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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 865 records · Page 48Linked to original sources

Prolongation of cell cycle transit time and the presence of non-cycling cells in human lymphoblastoid cells cultured under adverse conditions.

The growth characteristics of B lymphocytes infected with Epstein-Barr virus (lymphoblastoid cells) have been investigated by flow cytometric analysis of DNA content and by estimation of cell culture doubling times. It was found that the manipulative procedures involved in the cell cycle analysis resulted in a slowing of the growth rate. This slowing of growth was brought about by the prolongation of cell cycle transit times and by the entry of cells into a short-lived non-cycling pool. The entry of a proportion of the cells into the non-cycling pool may be the normal response of lymphoblastoid cells to non-optimal conditions. The non-cycling cells survived in culture with a T 1/2 of approximately 30-60 hr and continued to secrete immunoglobulin. Their surface transferrin receptors were considerably reduced, which suggests that the failure to divide may have resulted from a failure of growth factor receptors to reach a threshold value following mitosis.

B-Lymphocytes↗

Systemic release of a mast cell proteinase following nematode infections in sheep.

An enzyme-linked immunosorbent assay (ELISA) for sheep mast cell proteinase (SMCP) has been developed. Concentrations of SMCP in homogenates of abomasal tissue from parasite-immune sheep (341 micrograms SMCP/g tissues) were raised when compared to those in normal (non-infected) abomasa (0.145 micrograms SMCP/g tissue). SMCP was not detected in sera from normal animals challenged with Haemonchus contortus but was present (less than 1.0 ng SMCP/ml) in sera from 8/11 immune sheep 2 h after intra-abomasal challenge with 1 x 10(6) exsheathed Haemonchus larvae. In two further experiments, the SMCP response in gastric lymph was monitored after homologous larval challenge in sheep immune to Ostertagia circumcincta and in normal controls. SMCP (less than 1.4 ng SMCP/ml) was detected in lymph from 2/3 and 4/5 immune animals between 1 and 4 days post-challenge with 50,000 larvae, but not from normal animals. SMCP was not detected in lymph from immune animals following challenge with 1000 Ostertagia larvae. The relatively low concentrations of SMCP in blood and lymph reflect the presence of proteinase inhibitor(s) which interfered with the ELISA.

Abomasum↗

Role of activity-induced thermogenesis in twenty-four hour energy expenditure of lean and genetically obese (ob/ob) mice.

The contribution made by spontaneous physical activity to 24 h energy expenditure has been assessed in lean and ob/ob mice living at 28 degrees C. Measurements were made in young animals when the ob/ob mice were the same body weight as their lean littermates, and again when they were adult and the ob/ob mice were twice as heavy as their littermates. In the young ob/ob mice, not only was 24 h heat production lower than in their lean littermates (P less than 0.005) but so also was motor activity (P less than 0.01). In adults, total 24 h heat production was similar in lean and obese animals, and thus on the basis of metabolic body size it was considerably lower in the obese adults (P less than 0.005). The obese adults were also significantly less active than their lean littermates (P less than 0.05). Differences between genotypes were particularly marked during the night. Partition of 24 h energy expenditure into the two components of rest and activity showed that in the young ob/ob mice the lower heat production occurred because they expended 31% less energy on rest and 47% less on activity than did their lean littermates. In the obese adults, the lower heat production per unit metabolic body size was accounted for by 16% less energy being expended on rest and 74% less on activity than in the lean mice. It is concluded that differences in motor activity between lean and ob/ob mice could account, at least in part, for the development and maintenance of obesity in these animals.

Animals↗

In vivo studies with two phospholipase C fractions from Pseudomonas aeruginosa.

Two phospholipase C fractions were detected in culture supernatants from Pseudomonas aeruginosa ATCC 19660, PAO1, and D10C by preparative polyacrylamide gel electrophoresis. Both hemolytic fractions from strain ATCC 19660 were isolated by polyacrylamide gel electrophoresis and were found to cause paralysis, death, dermonecrosis, footpad swelling, and vascular permeability in mice. In vivo toxicity was directly associated with enzymatic activity.

Animals↗

Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine.

Liver biopsies were performed on 51 regularly transfused patients with beta thalassaemia, age range 5-36 (mean 18.6) years, who had received regular subcutaneous desferrioxamine (DFX) treatment for periods between one and eight years (40 for eight years). The biopsy specimens were examined by light microscopy and immunofluorescence for hepatitis B virus surface and core antigens (HBsAg and HBcAg), and the iron content was determined chemically. The results were compared with serum ferritin concentration and aspartate transaminase (AST) activity and with hepatitis B virus serology. Biopsy specimens, in which chemical liver iron had been determined in 12, were also available from 17 patients. Mean serum ferritin (+/- SD) had fallen from 5885 (3245) micrograms/l to 1638 (976) micrograms/l in 36 patients after eight years' chelation, while mean (+/- SD) liver iron concentration had fallen from 2945 (900) micrograms/100 mg dry weight to 857 (435) micrograms/100 mg dry weight in 12 of them. All biopsy specimens examined were negative for HBs and HBc antigens. The presence of histological features of hepatitis was associated with increased liver iron content, increased fibrosis, and with progression of fibrosis between the two biopsies. Procollagen III peptide was assayed in 28 patients but did not correlate with the degree of hepatitis, fibrosis, or with chemical liver iron content. We conclude that with regular subcutaneous DFX, mean concentrations of serum ferritin and liver iron are maintained in these patients at about five and 10 times the normal value, respectively, and that progression of liver damage is more likely to be due to viral hepatitis, presumably related to the parenterally transmitted non-A, non-B agents than to iron overload.

Adolescent↗

Vasopressin-induced changes in the three-dimensional structure of toad bladder apical surface.

The apical plasma membrane of toad bladder granular cells undergoes a rapid and dramatic increase in water permeability in response to vasopressin stimulation. Previous studies have shown that this permeability increase is accompanied by characteristic changes in the morphology of this membrane and that these changes may be involved in the hormonal response. In this report, we have used the technique of rapid freezing and freeze drying to obtain high resolution stereo images of the surface of the granular cell apical plasma membrane before and during vasopressin stimulation. Using this approach, we confirmed that vasopressin induces a ridge-to-villus transformation of the cell surface even in the absence of osmotic water flow, but now show that this transformation occurs at least in part via a retraction of segments of preexisting ridges, rather than by the growth of new microvilli from the apical cell surface. This is also demonstrated by the finding that vasopressin induces the ridge-to-villus transformation of the cell surface even in the presence of cytochalasin D. In addition, the rapid-freeze, freeze-dry technique reveals that the surface glycocalyx of the epithelial cells consists of a complex, three-dimensional network of filaments that is heterogeneous among different cells. Finally, vasopressin-induced tubular invaginations of the apical plasma membrane were visualized in stereomicrographs, and the number and size of such invaginations were altered in the presence of cytochalasin D. These may represent surface images of vasopressin-induced exo- and endocytotic events that are related to membrane permeability changes.

Animals↗

Exacerbation of hypertension by high chloride, moderate sodium diet in the salt-sensitive spontaneously hypertensive rat.

In salt-sensitive spontaneously hypertensive rats (SHR-S) of the Okamoto strain, dietary salt loading causes an exacerbation of hypertension that is associated with a decrease in noradrenergic input to the depressor neurons in the anterior hypothalamus. In the present study, the contribution of chloride to the salt-induced hypertensive response was examined in the SHR-S, in order to test the hypothesis that diets high in chloride but moderate in sodium elevate blood pressure in genetically predisposed subjects. SHR-S were fed diets high in NaCl (1.97% Na+, 2.93% Cl-; 5% NaCl), high in chloride (2.93%) but moderate in sodium (0.39%) or moderate in NaCl (0.39% Na+, 0.61% Cl-; 1% NaCl). After 2 weeks, rats on the high (5%) NaCl diet exhibited a significant elevation in blood pressure compared to rats on the moderate (1%) NaCl diet, and this elevation was maintained throughout the next 3 weeks. SHR-S on the high chloride diet were not significantly more hypertensive than 1% NaCl-fed SHR-S during the first 3 weeks, but during the fourth and fifth weeks, SHR-S on the high chloride diet displayed a significant exacerbation of hypertension. The diet-induced elevation in blood pressure in groups fed either the 5% NaCl or high chloride (compared to 1% NaCl) diets was associated with significant decreases in norepinephrine stores in the anterior hypothalamic region, but no other changes in monoamines or monoamine metabolites in this region or in the posterior hypothalamic region. The high chloride diet did not increase blood pressure in normotensive Wistar-Kyoto rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stress-induced disruption of parturition in the rat may be mediated by endogenous opioids.

Plasma samples were obtained before and during parturition from conscious rats implanted chronically with a jugular cannula. Rats were either allowed to remain in their nesting cage throughout parturition, or were moved immediately following the birth of the second or third pup into an empty glass chamber. The time-course of parturition was prolonged for mother rats which were moved in mid-parturition to this unfamiliar environment. However, in rats given an i.v. injection of the opioid antagonist naloxone at the time of transfer, parturition followed a normal time-course, and plasma oxytocin levels were significantly higher than in animals injected with saline. Thus our hypothesis is that stress activates opioid pathways which delay parturition by inhibiting oxytocin release. Opioid-mediated mechanisms may similarly be responsible for some problems in human parturition.

Animals↗

The immune response to hepatitis B virus.

Cell-mediated immune response to nucleocapsid determinants, including HBcAg and HBeAg, are important in the clearance of HBV-infected hepatocytes. This process is modulated by interferon and humoral responses to these antigens. Antibodies to the envelope proteins contribute to protective immunity, but the relative importance of pre-S and S determinants in evoking a response and the relative contributions of these antibodies in virus neutralization remains unclear. It is known, however, that antibodies binding to the RFHBs1 epitope on the HBs sequence 124-137 are capable of protecting against further infection and are present in convalescent subjects and in recipients of the plasma-derived and recombinant hepatitis B vaccines. Detailed analysis of the specificity of the anti-HBs response in vaccinees shows it to be qualitatively similar to that seen during recovery from natural infection.

Animals↗

Post-marketing surveillance of enalapril: experience in 11,710 hypertensive patients in general practice.

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).

Adolescent↗

Xiaoke, a traditional Chinese treatment for diabetes. Studies in streptozotocin diabetic mice and spontaneously diabetic BB/E rats.

Xiaoke tea is consumed as a traditional herbal treatment for diabetes mellitus in China. An aqueous extract of Xiaoke (1 g of dried plant preparation in 64 ml of water), supplied ad lib in place of drinking water during the induction and development of streptozotocin diabetes in mice, reduced (about 30%) plasma glucose concentrations by 25 days. The polydipsia and hyperphagia of the streptozotocin diabetic mice were also reduced by Xiaoke, and the effects lapsed after treatment was withdrawn. Xiaoke did not significantly alter plasma insulin concentrations. Consumption of the Xiaoke extract by insulin-treated diabetic BB/E Wistar rats did not affect glycaemic control or body wt. When insulin treatment was reduced and discontinued, Xiaoke failed to prevent the progression of severe hyperglycaemia and weight loss. The results suggest that the slowly generated antihyperglycaemic effect of Xiaoke in streptozotocin diabetic mice may involve an extrapancreatic effect on food intake, glucose production or glucose clearance. However, as evidenced in BB/E rats, Xiaoke does not substitute for insulin in the absence of endogenous insulin secretion.

Animals↗

Transport of horseradish peroxidase from the cell surface to the Golgi in insulin-secreting cells: preferential labelling of cisternae located in an intermediate position in the stack.

We have used serial sectioning to study the topology of Golgi cisternae in insulin-secreting cells during secretion-stimulated endocytotic uptake of exogenous horseradish peroxidase (HRP). HRP-labelled cisternae were followed on several series of consecutive sections. This revealed that labelled cisternae could always be traced to a position in the Golgi stack intermediate between the cis and the trans poles. This occurred in spite of the apparent cis or trans locations of HRP-containing cisternae on some sections. The latter images could be explained by the lack of the true cis or trans (clathrin-coated) cisternae at certain levels of the stack.

Animals↗

Characterization of alcohol dehydrogenase in young soybean seedlings.

Molecular properties of alcohol dehydrogenase (ADH) were examined in young soybean seedlings. Soybean radicle tissue is ADH-rich. Enzyme specific activity decreases slowly with the development of roots and becomes almost undetectable when the first true leaves appear. Soybean ADH was not found to be inducible by flooding. 2,4-Dichlorophenoxyacetic acid (2,4-D) treatment increased ADH specific activity as much as 14-fold. Only one ADH isozyme was detected by isoelectric focusing. By DNA-DNA hydridization, soybean ADH genomic sequences were shown to be partly homologous to maize ADH1 cDNA. The presence of more than one Adh gene in soybean is discussed.

2,4-Dichlorophenoxyacetic Acid↗