Biomedical subjects
Publications and source records attributed to S Wilson.
Experiences arising from the work of a multi-disciplinary psychotherapy liaison team in the primary care setting are described. Special emphasis is given to the difficulties encountered in working relationships. Attention is drawn to the complexity of the inter-professional relationship, its unconscious roots, and its influence on the quality of patient care.
The latencies and latency rates of H and F waves were determined by percutaneous stimulation of the ulnar and the tibial nerves of healthy cats. In the ulnar and tibial nerves, the latency rates of H wave evoked compound action potentials were 49.1 +/- 7.3 and 44.1 +/- 2.7 m/s, respectively, and of F waves were 68.1 +/- 9.6 and 57.1 +/- 6.2 m/s, respectively. The H wave response of cats was more variable in latency and amplitude than that reported in the dog.
We have used a quantitative "experimental" metastasis assay in the embryonic chick, an immunodeficient host, to examine in vivo growth properties of ras oncogene-transformed NIH3T3 cells. We found that two independently derived populations of NIH3T3 cells that had been morphologically transformed with the T24 human H-ras oncogene were able to grow in vivo following i.v. injection. Nontransformed control NIH3T3 cells with normal morphology did not grow in this assay. Spontaneously arising morphological transformants from control NIH3T3 cell populations were also tested and did not grow in this assay. We conclude that the H-ras gene can confer experimental metastatic ability on nonmetastatic NIH3T3 cells, that the ras gene alters the cells in some way beyond in vitro morphological transformation, and thus that the in vitro transformation assay detects only part of the malignant phenotype of these cells.
The suggestion that defective thermoregulatory thermogenesis in the genetically obese (ob/ob) mouse is due to a low thermic response to noradrenaline has been investigated using both noradrenaline and the longer-acting sympathomimetic compounds, ephedrine and BRL 26830A. Below thermoneutrality (23.5 degrees C) the metabolic rate of obese mice was lower than that of their lean littermates, whereas at a thermoneutral temperature (31 degrees C) the metabolic rate of the obese mice was as high as that of lean mice. This confirms the view that the ob/ob mouse has defective thermoregulatory thermogenesis. However, in C57BL/6 mice, this defect is not due to a failure to respond to noradrenaline, because at 31 degrees C the maximum thermic effects of noradrenaline, ephedrine and BRL 26830A were as high in obese as in lean mice and at 23.5 degrees C they were higher in obese than in lean mice. Furthermore, the response of brown adipose tissue to beta-adrenoceptor stimulation appears normal since noradrenaline caused a normal rise in brown adipose tissue temperature, and treatment with noradrenaline or BRL 26830A in vivo caused a normal increase in GDP binding by brown adipose tissue mitochondria. At 31 degrees C propranolol depressed metabolic rate equally in lean and obese C57BL/6 mice, whereas at 23.5 degrees C it depressed metabolic rate more in lean than obese mice. In contrast to C57BL/6 mice, Aston ob/ob mice showed a reduced thermic response to noradrenaline. These results suggest that defective thermoregulatory thermogenesis in the ob/ob mouse is primarily due to a reduced ability to raise sympathetic tone, but in some strains an additional failure in the thermic response to noradrenaline may develop.
EC50 and relative intrinsic activity values were obtained for isoprenaline, fenoterol, salbutamol, prenalterol and three new beta-adrenoceptor agonists, BRL 28410, BRL 35113 and BRL 35135 on rat white adipocyte lipolysis, rat atrial rate and tension, rat uterus tension and guinea-pig tracheal tension. Fenoterol and salbutamol were selective for tracheal and uterine responses, prenalterol was selective for atrial responses, but BRL 28410, BRL 35113 and BRL 35135 were selective for the adipocyte lipolytic response. pA2 values for propranolol, practolol, ICI 118,551 and sotalol were obtained on adipocytes, atria and trachea. pA2 values for propranolol and sotalol were much lower on adipocytes than on atria or trachea. The pA2 value for practolol was lower on adipocytes than on atria and the pA2 value for ICI 118,551 was lower on adipocytes than on trachea. Both agonist and antagonist studies therefore suggest that the rat adipocyte lipolytic receptor does not fit into the current beta 1/beta 2-adrenoceptor classification.
In 10 cats, an ipsilateral section of the inferior alveolar nerve was performed following which horseradish peroxidase was deposited in cavity preparations of either ipsicentral incisors (8) or canines (2). The animals were sacrificed in 24 h, and the ipsilateral nerve to mylohyoid and both semilunar ganglia were prepared histochemically for observation. Labeled axons were found in 6 of 8 cats, whose incisors were prepared, and 4 of the 6 had labeled ganglion cells. In the two remaining cats with incisor preparations, no labeled ganglion cells were found; however, labeled axons were found in the mylohyoid nerve. Neither labeled axons or cells were found in those cats whose canines were prepared. One case of cross-innervation was noted. These results suggest that in addition to the inferior alveolar nerve, the nerve to mylohyoid and possibly other accessory neural pathways are involved in incisor innervation in cats.
Cold acclimation increases the thermogenic capacity of brown adipose tissue (BAT) and this is associated with both a general hypertrophy of the tissue and a selective increase in the proportion of a specific 32,000 molecular weight, GDP-binding protein in the mitochondrial membrane. This protein regulates the activity of the major thermogenic pathway of BAT. Although noradrenaline mediates the acute thermogenic response to cold, repeated injections of this hormone fail to mimic cold acclimation in that they do not increase the proportion of 32,000 molecular weight (32K) protein. However, noradrenaline is rapidly metabolised in vivo and effective levels would only be maintained over a short period of time following administration of the hormone. We have therefore investigated the effects of two long-acting sympathomimetic compounds: fenoterol, a beta-adrenoceptor agonist, and ephedrine, which causes release of noradrenaline from nerve terminals. Chronic treatment with both of these compounds increased the GDP-binding ability of BAT mitochondria and the proportion of 32K protein as measured by gel electrophoresis. We suggest that prolonged stimulation of beta-adrenoceptors, probably in BAT, but possibly also in other tissues, is sufficient to produce a selective increase in GDP-binding protein in BAT, and it is unnecessary to invoke any factor that is not a consequence of beta-adrenoceptor stimulation to explain the effect of cold.
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Gliquidone (Glurenorm) and glibenclamide were compared in a cross-over study of 20 non insulin dependent diabetics. Both drugs achieved similar levels of control, as measured by self home monitoring, glycosylated haemoglobin and N-acetyl-beta-D-glucosamidase levels. However, with glibenclamide hyperglycaemic control was only achieved at the expense of more hypoglycaemic episodes. The study examined the tailoring of drug dosage to the patients needs and found that in the majority of patients it was necessary to give both glibenclamide and gliquidone thrice daily. It confirmed the acceptability of self glucose monitoring in a home population.
Further biochemical characterisations of the 20 kd and 67 kd EPF active polypeptides from pregnant ewes' sera are described. Both polypeptides are shown to possess compact, disulphide linked domains which are almost totally resistant to proteolytic attack without prior reduction. In contrast to previous reports on the influence of ammonium sulphate on the expression of EPF activity, neither the biochemical nor the activity characteristics of either polypeptide is changed by ammonium sulphate fractionation. In addition, direct comparative studies have been performed which clearly distinguish the EPF active polypeptides from the known ovine hormones, prolactin, placental lactogen and growth hormone.
The intracellular sites of storage for human decidual- and pituitary-derived prolactins have been determined by measuring the hormones in subcellular fractions following differential and density gradient centrifugations. In decidual tissue, 78 +/- 4% (mean +/- SE, n = 5) of the prolactin was detected in the post-microsomal supernatant, while 98% of the prolactin in the pituitary was detected in mitochondrial and microsomal particulate fractions. Following centrifugation on sucrose density gradients, decidual prolactin was distributed diffusely throughout the gradients, while greater than 90% of the pituitary prolactin sedimented as a single peak with a mean density of 1.22 g/cm3. These studies indicate that, unlike pituitary prolactin, decidual prolactin is not stored in secretory granules. Differences in the intracellular storage sites of decidual and pituitary prolactins may explain observed differences in the regulation of prolactin secretion by decidual and pituitary tissues.
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The distance between the branching point of the mylohyoid nerve to the entrance of the inferior alveolar nerve into the mandibular canal was studied in 37 adult human cadavers. On the average, this branching distance was 14.7 mm, which is greater than previously reported. Also found was a 43% incidence of extension of the mylohyoid nerve beyond the muscle to foramina on the lingual aspect of the mandible. If the mylohyoid nerve mediates sensory information from the anterior incisors, then the factor of an increased branching distance may become important in terms of the dilution of the anesthetic agent during diffusion and the amount of nerve length exposed to the anesthetic agent. These findings may also account in part for the purported greater success of the so-called Gow-Gates type of injection technique compared with that of the conventional mandibular block.
We have developed a highly efficient system for producing hepatitis B virus surface antigen in cultured mammalian cells. This system utilizes a recombinant bovine papilloma virus in which the hepatitis surface antigen coding sequences are inserted into the 5' untranslated region of the mouse metallothionein-I gene. Mouse fibroblasts stably transformed with this molecule produce surface antigen at levels as high as 10 mg/L/24 h and can be maintained in continuous culture for up to 85 days.
Studies on BRL 26830A in rodents have shown that thermogenic beta-adrenoceptor agonists have potential for the therapy of obesity. BRL 26830A reduced body weight gain in ob/ob mice and fa/fa rats by reducing lipid accumulation. It had no effect on lean body mass. BRL 26830A did not reduce food intake, its anti-obesity effect being due to stimulation of energy expenditure. This thermic effect was enhanced in the obese animals by repeat dosing. BRL 26830A did not affect body weight gain in the lean counterparts of the obese animals because its thermic effect in lean animals was reduced by repeat dosing. Brown adipose tissue is an important site of BRL 26830A-induced thermogenesis. A single dose of BRL 26830A raised brown adipose tissue temperature, depleted brown adipose tissue lipid and unmasked GDP-binding sites in brown adipose tissue mitochondria. Repeat dosing caused hypertrophy of brown adipose tissue and improved cold tolerance in mice. In-vitro studies showed that the rat brown adipocyte beta-adrenoceptor does not fall into the beta 1/beta 2 classification and BRL 28410, which mediates the biological effects of BRL 26830A in vivo, selectively stimulated the brown adipocyte receptor. It is concluded that BRL 26830A achieves its anti-obesity effect by mimicking natural mechanisms involved in thermogenesis and the control of body weight.
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Synapses between neuroblastoma-hybrid cells and myotubes exhibit a high degree of plasticity. Increase of cyclic adenosine monophosphate (AMP) levels of the hybrid cells for several days results in the appearance of functional voltage-sensitive Ca2+ channels, which are required for evoked secretion of acetylcholine. The results show that cyclic AMP regulates synaptogenesis by regulating the expression of voltage-sensitive Ca2+ channels, and suggest that cyclic AMP affects posttranslational modifications of some glycoproteins and cellular levels of certain proteins.
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