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Biomedical subjects

M J Bonner

Publications and source records attributed to M J Bonner.

15 recordsLinked to original sources

Prenatal and neonatal pharmacologic stress on early behavior and sexual maturation in the hamster.

Exposure to phenobarbital in utero results in sex-dependent altered neonatal behavior and reproductive maturation in hamsters. Prenatal phenobarbital-exposed (40 mg/kg subcutaneous to pregnant dams) male pups have at least 30% less pivoting activity and ultrasonic calling (high-frequency sounds produced by pups when separated from the nest) when compared with control pups born to saline-injected dams. As prenatal phenobarbital-treated male and female hamsters mature, there is a dose-dependent (20, 40, and 60 mg/kg) 2- to 5-day delay, respectively, according to sex, in puberty onset. Both sexes exhibited 30% lighter than control's adrenal weights associated with prenatal phenobarbital exposure. Although gonadal weights for males exposed to phenobarbital in utero were not affected, females had up to 33% lighter ovarian weights when compared with controls. Females exposed to phenobarbital in utero also had approximately 40% more irregular estrous cycles. Gonadal hormones act by means of Central Releasing Factor on pituitary ACTH secretion. Additional treatment during the neonatal period with 10 IU ACTH decreased the percentage of irregular estrous cycles and shortened the delay in puberty onset to near-control values in prenatally phenobarbital-treated females.

Adrenal Glands↗

Enhancing commitment improves adherence to a medical regimen.

A commitment-based intervention was evaluated for improvement of adherence to a 10-day antibiotic regimen. Experimental Ss made verbal and written commitments for adherence and completed tasks designed to increase their investment in a medication regimen. Control Ss performed similarly structured tasks unrelated to the medical regimen. Adherence, measured by unannounced pill counts, was significantly higher for experimental subjects than for control Ss. Self-reported adherence was significantly correlated with posttest self-efficacy but not with pretest self-efficacy. Adherence to a medical regimen may be improved by strategies conceptually based on the investment model of commitment, which provides a useful framework for further study of adherence.

Adolescent↗

Free radicals enhance basal release of D-[3H]aspartate from cerebral cortical synaptosomes.

Excessive generation of free radicals has been implicated in several pathological conditions. We demonstrated previously that peroxide-generated free radicals decrease calcium-dependent high K(+)-evoked L[3H]-glutamate release from synaptosomes while increasing calcium-independent basal release. The present study evaluates the nonvesicular release of excitatory amino acid neurotransmitters, using D-[3H]aspartate as an exogenous label of the cytoplasmic pool of L-glutamate and L-aspartate. Isolated presynaptic nerve terminals from the guinea pig cerebral cortex were used to examine the actions and interactions of peroxide, iron, and desferrioxamine. Pretreatment with peroxide, iron alone, or peroxide with iron significantly increased the calcium-independent basal release of D-[3H]aspartate. Pretreatment with desferrioxamine had little effect on its own but significantly limited the enhancement by peroxide. High K(+)-evoked release in the presence of Ca2+ was enhanced by peroxide but not by iron. These data suggest that peroxide increases nonvesicular basal release of excitatory amino acids through Fenton-generated hydroxyl radicals. This release could cause accumulation of extracellular excitatory amino acids and contribute to the excitotoxicity associated with some pathologies.

Animals↗

Effect of oxidative stress on excitatory amino acid release by cerebral cortical synaptosomes.

Previous studies in our laboratory have suggested that an oxidation reaction is responsible for the actions of free radicals to decrease synaptic potentials. Recently we observed that free radicals both decreased depolarization-induced vesicular release and enhanced basal, nonvesicular release of the excitatory amino acid, [3H]L-glutamate. In order to evaluate the contribution of oxidative reactions to this latter effect, we evaluated the actions of the oxidizing agent chloramine-T on synaptosomal release of excitatory amino acids, using [3H]D-aspartate as the exogenous label. Basal and depolarization evoked [3H]D-aspartate release were calcium-independent and nonvesicular. Chloramine-T pretreatment significantly increased basal release, while having no effect on high K(+)-evoked release. These data suggest that an oxidative process can mimic the free radical increase of basal release, as well as the decrease in synaptic potentials. On the other hand, the calcium-independent-evoked release may involve a different mechanism. Our results demonstrate that under basal, nondepolarizing conditions, oxidative stress exerts an adverse effect on the presynaptic nerve terminal, resulting in an increased release of potentially damaging excitatory amino acid neurotransmitters.

Amino Acids↗

The role of the septohippocampal pathway in the mediation of colchicine-induced compensatory changes in the rat hippocampus.

To study the involvement of the septohippocampal pathway in colchicine-induced changes in the hippocampus, colchicine was used to lesion the septum and/or hippocampus of male, Fischer-344 rats. Rats were killed 12 weeks post-lesion and histochemical and biochemical measurements were performed. [3H]-QNB binding, choline acetyltransferase (ChAT) activity and agonist-stimulated release of inositol phosphates (IPs) were measured in hippocampal slices. AChE histochemistry was also performed to visualize AChE positive fibers in the hippocampus. Increases in ChAT activity, AChE staining and carbachol-stimulated IP release observed in hippocampal-lesioned animals were attenuated in animals receiving both septal and hippocampal lesions. However, the decrease observed in [3H]-QNB binding sites after intradentate colchicine was not affected by septal lesions. Subsequent studies also found enhanced sensitivity to excitatory amino acid (EAA)-stimulated IP release in hippocampal-lesioned animals. Similar to the changes observed in carbachol-stimulated PI hydrolysis, this increase was also long-lasting. However, the hyperstimulation of EAA-induced IP release was not attenuated by the septal lesion. Thus, it appears that the neurochemical and morphological changes observed in the hippocampus following intradentate colchicine are dependent upon more than one afferent projection to the hippocampus.

Animals↗

Peroxide effects on [3H]L-glutamate release by synaptosomes isolated from the cerebral cortex.

Basal (non-depolarized) and high K(+)-stimulated [3H]L-glutamate release in the presence and absence of Ca2+ were assessed using presynaptic nerve terminals (synaptosomes) isolated from the cerebral cortex of the guinea pig. Basal glutamate release was found to be Ca(2+)-independent and was significantly increased following treatment with hydrogen peroxide (H2O2). On the other hand, depolarization-induced release had both a Ca(2+)-dependent and Ca(2+)-independent component. Both components of stimulated release were suppressed by H2O2. In fact, Ca(2+)-dependent evoked release was virtually eliminated by H2O2 pretreatment. The data suggest that H2O2 exerts a differential effect on the neurochemical mechanisms involved in basal and stimulated glutamate release at the presynaptic nerve terminal.

Animals↗

Compensatory alterations in receptor-stimulated phosphoinositide hydrolysis in the hippocampus vary as a function of dose of colchicine.

The stimulation of inositol phospholipid (PI) hydrolysis by various receptor agonists was measured in the hippocampus of rats 12 weeks after various concentrations (0.5-2.0 microgram/site) of colchicine were infused into the dentate gyrus. Colchicine produced a dose-related decrease in the average width and length of the granule cell line; the pyramidal cells in CA1 and CA3 regions of the hippocampus were affected only at higher concentrations of colchicine. Compensatory increases in receptor-mediated hydrolysis of phosphoinositides (PI) in hippocampal slices were seen at 100 microns carbachol and ibotenic acid in rats receiving 1.5-3.5 microgram colchicine/site. Compensatory increases in norepinephrine (100 microns) and N-methyl-D-aspartate (100 microns) stimulated PI were seen at 2.5-3.5 and 3.5 micrograms colchicine/site, respectively. Compensatory increases in PI hydrolysis were not seen in slices from animals receiving 0.5 microgram colchicine/site. These data support the hypothesis that the signal transduction system in the hippocampus undergoes a compensatory change following experimentally induced destruction of dentate gyrus granule cells. In addition, these changes occur for more than one neurotransmitter and the alterations vary as a function of the size of the lesion.

Animals↗

The influence of sepsis and ischemia on the natural history of the diabetic foot.

One hundred seventeen diabetic patients with lesions involving 174 extremities were reviewed to evaluate the natural history of the problem and specifically those factors that influence its course both acutely and chronically. The extremities of diabetic patients with foot lesions can be categorized based on severity of infection and presence of ischemia. Half of these patients developed lesions in the contralateral extremity either concurrently (synchronous) (7%) or later (metachronous) (43%). Major amputation was required in 59 of the 174 extremities evaluated (34%). In patients with metachronous lesions, unilateral amputations were required in 28 per cent of patients and bilateral amputations in 26 per cent. Limb salvage by revascularization required 1.4 operations per extremity, carried 2 per cent operative mortality and was successful in 66 per cent. Although 24 per cent of these patients died within 5 years of the initial presentation of their foot lesions, these data suggest that limb salvage attempts are reasonably successful and relatively safe. The combination of extremity sepsis and ischemia in the diabetic adversely effects the survival of both the extremity and the patient.

Amputation, Surgical↗

A radioimmunoassay for immunologic phenomena in pneumococcal disease and for the antibody response to pneumococcal vaccines. I. Method for the radioimmunoassay of anticapsular antibodies and comparison with other techniques.

A radioimmunossay is described which uses a 14C biosynthetically internally labeled antigen. This modified Farr technique has been standardized by quantitative precipitation and compared with hemagglutination and mouse protection. Specificity was established by use of heterologous hyperimmune sera and by use of unlabeled pneumococcal polysaccharides for inhibition. Reproducibility has been evaluated for different preparations of antigens and varying storage conditions of sera. The system has been applied to a wide variety of studies requiring analysis of human and animal sera.

Animals↗