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Biomedical subjects

N Noble

Publications and source records attributed to N Noble.

12 recordsLinked to original sources
PubMed2006

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis.

Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

Animals↗
PubMed2001

Maximizing hemodynamic-independent effects of angiotensin II antagonists in fibrotic diseases.

Better understanding of the hemodynamic-independent actions of the renin-angiotensin system (RAS) may lead to improved therapies for heart, kidney, and liver fibrosis. The conventional view of the RAS is that its role is solely hemodynamic. Pharmacologic blockade of the RAS is beneficial in treating hypertension, as well as primary renal and cardiac diseases. Recent findings from clinical trials and several laboratories that used different experimental approaches have revealed a whole new dimension to the RAS that is beyond the realm of hemodynamics. The RAS is best viewed as part of a system of interconnected molecules biologically designed to be activated after tissue injury to promote tissue repair and, when in excess, tissue fibrosis. This new understanding of the RAS has important clinical implications. It predicts and explains why blockade of the RAS with angiotensin-converting enzyme inhibitors (ACEI), the newer receptor antagonists, or both together, will significantly slow the progression of fibrotic disease. However, it further suggests that higher doses and/or a combination of angiotensin II blockade with another agent or agents might truly halt progressive fibrosis.

Angiotensin II↗
PubMed1981

Effects of delipidated serum and lipoprotein-deficient serum on sterol biosynthesis and efflux in cultured skin fibroblasts - a comparison of the behaviour of cells from a control with those from a heterozygote and homozygote for familial hypercholesterolaemia.

The biosynthesis and efflux of sterols from cells into the medium were investigated in skin fibroblasts from a control, a patient with obligate heterozygous familial hypercholesterolaemia and a patient with the homozygous condition. The behaviour of the cells was studied in two lipid free media (lipoprotein deficient and delipidated serum), with and without the addition of low density lipoproteins (LDL) in order to find experimental conditions which showed maximum differences between the three cell lines. Incorporation of [14C]acetate into sterols in the presence (repression) and absence (induction) of LDL was similar in the normal and heterozygous cells, whereas the homozygous cells showed reduced repression and increased induction. In all three cell lines induction of sterol synthesis was greater with delipidated than lipoprotein deficient serum. The efflux of sterols in both the presence and absence of LDL did not differ between the three cell lines, but it was greater when LDL was added to the medium and when delipidated serum was used. Sterol biosynthesis and efflux from the cells of the heterozygote did not differ significantly from those of the control.

Adult↗
PubMed1981

Effect of buffer constituents on rat liver 3-hydroxy-3-methyl glutaryl coenzyme A reductase.

Rat liver microsomes prepared in Tris buffer exhibited 3 to 10 times higher 3-hydroxy-3-methyl glutaryl CoA reductase specific activity than microsomes prepared with potassium phosphate buffer. This higher activity was observed in rats killed during mid-light cycle, but microsomes from rats killed during mid-dark cycle showed no significant difference in enzyme activity between buffers. When microsomes prepared in the 2 different buffers were preincubated with ATP and MG++, enzyme activity was inhibited to the same extent. The cytosol fraction in each of the 2 different buffer preparations possessed similar phosphatase activity. The higher 3-hydroxy-3-methyl reductase activity in Tris buffer, therefore, does not appear to be due to differences in phosphorylation or dephosphorylation activity.

Adenosine Triphosphate↗
PubMed1981

Infected ventricular septal defect.

This paper reports a case of recurrent septic pulmonary emboli resulting from bacterial endocarditis on a ventricular septal defect. This was managed by the removal of vegetations, resection of the septal leaflet of the tricuspid valve, closure of the ventricular septal defect, and pulmonary embolectomy. The literature regarding the incidence and mortality of bacterial endocarditis on ventricular septal defects, and the management of the infected tricuspid valve, is reviewed. The patient remains well two and a half years after surgery.

Adult↗
PubMed1978

Association in Long-Evans hooded rats of red cell 2,3-diphosphoglycerate levels with hemoglobin types.

Two sublines of commercially available Long-Evans hooded rats have been developed by genetic selection. These sublines have widely differing levels of erythrocyte 2,3-diphosphoglycerate (DPG) due to different alleles at a single genetic locus. In the present work, it is shown that rats from the commercial population are also polymorphic at a hemoglobin locus, probably involving two alleles of the IIIbeta-globin chain locus. Particular hemoglobin types have been found to be strongly associated with certain DPG types, not only in the high-DPG and low-DPG lines but also in the commercial population. Two explanations for this association are considered. One is a single-locus hypothesis, with hemoglobin allelic variation causing DPG variation, and the other is a two-locus hypothesis, with marked linkage disequilibrium.

Alleles↗
PubMed1977

Lipid and lipoprotein concentrations in 1604 men and women in working populations in north-west London.

Serum lipid and lipoprotein concentrations in men and women vary with age, and so-called "normal" limits should take account of this. Serum cholesterol, triglyceride, and phospholipid concentrations were measured in 1027 men and 577 women in five working populations in north-west London, and lipoprotein electrophoresis and quantitative analyses of lipoprotein concentrations were also performed. In men the best fit between serum cholesterol, triglycerides, and phospholipids, on the one hand, and age, on the other, was given by a curvilinear relationship expressed as a quadratic regression. In women the best fit was given by a linear regression. White men had higher serum cholesterol and triglyceride concentrations than Black men, and these differences were reflected in the distributions of the lipoproteins. There were no differences between values in White and Black women. Young women on oral contraceptives had lipid concentrations similar to those of older women not on these preparations. These data suggest that the adoption of concentrations of serum cholesterol (275-300 mg/100 ml (7-1-7-8 mmol/l) and triglycerides (175-200 mg/100 ml (2-0--2-3 mmol/l) recommended by a recent report on the prevention of coronary disease as limits above which special attention should be given to the management of hyperlipidaemia could result in as few as 2% of younger men or as many as 31% of older men being selected for treatment.

Adolescent↗