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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 829 records · Page 46Linked to original sources

A rise in the plasma activities of hepatic enzymes is not a common consequence of hypoglycaemia.

Eight otherwise healthy insulin-dependent diabetic patients were subjected to controlled, symptomatic hypoglycaemia for 20 min (median glucose concentration 1.7 mmol/l, range 1.0-2.6 mmol/l). Concentrations of plasma adrenaline and plasma vasopressin were significantly increased, indicating normal counter-regulatory responses for these hormones. Plasma activities of the hepatic enzymes AST, ALT, LDH, GGT, and CK did not increase during or following the period of hypoglycaemia. Thus, abnormal plasma enzyme activities noted after clinical hypoglycaemia should be fully investigated, and not disregarded as due to the hypoglycaemic episode.

Adult↗

In utero exposure to organic solvents and human neurodevelopment.

Recent reports of growth and mental retardation in infants whose mothers abused solvent-containing substances, and of an association between central nervous system malformations and solvent exposure, have suggested that in utero exposure to organic solvents may have a profound effect on the development of the human brain. The present investigation compared the neurobehavioral development of 41 children whose mothers worked with organic solvents during pregnancy with a group of matched, unexposed children. The children were compared on a variety of measures, including the McCarthy Scales of General Abilities, growth (weight, height and head circumference) and mother's report of developmental milestones, behavior and personality. Potential confounders were controlled for in multiple regression analyses. Despite adequate power, no differences could be found between the two groups on any of the measures of neurobehavioral development or growth. This study suggests that in utero exposure to relatively low levels of organic solvent is not associated with adverse neurodevelopmental outcome.

Brain↗

Thyroid hormone nuclear receptors in skeletal muscle as influenced by environmental temperature and energy intake.

Young litter-mate pigs were kept at either 10 or 35 degrees C and fed either a high (H) or a low (L) food intake producing four groups: 10 H, 10 L, 35 H and 35 L. The numbers of receptors for thyroid hormone in the nuclei of skeletal muscle were estimated and found to be greatest in the 35 H group and least in the 10 L group. The numbers of receptors in the 10 H and 35 L groups were similar and took intermediate values. It is suggested that the differences in receptor numbers represent an adaptation which regulates the tissue response to thyroid hormone. Some possible consequences of this adaptation are discussed.

Animals↗

Lectin-gold labeling of glycoconjugates in normal and Brattleboro rat papilla: effect of vasopressin.

Some reports suggest that the plasma membrane glycocalyx of collecting duct epithelial cells, as well as interstitial glycoconjugates, may be involved in vasopressin action and urinary concentration. In view of this, we have used the lectin-gold technique to map and quantify Helix pomatia lectin (HPL)-binding sites in the inner medulla of kidneys from normal Long-Evans rats, vasopressin-deficient Brattleboro rats, and Brattleboro rats treated for up to 5 wk with exogenous vasopressin. The results show that the labeling of epithelial cell plasma membranes from collecting ducts and thin limbs of Henle is not different between normal and Brattleboro rats, and the labeling is not modified by chronic vasopressin treatment. In contrast, the heavy interstitial labeling seen in normal rats is virtually absent from Brattleboro rats, but it is progressively restored by chronic vasopressin treatment of Brattleboro rats. These results show that vasopressin does not modify HPL-binding glycoconjugates on epithelial cell plasma membranes, but that vasopressin treatment has a major effect on HPL-binding glycoconjugates in the medullary interstitium.

Animals↗

Opioid-noradrenergic interactions in the neurohypophysis. II. Does noradrenaline mediate the actions of endogenous opioids on oxytocin and vasopressin release?

The function of noradrenaline in the rat neurohypophysis was investigated by examining the effects of selective adrenergic receptor agents on electrically evoked release of oxytocin, arginine vasopressin, and noradrenaline using the [3H]-noradrenaline technique. Since endogenous opioids in the neurohypophysis suppress release of both neurohormones and of noradrenaline, we assessed the role of noradrenaline in mediating opioid actions on neurohormone secretion by examining modification of the action of the opioid antagonist naloxone by adrenergic receptor agents. The data suggest (1) that in addition to opioid receptors, 'presynaptic' alpha 2-receptors regulate release from neurohypophysial noradrenaline terminals; (2) noradrenaline released from neurohypophysial terminals acts on beta- and alpha 1-receptors to facilitate both oxytocin and arginine vasopressin release: this action only becoming evident at elevated levels of endogenous noradrenaline release attained following removal of presynaptic opioid or alpha 2-regulation, and (3) opioid peptides within the neurohypophysis act to inhibit oxytocin and, to a lesser extent, arginine vasopressin secretion, partly through inhibiting release of facilitatory noradrenaline. We propose a model in which opioids act in the neurohypophysis both independently of noradrenaline via kappa-receptors on neurosecretory terminals or pituicytes and also via interaction with the noradrenaline system.

Animals↗

Localization of a proton-pumping ATPase in rat kidney.

The distribution of vacuolar H+ATPase in rat kidney was examined by immunocytochemistry using affinity-purified antibodies against the 31-, 56-, and 70-kD subunits of the bovine kidney proton pump. Proximal convoluted tubules were labeled over apical plasma membrane invaginations, and in the initial part of the thin descending limb, apical and basolateral plasma membranes were moderately stained. Thick ascending limbs and distal convoluted tubules were apically stained although the intensity was greater in the distal convoluted tubule. Collecting duct principal cells were virtually unlabeled, but intercalated cells had intense staining with an apical, basolateral or diffuse pattern in the cortex, and exclusively apical staining in the medulla. These results (a) show the presence of an H+ATPase in the apical plasma membrane of the proximal tubule that may contribute to H+ transport in this segment; (b) provide direct evidence that the intercalated cell contains most of the H+ATPase detectable in the collecting duct, supporting its proposed role in H+ transport; (c) demonstrate that subpopulations of cortical intercalated cells have opposite polarities of an H+ATPase, consistent with the presence of both proton- and bicarbonate-secreting cells; and (d) suggest a role for the H+ATPase in acid/base regulation or H+ transport in segments other than the collecting duct and the proximal tubule.

Animals↗

A clinical trial of the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity.

Twenty-nine overweight schizophrenic patients maintained on depot neuroleptic injections who wished to lose weight took part in a double-blind, placebo-controlled trial of 30 mg D-fenfluramine. All subjects received dietary advice. Sixteen patients completed the 12-week trial. Rate of weight loss was significantly greater in those taking D-fenfluramine. Side-effects were reported, but no deterioration in mental state was noted.

Adult↗

Endogenous opioid actions and effects of environmental disturbance on parturition and oxytocin secretion in rats.

Blood samples were taken from conscious, chronically-catheterized rats during parturition for measurement of oxytocin by specific radioimmunoassay. After the birth of the 3rd pup, rats were allowed to remain in their nesting cage (undisturbed rats) or were transferred for 45 min to a glass bowl (disturbed rats); at the time of transfer, rats were given an i.v. injection of the opioid antagonist naloxone or saline vehicle. Subsequent parturition was prolonged in saline-treated disturbed rats, but not in naloxone-treated disturbed rats. Parturition was significantly hastened in naloxone-treated undisturbed rats. Naloxone injections were followed by a large rise in plasma oxytocin concentrations in disturbed and undisturbed rats. We conclude, from a statistical analysis of the relationship within experimental groups between plasma oxytocin concentration and speed of parturition, that the effects of disturbance and of naloxone upon parturition may be accounted for, at least in part, by their effects upon oxytocin release. However, the effects of disturbance on parturition may not be mediated entirely by activation of opioid pathways. Naloxone did not potentiate oxytocin release in non-pregnant rats, or on Day 1 post partum, but did potentiate oxytocin release on Day 22 of pregnancy even in rats before the onset of parturition. Endogenous opioid pathways regulating oxytocin release therefore appear to be active during late pregnancy and during parturition itself.

Animals↗

Community health effects of a municipal water supply hyperfluoridation accident.

For 12 hours, excess hydrofluorosilicic acid was diverted to a 127-home community water supply. Fluoride levels peaked at 51 parts per million (ppm). Water acidification caused copper to leach from the domestic plumbing; raising copper levels to 25-41 ppm. Fifty-two (33 per cent) of those who drank hyperfluoridated water developed mild gastroenteritis. Vomiting was uncommon and symptom onsets usually occurred greater than 30 minutes after drinking water; suggesting that fluoride, rather than copper, caused illness. Skin contact with hyperfluoridated water caused itching and skin rashes.

Accidents, Occupational↗

Vasopressin stimulates endocytosis in kidney collecting duct principal cells.

In target epithelia, a vasopressin-induced water permeability increase is accompanied by the appearance of intramembranous particle (IMP) clusters, probably representing water-permeable patches, in the apical plasma membrane of responding cells. In the collecting duct principal cell, we have previously shown that these clusters are located in clathrin-coated pits. To determine whether vasopressin induces the endocytic uptake of these membrane domains in principal cells, we have examined the uptake of horseradish peroxidase (HRP) by principal cells of normal rats, vasopressin-deficient Brattleboro rats, and vasopressin-treated Brattleboro rats, following intravenous injection of HRP. By quantitative electron microscopy, principal cells of Brattleboro homozygous rats were found to take up much less HRP into cytoplasmic vesicles than normal rats, and HRP uptake was increased to normal levels in vasopressin-treated Brattleboro rats. Many invaginating coated pits at the cell surface were loaded with HRP reaction product, indicating their participation in the observed endocytosis of HRP. We conclude that vasopressin stimulates endocytosis in collecting duct principal cells. Since we have already shown that IMP clusters are found in coated pits at the cell surface, the endocytic removal of these putative water-permeable patches from the apical membrane seems to occur via a clathrin-mediated mechanism in this tissue.

Animals↗

Rat IL-3 stimulates the growth of rat mucosal mast cells in culture.

Rat mast cells with the properties of mucosal mast cells (MMC) proliferate in cultures of haemopoietic tissue in the presence of conditioned medium (CM) from antigen- or mitogen-activated T lymphocytes. The present study shows that recombinant rat interleukin-3 (rIL-3) both stimulated the development of MMC from bone marrow (BM) precursors and maintained the proliferation of rat MMC lines in an identical manner to that of CM. The content per cell of the MMC granule-specific proteinase RMCPII was similar in both IL-3- and CM-stimulated cultures. Passage of CM through DEAE-cellulose separated two active peaks that stimulated autologous MMC proliferation. The biochemical properties of peak 1 were similar to those of murine IL-3 and stimulated multi-potential stem cell development in soft agar cultures of BM cells from rats treated with 5-fluorouracil (which enriches for haemopoietic stem cells). RIL-3 was also active in this assay whereas peak 2 was not, demonstrating that peak 1 contained IL-3 activity. The presence of MMC in the majority of multi-potential colonies in the soft agar cultures confirmed the early stem cell origin of the MMC lineage. The cultured BM-derived mast cells in the rat are analogues of the MMC subset that is most readily observed proliferating in the gastrointestinal tract in response to helminth parasite infection. The demonstration that IL-3 is responsible for the development and proliferation of MMC should lead to a better understanding of the functional roles of these cells.

Animals↗

Comparative study of the lipid composition of the liver and bile from broiler birds during growth and egg laying.

A comparative study was made of biliary and liver lipid compositions during the growth and egg laying periods of the broiler bird. The liver lipids showed high concentrations of triacylglycerols at seven weeks old which increased when egg laying proceeded. At seven weeks old the lipids of the bile also showed high levels of triacylglycerols which decreased with the onset of egg laying but increased slightly as egg laying proceeded. At seven weeks old the fatty acid composition of the bile triacylglycerols differed from that of the liver which in turn was different from that of the liver at the onset of egg laying. In particular the bile triacylglycerols had lower levels of oleic but higher levels of arachidonic and docosahexaenoic acids. By the late egg laying period, the fatty acid compositions of the bile and liver triacylglycerols were similar. The unique bile lipid composition and its changes are discussed in relationship to the major features of liver lipid metabolism in the broiler bird and the mechanism of lipid deposition during egg laying.

Animals↗

Comparable effects of 1800- and 2400-rad (18- and 24-Gy) cranial irradiation on height and weight in children treated for acute lymphocytic leukemia.

To examine the effects of "low-dose" cranial irradiation on growth and to determine if one can predict patients in whom growth will be most affected, we studied 47 children with acute lymphocytic leukemia who had been treated with 2400 rad (24 Gy), 1800 rad (18 Gy), or no whole-brain irradiation. Serial measurements of height, weight, and weight for height were obtained by retrospective chart review. The effects of 1800 rad (18 Gy) and 2400 rad (24 Gy) treatment were indistinguishable. Height percentiles among irradiated patients decreased by a mean of 12% six months after diagnosis, and growth generally did not catch up. Moreover, although 33 irradiated patients maintained heights within the normal range, In 11 patients (33%) a dramatic falloff occurred such that by three years following diagnosis their height for age was more than 30 percentiles below the original value. These patients were all identifiable at six months since their height percentiles had already decreased by more than 15%. Although weight percentiles did not change following irradiation, the weight-for-height ratio increased and patients were relatively stockier three years after therapy than they had been at diagnosis. In patients who had received chemotherapy alone, the weight-for-height ratio also increased, but this appeared to be due to a disproportionate increase in weight. Longer follow-up and evaluation of larger cohorts of patients treated with 1800 rad (18 Gy) will be needed to confirm these results.

Adolescent↗