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Biomedical subjects

V Dzau

Publications and source records attributed to V Dzau.

12 recordsLinked to original sources
PubMed2001

Genetic variation in aldosterone synthase predicts plasma glucose levels.

The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide polymorphisms in the aldosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanese origin. Two polymorphisms--one in the putative promoter (T-344C) and another resulting in a lysine/arginine substitution at amino acid 173, which are in complete linkage disequilibrium in this population--were associated with fasting plasma glucose levels (P = 0.000017) and those 60 (P = 0.017) and 120 (P = 0.0019) min after an oral glucose challenge. A C/T variant in intron 1, between these polymorphisms, was not associated with glucose levels. Arg-173 and -344C homozygotes were most likely to be diabetic [odds ratio 2.51; 95% confidence interval (C.I.) 1.39-3.92; P = 0.0015] and have impaired fasting glucose levels (odds ratio 3.53; 95% C.I. 2.02-5.5; P = 0.0000036). These results suggest a new role for aldosterone in glucose homeostasis.

Adult↗
PubMed2000

Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations.

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.

Adult↗
PubMed2000

Measuring contributions to the research mission of medical schools.

The authors of this article, who were the members and staff of a research panel formed by the AAMC as part of its mission-based management initiative, reflect on the growing interest in quantitative information in the management of the research mission of medical schools. They note the serious limitations of any such system of measures for research, particularly its inability to represent directly the quality of the research effort. Despite these concerns, the authors acknowledge that leaders in academic medicine have always used quantitative measures in one form or another to compare performance or assess progress. Two factors appear to be driving increases in this practice: (1) the need to demonstrate to institutional stakeholders that resources are being used wisely and that the school's performance justifies continued investment in the research mission; and (2) the need to fashion an economic strategy to manage precious institutional resources, particularly research space. Given these realities, the authors offer guidelines for the proper development and use of measures to assess contributions by faculty, departments, and institutions to the research mission. They also comment on the measures most commonly used in four areas: grants and other revenue-generating activities; publications; faculty members' research reputation and contributions to the national research enterprise; and support to the general research mission of the school. The authors conclude that quantitative information can help institutional leaders in important management decisions. However, the potential for misuse is great. The key is always to regard this information as an aid to judgment, not a substitute for it.

Research↗
PubMed1998

Complete reversal of ischemic wall motion abnormalities by combined use of gene therapy with transmyocardial laser revascularization.

INTRODUCTION: Transmyocardial laser revascularization is believed to induce an angiogenic response within ischemic myocardium. We evaluated transgene expression in the setting of transmyocardial laser revascularization and hypothesized that intramyocardial injection of plasmid DNA encoding the gene for vascular endothelial growth factor could enhance the revascularization achieved by transmyocardial laser revascularization, resulting in improved cardiac function. METHODS: Ten Yorkshire pigs had carbon dioxide-transmyocardial laser revascularization or acupuncture sites with injections of an expression plasmid encoding the gene for beta-galactosidase with or without HVJ-liposomes. Three days after transduction, transgene expression was determined by enzyme-linked immunosorbent assay. Six weeks after placement of a constrictor on the left circumflex artery, 29 pigs were randomized to ischemic controls (n = 5), transmyocardial laser revascularization (n = 4), transmyocardial laser revascularization with expression plasmid beta-galactosidase injections (n = 5), expression plasmid-vascular endothelial growth factor injections (n = 4), or transmyocardial laser revascularization with expression plasmid-vascular endothelial growth factor (n = 5) and harvested 6 weeks after therapy. Six transmyocardial laser revascularization pigs had either expression plasmid beta-galactosidase or expression plasmid-vascular endothelial growth factor injections and were harvested at 2 weeks. Normal pigs (n = 5) were included for comparison. Left ventricular free wall motion was assessed by a cardiologist in a blinded manner. RESULTS: Transgene expression did not vary significantly with or without HVJ-liposomes in transfected transmyocardial laser revascularization myocardium. However, expression was detected in 56 of 60 (93%) transmyocardial laser revascularization-transfected sites, but in only 10 of 20 (50%) non-transmyocardial laser revascularization sites (P < .001). All (5 of 5 hearts) of the transmyocardial laser revascularization-vascular endothelial growth factor treated hearts displayed no evidence of wall motion abnormalities. Only these hearts had a statistically significantly different rate of wall motion abnormality compared with ischemic controls (P = .004). CONCLUSION: Transfection efficiency was improved with the use of transmyocardial laser revascularization. Wall motion abnormalities were completely reversed within 6 weeks after transmyocardial laser revascularization with the direct injection of an expression plasmid encoding vascular endothelial growth factor.

Animals↗
PubMed1991

Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement.

Advances in cardiovascular research during the past two decades have resulted in an improved understanding of the chain of events that lead to end-stage coronary artery disease. These developments have been paralleled by therapeutic advances that now make it possible to intervene at virtually every stage in the development of advanced cardiac disease, from asymptomatic persons at risk of developing coronary atherosclerosis to patients with end-stage heart failure. By interrupting this chain of events, perhaps at multiple sites, it may be possible to prevent or slow the development of symptomatic heart disease and hopefully prolong life. Many opportunities exist for obtaining further information regarding the underlying pathophysiology, the fundamental mechanisms of action of interventions designed to prevent and/or treat the development of myocardial ischemia and cardiac failure and for effecting favorably the natural history of various forms of heart disease.

Coronary Disease↗
PubMed1986

Acute thrombosis of a composite ascending aortic conduit containing a Bjork-Shiley valve during pregnancy: successful emergency cesarean section and operative repair.

A 31-year-old female had an ascending aortic conduit with a Bjork-Shiley valve placed for an aortic dissection. A year later she became pregnant and was placed on heparin instead of coumadin therapy. She then developed a distal aortic dissection and was hospitalized for close medical monitoring of fetal status and maturity. At 33 weeks of gestation the aortic valve thrombosed, resulting in pulmonary edema and cardiac arrest. Emergency cesarean section and replacement of the aortic valve and ascending aortic conduit was successful in salvaging mother and child. Both are well at 2 years followup. The case illustrates the hazards of prosthetic valves in pregnant patients and cardiac surgery during pregnancy. These issues are reviewed along with the details leading to successful surgical management.

Adult↗
PubMed1982

Renin synthesis by canine aortic smooth muscle cells in culture.

Angiotensin-I generating activity has been detected in homogenates of arterial tissue but it remains unclear whether this enzymatic activity results from the presence of renin itself or from the action of other proteases such as cathepsin D. In an assay system employing anephric dog plasma as substrate and buffered to pH 7.4, we detected angiotensin-I generating activity in homogenates of canine aortic smooth muscle cells. This enzymatic activity was in large part inhibitable by renin-specific antisera raised to pure canine renal renin. Immunofluorescent study of cultured arterial smooth muscle cells was also performed using renin specific antiserum. Granular cytoplasmic immunofluorescence was detected when specific antirenin serum was used but not when preimmune serum was employed. The addition of pure canine renin to the renin antiserum during staining suppressed the granular immunofluorescence confirming the specificity of staining. Finally, biosynthetic radiolabelling studies were performed. Immunoprecipitation of newly synthesized proteins with antirenin serum and staphylococcal protein A followed by gel electrophoresis and autoradiography demonstrated the synthesis of an immunoreactive protein with the molecular weight of renin. Pretreatment of the antirenin serum with pure canine renin resulted in the disappearance of this immunoreactive protein band. Thus these studies provide multiple lines of evidence to indicate the in situ synthesis of renin by vascular smooth muscle cells.

Animals↗
PubMed1980

A trial of two strategies to modify the test-ordering behavior of medical residents.

We studied two methods to reduce the ordering of laboratory and radiologic tests by medical residents in their first postgraduate year. Dividing the residents into three groups, we compared the effect of concurrent chart review and discussion in one group with the effect of a moderate financial incentive for limited ordering of tests in a second group. The third group of residents served as a concurrent control, and data on the testing patterns of residents at the same hospital during the year before the study provided a retrospective control.

Boston↗
PubMedDate not supplied

Monoclonal antibodies binding renal renin.

Somatic-cell fusion of normal antibody-producing spleen cells with cells from a plasmacytoma culture results in a culture of hybrid cells from which a monoclonal line may be selected. These lines are immortal and may be amplified as tumors in syngeneic animals to produce large quantities of antibodies characterized by molecular homogeneity. We report the application of this technique to the production of antibodies binding canine renin. Balb/c mice were immunized with pure canine renal renin and their spleen cells fused with the NS-1 myeloma line. In two separate fusions, nine clones of cells were isolated that bound canine renal renin but did not cross-react with a number of protein antigens tested. One of these antibodies cross-reacted with renins of several different species, including human renin. Binding inhibition studies carried out with one of these monoclonal antibodies demonstrated a dissociation constant for renin of 10(-7) M. These monoclonal antibodies have great potential in answering significant questions concerning the structure, biosynthesis, tissue localization, and physiologic actions of renin.

Animals↗