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Biomedical subjects

D Burton

Publications and source records attributed to D Burton.

At least 91 records · Page 5Linked to original sources

Further assessment of a pharmacological effect of Tris buffer.

1. Data are presented confirming that Tris buffer can potentiate teleost melanophore responses to noradrenalin, as recently reported for the first time in Poecilia reticulata (Visconti and Castrucci, 1985). 2. In vitro melanophore responses of Pseudopleuronectes americanus were compared in Tris- and bicarbonate-buffered physiological saline solutions. 3. Dose-response curves demonstrate that Tris significantly potentiates melanophore responses to noradrenalin doses between 10(-6) and 10(-5)M in this species. 4. Time-response curves further characterized this effect of Tris on melanophore activity, quantifying the enhancement of the melanosome aggregation rate as well as the dose-related equilibrium levels.

Animals↗

The metabolism of synthetic leukotriene B4 in synovial fluid and whole human blood.

The metabolism in vitro of synthetic leukotriene B4 (LTB4) in synovial fluid from rheumatoid arthritis and osteoarthritis patients and in whole blood from these same patient groups and from normal volunteers has been studied. A linear relationship existed between a plot of the time of incubation of samples with LTB4 and the percentage of the initial concentration of LTB4 at each time point. The slope of this line, the rate constant for metabolism, has been used to compare different samples. LTB4 was metabolised more rapidly in the synovial fluid of rheumatoid arthritis patients than osteoarthritis patients. Furthermore, LTB4 was metabolised more rapidly in the blood of rheumatoid arthritis patients than either osteoarthritis patients or normal volunteers. These differences in metabolism correlate with the polymorphonuclear leukocyte (PMN) and albumin content of samples. It is suggested that binding of LTB4 to albumin in vivo will in part determine the available concentration of LTB4 in inflammatory lesions.

Arthritis, Rheumatoid↗

Crystal-induced inflammation in the rat subcutaneous air-pouch.

Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals initiated acute inflammatory reactions characterized by increased plasma extravasation and polymorphonuclear leukocyte (PMNL) accumulation in the rat subcutaneous air-pouch. Pretreatment of rats with colchicine (1 mg kg-1, s.c.) inhibited PMNL accumulation induced by either crystal type but had a greater inhibitory effect on MSU-induced plasma extravasation compared with that induced by CPPD crystals. Colchicine (1 mg kg-1, s.c.) did not reduce histamine-induced plasma extravasation in the air-pouch. The lipoxygenase product of arachidonic acid metabolism, leukotriene B4 (LTB4), was detected in MSU-induced exudates but not in CPPD-induced exudates. Pretreatment of rats with colchicine (1 mg kg-1, s.c.) inhibited LTB4 production in MSU-induced exudates.

Animals↗

The effects of changes in physical activity on major cardiovascular risk factors, hemodynamics, sympathetic function, and glucose utilization in man: a controlled study of four levels of activity.

The effects of four levels of activity on heart rate, blood pressure, cardiac index, total peripheral resistance index (TPRI), norepinephrine (NE) spillover rate, insulin sensitivity, and levels of lipids and some hormones were studied in 12 normal subjects. The randomized periods were (1) 4 weeks of below-sedentary activity, (2) 4 weeks of sedentary activity, (3) 4 weeks of 40 min of bicycling three times per week, and (4) 4 weeks of similar bicycling seven times per week. Exercise three times per week reduced resting blood pressure by 10/7 mm Hg (p less than .01) and it was reduced by 12/7 mm Hg after exercise seven times per week (both p less than .01). This was associated with reduction in TPRI, an increase in cardiac index, and cardiac slowing. At the highest level of activity, NE spillover rate, an index of sympathetic activity, fell to 35% of the sedentary value (p less than .001) in eight of 10 subjects. In two other subjects NE spillover rate rose, although blood pressure and TPRI were reduced. Metabolic changes included lowering of total cholesterol, but high-density lipoprotein level was unchanged. Insulin sensitivity rose by 27% after exercise three times per week, but declined to sedentary levels with seven times per week exercise. Maximum oxygen uptake increased linearly with activity. Exercise performed three times per week lowers blood pressure and should reduce cardiovascular risk. The same exercise seven times per week enhances physical performance with little further reduction in cardiovascular risk factors. Exercise is potentially a major nonpharmacologic method of lowering blood pressure.

Adult↗

Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.

The analysis of plasma kinetics of the sympathetic neurotransmitter norepinephrine can be used to estimate sympathetic nervous "activity" (integrated nerve firing rate) for the body as a whole and for individual organs. In 12 patients with cardiac failure (left ventricular ejection fraction 10% to 39%), the mean arterial plasma norepinephrine concentration was 557 +/- 68 pg/ml (mean +/- SE) compared with 211 +/- 21 pg/ml in 15 subjects without heart failure (p less than .002). The difference was due to both increased release of norepinephrine to plasma (indicating increased "total" sympathetic activity) and reduced clearance of norepinephrine from plasma. The increase in sympathetic activity did not involve all organs equally. Cardiac (32 +/- 9 vs 5 +/- 1 ng/min; p less than .002) and renal (202 +/- 45 vs 66 +/- 9 ng/min; p = .002) norepinephrine spillover were increased by 540% and 206%, respectively, but norepinephrine spillover from the lungs was normal. Adrenomedullary activity was also increased in the patients with heart failure, whose mean arterial plasma epinephrine concentration was 181 +/- 38 pg/ml compared with 71 +/- 12 pg/ml in control subjects (p less than .02). There is marked regional variation, inapparent from measurements of plasma norepinephrine concentration, in sympathetic nerve activity in patients with congestive heart failure. The finding of increased cardiorenal norepinephrine spillover has important pathophysiologic and therapeutic implications.

Female↗

A novel monoclonal antibody-defined antigen which distinguishes human non-small cell from small cell lung carcinomas.

Spleen cells from BALB/c mice hyperimmunized with the human epidermoid lung carcinoma cell line T222 were fused with NS-1 mouse myeloma cells to produce monoclonal antibodies to human lung cancer antigens. Hybridoma culture supernatants were tested by an enzyme-linked immunosorbent assay for reactivity against a panel of human lung tumor cell lines. Supernatant from hybridoma EA1 (immunoglobulin G1) displayed strong reactivity with four of four non-small cell lung carcinomas but did not react with three of three small cell lung carcinoma (SCLC) cell lines. This hybridoma was cloned by limiting dilution and utilized to generate ascites antibody for subsequent immunohistochemical and antigen characterization studies. Evaluation of fresh frozen tumor tissue sections by immunoperoxidase staining methods revealed EA1 reactivity with the vast majority of non-SCLCs tested (21 of 21 epidermoid, 17 of 18 adenocarcinomas, four of four large cell, two of two bronchioloalveolar) and no reactivity with nine of nine small cell lung carcinomas. EA1 also stained bronchial epithelium and other benign and malignant epithelial tissues. The EA1 antigen was determined to have a molecular weight of 75,000 by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human non-SCLC tumor extracts. These data imply that EA1 recognizes a novel antigen expressed by non-SCLCs and other epithelial tissues. The absence of EA1 reactivity with SCLCs suggests that this monoclonal antibody may find future application in distinguishing non-SCLC from SCLC and prove useful in furthering our understanding of the histogenesis of lung carcinomas.

Adenocarcinoma↗

Epidermal cellular proliferation and differentiation in sexually mature male Salmo salar with androgen levels depressed by oil.

Sexually mature male Salmo salar exhibit epidermal thickening and an increase in goblet cell concentration during the spawning season. The ventral skin, which is likely to experience most abrasive contact during the spawning period, has the thickest epidermis and the greatest goblet cell concentration. Following exposure to crude oil there is inhibition of cellular proliferation and elongation associated with epidermal thickening, and also inhibition of mucigenesis. Data on the androgen levels in these fish, and data from earlier studies involving treatment with hormones, indicate that oil-related epidermal effects during the spawning period are most likely systemic in origin, probably arising from reduced plasmatic androgen levels.

Androgens↗

Covalent modification of bacterial glutamine synthetase: physiological significance.

Stadtman, Holzer and their colleagues (reviewed in Stadtman and Ginsburg 1974) demonstrated that the enzyme glutamine synthetase (GS) [(L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2] is covalently modified by adenylylation in a variety of bacterial genera and that the modification is reversible. These studies further indicated that adenylylated GS is the less active form in vitro. To assess the physiological significance of adenylylation of GS we have determined the growth defects of mutant strains (glnE) of S. typhimurium that are unable to modify GS and we have determined the basis for these growth defects. The glnE strains, which lack GS adenylyl transferase activity (ATP: [L-glutamate: ammonia ligase (ADP-forming)] adenylyltransferase, EC 2.7.7.42), show a large growth defect specifically upon shift from a nitrogen-limited growth medium to medium containing excess ammonium (NH4+). The growth defect appears to be due to very high catalytic activity of GS after shift, which lowers the intracellular glutamate pool to approximately 10% that under preshift conditions. Consistent with this view, recovery of a rapid growth rate on NH4+ is accompanied by an increase in the glutamate pool. The glnE strains have normal ATP pools after shift. They synthesize very large amounts of glutamine and excrete glutamine into the medium, but excess glutamine does not seem to inhibit growth. We hypothesize that a major function for adenylylation of bacterial GS is to protect the cellular glutamate pool upon shift to NH4+ -excess conditions and thereby to allow rapid growth.

Bacterial Proteins↗

How hypertension redevelops after cessation of long-term therapy.

Long-term therapy (1.5-27 years, average 7.5 years) was ceased in 11 patients with essential hypertension. The return of supine hypertension during the ensuing 10 weeks was slow and incomplete, contrasting with previous studies when blood pressure (BP) had been lowered for shorter periods. After prolonged therapy in these patients, non-autonomic total peripheral resistance index (TPRI) was near normal, but left ventricular mass index (LVMI) was still high in six of the 11 patients. The latter was directly related to duration of effective treatment of BP and to BP when therapy was stopped. These findings may indicate that with antihypertensive therapy, structural changes in the peripheral vasculature regress more quickly than cardiac hypertrophy.

Adult↗

Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands.

Chromogranin A is the major soluble protein co-stored and co-released with catecholamines from catecholamine storage vesicles of adrenal medulla and sympathetic nerve. We recently described a widespread distribution of chromogranin, by radioimmunoassay, in all polypeptide hormone producing tissues. To define the microanatomy of this distribution, we studied the immunohistology of chromogranin in normal bovine endocrine tissues using an antibody directed against bovine chromogranin A. The indirect anti-peroxidase technique was used, with a protein A bridge. Chromogranin staining was ubiquitous in polypeptide hormone producing endocrine tissues, and the staining was specific as judged by blockade of the staining reaction by pre-adsorption of the specific antiserum with purified bovine chromogranin A. Staining was present in adrenal medullary chromaffin cells, thyroid parafollicular C cells, parathyroid chief cells, pancreatic islet cells, intestinal enteroendocrine cells, and anterior pituitary cells. Staining was absent from the exocrine portions of these tissues, and from purely exocrine tissues. Thus, chromogranin may have a widespread, though as yet undefined, role in the neuroendocrine secretory process.

Adrenal Medulla↗

Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumors and normal endocrine tissues.

Chromogranin A, the major soluble protein costored and coreleased by exocytosis with catecholamines from the adrenal medulla, has recently been detected in several bovine polypeptide hormone producing tissues. We therefore searched for chromogranin, by immunohistology, in human polypeptide hormone producing tumors as well as normal human endocrine tissues. The chromogranin A antigen was purified from catecholamine storage vesicles of human pheochromocytoma, to which rabbit antisera were developed, allowing immunohistologic studies by the indirect rabbit anti-peroxidase technique. Specific chromogranin staining was noted in all polypeptide hormone producing human tumors studied (pheochromocytoma chromaffin cells, n = 3; medullary thyroid carcinoma parafollicular C cells, n = 2; thyroidal C cell hyperplasia cells, n = 1; parathyroid adenoma chief cells, n = 1; pancreatic islet cell tumor islet cells, n = 1; oat cell carcinoma cell line M-103) as well as in all normal polypeptide hormone producing tissues (adrenal medulla chromaffin cells, parathyroid chief cells, thyroid parafollicular C cells, pancreatic islet cells, gut enteroendocrine cells, and anterior pituitary cells). Chromogranin may have a widespread distribution in human polypeptide hormone producing tissues, and may be a useful histologic marker for peptide producing tumors.

Adrenal Gland Neoplasms↗

Partial purification of the epidermal G2 chalone based on an in vivo assay system.

The epidermal G2 chalone was partially purified from hairless mouse skin extracts by means of chromatography and ultrafiltration and tested in vivo on hairless mouse epidermis. The active component had a molecular weight of less than 10,000 daltons. It significantly but had no effect on epidermal cells at the G1/S transition. Extracts from mouse spleen or skeletal muscle treated in the same way as the skin extracts had no inhibitory effect on epidermal G2 cells.

Animals↗

Distribution of immunoreactive calcitonin in the rat pituitary gland.

Immunohistochemical (immunoperoxidase) studies were performed on 478 sections from 97 rat pituitary glands with rabbit antisera to unconjugated human synthetic calcitonin beta-endorphin, and/or ACTH-(17--39). Calcitonin-positive cells were present in a majority of the anterior lobes studied, whereas they were present in only a minority of the intermediate lobes. Calcitonin-positive cells were also present in chronically thyroidectomized animals. Beta-Endorphin-positive cells were uniformly present in the intermediate lobes as were the ACTH-positive cells. In the anterior pituitary lobes, beta-endorphin-positive cells were more populous than the ACTH-positive cells, and in general, there was a dissociation of the cellular elements containing beta-endorphin, ACTH, and calcitonin. Although it remains possible that there is calcitonin-like immunoreactivity within a precursor molecule that is differentially processed by pituitary cells, these studies are more consistent with the view that immunoreactive calcitonin is present in pituitary cells which are not as yet precisely and consistently related to any identifiable population of hormone-producing cells.

Animals↗

Nitrogen control in Salmonella: regulation by the glnR and glnF gene products.

The product of the glnR gene is required for nitrogen regulation of the synthesis of glutamine synthesis (Gln synthetase) [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] and two periplasmic transport proteins that are subject to nitrogen control in Salmonella. Strains with mutations to loss of function of the glnR product [e.g., a strain with a Tn10 insertion or one with an ICR-induced (frameshift) mutation in glnR] have about 3% as much Gln synthetase as a fully derepressed wild-type strain and are unable to increase synthesis of this enzyme or periplasmic transport proteins in response to nitrogen limitation. The structural gene for Gln synthetase, glnA, and those for the periplasmic transport proteins are unlinked on the chromosome; thus, glnR appears to encode a diffusible positive regulatory element. Consistent with this, the mutant glnR allele is recessive to the wild-type allele with regard to expression of glnA (synthesis of Gln synthetase). Although glnR is closely linked to glnA, strains with mutations to complete loss of function of the glnR product can be distinguished from glnA strains by their ability to produce detectable Gln synthetase and to grow in the absence of glutamine. To demonstrate unequivocally that glnR is distinct from glnA, we have purified and characterized Gln synthetase from a strain with a Tn10 insertion in glnR. Because the properties of Gln synthetase from the insertion mutant, most importantly the carboxyl-terminal sequence of amino acids, are the same as those of synthetase from wild type, the Tn10 insertion cannot be in glnA (if it were, the carboxyl terminus of Gln synthetase would have to be altered); therefore we conclude that the Tn10 insertion is in a regulatory gene, glnR, which is distinct from glnA. A model for the function of the glnR product together with the previously defined glnF product in mediating nitrogen control is discussed.

Carrier Proteins↗

[Dietary fiber].

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Cellulose↗