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Biomedical subjects

H Boyd

Publications and source records attributed to H Boyd.

At least 19 recordsLinked to original sources

Inescapable shock, neurotransmitters, and addiction to trauma: toward a psychobiology of post traumatic stress.

Chronic post traumatic stress has been described as a "physioneurosis" (Kardiner 1941), that is, a mental disorder with both psychological and physiological components. The behavioral sequelae of inescapable shock in animals and of massive psychic trauma in people show a striking parallel. Inescapable shock in animals leads to both transient catecholamine depletion and subsequent stress-induced analgesia. We postulate that the numbing and catatenoid reactions following trauma in humans correspond to the central nervous system (CNS) catecholamine depletion that follows inescapable shock in animals. We further explore the evidence for a human equivalent of "stress-induced analgesia" in animals, which is known to be mediated by endogenous opioids. Although reexposure to trauma may produce a paradoxical sense of calm and control due to endogenous opioid release, a cessation of traumtic stimulation will be followed by symptoms of opioid withdrawal and physiological hyperreactivity mediated by CNS noradrenergic hypersensitivity. This hyperreactivity can, in turn, be temporarily modified by reexposure to trauma. This factor could account for voluntary reexposure to trauma in many traumatized individuals and would provide a complementary formulation to the conventional psychodynamic concept of attempted mastery of the psychosocial meaning of the trauma.

Animals

Monitoring pre-service reproductive status in dairy cows.

Combinations of oestrus detection, ovarian palpation and milk progesterone assays were used to monitor pre-service reproductive status of cows in two dairy herds over two successive years. Non-cyclical cows were identified as having no luteal tissue in their ovaries on two occasions 10 days apart. Absence of luteal tissue was determined by the presence of basal mild progesterone initially followed either by a repeat of this result or by failure to palpate a corpus luteum per rectum. In the period 32 to 56 days post partum the number of non-cyclical cows on farm A years 1 and 2 was eight out of 31 (25 . 5 per cent), and 10 out of 62 (16 . 1 per cent) and on farm B years 1 and 2 was 10 out of 68 (14 . 7 per cent) and 11 out of 85 (12 . 9 per cent) respectively. The farm A herd was high yielding, (average lactation 6380 litres), whereas the farm B herd was of average yield (4717 litres). In both herds 60 day milk yield was not related to cyclical status of pre-service cows. There was however a trend toward a greater proportion of young cows being non-cyclical. With the exception of a prolonged calving to conception interval for farm A in year 1, whether a pre-service cow was cyclical or not had no effect on when the cow was first served or on when the animal conceived. The routine incorporation of pre-service monitoring to herd fertility control programmers may however be of value in recognising the incidence of non-cyclical cows and giving an early indication of oestrus detection efficiency.

Animals

Progesterone assays and rectal palpation in pre-service management of a dairy herd.

Fifty-one dairy cows were examined three times at weekly intervals during weeks 5 to 7 after calving. Rectal palpation of the ovaries and plasma progesterone assay were used to determine cyclic ovarian function. Eight of 51 cows exhibited true anoestrus by day 49 after calving. Only 23 of 43 cycling cows were served by day 77, the end of the target period for first service. In 77 per cent of 142 examinations, rectal palpation and progesterone assay gave compatible results. Most incompatibility occurred early or late inthe cycle, or in association with cystic structures in the ovaries. Eleven of the 51 cows had cysts in the ovaries but cyclicity and fertility were not adversely affected.

Animals

beta-adrenergic receptor and adenylate cyclase in transverse tubules of skeletal muscle.

Experiments were carried out to clarify the sites of action of beta-adrenergic agonists in skeletal muscle microsomes. Microsomes were fractionated into longitudinal reticulum, terminal cisternae, and isolated transverse tubules. Transverse tubules were selectively labeled and tracked with [3H]ouabain. beta-adrenergic receptor was identified by [3H]dihydroalprenolol binding. Assays of beta-adrenergic receptor, adenylate cyclase, and protein kinase-stimulated phosphorylation showed: 1) beta-adrenergic receptor was detected in transverse tubules with a receptor density of 0.61 pmol/mg of protein. No significant binding was detected in longitudinal reticulum or in terminal cisternae. 2) Isoproterenol-stimulated adenylate cyclase was present in microsomes but was similarly confined to the transverse tubular fraction. The activity of F- stimulated cyclase in transverse tubules was 2.3 nmol/mg of protein/min. 3) No phosphorylation of microsomes by cyclic AMP and protein kinase could be detected. We conclude that the action of epinephrine on skeletal muscle is mediated through receptors and adenylate cyclase in the external membrane.

Adenylyl Cyclases

A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism.

We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis...

3',5'-Cyclic-AMP Phosphodiesterases

Hormone receptors and cyclic nucleotide metabolism in cancer cells.

The possibility of a relationship between cyclic AMP formation and metabolic processes in tumours has been investigated. Changes in basal activity and hormone-responsiveness of adenylate cyclase were demonstrated in plasma membranes and intact cells from pre-cancerous liver of rats fed a diet containing the carcinogen 3'-methyl-4-dimethylaminoazobenzene. Basal adenylate cyclase activity in hyperplastic parathyroid gland membranes was 200% higher than that in parathyroid adenoma membranes, corresponding with their relative rates of parathyroid hormone secretion in vitro. Membrane adenylate cyclase activity in hypernephromas was consistently 100--300% higher than in adjacent human renal cortex. Furthermore the adenylate cyclase activity of the tumour membranes was not influenced by a wide range of hormones which were effective stimulants in 'normal' renal cortex membranes. Conversion of 25-hydroxycholecalciferol to 1,25-dihydrocholecalciferol could not be demonstrated in either hypernephroma or adjacent renal cortical tissue. However, three of the four hypernephromas tested secreted a bone-resorbing factor. Cyclic AMP formation was increased by salmon, human and porcine calcitonins in both plasma membranes and intact cells from a poorly differentiated epidermoid cell carcinoma which was itself secreting calcitonin in culture. This phenomenon might be related to a feedback regulation of calcitonin production in this cell line. The observations are consistent with the concept of a relationship between cyclic AMP formation and certain metabolic functions (e.g. hormone production) in tumour cells.

Adenocarcinoma