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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
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

An alpha 2 receptor mediates the selective inhibition by noradrenaline of nociceptive responses of identified dorsal horn neurones.

Extracellular recordings were made of 59 neurones with long, ascending projections (spinocervical tract (SCT) and dorsal column postsynaptic (DCPS) neurones) in the lumbar dorsal horn of anaesthetized and paralyzed cats. All showed prominent excitatory responses to innocuous stimuli, applied to their cutaneous receptive fields on the ipsilateral hindlimb. The majority of the population investigated (83%) was multireceptive, being activated by noxious as well as innocuous cutaneous stimuli. Drug effects were examined on a regular cycle of responses to these cutaneous stimuli and also to DL-homocysteic acid (DLH). In 49 multireceptive SCT and DCPS neurones, ionophoretically-applied L-noradrenaline (NA) produced a potent selective inhibition of the nociceptive responses (to heat or pinch) in 40 out of 44 SCT and 3 out of 5 DCPS neurones, with no statistically significant change in the responses to innocuous brush or DLH, or in spontaneous activity. NA had no effect on the majority of cells (8 out of 11) that responded only to innocuous stimuli. In 19 SCT neurones that showed NA-selectivity, the alpha 2-selective agonists clonidine (in 12 out of 15) and metaraminol (in 2 out of 3) mimicked this selective effect, whereas, the alpha 1 agonist, phenylephrine and the beta agonist, isoprenaline did not. Furthermore, the alpha 2 antagonists, yohimbine and idazoxan (RX781094), either reversed or reduced the potency of the NA-elicited inhibition of nociceptive responses in all 7 SCT neurones tested. These results are discussed in relation to other evidence for spinal antinociceptive effects of noradrenergic systems acting at a spinal level and the possible involvement of an alpha 2 receptor in such effects.

Animals↗
PubMed1985

A simple in vitro approach to the estimation of the biopotency of drugs affecting adrenal steroidogenesis.

Dispersed guinea-pig adrenal cells can be maximally stimulated to secrete cortisol by adrenocorticotrophin (ACTH greater than 50 ng/l). Further, this stimulation appears to be specific to ACTH alone, with other naturally occurring chemicals (e.g. steroids, protein hormones) at supra-physiological concentrations being without effect on cortisol production. The effect of drugs of differing structure and therapeutic function (aminogluthethimide, metyrapone, trilostane, 17-ketotrilostane, danazol, epostane, megestrol acetate, stanozolol and etomidate) on ACTH-stimulated (50 ng/l) cortisol production has been tested in this system. All the drugs depressed steroid output in a similar dose-related fashion. The concentration of drug which inhibited cortisol output by 50% was (mumol/l, mean +/- SEM): etomidate 0.097 +/- 0.002: epostane 0.44 +/- 0.02: 17-ketotrilostane 0.55 +/- 0.04: trilostane 1.3 +/- 0.1: metyrapone 3.5 +/- 0.6: megestrol acetate, 11 +/- 2: danazol 22 +/- 2: aminogluthethimide 41 +/- 5: stanozolol 50 +/- 4. Thus, etomidate, an anaesthetic, is more potent than the established anti-steroidogenic drugs metyrapone, aminogluthethimide and trilostane. Further, direct anti-steroidogenic effects have been demonstrated for megestrol acetate and stanozolol for the first time. We conclude that this technique offers a promising new approach to the assessment of biological potency of drugs affecting endocrine tissues.

Adrenal Glands↗
PubMed1985

Some characteristics of human adrenal microsomal 21-hydroxylase activity.

The following general characteristics of 21-hydroxylase activity were determined using pooled microsomes obtained from three glands. Enzyme activity exhibited a broad pH dependence, being optimal between pH 7.4-pH 7.8, and was maximal with NADPH in the range 2 to 4.75 X 10(-4)mol/l. No microsomal 21-hydroxylase activity was detected in the absence of NADPH or substrate and when heat denatured microsomes were employed. Enzyme activity was depressed by greater than 75% in the presence of 100% oxygen or nitrogen. In a second set of experiments, microsomal fractions were prepared individually from 7 glands. In the presence of 17 alpha-hydroxy progesterone (2.0 X 10(-7) and 2.0 X 10(-6)mol/l) product formation was linear with time for up to 90 s when the microsomal protein concentration was 5, 10 and 20 micrograms/ml. Between 5 and 30% of the substrate was converted during the first 60 s. In 5/7 of the glands the addition of the autologous cytosol (20 micrograms protein/ml) was without effect, and enzyme activity (using a 60 s reaction and either 2.0 X 10(-7) or 2 X 10(-6)mol/l 17 alpha-hydroxy progesterone was directly proportional to the microsomal protein concentration (range 0-20 micrograms/ml). With the other 2 adrenals 21-hydroxylation was not proportional to the same range of microsomal protein concentrations, although it became so upon the addition of cytosol, which significantly augmented activity. There was considerable variation in enzyme activity between glands from different individuals (Vmax ranging from 2.6 to 16.6 X 10(-9) mol/min/mg protein) and in the apparent Km's (from 0.22 to 1.1 X 10(-6)mol/l). In the two preparations sensitive to cytosol, the Vmax increased 2-fold, and the Km was 3 times lower. Cytosol was without effect upon the kinetic characteristics of the other 5 microsomal preparations. Ascorbic acid (1 X 10(-3) mol/l) depressed enzyme activity by 25-43% whereas oxidised and reduced glutathione (1 X 10(-3) mol/l) showed a slight and variable effect upon 21-hydroxylation.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Apparent reversals in trapezia: confirmation of the 'tan apex ratio' heuristic.

A new model for predicting the frequencies of apparent reversals in rotating trapezia, proposed by the authors in 1983, is validated and extended in two studies. Experiment 1 showed that the model retained its predictive efficiency over an increased range of shapes and viewing distances, and with trapezia made of sheet metal and not, as previously, of wire. Experiment 2 was designed to investigate an unexpected effect, in which the specificity of prediction was found to decrease as the corners of the stimulus objects were slightly rounded.

Humans↗
PubMed1985

Effect of propofol, thiopentone and etomidate on adrenal steroidogenesis in vitro.

The i.v. anaesthetic agents propofol, thiopentone and etomidate inhibited ACTH-stimulated production of cortisol by guineapig dispersed adrenal cells in a dose-related manner. For two of the drugs, propofol and thiopentone, inhibition occurred over a similar concentration range: 2 X 10(-5) - 5 X 10(-4) mol litre-1. With etomidate, inhibition occurred over a much lower concentration range (5 X 10(-8) - 5 X 10(-6) mol litre-1). The concentrations of anaesthetic which induced 50% inhibition of cortisol secretion were propofol 1.7 X 10(-4), thiopentone 1.6 X 10(-4), and etomidate 1.0 X 10(-7) mol litre-1.

Adrenal Glands↗