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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 235 records · Page 13Linked to original sources
PubMed1985

(TAA)n within sequences flanking several intrachromosomal variant surface glycoprotein genes in Trypanosoma brucei.

In Trypanosoma brucei telomeric copies of intrachromosomal variant surface glycoprotein (VSG) genes are produced through a gene conversion mechanism and are expressed if the telomere is or becomes transcriptionally activated. We have analyzed a sequence that occurs 1 to 1.5 kb 5' to several intrachromosomal VSG genes. This flanking sequence has three distinct sections: a 5' section containing 5 to 116 TAA or TAA-like tandem repeats; a moderately conserved sequence with an alternating GT characteristic; and a highly conserved 3' sequence that is largely alternating TA. Restriction mapping data and the location of this sequence suggest that it occurs at or near the 5' gene conversion boundary. This sequence, however, is not 5' to all VSG genes. These data suggest that this flanking sequence alone is not sufficient for VSG gene expression but that it may function in gene conversion for many, but not all, VSG genes.

Animals↗
PubMed1985

Histologic diagnosis of benign adnexal skin tumors. An algorithmic approach.

Adnexal lesions have traditionally been classified according to their histogenesis. Frequently this approach is not particularly helpful in the initial evaluation of these lesions. A diagnostic algoithm based on morphologic characteristics alone provides a more orderly and logical approach to their diagnosis.

Adenoma↗
PubMed1985

Human C5a modulates monocyte Fc and C3 receptor expression.

FcIgG and C3 (CR1 and CR3) receptors are responsible for binding opsonized particles, phagocytosis, and immune adherence reactions by circulating and tissue-fixed mononuclear phagocytes. Alterations in the expression of these receptors may thus significantly influence the function of these cells. Because chemoattractants have been shown to both recruit and modulate the function of monocytes, this study specifically examines the effects of human C5a and N-formyl-methionyl-leucyl-phenyl-alanine (FMLP) on human peripheral blood monocyte FcIgG and C3 receptor expression in vitro. Adherent, elutriator-purified monocytes were incubated with C5a (10(-7) to 10(-10) M) or FMLP (10(-5) to 10(-10) M) for 30 min at 37 degrees C, and FcIgG receptor expression was assessed by rosetting with sheep erythrocytes sensitized with limiting dilutions of IgG. Human C5a caused dose-related increases in Fc rosettes of 28% at 10(-9) M, 63% at 10(-8) M, and 167% at 10(-7) M (p less than 0.01). In contrast, no significant increases in monocyte Fc receptor expression were induced by FMLP. Similar rosetting experiments were performed with sheep erythrocytes opsonized with limiting amounts of human C3b to assess C3b receptor expression on adherent human monocytes stimulated with C5a (10(-7) to 10(-10) M) or FMLP (10(-6) to 10(-9) M) for 30 min at 37 degrees C. Again, human C5a caused dose-related increases in monocyte C3b rosette formation; at 10(-8) M and 10(-7) M concentrations of C5a, these increases equaled 119% and 196%, respectively (p less than 0.05). In these experiments, 10(-6) M FMLP also caused a significant increase of 110% in monocyte C3b rosette formation (p less than 0.05). Modulation of monocyte cell surface receptors by human C5a or FMLP was also examined by measuring cell fluorescence and side scatter by dual channel flow cytometry after staining normal leukocytes in citrated venous blood with receptor-specific monoclonal antibodies. These flow cytometric studies demonstrated that both C5a and FMLP induce dose-related increases in CR1 (C3b receptor) and CR3 (iC3b receptor) expression in both monocytes and neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)

Complement C5↗
PubMed1984

The effects of extracellular K+ and angiotensin II on cytosolic Ca++ and steroidogenesis in adrenal glomerulosa cells.

We evaluated changes in cytosolic calcium concentration (Ca++) and steroidogenesis in rat adrenal glomerulosa cells (GC) stimulated with potassium (K+) or angiotensin II (AII). Cytosolic Ca++ concentration was determined using the Ca++-sensitive, fluorescent dye QUIN 2. Raising extracellular K+ increased cytosolic Ca++ from 267 +/- 23 nM at 3.7 mM K+ to a maximum of 377 +/- 40 nM at 8.7 mM K+ (p less than 0.01, N = 23). AII also increased cytosolic Ca++ from 238 +/- 20 nM to a maximum of 427 +/- 42 nM at 10(-7) M (p less than 0.01, N = 16). In parallel studies, K+ and AII stimulated aldosterone secretion from QUIN 2-loaded GC at concentrations similar to those which raised cytosolic Ca++. QUIN 2-loaded cells were as responsive steroidogenically as unloaded cells and showed trypan blue exclusion of 98% suggesting that QUIN 2 did not compromise cellular viability. These results provide direct support for a role of cytosolic Ca++ as a second messenger during stimulation of aldosterone secretion by both K+ and AII.

Adrenal Cortex↗
PubMed1984

Reversible structure transition in gap junction under Ca++ control seen by high-resolution electron microscopy.

Deoxycholate-extracted rat liver gap junction was studied by high-resolution low-dose electron microscopy. Communicating channels between two adjoining cells supposedly form along the common axis of two apposed hexameric trans-membrane protein assemblies. These double hexamers are often arranged in large plaques on an ordered hexagonal net (8-9 nm lattice constant) and seem able to undergo structural alteration as a possible permeability control mechanism. Calcium is widely reported to uncouple gap junction, and we observed this alteration on exposure to Ca++ down to 10(-4) M concentration. When EGTA was added at matching concentrations, the alteration was reversible several times over one hour, but with considerable variability. It was imaged in the absence of any negative stain to avoid ionic and other complications. The resulting lack of contrast plus low-dose "shot" noise required digital Fourier filtering and reconstruction, but no detail was recovered below 1.8 nm. In other experiments with negative stain at neutral pH, gap junction connexons were apparently locked in the "closed" configuration and no transition could be induced. However, recovery of repeating detail to nearly 1.0 nm was possible, reproducibly showing a fine connective matrix between connexons . Whether this was formed by unfolded portions of the 28,000-dalton gap junction protein is not known, but its existence could explain the observed lattice invariance during the connexon structural transition.

Animals↗
PubMed1984

Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterisation.

Characterisation of receptor-mediated breakdown of inositol phospholipids in rat cortical slices has been performed using a direct assay which involves prelabelling with [3H]inositol. When slices were preincubated with [3H]inositol, lithium was found to greatly amplify the capacity of receptor agonists such as carbachol, noradrenaline, and 5-hydroxytryptamine to increase the amount of radioactivity appearing in the inositol phosphates. Using a large variety of agonists and antagonists it could be shown that cholinergic muscarinic, alpha 1-adrenoceptor, and histamine H1 receptors appear to be linked to inositol phospholipid breakdown in cortex. The large responses produced by receptor agonists allowed a clear discrimination between full and partial agonists as well as quantitative analysis of competitive antagonists for each receptor. Whereas carbachol and acetylcholine (in the presence of a cholinesterase inhibitor) were full agonists, oxotremorine and arecoline were only partial agonists. Very low concentrations of atropine shifted the carbachol dose-response curve to the right and allowed inhibition constants for the antagonist to be easily calculated. The nicotinic antagonist, mecamylamine, was ineffective. Noradrenaline adrenaline were full agonists at alpha 1-adrenoceptors, but phenylephrine and probably methoxamine were partial agonists. Prazosin, but not yohimbine, potently and competitively antagonised the noradrenaline inositol phospholipid response. Mepyramine but not cimetidine competitively antagonised the histamine response. These data provide strong confirmation for the potentiating effect of lithium on neurotransmitter inositol phospholipid breakdown and emphasise the ease with which functional responses at a number of cortical receptors can be characterised.

Animals↗
PubMed1983

Comparison of the high-mobility-group chromosomal proteins in rainbow-trout (Salmo gairdnerii) liver and testis.

Chromatography and characterization of the proteins extracted by 5% (w/v) HClO4 from rainbow-trout (Salmo gairdnerii) liver and testis show that the two tissues present a characteristically different spectrum of high-mobility-group (HMG) proteins. A variant subfraction of HMG C is found in liver, but is not detectable in testis, where even the main fraction of HMG C is present in only very low quantity. A protein, F, which appears to be related to protein H6 has similarly been isolated only from liver and not from testis. Quantification of the HMG proteins in total 5%-HClO4 extracts of trout liver and testis nuclei shows that, in relation to DNA, levels of HMG T1 and T2, and D are more than 2-fold, and C, 20-fold higher in liver than in testis. However, these differences do not result merely from the sequential withdrawal of HMG proteins at the same time that histones are replaced by protamines in the developing spermatid, since in testis, at some stages of maturation, levels of H6 are almost 2-fold higher than in liver. The implications of these findings for the function of HMG proteins are discussed.

Amino Acids↗
PubMed1983

Isolation from trout liver of a methionine-containing H1 subfraction, THImet.

A trout H1 subfraction, THImet, which contains one residue of methionine and a blocked N-terminal amino acid, has been isolated from trout liver. Cyanogen bromide cleavage of THImet and amino acid analysis and polyacrylamide gel electrophoresis of the cleavage products show that it contains a residue of methionine at about the same distance from the N terminus as mammalian H1o and avian H5. THImet is shown to be similar to, but not identical with, the protein derived from trout erythrocytes generally accepted as the equivalent in fish of avian H5.

Animals↗
PubMed1983

Coronary bypass surgery in juvenile onset diabetes.

Atherosclerotic cardiovascular disease is the major cause of death in insulin-dependent diabetics of juvenile onset (JODM). This report summarizes our experience in coronary artery bypass surgery performed between 1971 and 1980 on 13 JODM patients. Preoperatively, 12 of 13 patients had NYHA class IV symptoms with 78% of patients having either left main or multivessel coronary artery disease. With a mean follow-up of 4 years, 12 of 13 patients are alive and 8 of 12 are either NYHA class I or II. We conclude that in a select subset of JODM, bypass surgery can be performed with a low operative morbidity and mortality and results in long-term symptomatic improvement.

Adolescent↗
PubMed1983

Combining accurate defocus with low-dose imaging in high resolution electron microscopy of biological material.

High resolution (less than 2 nm) electron microscopy of biological specimens requires three exacting conditions to be met simultaneously: (a) fine specimen detail must be protected from destruction by the electron beam (low dose), (b) the electron optics must be adjusted to be capable of imaging that detail interpretably (accurate defocus), and (c) a suitable field of interest must be identified. We describe a method encompassing all three with an 80% success rate using only minor modifications to a transmission electron microscope, and no expensive on-line computing.

Animals↗
PubMed1983

Psychological, hormonal, and weight disturbances in functional amenorrhea.

The authors studied functional secondary amenorrhea in young women. There was a high incidence of weight disturbance. Hormone assays demonstrated a diminution of hypothalamic-pituitary function in the underweight group. The findings from psychiatric interviews and psychological testing revealed the prevalence of psychopathology with disorders of self concept, confusion of body image, faulty mechanisms of defence in dealing with affects and impulses and disturbances of interpersonal relationships. The onset of amenorrhea was often related to situations of stress. The results suggested that psychological factors were primary in the development of functional secondary amenorrhea.

Adult↗
PubMed1983

Effects of extracellular Ca++ and Mg++ on cytosolic Ca++ and PTH release in dispersed bovine parathyroid cells.

We studied the effects of varying extracellular concentrations of Ca++ and Mg++ on cytosolic Ca++ concentration and PTH release by incorporating the Ca++-sensitive, fluorescent dye "QUIN 2" into dispersed bovine parathyroid cells. Increasing extracellular Ca++ from 0.5 to 2.0 mM led to a dose-dependent increase in cytosolic Ca++ from 179 +/- 8 to 646 +/- 68 nM (mean +/- SE, N = 13; P less than 0.01), which correlated closely (r = -.987, P less than .001) with the suppression of PTH secretion by the same Ca++ concentrations. Raising extracellular Mg++ from 0.5 to 3 mM also caused a dose-related increase in cytosolic Ca++ from 176 +/- 10 to 277 +/- 15 nM (N = 12, P less than 0.01) which correlated (r = -.959, P less than .01) with inhibition of PTH release. These results show a close inverse relationship between cytosolic Ca++ and PTH release with alterations in extracellular Ca++ or Mg++. Cytosolic Ca++ may, therefore, act as a second messenger mediating the effects of these divalent cations on PTH release.

Aminoquinolines↗