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Biomedical subjects

W J McConathy

Publications and source records attributed to W J McConathy.

At least 19 recordsLinked to original sources
PubMed1997

Neuroendocrine-associated behavioral patterns in the male Asian elephant (Elephas maximus).

Steroid-responsive behaviors have been reported in various species; however, the reports thus far on the male Asian elephant (bull) during musth are few in number and most have been conducted on single captive animals for short time periods. The purpose of this investigation was to perform a longitudinal study on steroid-responsive behavior in 3 male Asian elephants from a captive herd of 11 male Asian elephants in Nepal. Male Asian elephants were 18, 25, and 43 years old. The animals had serum collected for 11 months and were observed on a daily basis for aggressive behavior according to the Species Survival Plan (SSP) collection protocol on SSP data sheets. Testosterone (T) and dihydrotestosterone (DHT) were measured in each animal by radioimmunoassay. Testosterone levels rose during musth 26-fold compared to nonmusth, and DHT was elevated 12-fold in musth. Maximal aggressive behavior episodes occurred during peak elevations of T and DHT, with correlation coefficients of 0.82 and 0.89, respectively. Therefore, we suggest that the aggressive episodes are dependent on elevated circulating androgens acting on androgen-responsive neural tissues.

Animals↗
PubMed1997

Probing the structure of the ligand binding cavity of lipocalins by fluorescence spectroscopy.

The lipocalin superfamily constitutes a phylogenetically conserved group of more than 40 proteins that function in the binding and transport of a variety of physiologically important ligands. Members of this family subserve diverse functions as carriers of retinoids (retinol binding protein), odorants (odorant binding proteins), chromophores (insecticyanin, INS), pheromones (aphrodisin) and sterols (apolipoprotein D, apoD). Despite the pivotal importance of the ligand binding function of these proteins, a suitable approach for characterizing the molecular determinants of such binding has not been available. In studies using three homogeneously purified lipocalins INS, beta-lactoglobulin (BLG) and human apoD, we find that the fluorescence reporter BIS (1,1'-bi(4-anilino) naphthalene-5,5'-disulfonic acid) is an ideal candidate for use in rapid kinetic experiments and in fluorescence resonance energy transfer (FRET). These methods require only small amounts of reagents and yield molecular coordinates of the ligand binding cavity of lipocalins in solution that are in remarkably close agreement to those obtained from crystallographic work with solids. Extremely fast ligand binding dynamics is indicated.

Animals↗
PubMed1997

Left ventricular size and function in elite bodybuilders using anabolic steroids.

OBJECTIVE: To investigate the relationship between resistance training, anabolic steroid use, and left ventricular function. DESIGN: Sixteen competitive bodybuilders were recruited for an echocardiography study. SETTING: University of North Texas Health Science Center (Fort Worth, TX, U.S.A.); the cardiologist and technician were blinded as to subjects' drug status. SUBJECTS: Eight competitive heavyweight drug-free (DF) bodybuilders and eight competitive heavyweight body-builders on self-directed regimens of anabolic steroids. RESULTS: Average body mass indexes (BMI; kg/m2) for the drug-user (DU) and DF groups were not significantly different (34.1 +/- 2.8 and 32.0 +/- 4.3, respectively). Increases in left ventricular posterior wall and ventricular septal thickness were apparent in the DU group (p < 0.05). The ratio of echocardiographic findings to BMI revealed a significantly smaller left ventricular end-diastolic dimension (LVDEd/BMI; p < 0.05) in the DU group. The smaller LVDEd in DUs is coupled with a significantly disproportionate septal and posterior wall thickness in DUs when indexed to body mass compared to DFs. There was no direct evidence of diastolic dysfunction detected by mitral inflow velocity patterns. CONCLUSION: Anabolic steroids may potentiate concentric left ventricular hypertrophy with decreasing ventricular compliance without affecting cardiac function.

Adult↗
PubMed1997

Peripheral neuropathy and testosterone.

A 265 lb. (body mass index, 38.1) male elite bodybuilder suffered focal muscle atrophy that developed in his right vastus lateralis muscle within a month following a painful self-administered injection of testosterone. The subject did not lose any sensory or motor function immediately after the injection; however after several days to weeks, muscle atrophy and paresthesia ensued. The subject had an obvious atrophic zone in the right vastus lateralis muscle with approximately 40% loss of strength when compared to the left leg. In our view, the neuropraxia developed from direct neurotoxic effect of androgens or pressure exerted upon the nerve following injection of a bolus of liquid. This report is indicative of the many potential dangers associated with unsupervised androgen use which may include androgens as potential neurotoxins.

Adult↗
PubMed1995

The binding of animal low-density lipoproteins to human apolipoprotein(a).

Lipoprotein(a) [Lp(a)] is a risk factor for coronary artery disease. It is composed of lipids and apolipoprotein(a) [apo(a)] linked to apolipoprotein B (apoB) by a disulphide bond between Cys-4057 of apo(a)'s kringle 36 and possibly Cys-3734 of apoB. We call this the covalent apo(a): apoB-Lp interaction, to distinguish it from the non-covalent apo(a)/Lp(a): apoB-Lp interaction, which is probably mediated by apo(a)'s kringle 33 and residues 3304-3317 of apoB. The non-covalent interaction could be the initial interaction which brings apo(a) and apoB together prior to covalent linkage and Lp(a) formation. The non-covalent apo(a)/Lp(a)-binding site on apoB is evolutionarily more ancient than the covalent apo(a)-binding site on apoB. Both human and non-human low-density lipoproteins (LDLs) bind non-covalently to human apo(a)/Lp(a); however, only rabbit and human LDLs bind covalently to human apo(a). The non-covalent interaction between mouse LDL and human apo(a)/Lp(a) has a Kd of (1.7 +/- 1.33) x 10(-7) M (n = 3). This explains the co-localization of human apo(a) and mouse apoB in the atherosclerotic lesions of human apo(a) transgenic mice and supports our hypothesis that the non-covalent interaction is a contributing factor to apo(a) atherogenicity.

Animals↗
PubMed1995

A two-step model for lipoprotein(a) formation.

Lipoprotein(a) (Lp(a)), a risk factor for coronary artery disease, is a LDL-like particle with apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B (apoB), the main protein component of LDL. Apo(a) is highly homologous to plasminogen and its gene probably arose by duplication of the plasminogen gene. It has many repeats of kringle-4-like domain, classified as type 1 through type 10 (T1-T10). T9 is responsible for the covalent linkage between apo(a) and LDL. However, we found that T9 has no affinity for LDL. Therefore, an initial noncovalent interaction between apo(a) and LDL is necessary to bring T9 and LDL together. T6 and possibly T7 of apo(a) were identified as the kringles which mediate this initial interaction. With these findings, a two-step model for Lp(a) formation is proposed. This model should be useful in the design of Lp(a) formation inhibitors. These inhibitors are potential antihyperlipoprotein(a) drugs.

Amino Acid Sequence↗
PubMed1995

Apoc-III-beta-galactosidase hybrid distinguishes between VLDL and LDL phospholipids.

A plasmid directing the expression of preapolipoprotein C-III fused to beta-galactosidase was constructed. Escherichia coli harboring this construct produced the hybrid, with full beta-galactosidase activity, at 0.6% of total cellular protein. Purified preapoC-III-beta-galactosidase hybrid exhibited specific binding to very low density lipoproteins, which was inhibited by purified apoC-III. No binding to low density lipoproteins was observed. Binding was mediated by the phospholipids of very low density lipoproteins, as the hybrid had a specific affinity for phospholipids and no detectable affinity for triglycerides, cholesteryl esters, or cholesterol. The differential binding suggests that there are differences between the phospholipids of very low density lipoproteins and the phospholipids of low density lipoproteins.

Amino Acid Sequence↗
PubMed1995

Selective removal of plasma low density lipoprotein with the HELP system: biweekly versus weekly therapy.

PURPOSE: Biweekly (once every 2 weeks) heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels compared with weekly HELP therapy. PATIENTS AND METHODS: Biweekly treatments were given to high-risk, diet/drug resistant hypercholesterolemic patients (n = 23) after 6 months of weekly HELP therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-I and B, and fibrinogen were measured on plasma samples before and after treatment. RESULTS: Mean plasma volume treated was 2.8 l and mean treatment duration 1.7 h. Therapy complications were minimal. In 98% of 268 biweekly HELP treatments, LDL cholesterol levels were reduced by > 30%. For patients completing 6 months of biweekly therapy following 6 months' weekly therapy (n = 23), mean LDL cholesterol levels were reduced 138.5 mg/dl (111.2 mg/dl weekly) with a time-averaged decrease from mean pre-apheresis levels of 33% for biweekly therapy (39% weekly). Mean total cholesterol (161.2 mg/dl biweekly versus 132.9 weekly) and apolipoprotein B (104.6 mg/dl versus 92.6) levels were also reduced with each treatment. Mean HDL cholesterol was reduced only 6.1 mg/dl (6.3 mg/dl weekly). CONCLUSIONS: Biweekly HELP treatments can safely reduce LDL cholesterol levels as consistently as weekly HELP treatments. However, the higher pre-treatment LDL cholesterol levels with biweekly treatments may produce less therapeutic benefit than with weekly therapy.

Blood Component Removal↗
PubMed1995

The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein (a):apolipoprotein B-containing lipoprotein interaction.

Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease. It is characterized by apolipoprotein (a) [apo(a)] disulphide linked to apolipoprotein B (apoB), by Cys4057 of apo(a) and possibly Cys3734 of apoB. We call this the covalent apo(a):apoB-Lp interaction, to distinguish it from the non-covalent Lp(a):apoB-Lp interaction, mediated by the proline-binding kringle-4-like domain(s) of Lp(a). The Lp(a):apoB-Lp interaction was inhibited by an apoB peptide spanning residues 3304-3317. This peptide was found by a computerized search for sites on apoB similar to the plasminogen's kringle-4-binding site of alpha 2-antiplasmin. It probably constitutes part of the Lp(a)-binding site on apoB because: (1) it corresponds to the alpha 2-antiplasmin minimum binding domain for plasminogen's kringle-4; (2) the competitive nature of inhibition [KI = (1.5 +/- 0.7) x 10(-4) M, n = 5] suggested that it and apoB-Lp bound to Lp(a) by the same mechanism at the same site; and (3) it specifically bound Lp(a) and not apoB-Lp, and the bound Lp(a) was dissociated by inhibitors of the Lp(a):apoB-Lp interaction, 6-aminohexanoic acid and L-proline. Inhibition was independent of its proline residue, suggesting that proline in the context of a peptide is not a ligand for the kringle(s) which mediated the binding of Lp(a) to apoB-Lp.

Amino Acid Sequence↗
PubMed1995

Astrocytes synthesize and secrete the lipophilic ligand carrier apolipoprotein D.

Expression of the lipophilic ligand transporter, apolipoprotein D (apoD) by primary astrocyte cultures derived from neonatal mouse brain was investigated. Western blot analysis of cell lysates and media showed that apoD is constitutively secreted by astrocytes with little intracellular storage. The secreted apoD floated primarily at density 1.063-1.21 g ml-1 upon sequential ultracentrifugation indicating its association with lipids. Treatment of astrocytes with the carboxylic ionophore, monensin, resulted in intracellular retention and decreased secretion of apoD that was of slightly reduced M(r). Progesterone, a steroid hormone that binds to apoD with high affinity (10(-6) mol l-1) and the oxysterol, 25-hydroxycholesterol which is a potent regulator of cellular cholesterol homeostasis in mammalian cells, differentially stimulated apoD, but not apoE secretion. These results show that astrocytes synthesize and constitutively secrete apoD and suggest a physiologic role for this lipocalin in cholesterol metabolism in the nervous system.

Animals↗
PubMed1995

Serum lipids and apolipoproteins in women with breast masses.

BACKGROUND: Human mammary tissue metabolizes lipids from plasma, a process affected by female gonadal hormones. Both benign and malignant proliferation of breast tissue in women have been associated with changes in plasma lipid and lipoprotein levels. METHODS: One hundred consecutive women with breast masses (50 malignant, 50 benign) had diagnostic biopsies followed by axillary node dissection in those with cancer. Fasting serum samples were taken just prior to biopsy and analyzed for lipid fatty acid and lipoprotein levels. Malignant breast tissue was analyzed for hormone receptor binding. RESULTS: Low-density lipoprotein (LDL) components (total cholesterol, LDL-cholesterol, apolipoprotein B) were increased, but not significantly, in cancer patients compared to those with benign masses. Decreased levels of LDL-associated components were found in women with cancer recurrence by 3 years. Three apolipoproteins of high-density lipoprotein (apolipoprotein A-I, apolipoprotein A-II, apolipoprotein D) were more affected by the presence of breast masses than the lipids were. Fibrocystic disease, type of hormone binding, and recurrence within 3 years were significantly related to apolipoprotein changes, especially apolipoprotein D levels with hormone receptor binding and the apolipoprotein A-I/apolipoprotein B ratio with breast cancer recurrence. CONCLUSIONS: Prior to diagnostic biopsy, serum lipid and apolipoprotein components of low-density lipoproteins were increased in women with fibrocystic disease and early stage cancer but decreased in women with early recurrence. However, apolipoprotein A-I, apolipoprotein A-II, and apolipoprotein D, of the high-density lipoproteins, were more affected than serum lipids. The ratio of apolipoprotein A-I to apolipoprotein B serum levels at time of biopsy was the best predictor of cancer recurrence.

Adult↗
PubMed1995

Sudden cardiac death in a 20-year-old bodybuilder using anabolic steroids.

Anabolic steroid use is widespread and has been associated with a variety of pathological conditions. The subject of this case is a 20-year-old amateur bodybuilder who died of sudden cardiopulmonary arrest. He had no previous medical complaints but had a history of anabolic steroid abuse and a hypertrophic heart (515 g) at autopsy. This case presentation will discuss the cardiovascular effects of these drugs and the possible impact of long-term abuse.

Adult↗
PubMed1994

Purification and molecular cloning of human apolipoprotein F.

In our effort to study proteins that are involved in high density lipoprotein metabolism, we have identified apolipoprotein F and isolated a full length cDNA clone. Apolipoprotein F, with an apparent molecular mass of 29 kilodaltons, was purified from human high density lipoproteins using a modified two dimensional electrophoresis procedure. The cDNA, with a size of 1735 base pairs, was cloned from a Hep G2 cDNA library. The cDNA encodes apolipoprotein F, which is composed of 162 amino acids, and predicts that apolipoprotein F is a proteolytic product of a larger protein. Northern blot analysis indicates that apolipoprotein F mRNA is detected only in liver for the tissues examined. The gene was mapped to human chromosome number 12 using a human/rodent somatic cell hybrid mapping panel.

Amino Acid Sequence↗
PubMed1994

Triglyceride-rich lipoprotein interactions with Lp(a).

We found a significantly reduced incidence of increased lipoprotein(a) (Lp(a)) levels in subjects with triglycerides (TG) greater than 150 mg/dl compared with those with TG levels lower than 150 mg/dl. This was the case in patients with angiographically documented coronary artery disease (CAD) and in subjects with no CAD. We explored the potential role of lipoprotein lipase (LPL) in mediating this relationship. Lp(a) and LDL2 exhibited a minimal effect on the rate constant for degradation of VLDL-TG by LPL (13% inhibition). Binding analyses indicated no differences between VLDL and LDL with respect to Lp(a) binding, and lipolysis only reduced binding by 30% at 75% degradation of VLDL-TG. Our study indicates that the inverse relationship between elevated plasma TG and Lp(a) levels is not caused by activation of LPL by Lp(a) either due to failure of Lp(a) to bind to VLDL or its lipolytic remnants. It is hypothesized that this relationship could stem from the enhanced clearance of TG-rich lipoproteins in individuals with higher levels of Lp(a) by receptor-mediated events.

Adult↗
PubMed1994

Plasma lipids and cholesterol esterification in Alzheimer's disease.

Eight patients and eight age matched controls were recruited to study parameters related to plasma lipoprotein metabolism in Alzheimer's disease based on previous studies in Down's syndrome (A.G. Lacko et al., Clin. Chim. Acta, 132 (1983) 133). The fractional rate of cholesterol esterification (% cholesterol esterified per hour) was 16% lower in the patient group compared with controls. Correlational analyses of lecithin/cholesterol acyltransferase (LCAT) activity and plasma lipids revealed additional differences between the Alzheimer's patients and control subjects. These data are strikingly similar to those obtained earlier with Down's syndrome patients. These data, combined with analyses of cholesteryl ester transfer protein (CETP) levels, suggest that reverse cholesterol transport in general and CETP activity in particular may be altered in Alzheimer's disease.

Aged↗