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Biomedical subjects

R Hay

Publications and source records attributed to R Hay.

At least 19 recordsLinked to original sources
PubMed1992

Histoplasmosis of the central nervous system.

Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed.

Adrenal Glands↗
PubMed1992

[Regulation of sterol carrier protein-2 in human luteal cells by LH and LH-RH].

Conversion of cholesterol to pregnenolone is the most important and, at the same time, the rate-limiting step of steroidogenesis. Sterol carrier protein-2 (SCP2) or nonspecific lipid transfer protein (nsL-TP) is an intracellular protein, which plays an important role in the pre- and transmitochondrial transport of cholesterol and for the mitochondrial synthesis of pregnenolone. Synthesis of pregnenolone in rat Leydig cells can be increased by LH and LH-RH; however, only LH leads to characteristic changes in intracellular concentrations of SCP2. This means that synthesis of pregnenolone is regulated in two different ways. In this study we aimed to find out whether such a 'second way' of steroidogenesis is also demonstrable for the human corpus luteum (i.e. human luteal cells). Human luteal cells were collected during follicle punctures and were cultured as described previously. We demonstrate that (human) LH/hCG are able to enhance pregnenolone synthesis; this process is accompagnied by typical changes of SCP2 and an increase in activity of 7-dehydrocholesterol reductase, which is a marker enzyme for SCP2. LH-RH was shown to exert no effect. Thus, we conclude that a second way of steroidogenesis (i.e. synthesis of pregnenolone) cannot be proved for the human corpus luteum.

Carrier Proteins↗
PubMed1991

Monoclonal antibodies to periodontal ligament cells.

Ten mouse monoclonal antibodies were prepared against cultured bovine periodontal ligament cells to be used as reagents for the study of periodontal disease and wound healing. Using standard immunohistochemical methods, these antibodies were found to recognize cell surface antigens in formalin-fixed bovine periodontium. Three of the 10 monoclonal antibodies (i.e., PDL-1, PDL-2, and PDL-10) cross-reacted with cells found in primate periodontium. While the isolated monoclonal antibodies appeared to distinguish subpopulations of cells located in the supporting tissues of teeth, immunohistological examination of other organs (dermis, kidney, skeletal muscle, thyroid, and parotid gland) indicated that a number of cell types of mesenchymal origin share an antigen(s) found on periodontal cells. The monoclonal antibodies described in this report should prove to be useful in studies of periodontal disease and guided tissue regeneration by providing both analytical reagents and immunochemical methods for isolating selected cell populations of the periodontium.

Animals↗
PubMed1989

Biogenesis of plasma lipoproteins in rat hepatoma McA-RH7777: importance of diffusion-mediated events during cell growth.

Cultured McA-RH7777 rat hepatoma cells actively synthesize and secrete plasma lipoproteins. However, synthesis of [14C]triglyceride declines monotonically throughout the early growth period and remains low in postconfluent cultures; and net secretion of [14C]triglyceride is 10-fold more efficient in logarithmically growing cultures than in postconfluent cultures. Secretion of apolipoproteins associated with very low density and low density lipoproteins is selectively reduced in postconfluent cultures. The temporal reductions in [14C]triglyceride production are related more strongly to increasing cell concentration (cells/cm3 medium) than to increasing cell density (cells/cm2 growth surface). We have allowed cells to grow either retained within small circular corrals or unrestricted in culture dishes. When seeded at equal density (10(4) cells/cm2) but at one-fifth the cell concentration, corralled cells synthesize twice as much [14C]triglyceride per cell after 2 and 4 d, and are 10 times as efficient in [14C]triglyceride secretion by 6 d of growth, as noncorralled cells. When seeded at equal cell concentration (10(5) cells/dish) but at 5 times the cell density, corralled cells are only 20% less efficient at [14C]triglyceride synthesis and secretion than noncorralled cells. Conditioned medium depresses synthesis and secretion efficiency of [14C]triglyceride. Orotic acid exposure also inhibits synthesis of [14C]triglyceride and secretion of certain [35S]apolipoproteins in early cultures, but it has no significant effect on late cultures. We conclude that diffusion-mediated events are important regulators of triglyceride and apolipoprotein production in growing rat hepatoma cells, but that events associated with formation of cell-to-cell contacts play a minor role in regulation of plasma lipoprotein biogenesis.

Albumins↗
PubMed1988

Purification and characterization of the pore forming protein of yeast mitochondrial outer membrane.

One of the major outer membrane proteins of yeast mitochondria was isolated and purified. It migrated as a single band with an apparent molecular weight of 30 kDa on a SDS-electrophoretogram. When reconstituted in lipid bilayer membranes the protein formed pores with a single channel conductance of 0.45 nS in 0.1 M KCl. The pores had the characteristics of general diffusion pores with an estimated diameter of 1.7 nm. The pore of mitochondrial outer membranes of yeast shared some similarities with the pores formed by mitochondrial and bacterial porins. The pores switched to substates at voltages higher than 20 mV. The possible role of this voltage-dependence in the metabolism of mitochondria is discussed.

Intracellular Membranes↗
PubMed1988

Apolipoproteins of the orotic acid fatty liver: implications for the biogenesis of plasma lipoproteins.

Rats fed orotic acid develop fatty livers characterized by triglyceride-laden, membrane-bounded vesicles designated "liposomes." We have measured the levels of apolipoproteins in isolated liposomes and other subcellular fractions by SDS-polyacrylamide gel electrophoresis, electrotransfer, and immunodecoration. Apolipoproteins Bh, Bl, E, and C appear to cofractionate; for these proteins, the liposomal pool represents a large portion of their total intracellular mass. However, liposomes are deficient in both variants of apoB relative to apoE and apoC when compared with rat plasma very low density lipoprotein (VLDL). Albumin and apolipoproteins A-I and A-IV are also found in liposomes, but this organelle represents a minor fraction of their total intracellular mass. The liposomal apolipoproteins show varying degrees of association with cisternal lipid and with organelle membranes. Orotic acid may selectively block VLDL production at the level of particle assembly or transorganellar movement. We conclude that liposomal contents probably represent exaggerated accumulations of VLDL assembly intermediates, and that the intracellular partitioning of high density lipoprotein-destined from VLDL-destined components occurs at an early stage in particle biogenesis. Moreover, some unique structural feature of apoB may effect movement of VLDL assembly intermediates through secretory organelles.

Animals↗
PubMed1987

Nutrition and biogenesis of plasma lipoproteins in nonhuman primates.

In this article we examine the production of very low-density lipoprotein (VLDL) by perfused livers obtained from chow- and cholesterol-fed nonhuman primates. These data illustrate two important features of VLDL production. First, VLDL is secreted from the liver in a form very close to that of its plasma counterpart. Thus for chow-fed animals, plasma VLDL and liver perfusate VLDL have similar lipid compositions. Second, the composition of VLDL can be modified significantly by diet in each of two primate species, the Rhesus monkey and the baboon. Rhesus monkey livers uniformly secrete larger quantities of VLDL and show more dramatic dietary effects than do baboon livers. Nevertheless, perfused livers from both species reveal qualitatively similar responses to dietary peanut oil and to lard fed in combination with cholesterol. Both fat-containing diets induce the livers to secrete VLDL enriched in cholesteryl ester compared with control perfusates yet still cholesteryl ester deficient compared with the animals' plasma VLDL. Peanut oil diet reduces the hepatic output of VLDL-associated apoprotein B and triglyceride, whereas lard increases hepatic secretion of VLDL-associated lipids and apoprotein E. We conclude that the nature of dietary fat plays an important role in determining the profile and composition of lipoproteins formed and secreted by the primate liver. We have also briefly reviewed the production of high-density lipoprotein, which is probably formed in the plasma from many sources, with special emphasis on the possible role of newly secreted lipid-poor apolipoprotein A-I and A-II.

Animals↗
PubMed1987

The infectious aetiology of tropical ulcer--a study of the role of anaerobic bacteria.

We have cultured anaerobic bacteria from patients with tropical ulcers. Fusobacteria were isolated most frequently. Anaerobes were always present, together with aerobes or facultative anaerobes, particularly in early phase ulcers, suggesting that the combination of organisms is important in the pathogenesis of the disease. Spirochaetes were identified in material examined by light and electron microscopy, but were not cultured.

Adolescent↗
PubMed1987

Light and electron microscopic features of tropical ulcer.

The histopathological features of 20 tropical ulcers with the electron microscopic findings on seven biopsy specimens are reported. The main findings were loss of epidermis associated with extensive dermal oedema, infiltration by polymorphonuclear leucocytes, and disruption of collagen bundles. The presence of micro-organisms at the site of tissue damage was shown and compared with the morphology of the organisms grown in culture. The most commonly identified bacteria were pleomorphic rods whose electron microscopic appearances accorded most closely with Fusobacteria grown in vitro. Spirochaetes, identified ultrastructurally as Treponema sp, were also present. There was no evidence of vasculitis to explain the rapid onset of ulceration, but necrotic changes seen in the dermis and the inflammatory cell infiltrate suggest that, associated with cell necrosis, bacteria previously shown in vitro have an important role in the pathogenesis of tropical ulcers.

Bacteroides↗
PubMed1986

Cross-linking analysis of yeast mitochondrial outer membrane.

By enrichment of contact sites between the two mitochondrial boundary membranes it has been shown that this fraction contained a high activity of glutathione transferase and hexokinase which was bound to the outer membrane pore protein (Ohlendieck, K. et al. (1986) Biochim. Biophys. Acta 860, 672-689). Therefore, an interaction between the three proteins in the contact sites has been suggested. Cross-linking experiments with isolated outer membrane of yeast mitochondria show that glutathione transferase and the pore protein are already associated in the free outer membrane. Porin appeared to adopt four different oligomeric complexes in the membrane, including interactions with a 14 kDa polypeptide, which has glutathione transferase activity. The latter polypeptide could be phosphorylated by intrinsic or extrinsic protein kinases, while the porin itself was not phosphorylated. Yeast hexokinase, when bound to the outer membrane, was able to cross-link to the pore protein.

Cell Membrane↗
PubMed1986

Neurofibromatosis.

Since first so named in 1882, von Recklinghausen's disease has been reported to have a wide variety of associated defects, including the more common intracranial and extracranial neuromas and the less common intracerebral tumors and large artery ectasias, aneurysms, and spontaneous fistulas, in addition to a variety of small vessel tumors and arteriovenous fistulas. A case is reported with the association of a vertebral artery spontaneous fistula along with spontaneous spinal fluid rhinorrhea and a Chiari type I malformation. Review of the literature reveals no report of either of the latter two associated with von Recklinghausen's disease.

Arteriovenous Fistula↗
PubMed1986

Alterations in molecular structure of renal mitochondria associated with cyclosporine A treatment.

We examined whether ultrastructural changes in renal mitochondria associated with Cyclosporine A treatment might reflect underlying alterations in mitochondrial molecular structure. A nonrejected renal transplant removed from a patient treated with Cyclosporine A showed a decreased level of beta subunit antigen of mitochondrial F1-ATPase compared to controls. This decrease was more marked in the medulla than in the cortex (56% vs. 70% of pooled controls). Spontaneously hypertensive rats treated with a high dose of Cyclosporine A showed a similar decrease of beta-subunit antigen in the renal medulla and decreased levels of two subunit antigens of cytochrome c oxidase, but had increased medullary levels of the alpha subunit antigen of the F1-ATPase. Such changes were not detected in a normotensive strain of rats. Our data indicate that Cyclosporine A administration is associated with structural alterations in renal mitochondria at the molecular level, predominantly in the medulla, and that additional renal damage due to ischemia or hypertension may predispose to this cyclosporine effect.

Adenosine Triphosphatases↗
PubMed1979

Translation in vivo and in vitro of proteins resembling apoproteins of rat plasma very low density lipoprotein.

Antibodies raised against rat plasma apoVLDL and a purified fraction of arginine-rich peptides (ARP) were labeled with Na125I and were shown to bind to polyribosomes isolated from rat liver. Antibody fractions enriched by selective affinity chromatography exhibited increased levels of binding to polysomes. Anti-apoVLDL immunoreactivity was further resolved into anti-ARP and anti apoB components, each reactive with a distinct polysome population. Binding was specific for rat polysomes, and was directed toward nascent polypeptide chains. About 2% of normal rat liver polysomes were recovered by indirect immunoprecipitation with anti-apoVLDL. Ribonucleic acid (RNA) extracted from this immunoprecipitate contained species with polyadenylate (poly[A] sequences characteristic of eukaryotic messenger RNA (mRNA). These species, purified by affinity chromatography on poly(U)-Sepharose, stimulated the in vitro synthesis of immunoprecipitable apoVLDL-like proteins by about 17-fold when compared to unfractionated rat liver mRNA. Most of the in vitro translation products precipitated by purified anti-ARP migrated identically on polyacrylamide gel electrophoresis with unlabeled purified ARP. Some implications of these findings with respect to plasma VLDL biosynthesis are discussed.

Animals↗