLE OF CYP3A4 AND CYP2C8 IN 10,11-EPOXIDE FORMATION SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYTOCHROME P450; CYP3A4; CYP2C8; CARBAMAZEPINE; DRUG METABOLISM; HUMAN LIVER MICROSOMES ID IMPORTANT DRUG-INTERACTIONS; ERYTHROMYCIN INTERACTION; CYTOCHROME-P-450; HYDROXYLATION; MICROSOMES; OXIDATION; ACETAMINOPHEN; PRINCIPLES; KINETICS; OXIDASE AB A number of drugs inhibit the metabolism of carbamazepine catalyzed by cytochrome P450, sometimes resulting in carbamazepine intoxication. However, there is little information available concerning the identity of the specific isoforms of P450 responsible for the metabolism of this drug. This study addressed the role of CYP3A4 in the formation of carbamazepine-10,11-epoxide, the major metabolite of carbamazepine. Results of the study showed that: (1) purified CYP3A4 catalyzed 10,11-epoxidation; (2) cDNA-expressed CYP3A4 catalyzed 10,11-epoxidation (V-max = 1730 pmol/min/nmol P450, K-m = 442 mu M); (3) the rate of 10,11-epoxidation correlated with CYP3A4 content in microsomes from sixteen human livers (r(2) = 0.57, P < 0.001); (4) triacetyloleandomycin and anti-CYP3A4 IgG reduced 10,11-epoxidation to 31 +/- 6% (sixteen livers) and 43 +/- 2% (four livers) of control rates, respectively; and (5) microsomal 10,11-epoxidation but not phenol formation was activated 2- to 3-fold by alpha-naphthoflavone and progesterone and by carbamazepine itself (substrate activation). These findings indicate that CYP3A4 is the principal catalyst of 10,11-epoxide formation in human liver. Experiments utilizing a panel of P450 isoform selective inhibitors also suggested a minor involvement of CYP2C8 in liver microsomal 10,11-epoxidation. Epoxidation by CYP2C8 was confirmed in incubations of carbamazepine with cDNA-expressed CYP2C8. The role of CYP3A4 in the major pathway of carbamazepine elimination is consistent with the number of inhibitory drug interactions associated with its clinical use, interactions that result from a perturbation of CYP3A4 catalytic activity. C1 UNIV WASHINGTON,DEPT PHARMACEUT,SEATTLE,WA 98195. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM07750, GM32165]; NINDS NIH HHS [NS17111] NR 45 TC 313 Z9 321 U1 2 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 1 PY 1994 VL 47 IS 11 BP 1969 EP 1979 DI 10.1016/0006-2952(94)90071-X PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NR730 UT WOS:A1994NR73000006 PM 8010982 ER PT J AU SHARIEF, FS LI, SSL AF SHARIEF, FS LI, SSL TI NUCLEOTIDE-SEQUENCE OF HUMAN PROSTATIC ACID-PHOSPHATASE ACPP GENE, INCLUDING 7 ALU REPEATS SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 8 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUN PY 1994 VL 33 IS 3 BP 561 EP 565 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW561 UT WOS:A1994NW56100017 PM 7951074 ER PT J AU SHARIEF, FS MOHLER, JL SHARIEF, Y LI, SSL AF SHARIEF, FS MOHLER, JL SHARIEF, Y LI, SSL TI EXPRESSION OF HUMAN PROSTATIC ACID-PHOSPHATASE AND PROSTATE-SPECIFIC ANTIGEN GENES IN NEOPLASTIC AND BENIGN TISSUES SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID MOLECULAR-CLONING; CDNA CLONING; SEQUENCES; RNA C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT SURG,DIV UROL,CHAPEL HILL,NC 27599. NR 16 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUN PY 1994 VL 33 IS 3 BP 567 EP 574 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NW561 UT WOS:A1994NW56100018 PM 7524903 ER PT J AU DAWID, IB TAIRA, M AF DAWID, IB TAIRA, M TI AXIS DETERMINATION IN XENOPUS - GRADIENTS AND SIGNALS SO BIOESSAYS LA English DT Note ID MESODERM INDUCTION; SPEMANN ORGANIZER; EMBRYOS; LAEVIS; ACTIVIN; FGF RP DAWID, IB (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 17 TC 6 Z9 6 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUN PY 1994 VL 16 IS 6 BP 385 EP 386 PG 2 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA NU744 UT WOS:A1994NU74400002 PM 7915901 ER PT J AU PILETZ, JE DEMET, E GWIRTSMAN, HE HALARIS, A AF PILETZ, JE DEMET, E GWIRTSMAN, HE HALARIS, A TI DISRUPTION OF CIRCADIAN MHPG RHYTHMICITY IN MAJOR DEPRESSION SO BIOLOGICAL PSYCHIATRY LA English DT Article DE DEPRESSION; MHPG; CIRCADIAN; RHYTHMS; NOREPINEPHRINE ID 3-METHOXY-4-HYDROXYPHENYLGLYCOL MHPG; URINARY MHPG; NOREPINEPHRINE METABOLISM; CATECHOLAMINE METABOLISM; CEREBROSPINAL-FLUID; AFFECTIVE-DISORDERS; MANIC-DEPRESSIVES; HOMOVANILLIC-ACID; DIURNAL-VARIATION; LOCUS COERULEUS AB Plasma concentrations of total (free plus conjugated) 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined every 3 hr for a 24-hr period in 32 unipolar depressed patients, 11 bipolar depressed patients, and 12 healthy subjects. Each subject's circadian MHPG rhythmicity was modeled by a sinusoidal function. Temporal parameters were estimated by linear least squares regression with a fixed 24-hr period. The variabilities associated with estimates of circadian amplitude and acorphase were roughly twice as large in the patients compared to healthy subjects. Phase advances were associated most significantly with the agitated rather than the retarded subtype of depression, and with first episode depressions. Treatment with desipramine (n = 26) did nor alter significantly any of the model parameters and had no effect on circadian variability in any patient group. The data overall support a dysregulation theory for depressive illness with phase advances representing one manifestation of such dysregulation. C1 UNIV MISSISSIPPI,MED CTR,DEPT PHARMACOL & TOXICOL,JACKSON,MS 39216. UNIV CALIF IRVINE,DEPT PSYCHIAT,IRVINE,CA 92717. NIMH,BETHESDA,MD 20892. RP PILETZ, JE (reprint author), UNIV MISSISSIPPI,MED CTR,DEPT PSYCHIAT & HUMAN BEHAV,GUYTON RES BLDG,RM 128,2500 N STATE ST,JACKSON,MS 39216, USA. FU NIMH NIH HHS [NIMH MH-33109, NIMH MH-37664] NR 69 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 1994 VL 35 IS 11 BP 830 EP 842 DI 10.1016/0006-3223(94)90018-3 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NN547 UT WOS:A1994NN54700002 PM 8054405 ER PT J AU POPIK, P MAMCZARZ, J VETULANI, J AF POPIK, P MAMCZARZ, J VETULANI, J TI THE EFFECT OF ELECTROCONVULSIVE SHOCK AND NIFEDIPINE ON SPATIAL-LEARNING AND MEMORY IN RATS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ELECTROCONVULSIVE SHOCK; SPATIAL LEARNING; SPATIAL MEMORY; CALCIUM CHANNEL BLOCKER ID CHANNEL BLOCKER NIMODIPINE; ANTIDEPRESSANT DRUGS; WORKING MEMORY; TERM-MEMORY; WATER-MAZE; RETENTION; THERAPY; ACQUISITION; NAVIGATION; BINDING AB Several traumatic events including brain contusion, electroconvulsive shock therapy, epileptic seizures and others, may cause short-term retrograde amnesia. In spite of much recent attention, pharmacological treatment of memory impairment has not been fully successful. In the present paper we report on the possible antiamnesic action of the L-type calcium channel blocker, nifedipine. Rats trained in the spatial memory task showed gradual improvement in the escape latency to find the submerged platform. After completion of the learning, they also showed a strong spatial bias toward the place that previously contained the target platform. Prolonged post-trial electroconvulsive shock induced memory impairment. The calcium channel blocker, previously reported as a ''cognitive enhancer'' given either before or after the learning trial revealed no antiamnesic effect Nifedipine also does not exert any action when given alone. These results suggest that the drug may not have antiamnesic action on human memory disturbed by electroconvulsive therapy. C1 POLISH ACAD SCI,INST PHARMACOL,KRAKOW,POLAND. RP POPIK, P (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 41 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 1994 VL 35 IS 11 BP 864 EP 869 DI 10.1016/0006-3223(94)90022-1 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NN547 UT WOS:A1994NN54700006 PM 8054409 ER PT J AU SONE, M SMITH, DM GHATEI, MA GOZES, I BRENNEMAN, DE FRIDKIN, M BLOOM, SR AF SONE, M SMITH, DM GHATEI, MA GOZES, I BRENNEMAN, DE FRIDKIN, M BLOOM, SR TI PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) VASOACTIVE-INTESTINAL-PEPTIDE (VIP) RECEPTOR SUBTYPES IN RAT-TISSUES - INVESTIGATION OF RECEPTOR-BINDING, A NOVEL VIP RECEPTOR ANTAGONIST AND CHEMICAL CROSS-LINKING SO BIOMEDICAL RESEARCH-TOKYO LA English DT Article ID MOLECULAR-IDENTIFICATION; HYPOTHALAMIC POLYPEPTIDE; FUNCTIONAL EXPRESSION; LIVER MEMBRANES; LUNG MEMBRANES; HUMAN BRAIN; PACAP; SITES; NEUROPEPTIDE; CELLS AB Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) have been subdivided into type I receptors and II receptors. Using rat brain stem as a tissue containing type I receptors and rat lung as a tissue containing type II receptors, we investigated the binding of I-125-labelled PACAP, vasoactive intestinal peptide (VIP) and the related peptide, helodermin to these and, by chemical cross-linking, the relative molecular weight of the receptors. Type I receptors showed an M(r) of 58,000 and type II an M(r) of 54,000. After deglycosylation type I receptors showed an M(r) of 49,000 and type II receptors an M(r) of 41,000 demonstrating a high degree of glycosylation of both subtypes. This compares with the predicted (unglycosylated) M(r)'s of the recently cloned rat brain type I receptor and rat lung type II receptor of 56,000 and 49,000, respectively. We also studied a hybrid VIP receptor antagonist (VIP-neurotensin) and showed it was unable to displace I-125-PACAP from type I receptors (K-i>10 mu M) but was effective at type II receptors and propose that this peptide could be used to differentiate between PACAP effects at the two receptor subtypes. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. NICHHD,DEV NEUROBIOL LAB,DEV & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. RP SONE, M (reprint author), HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT MED,DU CANE RD,LONDON W12 0NN,ENGLAND. NR 34 TC 5 Z9 5 U1 0 U2 0 PU BIOMED RES FOUND PI TOKYO PA KANDA PO BOX 182 CHIYODAKU, TOKYO 101-91, JAPAN SN 0388-6107 J9 BIOMED RES-TOKYO JI Biomed. Res. PD JUN PY 1994 VL 15 IS 3 BP 145 EP 153 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW230 UT WOS:A1994NW23000002 ER PT J AU FOLLMANN, DA PROSCHAN, MA GELLER, NL AF FOLLMANN, DA PROSCHAN, MA GELLER, NL TI MONITORING PAIRWISE COMPARISONS IN MULTIARMED CLINICAL-TRIALS SO BIOMETRICS LA English DT Article DE BONFERRONI INEQUALITY; GROUP SEQUENTIAL MONITORING; LOG-RANK TEST; MULTIPLE COMPARISON PROCEDURE; SEQUENTIALLY REJECTIVE; TYPE I ERROR; USE FUNCTION ID TESTS AB This paper proposes a method for monitoring multi-armed clinical trials on the basis of pairwise comparisons between arms. The set of pairwise test statistics is examined during the course of the trial in order to make decisions about hypotheses, continuation of treatment arms, and continuation of the trial. Strong control of the Type I error rate is achieved by modifying two-armed group sequential procedures of Pocock (1977, Biometrika 64, 191-199), O'Brien and Fleming (1979, Biometrics 35, 549-556), and Lan and DeMets (1983, Biometrika 70, 659-663) to multi-armed trials. In the fixed-sample situation, these methods reduce to either Dunnett's or Tukey's procedure for multiple comparisons. A simpler, more flexible approximation based on the Bonferroni inequality is suggested, as well as an analogue to a sequentially rejective procedure. RP FOLLMANN, DA (reprint author), NHLBI,BIOSTAT RES BRANCH,FED BLDG ROOM 2A11,BETHESDA,MD 20892, USA. NR 17 TC 55 Z9 55 U1 3 U2 13 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1994 VL 50 IS 2 BP 325 EP 336 DI 10.2307/2533376 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NX428 UT WOS:A1994NX42800001 PM 8068834 ER PT J AU THALL, PF SIMON, R AF THALL, PF SIMON, R TI PRACTICAL BAYESIAN GUIDELINES FOR PHASE-IIB CLINICAL-TRIALS SO BIOMETRICS LA English DT Article DE BAYESIAN INFERENCE; DESIGN; PHASE II TRIAL; PRIOR DISTRIBUTION; SAMPLE SIZE ID PREDICTIVE PROBABILITY AB A Phase IIB clinical trial typically is a single-arm study aimed at deciding whether a new treatment E is sufficiently promising, relative to a standard therapy, S, to include in a large-scale randomized trial. Thus, Phase IIB trials are inherently comparative even though a standard therapy arm usually is not included. Uncertainty regarding the response rate Theta(2) of S is rarely made explicit, either in planning the trial or interpreting its results. We propose practical Bayesian guidelines for deciding whether E is promising relative to S in settings where patient response is binary and the data are monitored continuously. The design requires specification of an informative prior for Theta(2), a targeted improvement for E, and bounds on the allowed sample size. No explicit specification of a loss function is required. Sampling continues until E is shown to be either promising or not promising relative to S with high posterior probability, or the maximum sample size is reached. The design provides decision boundaries, a probability distribution for the sample size at termination, and operating characteristics under fixed response probabilities with E. C1 NCI,DIV CANC TREATMENT,CTEP,BIOMETR RES BRANCH,ROCKVILLE,MD 20892. RP THALL, PF (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,BOX 237,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 24 TC 101 Z9 101 U1 2 U2 7 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1994 VL 50 IS 2 BP 337 EP 349 DI 10.2307/2533377 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NX428 UT WOS:A1994NX42800002 PM 7980801 ER PT J AU WACHOLDER, S WEINBERG, CR AF WACHOLDER, S WEINBERG, CR TI FLEXIBLE MAXIMUM-LIKELIHOOD METHODS FOR ASSESSING JOINT EFFECTS IN CASE-CONTROL STUDIES WITH COMPLEX SAMPLING SO BIOMETRICS LA English DT Article DE BIASED SAMPLING; EM ALGORITHM; INTERACTION; MATCHING; RANDOMIZED RECRUITMENT; SYNERGISM; 2-STAGE SAMPLING ID 2-STAGE CASE-CONTROL; LOGISTIC-REGRESSION; EXPOSURE; DISEASE; MODELS; DESIGN AB Case-control studies can often be made more efficient by using frequency matching, randomized recruitment, stratified sampling, or two-stage sampling. These designs share two common features: (1) some ''first-stage'' variables are ascertained for all study subjects, while complete variable ascertainment is carried out for only a selected subsample, and (2) the subsampling of subjects for ''second-stage'' variable ascertainment depends jointly on their disease status and their observed first-stage variables. Because first-stage variables alter the subsampling fractions, standard analyses require a multiplicative specification of any joint effects of a second- and a first-stage variable. We show that by making use of missing data methods, maximum likelihood estimates can be obtained for risk parameters of interest, even those characterizing interactions between first- and second-stage variables. Joint effects can thus be modelled flexibly, with allowance for both additive and multiplicative models. Preliminary data from a case-control study of lung cancer as related to age, sex, and smoking provide an example, leading to the suggestion that the combined effect of age and smoking is multiplicative. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP WACHOLDER, S (reprint author), NCI,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 403,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 23 TC 38 Z9 38 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1994 VL 50 IS 2 BP 350 EP 357 DI 10.2307/2533378 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NX428 UT WOS:A1994NX42800003 PM 8068835 ER PT J AU WEINBERG, CR GLADEN, BC WILCOX, AJ AF WEINBERG, CR GLADEN, BC WILCOX, AJ TI MODELS RELATING THE TIMING OF INTERCOURSE TO THE PROBABILITY OF CONCEPTION AND THE SEX OF THE BABY SO BIOMETRICS LA English DT Article DE COITAL FREQUENCY; EGG; EM ALGORITHM; FERTILITY; GENDER; OVULATION; OVUM; SPERM ID OVULATION; PREGNANCY; WOMEN; SPERM; RISK AB The probability that conception will result from intercourse on particular days of the menstrual cycle is of biological, demographic, and personal interest to many. We describe an existing model for conception as related to the timing of intercourse, and develop a method for fitting it by means of the expectation-maximization (EM) algorithm, using widely available software (GLIM). We then generalize the model to allow for effects on its parameters due to reproductively toxic exposures. A further extension allows one to address the question of whether the pattern of intercourse in a conception cycle has an influence on the sex of the resulting baby. We illustrate the methods by application to data from a prospective study of couples trying to begin a pregnancy. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP WEINBERG, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,MD B3-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 17 TC 43 Z9 43 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1994 VL 50 IS 2 BP 358 EP 367 DI 10.2307/2533379 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NX428 UT WOS:A1994NX42800004 PM 8068836 ER EF