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Biomedical subjects

B E Wilson

Publications and source records attributed to B E Wilson.

At least 19 recordsLinked to original sources
PubMed1999

Equilibrium dialysis study and mechanistic implications of coenzyme A binding to acetyl-CoA synthase/carbon monoxide dehydrogenase from Clostridium thermoaceticum.

Parameters for the binding of coenzyme A to acetyl-CoA synthase/carbon monoxide dehydrogenase from Clostridium thermoaceticum were determined by equilibrium dialysis. CoA bound to as-isolated native alpha 2 beta 2 enzyme with KD = 10 +/- 8 microM and n = 0.2 +/- 0.1 moles per alpha beta dimer, where KD is the thermodynamic dissociation constant and n is the number of CoAs bound per alpha beta dimer of the enzyme. The enzyme is heterogeneous; for example, only approximately 30% of alpha subunits contain A-clusters with labile Ni ions (the remainder have nonlabile Ni ions and are nonfunctional). The observed n value suggests that CoA binds only to alpha beta units with Ni-labile A-clusters. The CoA binding properties of enzyme lacking labile Ni was essentially the same, indicating that CoA does not bind directly to the Ni of the A-cluster. This was further evidenced by the observation that bound CoA did not inhibit removal of the labile Ni by 1,10-phenanthroline. CoA did not bind CO-reduced enzyme, and the EPR signal exhibited by the one-electron reduced and CO-bound form of the A-cluster was unaffected by the presence of up to 200 microM CoA. In contrast, CoA did bind Ti(III)-citrate-reduced enzyme (KD = 36 +/- 16 microM, n = 0.16 +/- 0.08). Implications of these results for the mechanism of catalysis are discussed.

Acetate-CoA Ligase↗
PubMed1996

Significant reversal of thyrotoxicosis-associated dilated cardiomyopathy with induction of the euthyroid state.

Thyrotoxicosis rarely precipitates heart failure. Older patients and those with underlying cardiac disease are at greater risk of experiencing this complication of thyrotoxicosis. A 43 year old male who presented with subclinical thyrotoxicosis, atrial fibrillation, and a dilated cardiomyopathy is discussed. There was no evidence of clinically significant underlying cardiac disease. At admission, the patient had an ejection fraction of 25%. Thyrotoxicosis was treated with propylthiouracil. At 14 weeks after hospitalization, the patient had an ejection fraction of 50% with significant reduction in cardiac chamber sizes and left ventricular mass index. He was biochemically euthyroid at that time. After ten months of propylthiouracil therapy, he had progressive improvement in cardiac function and decrease in left ventricular mass index. Thyrotoxicosis-associated cardiomyopathy may reverse significantly with treatment of thyrotoxicosis alone; this complication of thyrotoxicosis should be considered in any young individual with a dilated cardiomyopathy of unknown etiology.

Adult↗
PubMed1996

Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis.

Engagement of surface immunoglobulin on mature B cells leads to rescue from apoptosis and to proliferation. Levels of bcl-2 mRNA and protein increase with cross-linking of surface immunoglobulin. We have located the major positive regulatory region for control of bcl-2 expression in B cells in the 5'-flanking region. The positive region can be divided into an upstream and a downstream regulatory region. The downstream regulatory region contains a cyclic AMP-responsive element (CRE). We show by antibody supershift experiments and UV cross-linking followed by denaturing polyacrylamide gel electrophoresis that both CREB and ATF family members bind to this region in vitro. Mutations of the CRE site that result in loss of CREB binding also lead to loss of functional activity of the bcl-2 promoter in transient-transfection assays. The presence of an active CRE site in the bcl-2 promoter implies that the regulation of bcl-2 expression is linked to a signal transduction pathway in B cells. Treatment of the mature B-cell line BAL-17 with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in bcl-2 expression that is mediated by the CRE site. Treatment of the more immature B-cell line, Ramos, with phorbol esters rescues the cells from calcium-dependent apoptosis. bcl-2 expression is increased following phorbol ester treatment, and the increased expression is dependent on the CRE site. These stimuli result in phosphorylation of CREB at serine 133. The phosphorylation of CREB that results in activation is mediated by protein kinase C rather than by protein kinase A. Although the CRE site is necessary, optimal induction of bcl-2 expression requires participation of the upstream regulatory element, suggesting that phosphorylation of CREB alters its interaction with the upstream regulatory element. The CRE site in the bcl-2 promoter appears to play a major role in the induction of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from apoptosis. It is possible that the CRE site is responsible for induction of bcl-2 expression in other cell types, particularly those in which protein kinase C is involved.

Apoptosis↗
PubMed1995

Public cost and access to primary care for hyperglycemic emergencies, Clark County, Nevada.

Diabetes mellitus accounts for 5.8% of the total health care costs of citizens of the United States. Hospitalization expenses produce 40.5% of these costs. We sought to determine the public expenditure and major precipitators of admissions for uninsured diabetic hyperglycemic emergencies at a large public hospital. Of 247 diabetic emergency admissions over a 30 month period 49% (n = 121) of these patients had no medical insurance. The uninsured patients were younger and had relatively mild disease in comparison to the insured patients. These patients identified a primary physician in only 6% of the cases and had a higher incidence of admissions associated with lack of medications. We conclude that public funds to provide access to primary care and enhancement of employer-sponsored health insurance programs may decrease the numbers and costs of hospitalizations due to hyperglycemic emergencies in uninsured patients with diabetes mellitus.

Adolescent↗
PubMed1995

Effects of chromium supplementation on fasting insulin levels and lipid parameters in healthy, non-obese young subjects.

Trivalent chromium is an essential trace element for normal carbohydrate metabolism and insulin sensitivity. Because of this biological activity, chromium supplementation has been studied as a potential therapy of insulin resistant states and dyslipidemias, and has been promoted as a health aid to the general population. To determine if there is a risk of subclinical chromium deficiency in young, otherwise healthy adults, we evaluated the effect of chromium supplementation, versus placebo, on insulin levels and serum lipids in a double-blind, randomized trial in 26 young adults (mean age 36 years). Fasting levels of glucose, immunoreactive insulin (IRI), and lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) were measured before and after 90 days of daily supplementation with a chromium (III)-nicotinate preparation, containing 220 micrograms elemental chromium, or placebo. There were no statistically significant differences in the percentage change of fasting glucose, IRI or lipids between the chromium (n = 15) and placebo (n = 11) groups after 90 days of supplementation. However, those individuals within the chromium group with initial fasting IRI levels greater than 35 pmol/l had a significant decrease in IRI level after supplementation (P < 0.03) despite no significant changes in serum lipids. These subjects may benefit from chromium supplementation by improving insulin sensitivity and cardiovascular risk over time.

Adult↗
PubMed1995

Identification of constitutively activating mutation of the luteinising hormone receptor in a family with male limited gonadotrophin independent precocious puberty (testotoxicosis).

A family of male limited gonadotrophin independent precocious puberty was examined for activating mutation of the LH receptor. A transition of A to G in nucleotide 1733 of the human LH receptor gene was identified in all affected males and in an unaffected carrier female. The mutation was shown by identifying a new restriction site created by the mutation. This mutation appears to be a common feature of the disorder, as it has been reported previously in unrelated families. Therefore, the presence of this new restriction site can serve as a diagnostic tool in males at risk before the onset of symptoms, as well as identifying carrier females.

Adenylyl Cyclases↗
PubMed1995

Specific targeting of human hepatocellular carcinoma cells by immunoliposomes in vitro.

The monoclonal antibody AF-20 was raised against the human hepatocellular carcinoma (HCC) cell line FOCUS and binds with high affinity to a rapidly internalized 180-kd homodimeric glycoprotein that is abundantly expressed on the surface of human HCC and other human cancer cell lines. Immunoliposomes were produced by covalently coupling AF-20 to liposomes containing carboxyfluorescein. Interaction of immunoliposomes with various HCC cell lines in vitro was quantitatively assessed by flow cytometry and qualitatively analyzed by fluorescence microscopy. Liposomes bearing an isotype-matched nonrelevant monoclonal antibody (MAb) and cell lines not expressing AF-20 antigen served as controls. AF-20-immunoliposomes specifically bound to HCC and other human cancer cell lines expressing the AF-20 antigen and were rapidly internalized at 37 degrees C. Interaction of AF-20-conjugated liposomes with these cell lines was between 5 and 200 times greater than that of unconjugated liposomes, whereas no difference was observed between control liposomes bearing a nonrelevant antibody and unconjugated liposomes. Specificity of liposome-target cell interaction was confirmed by competitive inhibition assays. Kinetic analysis showed rapid association of AF-20 immunoliposomes with target cells, with saturation conditions being reached after 60 minutes. We conclude that the MAb AF-20 directs highly efficient, specific, and rapid targeting of immunoliposomes to human HCC and other human cancer cell lines in vitro. This targeted liposomal delivery system represents a promising approach for the development of immunotargeted diagnosis and therapy strategies against HCC.

Antibodies, Monoclonal↗
PubMed1994

Sympathomimetic drug abuse masking an endogenous hyperadrenergic state, Graves' disease.

Sympathomimetic drug use or abuse in a thyrotoxic individual can be clinically devastating as a result of enhanced cellular sensitivity to adrenergic stimulation. Thus, it is critical to recognize thyrotoxicosis in a patient with coexistent sympathomimetic drug abuse. This case report describes a patient with Graves' disease and severe hyperadrenergic symptomatology that was thought to result from sympathomimetic drug abuse.

Adolescent↗
PubMed1994

Thyrotoxicosis-induced congestive heart failure in an urban hospital.

Thyrotoxicosis has been associated with several cardiac complications, including atrial fibrillation (AF), functional cardiomyopathy, and congestive heart failure (CHF). Thyrotoxicosis-induced CHF has been considered an unusual complication of thyrotoxicosis, occurring generally in older patients. To determine the nature and frequency of this complication of thyrotoxicosis in an adult, hospitalized population, the authors consecutively evaluated all admissions to a 535-bed urban hospital during a 14-month period. Admitted during the study period were 177 individuals with a principal diagnosis of AF and 21 individuals with a principal diagnosis of thyrotoxicosis. Eleven of these individuals had concomitant AF and thyrotoxicosis, which was 6% of the AF group. Of these 11 patients, 5 had clinically apparent CHF without evidence of other organic heart disease (Group A) and 6 had only AF without clinical CHF (Group B). The 5 patients with CHF had a significantly lower mean age (36) than the 6 with thyrotoxicosis and AF only (P < 0.03). Echocardiography revealed Group A to have a mean of 2.8 cardiac chambers enlarged compared with a mean of 1 in Group B (P < 0.008). Four of the five patients with CHF had normal left ventricular function. Mean levels of serum thyroxine, albumin, hematocrit, left ventricular percent shortening, and left atrial diameter were similar in groups A and B. Based on the authors' data, thyrotoxicosis-induced CHF is not as rare a complication of thyrotoxicosis in young individuals as reported previously. Thyrotoxicosis-induced CHF most commonly has a dilated cardiomyopathy and high output failure.

Adult↗
PubMed1993

Case report: pseudoephedrine-associated thyroid storm: thyroid hormone-catecholamine interactions.

Thyroid storm is an increasingly rare, life-threatening manifestation of thyrotoxicosis that can be precipitated by many physiologic stressors. The exact mechanism by which thyrotoxicosis decompensates into thyroid storm in certain individuals is unknown. These individuals may have an enhanced cellular sensitivity to either catecholamines or thyroid hormone. Serum levels of catecholamines are usually low or normal in thyrotoxic individuals. Ingestion of sympathomimetic drugs in thyrotoxic individuals may precipitate thyroid storm. This article presents an unusual case of Graves' disease that decompensated into thyroid storm after the ingestion of an over-the-counter cold medication containing pseudoephedrine.

Adult↗
PubMed1992

Seasonal changes in hormone-sensitive and lipoprotein lipase mRNA concentrations in marmot white adipose tissue.

White adipose tissue (WAT) and plasma samples were obtained from yellow-bellied marmots (Marmota flaviventris) throughout the year. Mean plasma triacylglycerol (TG), free fatty acids (FFAs), and glycerol were determined. There was a clear increase in FFAs and decrease in mean TG and glycerol during the hibernation period when animals were fasting, suggesting increased lipolysis. RNA was isolated from WAT biopsies at four times in the year: spring, summer, fall, and winter. There were significant changes in the relative levels of mRNA for lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) during the body mass cycle of the marmot. The relative levels of LPL mRNA are high during the mass gain phase of the year and that of HSL mRNA are high during the fasting period when endogenous lipid is utilized. These results suggest that the genes for LPL and HSL are regulated seasonally to control the adipose mass depot in marmots.

Adipose Tissue↗