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Biomedical subjects

R Mitchell

Publications and source records attributed to R Mitchell.

At least 307 records · Page 17Linked to original sources

Benzodiazepine- and barbiturate-interactions with GABAA receptor responses on lactotrophs.

Modulation of the biphasic effect of muscimol on prolactin secretion by benzodiazepines and secobarbital was investigated, using an in vitro superfusion system. The stimulatory effect of low concentrations of muscimol was potentiated by both classes of drugs, and the effect of benzodiazepines appeared to be mediated by central-type benzodiazepine receptors. Neither benzodiazepines nor secobarbital affected the inhibitory response to muscimol. Clonazepam reduced the potency of bicuculline methiodide as an antagonist of the stimulatory effect, but did not alter the potency of picrotoxinin. These results demonstrate a selective potentiation of one component of the GABAA receptor effect on lactotrophs by benzodiazepines and barbiturates and provide evidence for a functional effect of these drugs at a site without the CNS.

Animals↗

Distribution of GABA binding site subtypes in rat pituitary gland.

GABAA and GABAB binding sites in rat pituitary gland were investigated using equilibrium binding assays in vitro. Specific binding of both [3H]GABA and [3H]muscimol could be detected in both anterior and neurointermediate lobes, with a relative concentration in the anterior lobe. [3H]GABA binding was discriminated into GABAA and GABAB receptor type binding using baclofen. GABAB sites were detectable in the anterior but not in the neurointermediate lobe. Saturation analysis of [3H]muscimol binding to whole pituitary gland membranes demonstrated that the pituitary contains two classes of GABAA sites differing in affinity, as found in the CNS, although the number of sites is considerably lower than in the CNS.

Animals↗

Frozen recovered red cell boosting of female donors for anti-D-production.

A selected group of women previously immunized in pregnancy by the Rh(D) antigen were boosted with 0.5 ml of Rh(D)-positive frozen recovered red cells from an accredited donor panel. The response was prompt and sustained and increased the anti-D content by almost 10-fold. In spite of the reduced rate of clinical immunisation to the Rh(D) antigen, it was possible to recruit females with anti-D, acquired in pregnancy, for secondary boosting and a programme is recommended which maximizes efficiency and safety.

Adult↗

Uptake and autoreceptor-controlled release of [3H]-GABA by the hypothalamic median eminence and pituitary neurointermediate lobe.

The uptake and release of gamma-[3H]-aminobutyric acid ([3H]-GABA) by the median eminence and the neurointermediate lobe of the pituitary was investigated using sucrose homogenates as crude synaptosomal preparations. Uptake in both areas showed predominantly neuronal specificity and similar Km values, but the median eminence had a considerably greater Vmax value. Release of [3H]-GABA could be stimulated by elevated K+ concentrations, in a Ca2+-dependent manner. Stimulated release was reduced by muscimol, implying the existence of presynaptic autoreceptors in both areas. A number of other transmitters and peptide hormones were demonstrated to have no effect on stimulated release of [3H]-GABA in either area.

Animals↗

Secretory cells in the nucleus pulposus of the adult human intervertebral disc. A preliminary report.

A light microscopical study was conducted to ascertain the type of cells in the nucleus pulposus of the adult human intervertrebral disc. Three lumbar intervertebral discs were removed from each of 15 male and female adults at autopsy (ages ranged from 19 to 62 years). The tissue was fixed in formalin, decalcified in formic acid, dehydrated in a graded series of ethanol, embedded in paraffin, and serially sectioned at 7-10 micron. Tissue sections were affixed to albuminized glass slides and stained either by hematoxylin and eosin or hematoxylin and Van Gieson's stain. The cells of the bulk of the nucleus pulposus consisted of chondrocytes and a few fibroblasts; however, the subchondral matrix of the nucleus pulposos contained numerous stellate cells with (from 1 to 8) unusually long (up to 80 micron) primary cytoplasmic processes that often branch into secondary processes. The cell processes contained cytoplasmic varicosities at various intervals along their lengths; and their endings often expanded into bulbous, vesicle-filled process terminals. The surrounding extracellular matrix usually contained numerous, vesicle-filled, eosinophil matrix bodies. Morphological similarities of cytoplasmic varicosities, process terminals, and matrix bodies, as well as the apparent budding of process terminals, suggest that these previously unidentified cells are secreting an unknown matrix component into the subchondral matrix of the nucleus pulposus of the adult human.

Adult↗

On the assessment of the in vitro biopotency and site(s) of action of drugs affecting adrenal steroidogenesis.

Dispersed guinea-pig adrenal cells have been employed in the in vitro estimation of the biological potency and sites of action of drugs acting against the adrenal. The effect of 12 drugs on cortisol secretion from cells stimulated with adrenocorticotrophin (ACTH, 50 ng/L, a 95% saturating dose) has been tested. All the drugs depressed cortisol output in a dose-related fashion. The concentration of drug which inhibited secretion by 50% was (mumol/L, mean +/- SEM): etomidate 0.1 +/- 0.002; epostane 0.44 +/- 0.02: 17-ketotrilostane 0.55 +/- 0.04: trilostane 1.3 +/- 0.1: metyrapone 3.5 +/- 0.6: cyproterone acetate 4.6 +/- 0.2: megestrol acetate 11 +/- 2: danazol 22 +/- 2: aminoglutethimide 41 +/- 5: stanozolol 50 +/- 4: thiopentone 160 +/- 18: propofol 170 +/- 18. The sites of the anti-steroidogenic effect of seven of these drugs have also been established using a method based upon the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of cortisol by adrenal cells. Propofol acts between ACTH binding and pregnenolone production, trilostane, megestrol acetate and cyproterone acetate are 3 beta-hydroxysteroid dehydrogenase inhibitors whereas metyrapone, etomidate and thiopentone act at 11 beta-hydroxylase.

Adrenal Cortex↗

Intravenous immunoglobulin therapy for idiopathic thrombocytopenic purpura.

Twenty-two patients with idiopathic thrombocytopenic purpura were treated with high-dose intravenous immunoglobulin infusions using an intact intravenous immunoglobulin preparation and a product designed for intramuscular administration. Seventeen patients (77%) responded favourably (rise in platelet count to 100 X 10(9)/1 or above). Children responded better than the adults, and the acute cases better than the chronic. Splenectomy and the presence of detectable platelet antibody had no effect on the response rate. Both products induced identical responses.

Acute Disease↗

Effects of gamma-aminobutyric acid receptor agonists on the secretion of growth hormone, luteinizing hormone, adrenocorticotrophic hormone and thyroid-stimulating hormone from the rat pituitary gland in vitro.

The effects of the gamma-aminobutyric acid receptor agonists muscimol and baclofen were investigated on the secretion of GH, LH, ACTH and TSH from the anterior pituitary in vitro using a rapid superfusion system. A bicuculline-sensitive stimulatory effect of muscimol was demonstrated on the secretion of GH, LH and ACTH but not TSH. Baclofen had no effect on the basal secretion of any of the hormones, but inhibited LH-releasing hormone-stimulated release of LH and K+- and Ba2+-stimulated release of ACTH. The benzodiazepine Roll-6896 and the barbiturate secobarbital were found to potentiate the effect of muscimol on GH secretion. These results demonstrate the presence of GABAA receptors on somatotrophs, gonadotrophs and corticotrophs, and the presence of GABAB receptors on gonadotrophs and corticotrophs. Thyrotrophs appear devoid of GABA receptors.

Adrenocorticotropic Hormone↗

Animal fat effects on nutrient utilization.

Laying hens were employed to study the effects of carrier on the true metabolizable energy (TME) of tallow using corn, milo, soybean meal, wheat bran, and dehydrated alfalfa meal with tallow at 0, 2, 4, or 6%. In addition to bomb calorimetry measurements on feed and excreta samples, tallow TME values were calculated from absorbability data. Estimates of TME for tallow varied with carrier feedstuff from 7.19 kcal/g in soybean meal to 13.62 kcal/g when wheat bran was fed. For the corn, milo, and soybean meal series only fat retentions were significantly affected by tallow supplementation. Calculated tallow absorbabilities were 101.8% with corn, 95.8% with milo, and 107.3% with soybean meal. Highest tallow TME values were obtained with wheat bran and dehydrated alfalfa meal, apparently due to increase protein retention from wheat bran and to both improved protein retention and starch absorption with dehydrated alfalfa meal.

Animal Feed↗

The use of collagen in oral surgery.

The suitability of collagen as a biomaterial for soft tissue temporary cover or implantation is discussed. Current methods used to cover areas denuded of mucosa in the mouth using split skin, mucosa and dermal autografts are examined. The properties of an ideal mucosal graft are stated and the suitability of a collagen heterograft in the form of freeze dried, chemically treated pigskin is questioned. A collagen xenograft has been used as a biological cover for areas of the mouth where soft tissue has been excised, for example, a denture irritation hyperplasia or leukaplakia and when increased wound strength or support is required to enable a wound to heal satisfactorily for example an oroantral communication. The results of the work are encouraging, demonstrating in most instances, satisfactory healing with no excess of granulation tissue, satisfactory mechanical properties in the early stages to resist the forces of mastication; a low rate of infection and no evidence of a hypersensitivity reaction to the modified foreign protein being evident clinically. Current adverse reactions seen after an injectable form of collagen is used are mentioned. A collagen xenograft would thus appear to satisfy many of the criteria of an 'ideal' biological cover and merits further critical examination.

Adult↗

Decompression sickness incidence over 63 months of hypobaric chamber operation.

U.S. Army hypobaric chamber operations over a 63-month period were retrospectively reviewed, and incidence rates for decompression sickness were calculated. The overall incidence rate was 1.38/1000 exposures. The rate for interior technicians monitoring chamber operations was 6.16/1000 exposures. The rate for students was 0.64/1000 exposures. The increased incidence of decompression sickness for technicians was especially pronounced for the 10,668-m and 13,106-m flight profiles. Rapid decompression after the 7,620-m flight profile did not appear to increase the incidence of decompression sickness.

Altitude↗

Evidence for GABAB autoreceptors in median eminence.

The effect of the selective GABAB receptor agonist baclofen was examined on stimulus-induced release of [3H]GABA from crude synaptosomal preparations of median eminence (ME) and pituitary neurointermediate lobe (NI). Baclofen stereospecifically inhibited release of [3H]GABA in a concentration-dependent manner from ME but had no effect in NI. The effect of (+/-) baclofen was partly antagonized by the putative GABAB receptor antagonist delta-aminovaleric acid, but these experiments were complicated by a degree of heteroexchange. These results provide the first evidence for GABAB autoreceptors in the CNS.

Animals↗

Effects of GABA receptor agonists on [3H]dopamine release from median eminence and pituitary neurointermediate lobe.

The effects of GABAA and GABAB receptor agonists were examined on stimulus-induced release of [3H]dopamine ([3H]DA) from a synaptosomal preparation of median eminence (ME) and pituitary neurointermediate lobe (NI). Muscimol was found to inhibit [3H]DA release from ME in a bicuculline-sensitive, strychnine-insensitive manner, but had no effect in NI. Homocarnosine also inhibited [3H]DA release from ME. Baclofen had no effect in either area. These results demonstrate an interaction between two putative prolactin release inhibitory factors, DA and GABA, at the site of secretion into hypophysial portal blood.

Animals↗

Chemiosmotic coupling in cytochrome oxidase. Possible protonmotive O loop and O cycle mechanisms.

Using the principle of specific vectorial ligand conduction, we outline directly coupled protonmotive O loop and O cycle mechanisms of cytochrome oxidase action that are analogous to protonmotive Q loop and Q cycle mechanisms of QH2 dehydrogenase action. We discuss these directly coupled mechanisms in the light of available experimental knowledge, and suggest that they may stimulate useful new research initiatives designed to elucidate the osmochemistry of protonmotive oxygen reduction in cytochrome oxidase.

Biological Transport↗